Artículo 1 Risk factors for Clostridium difficile diarrhea in patients with inflammatory bowel disease ABSTRACT Background: Despite the growing incidence of Clostridium difficile diarrhea (CCD) in patients with inflammatory bowel disease (IBD), little is known about the associated risk factors. Method: A retrospective study comparing cases of CCD in patients with IBD to IBD carriers who did not develop CCD. A comparison was also made with patients who developed CCD but did not suffer IBD. Results: Three cases (20 %) with IBD and CCD had received antibiotics during the previous three months versus none of the controls (IBD without CCD, p = 0.22). Ten cases (67 %) received treatment with proton pump inhibitors (PPIs) versus 2 (13 %) in the control group (IBD without CCD, p = 0.001). Seven cases underwent colonoscopy and pseudomembranes were seen in one (14 %). Fourteen (93 %) patients demonstrated a favourable response to metronidazole. Patients with IBD and CCD presented with younger age (36 ± 10 years), a higher degree of community-acquired infection (13 patients, 87 %), immunosuppressive treatment (7 patients, 47 %) and less patients had received previous antibiotic treatment (3 patients, 20 %) than those with CCD without IBD. The proportion of patients who received treatment with PPIs was similar (66 % and 80 %, respectively p = 0.266). Conclusions: CCD in IBD carriers affects younger patients, the majority are community acquired (less nosocomial) and it is more related to previous treatment with PPIs than with the antibiotic treatment. Clinical evolution is also favourable. Key words: Clostridium difficile. Inflammatory bowel disease. Ulcerative colitis. Crohn's disease. Antibiotic-associated diarrhea. Metronidazole. Introduction The incidence of diarrhea due to C. difficile associated to IBD has increased over the last few years, being higher than the incidence found in the general population (1-5). This anaerobic, spore-forming bacterium is capable of producing toxins that give rise to disruption and inflammation of the colonic mucosa and, occasionally, can cause extraintestinal infection (6). It has been suggested that this infection could contribute to the development of some IBD outbreaks, overall in hospitalized patients (5,7). CCD in patients with IBD usually appears in the hospital setting and affects younger patients (9,10). Once C. difficile intestinal colonization has occurred, the risk of developing diarrhea, or remaining as a carrier, depends, among other circumstances, on the patient's immunological status and serum concentration of antibodies against C. difficile toxins (8). The adequate use of suitable drugs and hospital epidemiological measures to prevent C. difficile dissemination are the principal means to reduce its incidence (5,9). Included among the CCD risk factors identified within the general population are advanced age, comorbidities, hospitalization and previous use of antibiotics (6,9). It has been shown that systemic corticosteroid treatment favours its appearance in patients with IBD, however the relationship between previous exposure to antibiotics and CCD is lower than in other groups (10,11). Until now, few studies have analyzed the circumstances that trigger CCD in patients with IBD (6). For this reason, it was decided to analyze the risk factors for the development of CCD in patients with IBD and, specifically, improve our understanding of the role of proton pump inhibitors (PPIs) in the appearance of this infection. Method A retrospective, observational study was performed in patients with inflammatory bowel disease. The study cohort corresponded to IBD patients who were regularly attended by a system of appointments in a specialist consultation unit of a tertiary hospital in Madrid (Spain) between January 2005 and February 2014. Cases were defined as those patients who had three or more daily bowel motions for a period of at least 48 hours and were found to be positive for C. difficile in stool samples. For each case, another patient (control), paired for the period (month) and the environment of the episode (ambulatory or hospitalized), was randomly assigned from hospital patients with IBD that had not presented CCD during follow-up. Because two cases acquired the infection while hospitalized for other reasons, two controls (without CCD) were randomly chosen from IBD carriers who had been admitted to the gastroenterology ward during the same month as the cases. The other controls (13 patients) were IBD patients who did not present CCD and were examined in the gastroenterology service during the same month that the cases were diagnosed. Patients were not paired by age or gender in case these demographic variables could have a bearing on the risk of CCD. Subsequently, a comparison was made between a sample of 30 IBD patients with CCD and two controls per case selected from among patients treated for CCD in our hospital during the last 10 years. The variables studied were age, gender, IBD type, duration of disease, diabetes, prior colectomy, residence in a nursing home, hospital admission during the previous 3 months, comorbidity, treatment for IBD and administration of omeprazole (or other proton pump inhibitor) during the previous 3 months, systemic antibiotic during the previous month, clinical presentation, evolution, recurrence of infection or onset of diarrhea during the 2 months following the episode studied. The diagnosis of CCD was performed using detection of the glutamate dehydrogenase antigen (GHD) and toxins A and B through enzyme immunoassays (C. DiffQuikChek Complete Techlab®, Blacksburg, Vancouver). In the cases that were GDH antigen positive but toxin negative, the presence of the toxin B gene was determined by polymerase chain reaction (PCR) using the GenomEra CDX C. difficile assay (Abacus Diagnostica, Finland). Statistical analysis The Mann Whitney U test was used to compare quantitative variables. The chi-square test, with Yates' correction was used (when necessary) to compare qualitative variables. p values less than 0.05 were considered statistically significant. Given the limited number of patients, a multivariate analysis was not considered appropriate. Results Fifteen patients with IBD who presented CCD (cases) were included during the study period. The mean age was 36 ± 10 years, which was lower than that of the controls without IBD (41 ± 10 years, p = 0.039). Eleven cases (73 %) were male versus five among the controls (33 %, p = 0.028). None of the patients resided in a nursing home. Eight cases (53 %) had ulcerative colitis and seven (47 %) Crohn's disease (Table I). The median duration of the disease was 55 months in cases and 84 months in controls (p = 0.647). Two cases (13 %), who presented granulomatous colitis, had undergone colectomy due to failure to control inflammatory activity. Ten cases (66 %) received chronic treatment with omeprazole (20 mg daily, with the exception of one with 40 mg) versus two control patients (13 %, p = 0.009). Eight cases (53 %) received oral corticosteroid treatment with a mean dose equivalent of 25 mg/24 hours prednisone (p = 0.052). None of the cases was treated with rectally administered corticosteroids. Six cases (40 %) received continuous treatment with infliximab and one (6 %) with adalimumab. Three cases had been admitted during the previous three months. In addition, three cases (20 %) had received systemic antibiotics during the previous month compared to none of the controls (p = 0.222) (Table I). In two cases (13 %) the CCD appeared after one week of hospital admission and therefore was considered nosocomial acquisition. Thirteen patients with IBD and CCD (87 %) presented abdominal pain and four patients (27 %) vomiting. Fever was only detected in four patients (27 %) and weight loss in three (20 %). A decision had been taken to admit nine of the thirteen cases of community-acquired CCD (60 %) to hospital. Nine patients with IBD and CCD (60 %) presented leukocyte counts higher than 10,000/mm3 (mean leukocyte count 13,545/mm3). In seven cases (47 %), colonoscopy was performed during the episode of CCD. Pseudomembranes were seen in one of these (14 %), signs suggestive of moderately active IBD in another (14 %), and mild affectation in three cases (42 %). Six cases (40 %) presented diarrhea, which was attributed to their underlying disease, during the 2 months prior to diagnosis of the infection. Two patients with IBD and CCD (13 %) presented diarrhea after infection but without microbiological demonstration of C. difficile infection relapse. The diagnosis was made by toxin detection in 8 patients (53 %) and toxin-producing gene detection by PCR in the remaining seven cases (47 %). All patients were treated with 500 mg metronidazole every 8 hours. Only one case had a poor response that required a switch to fidaxomicin 200 mg/12 hours for 10 days. None of the patients with IBD and CCD required admittance to the ICU. One patient died in the case group (due to advanced chronic liver disease) and another in the control group (secondary to disseminated colorectal carcinoma), however these deaths were not related to the CCD. Comparing cases (CCD and IBD) with patients with CCD but without IBD, it was seen that the former were younger (36 ± 10 and 73 ± 17 years, respectively, p = 0.007). They also had a higher proportion community-acquired CCD (87 %) and immunosuppression therapy (including anti-TNF drugs), but less previous antibiotic therapy (Table II). No significant differences were observed in relation to previous treatment with PPIs, being 66 % in case IBD carriers and 80% in the comparison group (p = 0.266). Discussion The majority of CCD cases in IBD patients appeared in the community as has been observed in similar series (5,6). Only 20 % of the patients had been admitted during the previous months and, in 13 % of the cases, the CCD appeared during a hospital stay which was due to another disease. By contrast, the majority of the patients without IBD (53 %) suffered a nosocomial C. difficile infection (12). Patients with IBD and CCD were somewhat younger and were predominantly male compared to the controls. None of these findings were identified in previous series and should be interpreted with caution given the low power of the study (6). Advanced age has been identified as a risk factor for CCD in the general population, which is congruent with the older age of the patients without IBD (13). It should be noted that only 20 % of the cases had received antibiotics during the month preceding the episode of CCD. This epidemiological difference suggests the existence of intestinal flora alterations in IBD patients that could facilitate the spread of C. difficile (4,12,14-16). IBD patients may show a certain degree of immune stimulation, epithelial dysfunction and increased mucosal permeability which could also allow C. difficile colonization and proliferation (5,6,17). Consistent with other studies, no increased risk of infection was found among patients receiving anti-TNF drugs (17). Different previous studies have shown mixed results in the relationship between corticosteroid therapy and the risk of CCD. Various series have demonstrated an increased risk with systemic administration (18,19), others only with rectal application (5) and others have found no relationship between different types of treatment and the risk of CCD (4). The cases analyzed showed that systemic steroid therapy showed a trend toward statistical significance (p = 0.052) as a risk factor for CCD (18,19). It is possible that the immune impairment secondary to steroids and the subsequent reduction in antibody synthesis could be related to this result (20). The most significant finding of this study was the relationship between the administration of PPIs and the risk of CCD. The protective role of gastric acidity against vegetative forms of C. difficile, which limits its intrusion into more distal regions of the gastrointestinal tract, is well known (21). PPI treatment was initially associated with the carrier state and recurrences rather than the risk of the first episode of CCD (11,22). Subsequently it was also associated with the appearance of the first episode in general CCD series (23), but only in one of a series of patients with IBD (17). Even taking into account the small number of patients analyzed in this series, the use of these drugs should be questioned for patients with IBD, especially in cases with doubtful indications (24). The low mortality detected in patients with IBD and CCD is an expected result considering the relatively young patients and low comorbidity (6,12). None of the cases required colectomy or admission to the ICU (12,25). The response to metronidazole was adequate in most IBD cases which suggests the validity of metronidazole as treatment of choice in initial, non-serious episodes of CCD (26-28). Also noteworthy was the low risk of recurrence which is consistent with some previous experiences (29), but differs from that shown in other reports that have observed increased severity and recurrence in patients with IBD (30,31). C. difficile infection in IBD patients will pose a major problem in the coming years due to its growing incidence and the use of increasingly sensitive microbiological techniques, such as PCR, which can determine the capacity to produce toxins. Although the majority studies based on the general population and IBD have not shown any relevant significant clinical differences with respect to the diagnostic test used (17,32), others found lower severity when PCR was used (33). A subgroup of patients has been identified with diarrhea due to an outbreak of their disease in which C. difficile may have played a role as a mere contaminant (6,33,34). We cannot definitely rule out the possibility that some of our patients belong to this group, although the temporary response to specific treatment does not support this theory. Some authors have observed a higher incidence of CCD in active IBD patients (4) and it has been suggested that CD infection could participate in the initial pathogenesis of some outbreaks of IBD (3,7). Unfortunately, colonoscopy may not help to confirm CCD because pseudomembranes appear less frequently in patients with IBD (approximately 9 %), especially in the absence of fever (12,28,34,35). In fact, four of our patients exhibited endoscopic signs of activity together with microbiological detection of C. difficile infection. This peculiarity may be related to pathogenic differences in the infection associated with chronic IBD inflammation, with lower severity or, as noted previously, with the detection of cases with C. difficile colonization but whose diarrhea is due to another cause (12,32,34,35). Highlighted among the limitations of this study are its retrospective nature and the small number of patients, which may have influenced the lack of detection of other potential risk factors, such as previous antibiotic treatments. A multicenter study with greater statistical power will be necessary to further assess risk factors in these patients. In summary, CCD in patients with IBD is usually acquired out the hospital setting, is associated more with the administration of BP than with previous antibiotic therapy and usually has a favourable clinical evolution. Artículo 2 Evaluation of bariatric surgery patients at the emergency department of a tertiary referral hospital ABSTRACT Objective: To describe the profile of the bariatric surgery patients that were admitted to the Emergency Department (ED). Method: A retrospective review of the reasons why bariatric surgery patients go to our ED. We analyzed the first 30 days after the surgery. We evaluated the number and indications of admissions, the examinations ordered, and final diagnosis and destination of the patients. Results: From January 2010 to July 2012, 320 patients underwent bariatric surgery at our Institution. Fifty three patients (16.6 %) were admitted to the ED at leas t once. We found 58 admissions (1.1 admissions by patient). Patients who had duodenal switch and Roux-en-Y gastric bypass were the most representative (74 %). The main indications for admission were abdominal pain (50 %), and problems related to the surgical wounds (22.4 %). Blood test was the most performed examination (75.9 %). The most frequent final diagnosis was unspecific abdominal pain in 27 cases (46.6 %), and complications of the surgical wound in 10 patients (17.2 %). Nineteen patients (35.84 %) were admitted to the surgical ward from the ED, and 5 of them required surgical revision (9.4 %). Multivariate analyses showed that the type of surgery was the only predictor variable for the ED admission. Conclusions: Attending ED after bariatric surgery is not common, and less than a third of the patients required hospital admission. Just a small percentage of the examinations showed any pathological value. Readmission rate is very low. Surgical procedure is the only predictor for ED admission. Key words: Bariatric surgery. Emergency department. Complementary examinations. Referral center. Background Bariatric surgery (BS) represents several surgical procedures for the treatment of morbid obesity and its related comorbidities. Up to our days, BS has demonstrated to be the only effective and long term treatment for obesity (1) and its related diseases. Day by day, the number of BS patients increases, and next to it the absolute number of complications related to the surgery, some of them diagnosed at the emergency departments (ED). It has been estimated that BS has a morbidity rate around 4 % and mortality below 0.3 % (2). Following the adoption of new surgical procedures, new complications and consequences also appear, some of them previously quite uncommon or just unknown. On the other hand, medical education has an important deficiency in BS due to its relatively novelty, its scarce (or even null) specific weight in medical training plans, and due to be restricted to highly specialized referral centers. All these limitations imply that in several ED bariatric surgery patients, especially those operated at another hospital, represent and severe challenge for the physicians (3,4). These problems had been highly discussed by national and international scientific societies of BS. Those societies promoted educational campaigns about morbid obesity, BS procedures and their related complications (5). This paper evaluates and analyses the profile of the BS patients admitted to our ED, at a tertiary referral BS centre. Methods This is a retrospective study about the patients admitted to the ED of our centre (Referral and Tertiary University Hospital), after being discharged for primary bariatric surgery. Our armamentarium of primary bariatric procedures includes: Sleeve gastrectomy (SG), biliopancreatic diversion (BPD), laparoscopic gastric plication (LGP), duodenal switch (DS), and Roux-en-Y Gastric Bypass (RYGB). Revisional surgeries were excluded. Patients operated at our Hospital who went to ED during the first 30 days after discharge were included. For the analysis we reviewed all the electronic medical records of patients admitted for elective and primary BS from January 2010 and July 2012. We included at the database variables about indication for admission at ED, even it was medical or surgical. The variables we studied were: Primary bariatric procedure, number of admission by patient (between 0 to 3), the main symptom for admission, complementary examinations performed and their results, final diagnosis and destination after the admission at ED (discharge, admission to Surgical Ward, or emergency reoperation). It is a descriptive study where discrete variables are presented with their frequency, continuous variables with mean and range. Comparative analysis were done by the chi-square discrete and discontinuous variables, and continuous by t-Student test. The multivariable analysis was constructed by selecting the best model for prediction using the Cp of Mallows criteria. Significant differences were accepted were p remained below 0.05. Bellvitge University Hospital (Barcelona, Spain) has a Bariatric and Metabolic Unit formed by a multidisciplinary team with more than 20 years of experience. This unit complies the standard of quality and was accredited as a Centre of Excellence by Surgical Review Corporation (SRC) (former accreditation Centre for the American Society for Bariatric and Metabolic Surgery). The ED is a professionalized department with specialized physicians in general family medicine, internal medicine and surgeons with exclusive dedication for Surgical Emergencies. The multidisciplinary team validated our Bariatric Surgery Protocol in 2008, and it is being revised nowadays. The choice of each procedure is done based on overweight, related diseases, and social and psicopathological conditions of the patients. Complex cases are discussed on monthly basis meetings of the team. Two expert surgeons, one of them accredited by SRC as a surgeon of excellence by the ASMBS, perform the surgeries. By protocol diet onset is initiated early 24-48 hours after surgery. We also promote early mobilization after surgery and have restricted criteria for using intensive care units postoperatively. In all patients a pneumatic and methylene-blue dye test is done intraoperatively. During the first postoperative day a new methylene-blue dye test and a blood test are done. We do not use systematically acute-phase reactants. Imaging complementary examinations are reserved for those cases with high suspicious of complications. We maintain the clinical judge to restrict the use of all these tools. Finally, after hospital discharge patients are followed-up simultaneously by endocrinologists, dieticians, and surgeons one week after surgery, and after 1, 3, 6, 12, 18, and 24 months. After the second year, the follow-up is done yearly. Results Between January 2010 and July 2012 we operated 320 patients for BS: 112 RYGB (35.6 %), 95 SG (30.2 %), 76 DS (24.1 %), 28 LGP (8.9 %) and 4 DBP (1.3 %). Fifty three patients (16.6 %) were admitted at least once at the ED, during the first 30 days after surgery. This is our study group. Forty nine patients were admitted once (92.5 %), 3 (5.7 %) twice, and just 1 patient (1.9 %) three times. Globally, all 53 patients were admitted 58 times (1.1 admissions/patient). Table I summarizes the demographic characteristics of the patients included. Figure 1 represents the distribution of the admissions between the different types of surgery. Statistical analysis confirms that the distribution of admissions was not homogeneous (p = 0.016); patients after a DS or a RYGB concentrate most of the admissions. Both groups in combination represent the 74 % of all admissions. Acute abdominal pain was the main indication for admission, representing 29 patients (50 % of admissions), followed by problems with the surgical wounds in 13 cases (22.4 %). Complementary examinations performed at the ED are represented at table II. Distribution of them between the surgical procedures was not homogenous either. Ten patients (17.2 %) did not require any blood or imaging examination. Final diagnoses are represented in table III. Most of the patients were discharged as unspecific abdominal pain (46.6 %). Usually, unspecific abdominal pain is due to altered bowel movements after the diversion caused at the RYGB or the DS. Patients with impaired diet tolerance were mostly due to dietetic transgressions, without any case of stenosis or food impaction. Patients with intraabdominal infection were treated by radiological percutaneous drainage. Surgical site related complications include a vast number of minor problems, being pain and superficial infections the most frequent; they only required minor attentions and sanitary counseling. Nineteen patients (35.84 % of the study group, and 5.94 % out of all BS patients) were admitted to the Surgical Ward. The procedures that mostly required readmission were RYGB (7 patients) and DS (6 cases) (Fig. 2). Five patients (9.4 %) had to be reoperated on an emergency basis, 3 due to incarcerated port-site hernia (all patient operated for a DS), 1 hemoperitoneum (SG group) and 1 bowel occlusion (RYGB group). All 5 patients did well and had an uneventful postoperatory. In the 14 patients readmitted to Surgical Ward with no reoperation, the main indication was fever of unknown origin, intraabdominal collection and severe wound infections. None of the five reoperated patients had any complication during the first admission. In the study group the median hospital stay after BS was 4 days, compared to 3 days in those who did not go to ED. During the primary procedure, 6 patients (11.32 %) of the study group presented some complication after surgery versus 22 (8.4 %) of the other group, with no statistical significance (p = 0.468). None of the 53 study group patients had to be reoperated during the first admission. The univariate analysis showed that the surgical procedure was the only related variable to emergency admission (p = 0.0016). Multivariate analyses also confirmed this as a predictor factor. Sorting the surgical procedures by its complexity, the Odds ratio oscillated from 7.583 (2.03 to 28.3 95% CI) about LGP to SG; and 8.125 (2.64 to 25 95 % CI) of DS to SG. Discussion Our institution operates 150 scheduled bariatric procedures a year, which represent about 4 % of the total surgical volume of the hospital. The ED receives a median of 254 patients per day (92,808 admissions in 2013). This means that our series (53 patients) represents 0.06 % out of all admissions (0.7 % of the surgical patients at the ED). Our study shows an emergency admission rate of 16.6 % of the scheduled patients. Our morbidity rate does not differ from the quality standards defined by the International Surgical Societies of Bariatric Surgery (6,7). This paper presents one of the first series from our country about emergencies after bariatric surgery. The consultation rate at the ED is relatively low for the complexity of the patients and their disease. Most of the patients are diagnosed of unspecific abdominal pain or surgical wound complications, both are minor complications after the surgery. Only 5 patients were diagnosed of major complications and required emergency surgery, all of them underwent an uneventful evolution. Finally, 14 patients required hospital admission for observation or specific treatment. Univariate and multivariate analysis concluded that the type of surgery is the only variable that predicts the ED consultation. In our area there are other 3 tertiary hospitals with big volume of bariatric surgery (more than 50-100 patients per year). None of them have ever presented or published any result about emergency consultations after bariatric surgery. In the literature, papers from Saunders (8,9) and Nguyen (6) showed similar results related to emergency reconsultations, indications and complications diagnosed. The main differences with our study are that those papers come from private North-American centres and the type of surgeries performed. Despite these papers do not take into account DS or LGP, they agree that the most complex surgeries are more likely to have complications, and therefore require more ED admissions. The range of complications we may observe at the ED is wide: Acute or subacute bleedings, sepsis due to delayed or late onset leaks, occlusive patterns due to internal hernias or port-site hernias... (2,6,8,9). Other types of consultations are those related to food tolerance, that may increase if the restrictive procedures continue to grow up. It is very important that the ED physicians know the anatomy and pathophysiology of those bariatric procedures. The ignorance of bariatric surgery may lead to a late diagnose and a poor (or even fatal) evolution of those patients (10). Acute abdominal pain and complications of the surgical wounds were the most important indications for ED admission. The distribution of the visits was not homogenous between the different types of surgeries (p = 0.016). Patients operated for DS and RYGB represent the main group of consultations. The greater technical complexity of both procedures predisposes those patients as the main candidate to ED admission. Moreover, both techniques are indicated to the more complex patients due to greater overweight or comorbidities. Related to the examinations requested at the ED, we may highlight that most of the patient had a blood test (75.9 %) and a plain abdominal X-ray (70.7 %). Just with these two examinations we achieved the initial screening of the most severe complications. CT scan (done just in 27.6 % of the patients) was reserved for patients with the most complex surgeries -as duodenal switch- or for those with suspicion of intestinal occlusion, due to internal hernia or port-site hernias (11). Upper endoscopy and esophagus-gastric (US) contrast swallow were the less requested examinations. Both procedures may be very useful for bariatric surgery patients, but its availability at ED is not always possible. Both examinations have restrictive indications and are reserved in case of suspicion of concrete complications related to food intolerance. The type of surgery or the main symptom should orientate the examinations. The paper from the American Society for Metabolic and Bariatric Surgery (ASMBS) for the management of emergencies after bariatric surgery orientates the diagnosis protocol around the main symptom. This is the best and fastest way to achieve a final diagnosis. In this revision we may find that we follow quite well these guidelines (3,12). Bariatric surgery patients have different characteristics to normal population. Apart from the new and different surgical procedures, some of them experimental, morbid obesity implies some physiological disturbances. Morbid obese patients have a very low functional physiological reserve that obligates to a fast and direct diagnosis, and an aggressive and early treatment of the complications. On the other hand, their anthropometric characteristics make very difficult physical and imaging examinations. The big subcutaneous adiposity makes very difficult the evaluation of peritonism or the venous access (both central and peripheral). Moreover, most of the technical imaging equipment available at the ED has weight limitations that may exclude some of the bariatric surgery patients. These limitations are the main reason to recommend the evaluation of these patients at referral centers. Most of the patients of our series (46.6 %) were diagnosed of unspecific abdominal pain, followed by complications of the surgical wound (17.2 %). It is very remarkable that all the complications we registered are surgical; we did not find any medical complications. From the ED, 32.1 % of the patients were admitted to the surgical ward (5.3% out of all the bariatric surgery patients for our period of study). Only 5 patients (9.4 % of the series) required emergency surgery (1.6 % from the initial group), with satisfactory evolution after surgery in all of them. The multidisciplinary approach (13) of the bariatric surgery in our Institution allows that the patients arrive to surgery with good medical control of the medical comorbidities, which may be the reason for not having any medical complication registered in our series. These results are also a consequence of a very good and significant work done by Infirmary (14) in sanitary education and prevention of complications during the hospitalization. We also observed that as the main complications are minor complications, maybe some aspects of the medical education should be improved. The design of the paper as an observational and unicentric study is the main limitation. Our Institution is a referral and tertiary centre of a not very wide area, so we estimate that the reliability of our results is high. Moreover, we have a follow-up rate near 75 % at 5 years after bariatric surgery, one of the highest in the literature. In conclusion, Emergency department consultations after bariatric surgery have a lower rate than we expected for a complex surgical procedure. The main consultations are minor complications, which means that the standardized work-up during the preoperative time and postoperative hospital stay let us reduces the major complications before the discharge. This paper shows also that we have low major complication rates, but we should improve in prevention of minor complications. Artículo 3 Acute abdomen in patients with systemic lupus erythematosus and antiphospholipid syndrome. Importance of early diagnosis and treatment ABSTRACT Systemic lupus erithematosus (SLE) is an autoimmune disease with multiorgan involvement caused principally by vasculitis of small vessels. The gastrointestinal tract is one of the most frequently affected by SLE, with abdominal pain as the most common symptom. An early diagnosis and treatment of lupus enteritis is essential to avoid complications like hemorrhage or perforation, with up to 50 % of mortality rate. However, differential diagnosis sometimes is difficult, especially with other types of gastrointestinal diseases as digestive involvement of antiphospholipid syndrome (APS), moreover when both entities may coexist. We describe the case of a patient with both diseases that was diagnosed with lupus enteritis and treated with steroid therapy; the patient had an excellent response. Key words: Systemic lupus erithematosus. Antiphospholipid syndrome. Lupus enteritis. Vasculitis. Steroids. Introduction Systemic lupus erithematosus (SLE) and antiphospholipid syndrome (APS) are two autoimmune diseases with multiorgan involvement caused principally by vasculitis of small vessels. However, pathophysiology is different in both diseases. The vasculopathy that characterizes SLE is an inflammatory type secondary to immuno-complex deposits in vessel walls, meanwhile APS is characterized by a state of hypercoagulability due to the presence of autoantibodies, potentially resulting in thrombosis. Historically, APS was described as a clinical manifestation of SLE. Since 1985, several studies have reported differences between both diseases, and so APS must be considered as a different entity (1,2). Gastrointestinal manifestations are relatively frequent in patients with SLE, reaching up to 40 % in cases of active disease. Symptoms may vary from unspecific abdominal pain to life-threatening acute abdomen, known as mesenteric vasculitis or lupus enteritis (LE). Early diagnosis and treatment are crucial to avoid complications as hemorrhage, necrosis or intestinal perforation with a high mortality of up to 50 % (2,3). On the other side, gastrointestinal involvement is rare in APS (approximately 1.5 % of patients), and includes predominantly affectation of the liver and spleen. However, it is necessary to bear APS in mind in differential diagnosis of acute abdomen, since it may cause a massive intestinal thrombosis known as Asherson's syndrome (4). We describe the case of a patient with SLE and APS, with abdominal pain and semiology compatible with acute abdomen that was diagnosed with lupus enteritis and treated medically with steroid therapy, resulting in a rapid improvement of her gastrointestinal symptoms. Case report A 55-year-old woman, with previous diagnosis (40 years before) of SLE with involvement of the kidney, central nervous system and skin, had a concomitant APS with peripheral vasculopathy and amputation of both inferior limbs. She was admitted with abdominal pain, nausea, vomiting, diarrhea, abdominal distension and anorexia during the last two weeks, with worsening during the three days previous to her admission. Neither fever nor other symptoms suggesting activity of SLE were referred. Physical exploration revealed distended abdomen with tympanism, absence of bowel sounds and diffuse abdominal pain with unclear signs of peritoneal affectation (defense or rebounding sign). Laboratory tests showed leucopenia (3 x 103/mm3) and thrombocytopenia (99 x 103/mm3). Abdominal computed tomography (CT) findings were dilated small bowel, marked edematous thickening of the wall of the right colon and small bowel, and a mild amount of ascites. A diagnosis of intestinal ischemia probably related with APS was established and medical treatment was indicated, consisting basically on intestinal rest, intravenous fluids, non-steroid anti-inflammatory drugs (NSAIDs) and therapeutic doses of low-weight subcutaneous heparin. Initially, surgical exploration was discarded due to the extended period of duration of symptoms and the lack of clear signs of acute abdomen. Further laboratory data revealed persistence of leucopenia and thrombocytopenia, decreased complement factors (C3 and C4) and positive antinuclear antibodies (ANA), anticardiolipin, antiB2 GP1 and lupus anticoagulant. After four days without improvement of symptoms and persistence of dilatation of the lumen of the small bowel on abdominal X-ray, indication of a second CT was established, which showed similar but more pronounced findings if compared with the previous one: Dilated bowel, marked thickening of the wall of jejunum and ileum caused by edema ("double halo or target sign"), mesenteric edema, engorgement of mesenteric vessels and moderate ascites. Abdominal exploration had worsened too, showing clinical signs of acute abdomen, and surgeon on duty was called. Considering clinical profile, radiological findings and laboratory data, the possibility of LE was then suggested and extensively discussed, and intravenous administration of high doses of corticosteroids was initiated. She was treated with 1 g/d of 6-methylprednisolone (6-MP) during 48 hours and then reduced to 500 mg/d. Improvement of her symptoms was visible during the first 24 hours, and after three days the patient was asymptomatic and allowed us to reintroduce oral diet. Previous malnutrition and a respiratory infection requiring specific antibiotic therapy prolonged hospital stay, but patient was discharged 29 days later with a maintenance dose of 60 mg/d of prednisone with progressive withdrawal. Discussion Systemic lupus erithematosus (SLE) is a chronic inflammatory disease that belongs to the group of the diseases known as systemic vasculitis whose common pathologic feature is inflammation of the walls of small vessels, with other diseases like polyarteritis nodosa (PAN), Churg-Strauss syndrome, Wegener granulomatosis (WG) or Takayasu arteritis. SLE is characterized by the involvement of various organs, frequently skin, kidney, central nervous system and gastrointestinal tract. Unspecific gastrointestinal symptoms are frequently observed in this disease; anorexia, nausea or vomiting may be present in approximately 30-50 % of patients, being abdominal pain the most common symptom (around 20 %) (5-7). Lupus mesenteric vasculitis (LMV) is one of the most serious complications of SLE, with an estimated incidence ranging from 0.2 to 9.7 % of patients with active disease and less than 1 % of those ones with inactive disease. It is unusual that LMV constitutes the initial presentation of SLE. It is frequently associated with thrombocytopenia, lymphopenia and central nervous system and skin involvement. Triggering factors of LMV are unknown, but bacterial infections (associated with changes of the intestinal flora), animal viruses, cytomegalovirus infection, eosinophilia, chemicals, NSAIDs, metallic particles, caffeine, exercise and certain foods and herbal medicines have been proposed as potential etiologic factors (2,8). LMV affects preferentially the territory of superior mesenteric artery, especially jejunum and ileum (80-85 %), and it is produced by accumulation of immunocomplex deposits in the wall of the vessels (5). Although generally shows a benign and insidious clinical course, sometimes LMV may produce severe intestinal ischemia complicated with hemorrhage, ulceration and perforation, with a mortality that may reach up to 50 % (2,9). Early diagnosis and treatment are crucial to avoid these catastrophic complications. Contrast-enhanced CT is considered the most sensitive and specific noninvasive tool for diagnosis of LMV. Most common CT findings are segmental or multifocal bowel involvement alternating with normal segments of healthy bowel, bowel dilatation, engorgement of mesenteric vessels, mesenteric edema, bowel wall thickening with abnormal enhancement caused by submucosal edema called "double halo or target sign" (Fig. 1) and ascites (Fig. 2). Other CT findings suggestive of LMV are hepatosplenomegaly, retroperitoneal lymphadenopathy and pancreatitis (5-10). Ultrasonography is another noninvasive tool which may be helpful in both diagnosis and follow-up of LMV. Magnetic resonance imaging (MRI), double-contrast radiographic assessment of the upper and lower gastrointestinal tract, capsule endoscopy and Ga67 gammagraphy have shown to be useful, but these techniques have not been accepted widely. As affected vessels are usually deep and inaccessible, endoscopy-guided biopsy is not recommended for definitive diagnosis (2,5). The mechanism of injury is an inflammatory but not an atherosclerotic or embolic occlusion of small vessels. This is the reason why medical treatment is based on aggressive doses of intravenous corticosteroids and absolute intestinal rest, followed by a gradual steroids withdrawal and reintroduction of oral nutrition. Another option is prescription of cyclophosphamide (initial doses of 1-2 mg/kg/d and afterwards a monthly dose) or mycophenolatemofetil, but several authors recommend this therapy only in case of failure of steroid therapy. Finally, surgical evaluation and early laparotomy must be indicated if medical treatment is not successful (within 48 hours), because prognosis of these patients might be improved. Ultrasonography and abdominal CT are useful tools in follow-up of medical therapy. A combination of cyclophosphamide and corticosteroids must be prescribed if there is evidence of active disease after surgery (2,5-8). In recurrent forms micofenolate mofetil, azathioprine, ciclophosphamide and rituximab have been successfully used to prevent further recurrence in a limited numbers of patients. APS is an autoimmune disease characterized by recurrent arterial and venous thrombosis. Patients with APS show high levels of antiphospholipid antibodies (anti-cardiolipin, antiB2 GP1 antibodies and positive lupus anticoagulant). APS may be defined as primary in about 53 % of cases, but it may be associated with other autoimmune disease such as lupus, and then it must be defined as secondary. In fact, initially APS was described in a group of patients with SLE (secondary disease), but since 1985 primary APS must be considered an independent disease (1,4,11,12). It is a multiorgan disease, with similar clinical profile when compared with lupus: affectation of central nervous system (migraine, epilepsy, cognitive disorders), pulmonary (alveolar hemorrhage), hematological (thrombocytopenia, autoimmune hemolytic anemia), renal (glomerulonephritis), skin (livedo reticularis and cutaneous ulcers), recurrent fetal loss (1,13). Nevertheless, in APS is infrequent that gastrointestinal tract is affected (about 1.5 %), and when APS involves digestive system this affectation includes principally hepatic manifestations (Budd-Chiari syndrome, hepatic venous thrombosis), splenic or pancreatic infarction. Intestinal infarction is rare, but a catastrophic variant known as Asherson syndrome has been previously described. It is an accelerated form of APS resulting in diffuse intestinal infarction and multiorgan failure because of multiple small vessel occlusions, with up to 50 % of mortality rate. The most common precipitating conditions are infections (22 %) and surgical procedures (10 %). Other less common causes are anticoagulation withdrawal or low international normalized ratio (INR), medications, obstetric complications and neoplasia. Radiological findings (abdominal CT) in these patients are similar to other entities that lead to intestinal ischemia: enhancement of the wall of the bowel, free intraabdominal fluid, lack of enhancement of the arterial vasculature with intravenous contrast, intestinal pneumatosis and gas in the portal system. Medical support is a combination of intravenous glucocorticoids and anticoagulant therapy, associating initially low-molecular-weight heparin and warfarin and ciclophosphamide in cases with concomitant SLE. Duration of treatment depends on clinical course and an optimal length has not been well defined. Surgery must be reserved for cases of failure of medical treatment or presence of obvious peritonitis. Hydroxychloroquine, plasmapheresis and other immunomodulatory therapies (through a decrease of levels of anticardiolipin antibodies) have been purposed by several authors for thrombosis prevention in these patients (1,4,5,14,15). In our patient, the initial non-specific symptoms led us to a wrong diagnosis and therefore the beginning of steroid therapy was delayed. In spite of that, it is important to emphasize that the patient had a previous diagnosis of both entities, SLE and APS, and both were potentially responsible of the clinical profile. As soon as radiological CT images suggested the possibility of LMV we focused on it and an appropriate therapy was prescribed, but this delay could cause complications as hemorrhage or perforation with an associated high morbimortality. Immediate response to medical therapy with steroids confirmed the diagnosis. In summary, SLE and APS are two different autoimmune diseases with a few similar characteristics, and they may be present in the same patient concomitantly. Among 4-10 % of patients with APS will develop a fully established SLE in the future. Gastrointestinal affectation is more frequent in SLE, although both diseases may be the origin of an acute abdomen with a high rate of mortality. Therefore, a diagnostic effort must be performed in order to establish an adequate medical treatment, trying to avoid an undesirable medical course and surgery. Contrast-enhaced abdominal CT is considered the most useful tool for diagnosis of mesenteric vasculitis. Classical image "in reveille or double halo" suggests strongly the diagnosis of SLE, meanwhile CT findings of gastrointestinal affectation of APS are usually unspecific. Medical treatment must be considered the first option in both cases, with high doses of intravenous glucocorticoids in SLE, and glucocorticoids with anticoagulants in APS. Surgery must be reserved for cases without successful medical treatment or complications. Artículo 4 Eosinophilic cholecystitis: An infrequent cause of acute cholecystitis ABSTRACT Eosinophilic cholecystitis (EC) is a rare disease that is characterised by eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown, although many hypotheses have been made. Clinical and laboratory manifestations do not differ from those of other causes of cholecystitis. Diagnosis is histological and usually performed after analysis of the surgical specimen. We report the case of a woman aged 24 years, with symptoms of fever, vomiting and pain in the right upper quadrant. When imaging tests revealed acalculous cholecystitis, an urgent cholecystectomy was performed. Histological examination of the surgical specimen revealed eosinophilic cholecystitis. No cause of the symptoms was found. Key words: Eosinophilic cholecystitis. Acalculous cholecystitis. Introduction Eosinophilic cholecystitis is an uncommon condition of the gallbladder. It is characterised by an inflammatory infiltrate constituted mainly of eosinophils. Its aetiology is often unknown, although cases have been associated with hyper-eosinophilic syndrome, parasitosis, infections, drugs and medicinal herbs. Clinically, it is indistinguishable from common cholecystitis, although peripheral eosinophilia is sometimes observed, as is the case in hyper-eosinophilic syndrome and parasitic disease. When the effect is limited to the bladder, the treatment of choice is cholecystectomy, and the prognosis is usually favourable. Case report A 24-year-old woman presented to the emergency department complaining of abdominal pain, located in the epigastrium and radiating to the right upper quadrant, together with nausea, vomiting and fever of 39 oC for the past two days. The presence of choluria was also reported. The patient had no personal or family history of interest. She smoked about five cigarettes per day and was a habitual consumer of oral contraceptives. Physical examination revealed good general condition, with cutaneous-mucous jaundice and tenderness in the right upper quadrant, and a positive Murphy sign. Other results of the examination were normal. Laboratory analysis revealed the following alterations: Total bilirubin 3.76 mg/dL (range 0-1.2 mg/dL); direct bilirubin 3.5 mg/dL (range 0-0.5 mg/dL); indirect bilirubin 0.26 mg/dL (range 0-0.75 mg/dL); alanine aminotransferase 174 U/l (range 0-35 U/l); amylase 49 U/L (range 28-100 U/L); C-reactive protein 149.12 mg/L (range 0-5 mg/L); leukocytes 15,500 µl (range 4.8-10.8 µl); neutrophils 86.3 % (range 40-74 %); lymphocytes 4.2 % (range 19-48 %); monocytes 6.9 % (range 1-9 %); eosinophils 2.2 % (range 0-7 %); prothrombin activity 60.8 % (range 70-120 %), INR 1.34 (range 0.85-1.2); APTT 28.2 sec (range 23.5-33.2 sec). Abdominal ultrasound findings: Thin-walled acalculous gallbladder; non-dilated bile duct; no evidence of pancreatic abnormalities. In view of the clinical and laboratory findings, the patient was admitted to monitor the evolution of the condition and for further study. During admission, abdominal and cholangio MRI were performed to assess the bile duct, obtaining the following results: no dilatation; no evidence of bile duct filling defects; space-occupying lesion of 9 mm in segment 8 with uptake and density suggesting hemangioma; no evidence of alterations in pancreas or liver. Further analyses were performed, which revealed increased total bilirubin, decreased direct bilirubin, increased leukocytosis, increased C-reactive protein, and normal levels of amylase, transaminases and cholestatic enzymes. The patient had malaise, with increased pain despite analgesia, and painful abdominal tenderness, with a tightening in the epigastric right upper quadrant. In view of this situation, an urgent abdominal CT scan with IV contrast was performed (Fig. 1), which showed perivesicular oedema without calculi or biliary dilatation, with a small amount of free fluid in the Douglas pouch. There were no images suggestive of perforation or pancreatitis. The patient's clinical condition was worsening and presence of cholecystitis was suspected, and so an urgent cholecystectomy was performed, which revealed a thickened gallbladder wall with oedema on the rear surface. The pathology examination revealed the presence of a transmural infiltration, and of a more intense infiltration in the muscular layer, by eosinophilic polynuclear leukocytes (Fig. 2). After surgery, the patient was asymptomatic and was discharged a few days later. Discussion Eosinophilic cholecystitis (EC) is a rare and poorly understood disease of the gallbladder, which was first described in 1949. It can be considered an inflammatory condition of the gallbladder, in which the inflammatory infiltrate consists primarily of eosinophils (1). The aetiology of EC is unknown. In patients with eosinophilic infiltrate affecting other organs and tissues, it has been suggested that these lesions could be due to a local allergic reaction to substances released at sites of inflammation within the target organ or tissue. It has also been hypothesised that EC may be caused by hypersensitivity to bile acids (2,3). Cases have also been reported secondary to infections, parasitosis, allergies, hyper-eosinophilic syndrome, eosinophilia-myalgia syndrome, eosinophilic gastroenteritis, drugs and herbal medicines (4,5). In the absence of evident causes, we consider the present case to be an idiopathic EC (6). EC is three times more common in patients with acalculous cholecystitis than in patients with cholelithiasis (6). EC does not present any clinical or laboratory manifestation to distinguish it from common cholecystitis, and so it is difficult to detect prior to cholecystectomy and histological examination of the surgical specimen. Peripheral eosinophilia may or may not be present; when it is, it has been associated with hyper-eosinophilic syndrome, eosinophilic gastroenteritis and parasitosis. In addition, symptoms secondary to the eosinophilic infiltration of other organs have been described (8). Diagnosis is histological; EC is said to be present when the cellular infiltrate in the gallbladder wall is composed of more than 90 % eosinophils, and the cholecystitis is chronic with an eosinophilic (lympho-eosinophilic) component if the infiltrating inflammatory leukocyte population contains 50-75 % eosinophils (9). In imaging tests, ultrasound results may be normal or show signs suggestive of cholecystitis (gallbladder distension, wall thickening, perivesicular liquid or sonographic Murphy sign). A CT scan may reveal similar features, with perivesicular oedema or decreased attenuation in the adjacent liver, indicative of perihepatitis (10). EC prognosis is favourable. When the disease is confined to the bladder, the treatment of choice is cholecystectomy, preferably performed laparoscopically. Treatment with corticosteroids can be effective when the bile ducts are affected, or when the condition is associated with eosinophilic gastroenteritis. It is generally accepted that EC should not be considered a separate entity, because the clinical and laboratory manifestations are indistinguishable from those of common cholecystitis, and therefore it is considered more a histological finding than a pathology in itself. The importance of EC lies in the fact that it can be associated with other diseases, and therefore, when it is observed, possible associated syndromes should be investigated. Artículo 5 Octreotide long-active release in the treatment of gastrointestinal bleeding due to vascular malformations: Cost-effectiveness study ABSTRACT Introduction: Gastrointestinal hemorrhage due to vascular malformations has a negative impact on patients' quality of life and consumes an important quantity of resources. Objective: Analyze the cost-effectiveness of long-active releasing octreotide (OCT-LAR) in the treatment of gastrointestinal haemorrhage secondary to vascular malformations. Material and methods: Retrospective study, including 19 pacients that were treated with mensual injections of OCT-LAR between 2008-2013. The number of blood transfusions, hemoglobin levels, hospital admissions and possible side effects during the year before treatment and the year after the start of the treatment were assessed, and cost-effectiveness was analyzed. Results: After the beginning of the treatment with OCT-LAR, complete response was observed in 7 patients (36.8 %), partial response in 7 patients (36.8 %) and 5 patients (26.3 %) continued to require admissions, blood transfusions and/or endoscopic treatment. We observed significant reduction in the length of admission per year (in days) before and after the start of the treatment (22.79 versus 2.01 days, p < 0.0001) as well as in the number of blood transfusions administered (11.19 versus 2.55 blood transfusions per year, p = 0.002). The mean haemoglobin levels increased from 6.9 g/dl to 10.62 g/dl (p < 0.0001). We observed reduction of costs of 61.5 % between the two periods (from 36,072.35 € to 13,867.57 € per patient and year, p = 0.01). No side effects related to treatment were described. Conclusion: In conclusion, OCT-LAR seems to be a cost-efficient and safe pharmacological treatment of gastrointestinal haemorrhage secondary to vascular malformations, mainly in patients in whom endoscopic or surgical treatment is contraindicated. Introduction Gastrointestinal haemorrhage secondary to vascular malformations represents an important clinical problem that has a major negative impact on the quality of life of patients, as it frequently requires numerous therapeutic interventions, and is therefore associated with high economical burden (1). The natural history of vascular malformations has not been entirely understood, although some factors such as hypoxy and subsequent release of epithelial growth factors may play a role in its physiopathology and may be used as a target of future therapies (2-4). Endoscopic interventions are the mainstay in both diagnosis and treatment of vascular malformations. The most frequently implicated therapeutic method is argon plasma coagulation; however, due to relatively high rebleeding rate some patients may require various treatment sessions (5). Repeated endoscopies may carry high risk of complications, mainly in elderly patients with important comorbidity, who represent a significant proportion of the affected population. Conservative medical treatment with octreotide and octreotide LAR has therefore been intended as a maintenance therapy with promising results in this group of patients (5-7). The objective of the present study was to assess the long-term effect and cost-effectiveness of OCT-LAR in the treatment of gastrointestinal bleeding from vascular malformations in our centre. To our knowledge there is no other published study that evaluates the economical impact of treatment with this drug. Material and methods Our hospital is a tertiary centre that attends the area with approximately 638,000 inhabitants. Our Department of Gastroenterology consists of three sections: Gastroenterology, hepatology and endoscopy. Patients that suffer from recurrent gastrointestinal bleeding from vascular lesions are assessed and treated in the Clinic of Gastroenterology and Endoscopy. We performed a retrospective study, in which we included all patients with recurrent gastrointestinal bleeding secondary to vascular malformation that were treated with mensual administration of OCT-LAR between January 2008 and December 2013 in our centre, in total 24 patients when the study started. Patients Clinical evaluation and indication of OCT-LAR treatment in each patient was performed by a responsible consultant in the clinic. Given that the treatment is administered off-licence, a protocol was elaborated and at least two of the following criteria had to be fulfilled in order to be able to prescribe OCT-LAR: - Recurrent gastrointestinal bleeding with necessity for blood transfusion (more than 4 transfusions per year) or frequent hospital admissions (more than 2 hospital admissions per year or more than 10 admissions to emergency department per year). - Important comorbidity (ASA III or IV) and high risk related to performing surgical or repeated endoscopic interventions. - At least 3 sessions of unsuccessfull endoscopic treatment, and continuous need for high transfusional requirements and/or admissions. - Multiple lesions with difficult endoscopic access and high transfusional requirements and/or admissions. We found 24 pacients that fulfilled at least two of the above mentioned criteria. Five of those were excluded from the study: Three because they died from different causes than digestive bleeding few months after the start of the treatment, and two because they started the treatment recently (2 and 3 months before the start of the study, respectively), which means the response to the therapy could not be correctly evaluated (Fig. 1). In order to assess the efficiency of the treatment, we collected the variables during one year before and one year after the start of OCT-LAR , excluding the time before the diagnosis. Data sources In our centre, OCT-LAR is used off-licence and data of all the patients that were given the treatment in this indication are stored in the Department of Pharmacy. We reviewed clinical history of these patients (electronically in the hospital intranet or in written form as obtained from the archive of the hospital), including their previous medical history, relevant comorbidity, medication that interferes with blood coagulation or agregation, levels of haemoglobin, necessity of blood transfusions, administration of iron supplements orally or intravenously and its doses, administration of subcutaneous erytropoetin, number of diagnostic and therapeutic endoscopies, hospital admissions related to gastrointestinal haemorrhage and total length of admissions per year (in days). In our hospital, the economical evaluation of health servicies is based on the system of codification of Group of Related Diagnosis (Grupo de Diagnóstico Relacionado; GDR). Each hospital admission, visit to the emergency department or ambulatory assistence receive a numeric code based on the final diagnosis according to CIE-10. Each code has an economical value asigned by health authorities of each Spanish independent community. Equally, depending on the length and number of services rendered, a unit is asigned to each of the codes, that represent the number of times that suggests how many times the codified value can be multiplied in order to reach the final value that is invoiced. In order to obtain the costs for the purpose of our study, we contacted the Department of Codification in the central hospital archive, and we collected the codes and the units of each hospital assistence of all patients using the programme HCIS. The equivalent value in euros was calculated using the "Boletín oficial de la comunidad de Madrid 215 (BOECM 215)" issued on the 10th of September 2013 where the monetary equivalence of each code is described. In order to obtain the value of services that are not codified, such as digestive endoscopies, we asigned a mean value to the upper gastrointestinal endoscopies, colonoscopies and capsule endoscopies according to the data available in the department of costs of our hospital. The Department of Pharmacy provided us with the value of each presentation of the drug at the purchase price. The costs also include the price of all medication administered during the admissions, such as erythropoetin and intravenous iron supplements, as well as of any other treatments and investigations that were performed. In our hospital there is no day centre in which procedures such as intravenous iron administration or blood transfusions could be performed, and patients requiring these measures are usually admitted to the emergency department. The costs included the last year before the start of the treatment and the first year afterwards. The costs related to the investigations which lead to the final diagnosis were excluded from the analysis in order not to bias the beneficial effect of the drug. Definitions The diagnosis of vascular malformations of the digestive tract (angiodysplasias or watermelon stomach) was established by endoscopic studies (upper GI endoscopy, colonoscopy or capsule endoscopy), associated or not with relevant imaging techniques (for example computer tomography with intravenous contrast). Therapeutic interventions In our centre, the treatment of vascular lesions with OCT-LAR is performed according to a protocol developed by colaboration of Department of Gastroenterology and Pharmacy, always off-licence and after excluding all other treatment possibilities due to motives that were described previously. We started with the dose of 10 mg administered monthly by intramuscular injection; the effect was reviewed at least every 3 months, and the dose was increased to 20 or 30 mg monthly (or not) according to the clinical response. In some cases we started directly with the dose of 20 mg or 30 mg monthly, based on the criteria of the prescriber. Once the treatment was started it was maintained indefinitely if the patient continued to present good response. Measuring effectivity After the start of the treatment, the number of blood transfusions, levels of haemoglobin, hospital admissions including the length of admission, admissions to the emergency department, necessity for endoscopic treatment and possible side effects were assessed at least once every three months. The criteria for response were defined as follows: - Complete response: No further need for blood transfusions, admissions nor endoscopic treatment, with mean blood hemoglobin of at least 9.5 g/dl. - Partial response: At least 50 % decrease in the necessity for blood transfusions, admissions or endoscopic treatment, with mean blood hemoglobin of at least 9.5 g/dl - No response: All the patients that did not fulfill the criteria of partial or complete response. Analysis of subgroups We have analyzed different subgroups in our cohort, nevertheless, they were not included in the present study given the small number of patients in each subgroup, which would then limit the validity of the obtained results. Statistical analysis The statistical analysis was performed using SPSS programme version 21.0 (IBM SPSS Statistics, Chicago, IL). Normal distribution was evaluated using the Shapiro-Wilk test for small samples. Continuous variables were expressed as media, mediana with confidence interval of 95 % and were compared using the t-Student test if normal distribution was confirmed, and using non-parametric tests (Wilcoxon test for related samples) if the distribution was not normal. We performed comparations between the year before and after the start of the treatment. P-value inferior than 0.05 was considered statistically significative. Ethical aspects The data were collected according to the ethical standards our centre. Results Finally 19 patients were included in the study, 17 men and 2 women, with mean age of 74.11 years (range 62-87, standard deviation 6.86). All patients had important comorbidity that limited the performance of exhaustive endoscopic therapy (ischemic heart disease, valvulopathy, cardiac arrhythmia like atrial fibrillation or ictus); three patients presented chronic obstructive pulmonary disease, three liver cirrhosis with portal hypertension and three chronic renal insufficiency. As far as concomitant medication was concerned, fourteen patients were on oral anticoagulants and/or antiaggregants: Seven of those were receiving simultaneous anticoagulant and antiaggregant medication, five only antiaggregants and two only anticoagulants. All 19 patients presented anemia which was difficult to control; eleven of them described overt recurrent hemorrhage in form of melena, hematochezia or rectorrhagia. Except for 1 patient with important cardiac and pulmonary comorbidity, all patients had an upper GI endoscopy and colonoscopy. Moreover, 15 patients underwent endoscopic study of small intestine with capsule endoscopy (15 cases) and/or enteroscopy (2 cases). Endoscopic study revealed angiodysplasias in 16 patients; 3 patients with liver cirrhosis presented hypertensive gastropathy, 2 of these lesions called watermelon stomach; only 1 patient with severe comorbidity did not undergo any endoscopy. Ten patients had angiodysplasias localized in the small intestine, three in the colon and three lesions affecting simultaneously both small and large bowels. No patient presented skin involvement or previous family history of gastrointestinal hemorrhage. Fifteen patients received previous endoscopic treatment, the mean number of sessions was 2.46 (range 1-8, SD 2.02). Argon plasma coagulation was the method of choice in all cases and no relevant complications were observed. The long-time success rate, however, was quite low, as all patients presented rebleeding, after mean time of 38.4 days (range 3-96 days) after the treatment. Likewise, the treatment did not reduce the necessity for hospital admissions and/or blood transfusions. Surgical interventions were contraindicated due to age and/or associated comorbidity. Baseline characteristics of all patients are resumed in table I. We compared the year before the start of treatment to the year afterwards in all patients. The mean time from the diagnosis to the start of the treatment with octreotide was of 25.42 months (range 11-48 months; SD 17.34). As for the anemia, we found significant reduction in the accumulated mean annual doses of iron supplements, counting with both oral and intravenous supplements during both periods (408.5 g per year vs. 203.6 g per year and patient; p = 0.002). Before starting OCT -LAR, 18 patients required treatment with iron (15 patients oral and intravenous and 3 patients oral) and afterwards, 15 patients continued to need supplements (7 patients both oral and intravenous and 8 patients oral). Similarly, we observed reduction in number of patients and the dose of darbepoetin alpha. During the first period, six patients received treatment with an accumulated dose of 396.7 mcg per year and per patient, while in the second period only half of them continued to receive darbepoetin, with an accumulated dose of 156.7 mcg per year and per patient (p = 0.013). Mean hemoglobin, mean dose of iron supplements per (both oral and intravenous), mean dose of darbepoetin alpha per year, mean length of admission in days per year and mean number of blood transfusions in the two periods are depicted in figures 2, 3 and 4. Twelve patients started treatment with the dose of 10 mcg of OCT-LAR, administered by intramuscular injection; of these, three required increase in dose to 20 mcg monthly, six patients initiated with dose of 20 mcg and one patient (number 19) directly with 30 mcg of OCT-LAR monthly. The mean duration of treatment was of 26.32 months, eleven patients received treatment during more than 24 months. For the purposes of this study we only analyzed the year before the start of the treatment and the year afterwards. Of these 19 patients included in the analysis, 13 continued with the same initial dose during a mean time of 18.8 months (range 11-26). Six patients required adjustment of dose. In three of them the dose was increased from 10 to 20 mcg after mean time of 7.5 months (range 4.5-12 months) due to persistent anemia and necessity for blood transfusions (patients number 6, 7, and 11) and in other three patients the treatment was stopped due to lack of the effect after 17, 19, and 22 months of administration (patients 7, 16, and 18). It is interesting that all these cases were patients with liver cirrhosis with portal hypertension. We have obtained complete response in 7 cases (36.8 %), partial response in another 7 patients (36.8 %). The rest of the patients (5/19; 26.32 %) precised the same or higher number of blood transfusions, iron and darbepoetin alpha supplements and/or endoscopic treatment and hospital admissions related to the gastrointestinal hemorrhage. All patients with complete or partial response presented angiodysplasia. Three of the five patients that did not respond to treatment had cirrhosis with lesions related to portal hypertension, associated with gastric antral vascular ectasia (GAVE) in two cases, and given the lack of response to OCT-LAR treatment, the drug was stopped in these three cases. When we compared the subgroup of patients that were receiving anticoagulants and/or antiaggregants to those that did not, we did not find any significant differences in the necessity of readmissions or number of blood transfusions. Before OCT-LAR was started, 13 patients underwent endoscopic therapy with mean number of 2.46 sessions per patient; of theses, only 5 required posterior endoscopic treatments, with a mean number of 1.2 sessions. All of them belonged to the group of patients with no response to treatment (patients 7, 11, 15, 16, and 18). When we compared the three different types of response (complete, partial and none), no statistically significant differences were found as far as mean hemoglobin levels, the length of the admission in days, mean number of blood transfusions or the mean costs in the period before the start of the treatment are concerned. In the period after the start of the treatment, we found statistically significant differences between the group with complete response (CR) and the group of partial response (PR) in the number of blood transfusions (0 and 1.13; p = 0.005), the mean annual dose of iron (27.8 g and 180.6 g; p = 0.003) and length of admission in days (0 and 11.8; p = 0.048). When the group with PR was compared to the group with no response (NR), statistically significant differences were found in the number of blood transfusions (1.13 and 7.8; p = 0.003), days of admission (5.4 and 11.8; p = 0.048), the mean annual dose of iron (180.6 and 480; p = 0.002) and total annual costs (11,269 € and 23,742; p = 0.002). The comparisons between the three groups are shown in figure 5. No side effects related to the OCT-LAR treatment were observed, only one patient was diagnosed with asymptomatic colelithiasis during the treatment, altough we do not know if it was present before the start of the therapy. The mean annual costs of the treatment before the start of OCT-LAR were of 36,072.34 € per patient (range 1,610.49 € to 122,840.50 €, SD 35,975.52 €) and in the period afterwards was of 13,867.57 € per patient (range 7,371.96 € to 36,891.64 €, SD 4,453.02 €), including the cost of the drug that in our Department of Pharmacy was of 614.33 € per dose in the presentation of 10 mg, 820.15 € per dose in the presentation of 20 mg and 1,025.97 € per dose in the presentation of 30 mg. Table II resumes the costs of the admissions to the hospital and the emergency department and the endoscopic treatments before and after the treatment. With the previous data we calculated reduction of 61.5 % of the mean costs between the two periods (from 36,072.35 € to 13,867.57 € per patient/year, p = 0.01). The item that implies the major expense was the hospital admission that represented 95 % in the period before the start of the treatment and 88 % of the costs in the later period. When we analyzed the costs of treatment of each patient separately, we observed similar costs reduction in fourteen of them, while five patients maintained similar or higher costs after the start of OCT-LAR. Two of the latter presented angiodysplasia with continuous need for blood transfusions but not hospital admissions and limited initial clinical response, which required adjustment of the dose of OCT. In the other two patients had liver cirrhosis with portal hypertension, no improvement in any of the assessed items was observed, and the fifth one did not present clear clinical response, although reduction in total treatment costs was appreciated (patient 7). Discussion Patients with chronic anemia related to gastrointestinal hemorrhage secondary to vascular lesions represent a diagnostic and therapeutic challenge for clinical gastroenterologists, as many of them suffer from relevant co morbidities that complicate the realization of invasive procedures. Moreover, the treatment of associated anemia implies major economical costs (4,6). We have performed a retrospective single-centre study that includes all the patients that have been treated with OCT-LAR in the above explained indication. We have excluded from the analysis all the patients whose treatment was shorter than 3 months, as we considered that it was an insufficient time to be able to evaluate its long-term benefit. We intended to establish a group of control among patients with digestive bleeding and chronic anemia during the same study period. However, in our hospital, we only start the treatment with octreotide when endoscopic treatment failed or is not feasible due to associated risks, such as relevant comorbidity. Therefore, it was impossible to find a group of control with similar baseline characteristics, in which repeated endoscopic and/or surgical treatment would be contraindicated. Nevertheless, in all cases there was a minimum of 14 weeks gap between the last endoscopic intervention and the start of the treatment; which reduces the risk of possible overvaluation of previous costs. Similarly, another factor that could play an important role in the final results was the dose of antiaggregant or anticoagulant treatment, both of which are frequently used in this group of patients. Before the start of OCT-LAR was considered, the necessity of continuing with this medication was assessed by a cardiologist and/or neurologist in each patient; dose adjustment of treatment suspension was performed in strictly indicated cases. All these changes were performed before the period that was included in our study. There were no posterior changes in the dosage of antiaggregants or in the ranges of INR in patients treated with dicumarinics. Our results demonstrate an acceptable efficacy in the treatment of gastrointestinal hemorrhage due to vascular lesions, with partial and complete response in 36.8 % respectively, and treatment failure rate of 26.3 %. In the current literature there are few studies that would assess this type of treatment prospectively. Brown et al. (8) published a paper in which he analyzed three prospective studies that included a total of 62 patients with a global response rate (complete or partial) of 76 % (IC 95 % 0.64-0.85). Junquera et al. (9) studied 32 patients that received subcutaneous octreotide at a dose of de 50 mcg twice a day during 1-2 years, and compared them to 38 patients that received placebo. In his work there were 23 % patients in which the treatment failed. More recently Nardone et al. (10) published a retrospective study, including 98 patients with digestive bleeding secondary to angiodysplasias. His results are superposable to those observed in our study, obtaining a complete response in 40.9 %, recurrence of hemorrhage in 32.6 %, and no response in 26.5 % of all cases. A Spanish study presented by Molina et al. (11) that evaluated 11 patients with significant comorbidity and advanced age found complete response in 18 % of the patients, although significant reduction of transfusion requirements and length of hospital admissions were observed after the start of the treatment. The optimal dose of OCT-LAR can vary and is not well-defined in the literature; most often doses between 10 and 30 micrograms monthly are used, and most studies were performed using the dose of 20 micrograms monthly. Most of our patients received 10 micrograms monthly. We do not know if higher doses would produce major clinical benefit, and we have not found any studies that would compare different doses of the medication. The side effects described so far are usually mild (colelithiasis, nausea, vomiting, abdominal pain, diarrhea or difficult control of diabetes) (12). In our series of patients no adverse effects were observed, except for one case in which colelithiasis was incidentally diagnosed in an otherwise asymptomatic patient. Given the retrospective character of the data collecting, it is possible that some minor side effects were not registered in patients' clinical history. At this moment, the optimal length of treatment has not been established. In most studies, OCT-LAR is maintained between 1 and 2 years, and the effect of treatment was maintained over approximately 1 year after stopping the treatment (9). In our patients, the mean treatment duration of OCT-LAR was of 26.3 months (range 6-84 months; SD 17.8). Four patients that have been receiving treatment for more than 24 months, presented an excellent tolerance, maintaining clinical response with frequent previous exacerbations, which were the motives for long treatment administration. The treatment was stopped in three patients who failed to respond. Two patients who required increase in dose of OCT-LAR due to new episode of hemorrhage, presented good response to higher dose and continue with the treatment. In our study we concluded that treatment with OCT-LAR seems to be a reasonable and cost-effective therapeutic modality in patients with relevant comorbidities, given the significant reduction in total treatment costs resulting from decrease in number of hospital admissions and their length, decrease in admissions to emergency department, decrease in dose of iron supplements, darbopoetin and/or number of blood transfusions. To our knowledge, there is currently no similar study that would evaluate this aspect of the treatment and given high price of the drug we consider that it is essential to assess it, as it may change its use in this indication. Based on the results of the present study we consider that our criteria of the start of OCT-LAR therapy are reasonable and are in accordance with good clinical conduct. It should be emphasized that the reduction of costs has not been observed in patients that did not require frequent blood transfusions or hospital admissions, or in case of cirrhotics with portal hypertension, although limited number of patients prevents us from making further conclusions. Previous studies have described promising results in the treatment of EVAG in patients with cirrhosis (9,13). Nardone et al. (14) included 3 cirrhotic patients with portal hypertension and EVAG that were treated with octreotide, achieving complete response in one of them and decrease transfusion requirements during 2 years of follow-up. Thalidomide has been used as an alternative to the treatment with OCT-LAR. The data available in the literature are limited, based on case reports or series of cases, which have also shown effectiveness in terms of reduction of in transfusional requirements (including its capacity to complete resolution of the endoscopical image of vascular lesions) (15,16). In our centre, we have indicated the administration of thalidomide in case of only one patient, in whom the drug had to be stopped due to its adverse effects. As previously mentioned, the principal limitations of our study are the fact that it was retrospective, single-center and with small number of patients. However, our results are very similar to those in previously published studies, contributing additional information about the effectivity of the treatment. In conclusion, OCT-LAR seems to be an efficient treatment option in patients with chronic gastrointestinal haemorrhage secondary to vascular malformations, mainly in patients with relevant comorbidity that makes other therapeutical modalities more difficult. In spite of its relatively high costs, in the present study we describe a significant decrease in total costs in patients with clinical response. Prospective and multicentric studies are needed to confirm these results. Artículo 6 Infectious etiology of diarrheas studied in a third-level hospital during a five-year period ABSTRACT Introduction and objective: Infectious diarrheas are highly frequent and responsible for a major consumption of resources. This study identified the main diarrhea-causing microorganisms in a health area of Granada (Spain) and determined changes in the epidemiologic pattern over a five-year period. Material and method: A retrospective study was conducted based on results obtained in the Microbiology Laboratory of Hospital Universitario Virgen de las Nieves (Granada, Spain). Results: Out of the 25,113 stool microbiological and/or parasitological studies ordered, 2,292 microorganisms were identified in 2,152 samples from 1,892 patients. There was a predominance of bacterial diarrheas (50.1 %), mainly caused by Campylobacter spp. (22.2 %), whose frequency increased significantly during the last two years, and by Salmonella spp. (16.4 %), whose frequency remained stable during the whole study period. We highlight the high frequency of Rotavirus (33.5 %), although a significant decrease was observed during the last two years. Salmonella spp. was more frequently detected during the summer and autumn, Campylobacter spp. during the spring, and Rotavirus during the winter. Viral processes were predominant (53.3 %) in pediatric patients, mainly Rotavirus in under 2-yr-olds, whereas bacterial processes predominated in older children and adults. Diarrhea began at community level in 84.2 % of patients, requiring hospitalization in 25.8 % of cases, and diarrhea was nosocomial in the remaining 15.8 %. Conclusions: During the study period, there was a significant increase in the frequency of diarrhea caused by Campylobacter spp., a significant reduction in the frequency of diarrhea due to Rotavirus, and no change in the frequency of diarrhea due to Salmonella spp., all of which showing a marked seasonal distribution. Key words: Diarrhea. Rotavirus. Campylobacter spp. Salmonella spp. Introduction Infectious diarrhea is a clinical situation experienced by most humans on one or many occasions throughout their lives. Although usually self-limiting, with scant local or systemic repercussion, it can occasionally produce an important clinical deterioration that requires specific therapeutic measures or hospitalization and can even, in the most severe cases, end in the death of the patient. It represents a major public health problem responsible for elevated health costs and resource consumption in both primary and hospital care (1,2). The characteristics of the diarrhea and the clinical situation of the affected individual largely depend on the pathogen involved and patient-related factors, such as age, immune response capacity, mucosal structure, and gut microbiota (3). The most frequently involved microorganisms are: bacteria, such as Salmonella spp., Campylobacter spp., Yersinia spp., Shigella spp., Aeromonas spp., Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, Clostridium difficile, or Clostridium perfringens, among others; viruses, such as Rotavirus, Norovirus or Adenovirus; and protozoa, such as Giardia lamblia, Cryptosporidium parvum, Isospora belli, Entamoeba histolytica, or Cyclospora cayetanensis. The digestive transmission of these microorganisms from the intake of contaminated food or water and their interpersonal transmission are responsible for outbreaks or epidemics, although most cases of diarrhea are sporadic. It is difficult to establish the true incidence of infectious diarrhea, because it is a self-limiting process and not all patients seek medical care for this condition (4). Moreover, microbiological studies are not always conducted and, when performed, do not always identify the pathogen (2). Although the main treatment, based on oral rehydration measures, is often adequate, some situations require specific antimicrobial treatment (1). This should be prescribed as a function of the clinical status of the patient and the microorganisms most frequently involved in the etiology of the process in each geographic area. The objective of this study was to identify the main microorganisms causing infectious diarrhea in our setting between 2007 and 2012 and establish their relative frequency and distribution according to the sex and age of patients, the origin of the sample or ordering department, and their annual and seasonal time course. Material and method A retrospective descriptive study was conducted using the data from the MicrobDynamic laboratory information system (Francisco Soria Melguizo, SA, Madrid, Spain) of the Microbiology Department of the Hospital Universitario Virgen de las Nieves (Granada, Spain) on the results of microbiological and/or parasitological diagnostic tests of stool samples from patients with episodes of diarrhea and/or non-acute abdominal pain, ordered between October 1, 2007 and September 30, 2012. The hospital complex comprises three hospitals (General/Specialty Hospital, Maternity/Child Hospital, and Traumatology and Rehabilitation Hospital) that meet the demands of the North Hospital Area of Granada province, which includes the Primary Care Health Districts of North Granada, Santa Fe, and Guadix and the Basic Health Area of Alcalá la Real (Jaén, Spain), serving a reference population of around 440,000 inhabitants. Figure 1 depicts the process of recovering data from the registry of microbiological samples. Searches of the laboratory information system yielded the results of all tests conducted in stool samples during the study period. Those with negative results were excluded (reported at the time as "no enteropathogenic bacteria detected", "negative antigen detection", "absence of fresh parasitic forms", or "absence of acid-fast organisms"): We only selected those with positive microbiological and/or parasitological results, i.e., indicating the presence of the microorganism (bacteria, virus, or parasite) detected and identified in the sample and therefore considered as etiologically responsible for the clinical process motivating the request for the study. A specific database was designed to collect relevant information based on the positive results selected. Data were gathered on: The affiliation of each patient (by clinical record number and his/her initials), dates of the reception of the sample and the emission of the report of the results, demographic variables (age, sex, and place of residence), outpatient or hospital origin of the sample (and, in the latter case, the department in which the patients were hospitalized), and, finally, the microorganism(s) identified. In order to avoid inclusion bias in the positive results, a control of duplicates was performed by using the clinical record number and initials of patients. In cases in which there was more than one positive result for a single patient, we ruled out studies with an interval of less than 7 days between the reception of the stool sample and the emission of a previous report and with the same microbiological and/or parasitological result, which were considered duplicate or control studies. Next, the Integrated System of Management and Information for Health Care in Andalusia (Spanish initials, DIRAYA) was used to review the digitalized clinical records of the selected patients and collect clinical data (presence of abdominal pain, dehydration, neurological disorders, or fever, characteristics of the stool, duration of the episode, and days of hospital stay, when appropriate), personal history of interest, hospital or community origin of the diarrhea (considered of hospital/nosocomial origin when the onset was more than 72 h after hospital admission or less than 72 hours after hospital discharge), and other analytical data. Non-parametric statistical tests were applied. Binomial tests were used to compare the detection frequency of each microorganism as a function of the patients' sex and age; and the Kruskal-Wallis and Mann-Whitney U tests were used to compare the length of hospital stay as a function of the etiology of the clinical process, to evaluate changes in the annual and seasonal distribution of each microorganism, and to establish the possible association of these changes with temporal variations in the number of microbiological and/or parasitological studies ordered. SPSS 18.0 software was used for the statistical analysis. P<0.05 was considered significant in all tests. Results Description and distribution of the microorganisms identified Out of a total of 25,113 requests for microbiological and/or parasitological studies during the five-year study period, 2,292 clinically relevant microorganisms were identified in 2,152 stool samples from 1,892 different patients, yielding an accumulated 5-year incidence of 430 cases/100,000 inhabitants in the reference population. According to these results, an average of around one study in ten yielded a positive result, with a mean of 38 microorganisms identified per month from a mean of around 419 requests per month. Table I shows the distribution of these microorganisms by genus and species and their percentage with respect to the number of requests for microbiological and/or parasitological study for each type of microorganism. We identified 1,149 bacteria (50.1 % of all microorganisms) from 15,062 requests for stool culture or C. difficile toxin detection by immunochromatography, giving a diagnostic performance of 7.6 positive results per 100 studies conducted. The best-performing diagnostic procedure was the detection of viruses in stool samples, with 1,001 viruses (43.7 % of identified microorganisms) being identified out of 3,049 requests, a mean of 33 positive results per 100 studies conducted. The detection of parasites was the worst-performing procedure, with 142 (6.2 %) being identified out of 7,002 requests, an average of 2 positive results per 100 studies conducted. Although there was a predominance of bacterial diarrheas, especially those caused by Campylobacter spp. (n = 509; 22.2 %) and Salmonella spp. (n = 377; 16.4 %), we highlight the elevated relative frequency of Rotavirus (n = 768; 33.5 %). Among the parasites, only G. lamblia, Entamoeba coli, E. histolytica, Endolimax nana, and Cryptosporidium spp. were detected in patients with diarrhea; the remaining parasites were identified in patients with non-specific abdominal discomfort or non-acute abdominal pain. A single microorganism was identified as responsible for the clinical process in 2,017 samples (93.7 %), while more than one microorganism was detected in 135 samples, most frequently a combination of two viruses (85 samples), notably Rotavirus-Adenovirus (78 cases). In 110 patients, the same microorganism was detected in two or more samples obtained with an interval of more than one week. Distribution of infections according to the sex and age of patients Among the 1,878 patients for whom sex was recorded (99.3 % of the total study sample), 53.0 % were males. Bacterial and viral infections were significantly more frequent in males (53.2 % vs. 46.8 %, p = 0.031; and 54.7 % vs. 45.3 %, p = 0.003; respectively), whereas parasitizations were more frequent in females (58.7 % vs. 41.3 %, p = 0.045). Among the 1,851 patients (97.8 %) for whom the age was recorded, the mean age was 14.9 ± 24.5 yrs (ranging from 1 month to 100 yrs); 75.5 % of patients were under-14-yr-olds, and the under-2-yr-old age range was the most frequent (47.1 %). Among the infants, there was a higher frequency of viral (53.3 % of cases) versus bacterial (41.9 %) and parasitical (4.8 %) cases, although the classification by age ranges showed that this predominance was largely attributable to the high frequency of viral diarrhea due to Rotavirus in the under-2-yr-olds, with bacterial infections being more frequent at older ages. Among the adults, bacterial infections were significantly more frequent than the other etiologies considered together in all age ranges (78.2 % vs. 21.8 %, p < 0.001). Differences in the origin of the sample and department ordering the study Out of the 2,149 cases (99.9 %) for which the origin of the sample was recorded; 44.4 % derived from primary or specialized care outpatient departments, 34.6 % from hospital departments, and 20.1 % from the emergency area. therefore, most (64.5 %) of the microorganisms identified were from outpatient samples. In addition, 0.9 % of samples were from other hospitals -Hospital Provincial San Juan de Dios (Granada, Spain), Hospital de Alta Resolución de Alcalá la Real (Granada, Spain), and Complejo Hospitalario de Jaén (Jaén, Spain). The clinical samples in which bacteria and parasites were identified were mainly from outpatient departments, while the samples in which viruses were identified were mainly from hospital departments, notably the Pediatrics Department. Samples of under-2-yr-old patients were most frequently from hospital departments (Pediatrics, Pediatric ICU, or Pediatric Surgery), whereas those from older children were mainly from outpatient departments. Samples from adult patients aged between 15 and 44 yrs were most frequently from outpatient departments, especially from Primary Care and Gastroenterology Departments, while samples from older patients were most frequently from hospital departments. Out of the 1,811 (95.7 %) patients for whom the origin of the clinical process was recorded, it was community acquired in 1,525 patients (84.2 %), 393 (25.8 %) of whom required hospitalization, and it began during a previous hospitalization for a reason other than diarrhea or after hospital discharge in the other 286 patients (15.8 %). In both cases, the clinical process was nosocomial diarrhea, and it was an intercurrent process in 56 % of these patients. The diarrheas most frequently requiring hospitalization were those of viral origin (> 50 %) and, in all cases, more than half of the admissions were intercurrent. The mean hospital stay was 6.2 ± 6.5 days for the 393 patients requiring hospitalization, all as a consequence of diarrhea, but was 25.2 ± 38.1 days for those with intercurrent diarrhea (17 ± 15.3 days when the 26 patients with extreme hospital stays > 70 days are not considered). Table II summarizes the main demographic and epidemiologic data associated with the most frequently identified microorganisms. Diarrheas caused by Campylobacter spp., Rotavirus, and Adenovirus were significantly more frequent in males versus females, with no gender differences in those produced by Salmonella spp. or G. lamblia. Moreover, they were all (except for those produced by G. lamblia) significantly more frequent in under-14-yr-old children, especially the viruses, as commented above. In most cases, the samples were of community origin (Primary Care and Specialized Care Outpatients), given that in more than 75 % of cases, according to the etiology, the clinical process began at outpatient level and did not require hospitalization (except in the case of diarrhea due to Rotavirus, with around half of the samples coming from hospitalization rooms in the Pediatric Department, despite their more frequent outpatient onset, given the need for the hospitalization of patients as a consequence of the clinical course). When the diarrhea was caused by any of these microorganisms (Table II), the mean hospital stay was longer when the clinical process was caused by G. lamblia (23.3 days ± 21.2), Campylobacter spp. (22.3 days ± 47), or Rotavirus (20.5 days ± 43.5). However, there were no statistically significant differences (p > 0.05 in all cases) in hospital stay among these etiologies or in comparison to others, such as Salmonella spp. (10.1 days ± 19) or Adenovirus (18.9 days ± 27.3). Annual and seasonal distribution of infectious diarrheas Finally, we analyzed the annual (considering periods between October and September) and seasonal distribution of the number and type of microorganisms identified in relation to temporal variations in the number of requests for microbiological and/or parasitological studies of stool samples during the study period. A significant increase (p = 0.016) was observed in the detection of bacteria during the last two years, which was not a consequence of the increase in requests, which remained stable and with no seasonal variations. Considering only the most frequently identified bacteria (Fig. 2A), it can be observed that the frequency of Campylobacter spp. significantly increased during the last two years in comparison to the rest of the study period (p = 0.029), with more than double the number of cases during the last year with respect to the first three years, while cases of Salmonella spp. (and of other bacteria) remained stable during the study period. The seasonal distribution of these bacteria (Fig. 2B) showed that Salmonella spp. was more frequently detected during the summer and autumn and Campylobacter spp. during the spring. Moreover, there were peaks of higher relative frequency of bacterial diarrheas in June 2008, May 2011, September 2011, and August 2012. The annual development and seasonal distribution of predominant viruses were also analyzed, showing that Rotavirus was the most frequent during the period 2008-2010 (Fig. 2A), followed by a significant reduction (p = 0.043). Consideration of the frequency of Rotavirus as a function of the season (Fig. 2B) showed that the number of cases during the winter was significantly higher than in the other seasons (p = 0.016), which was not the case for the other viruses, especially Adenovirus, which showed no significant seasonal differences. There were peaks of higher relative frequency of viral diarrheas in April 2008 and May-July 2009, i.e., outside the winter period, although comparison of these frequencies with those observed for the same months in different years yielded no significant differences (p = 0.406). With respect to parasites, the relative frequency was in general low, with no significant annual or seasonal differences throughout the study period, although a peak was observed in July 2008. Discussion In our study, Rotavirus, Campylobacter spp., and gastroenteric Salmonella were, in this order, the most frequently identified microorganisms in stool samples from patients with diarrhea. In general, bacterial and viral infections were more frequent in males than in females at all age ranges, in agreement with observations by other authors. In adult ages, this may be attributable to the higher frequency of risk practices in males than in females, including less care in the handling of food or the greater consumption of undercooked food (5). However, this would not explain the higher frequency among male children, because no sex differentiation in risk practices can be affirmed in early ages. Various authors have reported that these three microorganisms show the highest incidence rates during infancy (6). We also found that the under-2-yr-old children had the highest frequency of viral diarrheas, especially due to Rotavirus (including frequent coinfections with Adenovirus), with bacterial infections being predominant at older ages. Among the latter, the mean age of pediatric patients with diarrhea caused by Campylobacter spp. was lower than the age of those with salmonellosis, as demonstrated in other studies (7), and this difference in age was also observed in the adult population. Most of the stool samples that yielded positive results were of out-of-hospital origin, because the clinical procedure began in an outpatient setting. However, among the under-2-yr-old patients, the stool samples were mainly from hospital departments, either because, despite the out-of-hospital onset, they required hospital admission, a common practice due to their young age and to the clinical characteristics of diarrhea, which can course with intense dehydration (8-10), or because the viral diarrhea was nosocomial, which is also frequent (11). Regardless of the etiology, patients with viral diarrhea more often required hospitalization and their mean hospital stay was longer than that of patients with bacterial diarrhea. Among the latter, hospitalization was more frequent when diarrhea was produced by Salmonella spp. but the duration of hospital stay, if required, was longer when the cause was Campylobacter spp. As indicated by other authors, there is a characteristic dissociation between the high frequency of diarrhea due to Campylobacter spp. and the low need for hospitalization, contrasting with observations in the case of Salmonella spp. (12). The greater length of hospital stays by patients with diarrhea due to G. lamblia is because the admission was intercurrent in 75 % of these cases. The present study also showed a significant increase in diarrheas caused by Campylobacter spp. and a significant decrease in those due to Rotavirus during the last two years of the study, with no change in diarrheas caused by Salmonella spp. No studies have been published in our health area that could indicate whether this a current trend; however, various studies conducted in other areas of Spain during the past two decades have demonstrated that there has been an epidemiologic change, from situations in which rates of infection due to Salmonella spp. were higher than those caused by Campylobacter spp. (13) to a completely opposite situation, with a progressive increase in the frequency of clinical cases produced by Campylobacter spp. (12,14,15). At any rate, this increase was observed during the last two years of the study and we could not establish whether it was due to epidemic outbreaks, because of the lack of recorded data to confirm this possibility with complete reliability; higher peaks of frequency of bacterial diarrheas were observed in May 2011, September 2011, and August 2012, which may correspond to outbreaks, but they were not documented as such. For this reason, cannot establish whether this trend will be maintained trend in subsequent years or is an exceptional situation that may subsequently be reversed. On the other hand, two oral vaccines against Rotavirus formed by live attenuated viruses (one monovalent, which includes serotype G1P1A, and another pentavalent, with serotypes G1 to G4 and P1A) have been commercialized in Spain since 2007, and both have demonstrated their effectiveness in various studies (16-18). Although these vaccines have not yet been included in the vaccine calendar, they are recommended by various scientific societies, including the Spanish Pediatrics Association (Asociación Española de Pediatría), and are frequently prescribed and recommended to parents by pediatricians for infants under 6 months old. According to some authors, this has translated into a gradual increase in vaccine coverage year by year (19) and has been associated with a significant reduction in the incidence of diarrheas by Rotavirus and especially in hospitalizations for this reason (8,19). However, some authors consider that it is difficult to determine the true data on vaccine coverage in our country, and it is therefore not possible to establish a definitive causal relationship (10). The pattern of seasonal distribution of the most frequent infectious diarrheas in this study was similar to that reported by other authors: Salmonella spp. was detected more frequently during the summer and autumn (13,20), Campylobacter spp. during the spring (5), and Rotavirus during the winter (8,19). Although it is possible that the detected peaks may correspond to epidemic outbreaks, the recorded data do not allow this to be definitively confirmed. Given that our study was retrospective and based on the reports emitted by the Microbiology Department, an important limitation is that these reports occasionally lacked some important demographic data for the patients (because they are sometimes not included in the order form attached to the sample or, in the case of requests from Primary Care, because it was not possible to access the clinical records electronically). Therefore, these data were not complete for all study patients. It was only possible to gather data, although incomplete, on data such as the sex and age of patients, the community or hospital origin of the sample, and the department ordering the microbiological study. Likewise, the systematic gathering of some important clinical data related to the clinical process in each of the study episodes was not possible (including personal history of interest, characteristics of the stool, pathological products, or presence of abdominal pain, fever, dehydration, neurological disorders, biochemical and/or hematological analytical disorders, etc.). This was because in most cases the medical reports and clinical records did not include this information, the report was incomplete in cases in which some data could be gathered, or it was not possible to differentiate whether clinical/analytical data in the report were due to the clinical process that originated the request for the microbiological and/or parasitological analysis or to other concomitant diseases. Thus, in the cases in which the same microorganism was detected in two or more samples obtained with an interval of > 1 week, it could not be determined whether this situation was due to a persistence of the microorganism in the patient or to a re-infection by the same microorganism, because there was no negative study between the two samples and there were no data indicating the clinical evolution of the patient during this time. Another important limitation is that, as in other studies, patients with symptoms of diarrhea and/or non-acute abdominal pain whose physicians did not order stool microbiological and/or parasitological study were not recorded; hence, the true data are underestimated and largely determined by the severity of the clinical process. Nevertheless, the data provided in the present study are comparable with those of various regional, national, and international studies conducted in similar situations. In conclusion, there was a significant increase in the frequency of diarrheas due to Campylobacter spp. in our health area during the study period and a significant decrease in those produced by Rotavirus, while the frequency of processes caused by Salmonella spp. did not change. These microorganisms also showed a marked seasonal distribution. Further periodical studies in the same area are necessary to definitively confirm these trends and verify whether they truly correspond to an epidemiologic change or simply respond to exceptional situations. Artículo 7 Quality standards in 480 pancreatic resections: a prospective observational study ABSTRACT Pancreatic resection is a standard procedure for the treatment of periampullary tumors. Morbidity and mortality are high, and quality standards are scarce in our setting. International classifications of complications (Clavien-Dindo) and those specific for pancreatectomies (ISGPS) allow adequate case comparisons. The goals of our work are to describe the morbidity and mortality of 480 pancreatectomies using the international classifications ISGPS and Clavien-Dindo to help establish a quality standard in our setting and to compare the results of CPD with reconstruction by pancreaticogastrostomy (1,55) versus 177 pancreaticojejunostomy). We report 480 resections including 337 duodenopancreatectomies, 116 distal pancreatectomies, 11 total pancreatectomies, 10 central pancreatectomies, and 6 enucleations. Results for duodenopancreatectomy include: 62 % morbidity (Clavien ? III 25.9 %), 12.3 % reinterventions, and 3.3 % overall mortality. For reconstruction by pancreaticojejunostomy: 71.2 % morbidity (Clavien ? III 34.4 %), 17.5 % reinterventions, and 3.3 % mortality. For reconstruction by pancreaticogastrostomy: 51 % morbidity (Clavien ? III 15.4%), 6.4 % reinterventions, and 3.2 % mortality. Differences are significant except for mortality. We conclude that our series meets quality criteria as compared to other groups. Reconstruction with pancreaticogastrostomy significantly reduces complication number and severity, as well as pancreatic fistula and reintervention rates. Key words: Pancreaticoduodenectomy. Pancreatectomy. Morbidity. Mortality. Quality Indicators. Health Care. Abbreviation list: ISGPS: International Study Group of Pancreatic Surgery; CDP: Cephalic duodenopancreatectomy; DP: Distal pancreatectomy; ASA: American Society of Anesthesiologists; BMI: Body mass index; PF: Pancreatic fistula; DGE: Delayed gastric emptying; PJ: Pancreaticojejunostomy; PG: Pancreaticogastrostomy; TP: Total duodenopancreatectomy; ERAS: Enhanced recovery after surgery; CP: Central pancreatectomy; GIST: Gastrointestinal stromal tumors; ICU: Intensive care unit. Introduction The increased number of pancreatic resections in specialized units has led to improved morbidity and mortality rates. Despite this, in our health care system, we have no postoperative quality standards specific for the two procedures most commonly used: Cephalic duodenopancreatectomy (CDP) and distal pancreatectomy (DP). Duodenopancreatectomy-related morbidity and mortality has been shown to decrease as the number of procedures per surgeon and hospital increases, even if limits are rather vague (1-4). Furthermore, quality references available mostly derive from series in health care environments where high-volume centers predominate (5). The description of complications as recently standardized by the ISGPS (6-8) and Clavien-Dindo (9,10) classifications (Table I) has been scarcely used in Spanish publications (5,11-14). This fact precludes case comparisons and hinders the establishment of quality standards adapted to our health care setting. The goals of our work are to describe the morbidity and mortality of 480 pancreatectomies using the international classifications ISGPS and Clavien-Dindo in order to help establish a quality standard in our setting, and to compare the results of CDP with reconstruction by pancreaticogastrostomy versus pancreaticojejunostomy. Patients and methods All patients undergoing pancreatic resection between June 1994 and June 2014 were included. Data were prospectively entered into a proprietary FileMaker Pro 3.0 database on patient discharge, also including readmissions within 30 days of discharge. Seventeen variables were studied: Demography, ASA classification, body mass index (BMI), diagnosis, surgical procedures, surgery date, surgical complications according to the ISGPS classification, pancreatic fistula (PF), delayed gastric emptying (DGE), bleeding and Clavien-Dindo, reintervention, infection, admission to ICU, need for radiological/endoscopic or transfusion procedures, mortality and its cause at 30 days or at any time point for inpatients, and hospital stay. Complications during readmission were added to overall results. Data before 2008 were adjusted to international classifications on a case-by-case basis, and reviewed by the primary author. Complications were deemed to be minor if Clavien I-II, and major if Clavien ? III-A, including mortality. All patients signed an informed consent according to the ethical guidelines provided by the Declaration of Helsinki as revised in 1975. According to pancreatic resection type patients were included in the following groups: CDP in two periods - from June 1994 to April 2008, where pancreatic reconstruction was performed by duct-to-mucosa pancreaticojejunostomy using a silicone drain (PJ) (15); and from April 2008 to June 2014, where the reconstruction of choice was by two-plane invaginated pancreaticogastrostomy as described by Delcore (PG) (16). Both cohorts were used to compare morbidity, mortality, and postoperative stay. Total duodenopancreatectomy (TP), where the whole pancreas is excised together with the duodenum and spleen, hence no suture or section border is present. Distal, body-tail or subtotal pancreatectomy, grouped together as distal pancreatectomies (DP) and categorized into two subgroups: Urgent (pancreatitis and trauma) or elective. Central pancreatectomy (CP), where a section of the proximal pancreas is performed and a portion of the pancreatic body is excised, with an anastomosis of the distal pancreas to the jejunum or stomach. Pancreatic enucleation, meaning the excision of a small pancreatic fragment around the lesion. Data will be presented according to pancreatic resection technique and comparing PJ versus PG. Preoperative study, technique, and postoperative care were standardized, and from 2008 on a clinical path based on a postoperative multimodal rehabilitation protocol (17) for CDP was implemented. Statistical study Mean and standard deviation, and median plus range were used for the descriptive analysis. A cohort comparison study was carried out for PJ versus PG. Qualitative variables were analyzed using the chi-squared and Fisher tests, whereas Student's t test or the Mann Whitney U test was used for quantitative variables. Data were analyzed with the SPSS 22.0 statistical package, and a p value of 0.05 was considered statistically significant for all comparisons. Results In all, 480 patients were included, and 5,893 data for all 17 variables under study were obtained; missing data amounted to 207 (3.2 %) (128 BMI and 53 DGE extent). Surgical technique was: 337 CDP (177 PJ, 155 PG, 5 excluded), 116 DP (11 urgent, 105 elective), 11 TP, 10 CP, and 6 enucleations (Fig. 1). CDP Of all 337 CDPs 5 were excluded from the study because of associated major surgery (2 total gastrectomies, 2 major hepatectomies, and 1 gunshot injury) (Table II). Diagnoses included: 119 pancreatic adenocarcinomas, 60 papillary adenocarcinomas, 34 cholangiocarcinomas, 34 chronic pancreatitis, 19 mucinous intraductal papillary neoplasms, 17 papillary adenomas, 15 neuroendocrine tumors, 8 duodenal adenocarcinomas, 5 serous cystadenomas, 3 metastases (2 from renal carcinoma, 1 from hemangiopericytoma), 2 mucinous cystadenomas, 2 cystadenocarcinomas, 14 others (3 ampullary stenoses, 3 colonic cancers, 2 biliary stenoses, 1 Castleman's disease, 1 gallbladder cancer, 1 gastric cancer, 1 lymphoma, 1 hamartoma, 1 duodenal GIST). Of all CDPs, 289 (87 %) were performed for tumors: 251 (75.6 %) malignancies, 33 (10 %) premalignant lesions, and 5 (1.5 %) benign growths; the remaining 43 were for inflammatory conditions (13 %). Complications A total of 206 patients (62 %) had at least one complication. Minor complications amounted to 121 (36.4 %) and major ones to 85 (25.5 %). Of patients with major complications, 25 (7.5 %) were III-A (22 percutaneous drains, 3 visceral artery aneurysm embolizations); 19 (5.7 %) were III-B (17 cases from reintervention and 2 radiographic procedures under general anesthesia); 18 (5.4 %) patients were IV-A (11 bleeding events with hemodynamic failure -5 GI, 5 visceral arteries, 1 hemoperitoneum- 7 reinterventions that required admission in an ICU); 12 (3.6 %) were IV-B (12 reoperated patients with organ failure). Mortality (Clavien V) was 11 patients (3.3 %), and causes included: 5 abdominal sepsis, 3 visceral artery bleeding, 1 hemoperitoneum, 1 bronchial aspiration, and 1 cardiac arrest from ventricular fibrillation. Of those who died, 4 were reoperated and 4 had pancreatic fistula. Pancreatic fistula PFs are described using two classifications: ISGFP and Clavien's. In 76 patients (22.9 %) PF was identified as per the ISGPF: A 18 (5.4 %), B 27 (8.1 %), C 31 (9.4 %). According to Clavien's classification: Grade I-II 28 (8.4 %), III 25 (7.5 %), and IV-V 25 (6.9 %). Of all 76 patients with PF, 27 (35.5 %) were re-intervened versus 14 (5.7 %) of those with no PF (p < 0.001); 4 patients died with PF (5.2 %) versus 7 (2.7 %) without PF (p = 0.27); 7 patients with PF (9.2 %) developed visceral artery bleeding versus 4 (1.5 %) without PF (p < 0.001). Delayed gastric emptying Our data from before the publication of the ISGPS classification were adapted to said system. In this process DGE was estimated to have an incidence of 100 %, but extent could only be obtained for 53 patients (15.9 %). The overall incidence of DGE was 114 (34.3 %), this being the most common complication. Its association with other abdominal complications was: 47 (64 %) PFs with DGE and 67 (35.4 %) PFs without DGE (p < 0.001); 41 (36 %) intra-abdominal abscesses with DGE and 27 (12.3 %) without DGE (p < 0.001); 27 (23.6 %) reinterventions with DGE and 14 (12.2%) without DGE (p < 0.001). Reintervention There were 41 reoperated patients (12.3 %), including readmissions within 30 days, which required 59 reinterventions (28 one, 8 two, 5 three). Causes, multiple at times, included: 26 grade-C pancreatic fistulas, 25 bleeding events, 22 intra-abdominal infections, and 1 evisceration. Reintervention-related mortality was 4 patients (9.7 %). Readmission The causes for all 30 (9 %) readmissions included: 10 digestive intolerance, 9 bleeding, 8 fever, and 3 abscesses that required percutaneous drainage. Stay Mean stay was 20 (17.14) days, with a median of (6-144) days. For patients with no complications mean stay was 10 (3.84) days; for Clavien < III 19.7 (9.03) days (p < 0.001); for Clavien ? III 36 (24.68) days (p < 0.001). For patients with PF it was 33.6 (23.51) days versus 16.2 (12.3) days without PF (p < 0.001). Comparison between PJ and PG The two cohorts show no significant differences in demography, operative risk or diagnosis. The procedures were performed by the same surgeons and two differences existed as regards the technique, namely the type of pancreatic anastomosis (PG vs. PJ); also, 87 (49.1 %) patients with PJ benefited from pyloric preservation. All PGs included antrectomy (Table III). The overall incidence of complications was significantly higher for PJ (71.2 %) versus PG (50.9 %) (p < 0.000). Differences were not significant for mild cases -37.2 % for PJ and 35.5 % for PG. In contrast, differences were significant for severe events -34.4 % for PJ and 15.5 % for PG (p < 0.000). This decrease in severe complications parallels the incidence of PF -29.9 % for PJ and 14.8 % for PG (p < 0.000). Differences are not only global but also regarding PF severity (Clavien ? III) -22 % for PJ and 5.8 % for PG. Regarding DGE, numbers are 45.7 % for PJ and 21.3 for PG (p < 0.000), which reflects the association between abdominal complications and DGE. Mortality was similar in both groups -3.3 % for PJ and 3.2 % for PG. The only variable where PG obtained poorer results was readmission rate within 30 days -13.5 % versus 5 % for PJ (p < 0.007). Distal pancreatectomy A total of 116 DPs were performed -105 scheduled vs. 11 urgent procedures (Table IV). Diagnoses included: 25 cystic tumors, 22 neuroendocrine tumors, 20 pancreatic adenocarcinomas, 17 complicated chronic pancreatitides (11 associated with total gastrectomy, 4 associated with colectomy), 3 renal carcinoma metastases, 2 solid papillary tumors, and 1 paraganglioma. Complications Only complications deriving from DP were included; 48 patients (44.7 %) had at least one complication, 31 (29.5 %) were mild and 17 (14.7 %) were severe. Of these, 11 (10.4 %) involved percutaneous draining of fistulas or intra-abdominal abscesses. Reintervention was necessary for 3 patients (1 early hemoperitoneum, 1 abscess, 1 ischemic cecal perforation). One patient died from myocardial infarction. Pancreatic fistula PF (ISGPF classification) developed in 26 patients (24.8 %) -grade A or B in 22 (21 %) and grade C in 4 (3.8 %). According to Clavien's classification 14 subjects (13.2 %) developed mild complications and 12 (11.3 %) developed severe complications. Seven (6.6 %) required percutaneous drainage, 3 (2.8 %) were reoperated upon. Pancreatic fistula accounted for half of complications. There were 13 (12.4 %) readmissions: 9 for intra-abdominal collections, 1 for visceral artery bleeding, 1 for splenic infarction, 1 for GI bleeding, and 1 for pancreatitis. A total of 11 (10.4 %) laparoscopies with conversion were carried out; 10 laparoscopic DPs were performed -3 with splenic preservation and 1 with vessel preservation. Two complications occurred- 1 PF and 1 wound infection. Total pancreatectomy Eleven TPs were performed -8 for adenocarcinoma, 2 for chronic pancreatitis, and 1 for a neuroendocrine tumor. Morbidity was lower as compared with CDP, and no deaths occurred (Table V). Central pancreatectomy Ten CPs were performed -3 type-II mucinous intraductal papillary tumors, 4 cystic tumors, and 3 neuroendocrine tumors. The distal pancreas was anastomosed to the jejunum on 5 occasions, and PG was used for the remaining cases. Complications amounted to 80 % -70 % were mild (Clavien I-II), all of them pancreatic fistulas of intra-abdominal infections solved with antibiotic therapy. One visceral artery bleeding event required reintervention to complete a distal pancreatectomy. No deaths occurred. Readmission for fever and intra-abdominal collections was required for 30 % of patients (Table V). Discussion This review of 480 pancreatectomies is to our knowledge the most extensive series reported in the literature by Spanish groups, both in total numbers and CDPs. Overall mortality in our series was 12 patients (2.5 %), with 11 (3.3 %) in 332 CDPs, which is comparable to other Spanish (12,13,18,19) as well as foreign (2,20,21) series. Hospital de Bellvitge (19) published a series of 204 CDPs for pancreatic adenocarcinoma. They used the IGSPF classification for PF, but not Clavien's classification for the other complications, which renders comparisons with our series difficult. PF rate was 10 % with PJ, better than in our series, but the fact that ductal pancreatic adenocarcinoma is usually associated with a hard pancreas and dilated Wirsung duct is to be considered, which entails a lower risk for PF. Reintervention and mortality rates were 13 % and 7 % versus 9.2 % and 1.5 % in our series. As regards CDP, the series by Figueras et al. (11)compared the results of 58 PJs and 65 PGs in a prospective, randomized study using the same technique for both types of pancreatic reconstruction as in our series. They conclude that PG significantly reduces PF incidence and severity. Severe complications for both techniques were 38.9 % versus 25.6 % in our series. If we consider only PGs, it was 63 % versus 50.9 % of our cases. The overall incidence of PF was 24.4 % [34 % for PJ and 15 % for PG (p = 0.014)]. In our series it was 22.9 % [29.9 % for PJ and 14.8 % for PG (p < 0.000)]. Regarding PF severity, their results were: 33 % grade B-C for PJ and 11 % for PG (p = 0.006). In our series we found 22 % for PJ and 12.3 % for PG (p = 0.000). Both series agree that PF incidence and severity are lower for PG. In the aforementioned paper DGE was 27.6 %, similar between PJ and PG, in contrast to our series, with an overall value of 34.3 % but with 45.7% for PJ and 21.3 % for PG (p < 0.000). Such difference may be accounted for by the association between abdominal complications and DGE, previously demonstrated by other authors (22). The second study that may compare to our series is a Belgian prospective, randomized, multicenter clinical trial on 329 CDPs (23), half PJs and half PGs, with stratification by Wirsung duct diameter (? 3 mm). Mean complications were 62 %, similar to our series, with no differences between the two reconstruction techniques. Nor were any differences in reintervention and mortality rates. Mean hospital stay was 18.5 days, with no differences between groups; in our experience, this was 26.7 days (19.93) for PJ and 13.2 days (9.22) for PG (p < 0.000). The conclusion reached by the Belgian study is that PG is more efficient than PJ for pancreatic fistula prevention and complication severity, but not for overall incidence. Differences in PJ outcome with our series may result from the different technique used duct-to-mucosa in our series, invaginated in the Belgian study. A randomized study showed that invaginated PJ was superior to duct-to-mucosa PJ (24), which may explain such differences with the results seen in the series by Figueras et al. (11) and in our series. PF holds a relationship with pancreatic texture and Wirsung duct diameter, and represents the primary cause of postoperative morbidity and mortality. In the Belgian series (26) PF increases death risk four-fold, and in the study by Figueras et al. (11) there is a HR of 7.29 for severe complications. In our experience PF is significantly associated with severe complications but not with mortality. In the prospective, randomized study by Fernández Cruz et al. (25) outcomes are better than above, but their comparison may be biased due to differences in PG technique. A meta-analysis in 2014 (26) summarizes the 7 prospective, randomized studies comparing PJ versus PG, 4 of them using the ISGPF classification. Conclusions are consistent with our findings: PG results in fewer PFs when compared to PJ (p < 0.001). Regarding quality standards, Sabater et al. (5) performed an elegant review of 6,336 CDPs for periampullary neoplasms during 2000-2010 using the ISGPS classification, and concluded that the acceptable quality limits are: < 55 % for morbidity (no specific classification is quoted), < 31 % for PF (as per the ISGPF classification; the authors also point out that 12 definitions of PF are presently used), and < 5 % for mortality. The four series mentioned above (11,19,23,25), as well as ours, meet the required quality criteria, but it should be noted that overall morbidity was not obtained using Clavien's classification. Spanish groups have reported their own standards -the first one was published in 2002 by Figueras et al. (27), who suggest that limits should be 10 % for mortality and 50 % for morbidity regarding CDP. In 2011, Fernández Cruz et al. (28) reviewed CDP complications. In 2013, Domínguez-Comesaña (12) reported on 117 pancreatectomies (61 CDPs -58 PJs-, 15 TPs and 40 DPs) with a morbidity of 59 % for CDP (PF 9.83 %, DGE 9.8 %, bleeding 16.4 %, reintervention 23 %, mortality 6.5 %). Two additional Spanish teams have reported series with similar results -Sabater et al. in 2009 (18) and Montiel et al. in 2010 (29). As for DP our series meets the quality criteria published by Sabater et al. (5), who reviewed 11 series with over 100 patients and acceptable quality limits at < 53 % for morbidity, < 31 % for PF, and < 1 % for mortality. A comparable series was reported by Goh (21), who discusses 232 open DPs during 21 years with a morbidity of 47 %, a mortality of 3 %, and a PF rate of 31 % (18 % A, 6 % B, 8 % C), similar to our results. CP is a procedure with the primary goal of pancreas preservation in benign or borderline lesions. It associates the morbidity of DP with that of pancreaticoenteric anastomosis; this explains our high morbidity rate of 80 % (Clavien ? III, 10 %), albeit with no deaths. In a French multicenter study (30) of 100 CPs with reconstruction by PG morbidity was 72 % (Clavien ? III, 18 %), with 6 % reinterventions and 3 % mortality. The limitations of our study have to do with a historical series where some mild complications may have been not counted in, since recorded complications had to be translated using international classifications. Furthermore, when comparing PJ versus PG sample volume was not estimated, although we deem the series adequate for our purposes. Conclusions The described CDP and PG series represents the most numerous reports by Spanish sites ever. Our findings meet the required morbidity- and mortality-related quality criteria as compared to current series and reported standards. We coincide with reported meta-analyses in that pancreatic reconstruction by PG offers better outcomes as compared with PJ (duct-to-mucosa) in terms of PF (frequency and severity), abdominal complications, severe morbidity, and hospital stay, even though mortality is not improved. For DP our findings are consistent with the reported standards, although a laparoscopic approach will likely improve them. Regarding CP, we agree with other teams that, being a conservative procedure to preserve pancreatic function, its mortality is high and the technique should reserve for younger patients with a low surgical risk. Artículo 9 Validity and reliability of the minimum basic data set in estimating nosocomial acute gastroenteritis caused by rotavirus ABSTRACT Introduction: Rotavirus is the principal cause of nosocomial acute gastroenteritis (NAGE) under 5 years of age. The objective is to evaluate the validity and reliability of the minimum basic data set (MBDS) in estimating the NAGE caused by rotavirus (NAGER) and to analyze any changes during the three years that the Rotarix® and Rotateq® vaccines were used in Spain. Material and methods: A descriptive, retrospective study was carried out in the University Hospital of Guadalajara (UHG) (Spain) between 2003-2009 using the MBDS, positive microbiological results for rotavirus (PMRs), and medical histories. Three methods of estimation were used: 1) An ICD-9-CM code 008.61 in the secondary diagnosis fields (DIAG2) of MBDS; 2) method 1 and/or PMRs with a current or recent hospitalization; and 3) the reference method or method 2 contrasted with patient medical histories. The validity of methods 1 and 2 was determined -sensitivity, specificity, predictive values and likelihood ratios (LRs)-, along with their agreement with method 3 (Kappa coefficient). In addition, the incidence rate ratio between the NAGER rate in 2007-2009 (commercialization period of both vaccines) was calculated with respect to 2003-2005 (pre-commercialization period). Results: Method 1 identified 65 records with a DIAG2 of 008.61. Method 2 found 62 probable cases, and the reference method, 49 true cases. The sensitivity of the MBDS was 67 %, the positive predictive value was 51 %, and both negative LR (LR-) and reliability were moderate (LR- 0.33, Kappa coefficient 0.58). During 2007-2009, the NARGE decreased by 5 cases per 103 hospitalizations by 9 per 104 days of hospitalization. Method 2 overestimated both the decline in incidence by 2 per 103 hospitalizations and the decreased risk per day of stay by 10 %. The MBDS found no differences between the two three-year periods, but, like method 2, showed an excellent level of diagnostic evidence (LR+ 67). Conclusion: The MBDS taken together with microbiological results, is more exact, safer and more reliable than the MBDS alone in estimating NAGER; and more useful in ruling out it. Nevertheless, the MBDS alone may be used to estimate and compare such disease in contexts with different prevalences. Key words: Rotavirus infections. Rotavirus vaccines. Gastroenteritis. Hospital infections. Medical registries. Spain. Abreviations AGE: Acute gastroenteritis; NAGE: Nosocomial acute gastroenteritis; NAGER: Nosocomial acute gastroenteritis caused by rotavirus; MBDS: Minimum basic data set; DIAG2: Secondary diagnosis fields; DIAG1: Principal diagnosis fields; UHG: Hospital Universitario de Guadalajara (Spain); PMRs: positive microbiology results for rotavirus; 95 % CI: 95 % confidence interval; PPV: Positive predictive value; NPV: Negative predictive value; IR: Incidence rate; LR: Likelihood ratio; IRR: Incidence rate ratio; IQR: Interquartile range. Introduction Nosocomial acute gastroenteritis (NAGE) caused by rotavirus (NAGER) occurs in 5 % in hospitalized children, leading to increased hospital stays and the use of extra hospital resources (1-3). Rotavirus is the main cause of NAGE in children under the age of 5 years (31-87 %) (4-7), with 70 % of cases occurring in children under 1 year of age (8). The seasonal pattern coincides with the winter peak of other pediatric viral infections (4), although this period is extended with respect to that of community-acquired rotavirus, starting in the autumn and finishing in the early spring (6). NAGER becomes full blown after a 3-day incubation period (3). Twenty to forty percent of all cases are asymptomatic or subclinical (6), which, together with the great stability of rotavirus, contributes to contagion and the low efficacy of control measures (9). In Europe, nosocomial cases constitute 14-51 % of all rotavirus infections in children under 5, with an incidence of 0.1 to 2.8 per every 103 hospital admissions (newborns: 4-7.3 per 103). The additional costs for treating the infection can range from 367 to 1,837 euros per case (4-6,10-12). The differences in incidence between countries reflect the heterogeneity of studies conducted on this disease, making comparisons difficult (10,11,13,14). The same occurs between Spanish regions. Few studies have been carried out on NAGER in Spain (3,4,6,8). In Europe as a whole, the average incidence rate is around 4.6 per 104 days of hospitalization (range: 0.1-6.8 per 104), which lengthens the average hospital stay between 4 and 12 days (13). The attack rate of symptomatic rotavirus infection can reach up to 56 % in outbreak periods (14,15). The Rotarix® and Rotateq® vaccines were first marketed in Spain in July, 2006, and February, 2007, respectively (4). At the time, they were not included in the Spanish vaccination schedule (16), nor were they added in 2013 (17) as they were not considered cost effective (18). However, given the morbidity of the disease and the increased burden on the healthcare system, vaccination is generally recommended (19). The new vaccines are considered safe, with a 5-10 times lower risk of intussusception (20) than that associated with Rotashield® in the past. With a universal vaccination program and assuming 90 % coverage, it is estimated that up to 58 % of NAGER cases in Spain could be avoided over a 5-year period (21). The recording of rotavirus in hospital information systems has been described as highly deficient (5), partly due to the elevated incidence of asymptomatic cases of NAGER (22). Furthermore, the attack rate of the disease after discharge may be as high as 16 %, and if these cases are mild or asymptomatic, they generally remain unreported. Nevertheless, the minimum basic data set (MBDS) and other similar tools have been used to assess the incidence of NAGER (8,10). It is uncertain whether the secondary diagnoses fields (DIAG2) in the MBDS constitute a valid method for identifying the disease, as they give no information of the time between hospitalization and onset; moreover, some microbiological diagnostic results are administered after hospital discharge. In a similar vein, the MBDS contains cases categorized as the principal diagnosis field (DIAG1), which in reality correspond to infections acquired during a prior hospitalization. Likewise, the consistency of DIAG2 in always giving equivalent results (diagnostic agreement) has not been determined. Although the code system is well-established, variability still arises due to the different experience of those doing the actual coding and how the clinicians filled out medical histories at discharge. The main objective of this study is to assess the validity and reliability of the DIAG2 of the MBDS in estimating NAGER. Also, to analyze any possible changes in incidence during the first three-year period that the new vaccines against rotavirus were commercially available in Spain. Material and methods This is a descriptive, retrospective study carried out at the Hospital Universitario de Guadalajara (UHG, Spain) between 2003 and 2009. Three data sources were used: 1. The MBDS of the UHG: The mandatory registry for hospital discharges for any reason in the pediatric and neonatal wards. 2. The computerized Modulab® registry of the Microbiology laboratory of the UHG: Positive microbiology results for rotavirus (PMRs) found with a rapid and simultaneous detection immunochromatographic kit for rotavirus and adenovirus (VIKIA Rota-Adeno®, bioMérieux). This method has a reproducibility of 100 %, a sensitivity of 92 % (95 % confidence interval (95 % CI) 84-99 %), and a specificity of 91 % (95% CI 78-100 %). Its positive predictive value (PPV) is 96 % (90-100 %) whereas its negative predictive value (NPV) is 83 % (67-98 %). 3. Medical histories from the central archives of the UHG, of the probable and possible nosocomial cases as defined below in methods 2 and 3, respectively. This project was approved by the hospital's Ethics Committee for Clinical Research of Guadalajara (Spain). Definition of the variable of interest and the estimation methods NAGER was defined as "the development of symptoms 72 hours after hospital admission and up to 72 hours after discharge" (3). The estimation methods were defined according to the following data selection criteria: 1. Method 1: Registry entries with a code of The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) 008.61 (rotavirus) in any of the DIAG2 of the MBDS, where the DIAG1 field was something other than 558.9 (unspecified AGE), 787.03 (vomiting), or 787.91 (diarrhea). 2. Method 2: Method 1 combined with PMRs coinciding with a current or recent hospitalization (within the last 3 days) according to the MBDS. The PMRs were joined with the MBDS, using the medical history numbers of patients as the crossover tool. We searched for codes of 008.61, 558.9, 787.03, 787.91, or 780.06 (fever) in the DIAG1 or the DIAG2 coinciding with a PMR. Probable nosocomial cases were defined as episodes (registry entries) in the MBDS with: - A DIAG1 other than 008.61 and a DIAG2 of 008.61 without PMR. - A DIAG1 other than 008.61 and a DIAG2 of 008.61, 558.9, 787.03, or 787.91 with PMR 72 hours after hospitalization or within the first 72 hours after discharge. Also, as an exception, newborns with PMR occurring ? 72 hours after hospitalization. - A DIAG1 of 008.61, 558.9, 787.03, or 787.91 and previous hospitalization with a DIAG1 other than 008.61 and a discharge within 72 hours preceding the second admission, besides a PMR from 72 hours after the first hospitalization or during the second. 3. Method 3 (reference or "clinical method"): Method 2 contrasted with patient medical histories. To find true nosocomial cases, we reviewed not only the medical histories of those cases categorized by method 2 as probable nosocomial cases, but also those of the possible nosocomial cases, that is, registries with a DIAG1 of 008.61, 558.9, 787.3, or 787.91 and a prior hospitalization with a DIAG1 other than 008.61 without PMRs. A data collection sheet based on one used in a prior study on NAGER (6) was elaborated to this end. Cases that were ruled out as being true nosocomial cases were categorized as false nosocomial cases or as community-acquired cases, both of which would be false positives according to method 2. Statistical analysis Frequency indicators were calculated for NAGER cases in the pediatric and neonatal wards, globally and by department, by age group, by year of study period, and by the two three-year periods (2003-2005 and 2007-2009), with their corresponding 95 % CI, with each method described. Prior to calculating incidence rates (IRs), lengths of hospital stays were previously estimated. We then determined the sensitivity and specificity (internal validity) for methods 1 and 2, along with external validity: The PPVs and NPVs (performance or safety) and positive and negative LRs (LHR+ and LHR-) (plausibility). In addition, Chamberlain's percentage of positive agreement (% PA) was calculated (23). We lastly estimated the kappa index values to determine the agreement of methods 1 and 2 with regard to the clinical method, using the Altman scale (24) in interpreting the data thus obtained. The seasonal pattern was described by means of the monthly distribution of the number of cases. To compare the prevalence of the disease among different pediatric age groups, three-year study periods, and estimation methods, the chi-square test was used. We compared the IR of NAGER in the three-year study period when Rotarix® and RotaTeq® were simultaneously available in Spain (2007-2009) with the previous three-year period (2003-2005), by calculating the incidence rate ratios (IRRs) with each method. The year 2006 was considered to be a transitional period, as only Rotarix® was then commercially available in Spain. All analyses were carried out with SPSS 15.0 software and the Epi InfoTM 7 application for Windows. A p value of 0.05 indicated statistical significance. Results Between 2003 and 2009, a total of 9,602 children were hospitalized for any reason in the UHG, 21 % in the neonatal ward. A DIAG1 of 008.61 appeared for 381 of the children hospitalized, with another 65 admissions listing it as a DIAG2 (Fig. 1). According to method 1, seven of every 103 children hospitalized at the UHG in the 2003-2009 period had acquired NAGER, with a prevalence 6 ‰ higher in neonatal patients than in pediatric patients (Table I). No registry entries coded as 780.06 appeared as a DIAG1 or DIAG2 concomitantly with PMR. Two of the 65 entries in the MBDS with a DIAG2 of 008.61, both for pediatric admissions, had no PMRs. We found 37 registry entries with a DIAG1 other than 008.61 with PMR 72 hours after hospitalization, 36 with a DIAG2 of 008.61, and 1 with a DIAG2 of 558.9, belonging to a pediatric patient (Fig. 1). Of the 36 patients with a DIAG2 of 008.61, 2 of the 23 entries coming from the pediatric ward corresponded to the same patient, but they were episodes from different years. In addition, we found 5 entries with a DIAG2 of 008.61 that corresponded to newborns with PMRs obtained ? 72 hours after hospitalization. Furthermore, there were 16 entries with a DIAG1 of 008.61 and 2 with a DIAG1 of 558.9, all with PMRs and a prior hospitalization for a DIAG1 other than rotavirus, who had been discharged in the previous 72 hours, all from the pediatric ward (Fig. 1). The final tally of probable nosocomial cases was 62, all of which were under 5 years of age and 18 of which were neonatal patients. According to method 2, seven of every 103 children hospitalized between 2003 and 2009 had acquired NAGER, with a prevalence a 3 ‰ higher in neonatal patients (Table I). We identified 11 entries with a DIAG1 of 008.61, 558.9, 787.3, or 787.91 who had been discharged within 72 hours prior to being readmitted, but without PMRs; these were classified as possible nosocomial cases and were added to the 62 probable nosocomial cases (Fig. 1). In total, 73 medical records were reviewed. The 2 probable nosocomial cases with a DIAG2 of 008.61 and no PMR turned out to be coding errors and were reclassified as false nosocomial cases. Of the 37 entries in the MBDS with a DIAG1 other than 008.61 and PMRs 72 hours after hospitalization, 6 turned out to have been community-acquired and 31, including all the neonatal cases, were true nosocomial cases. The 5 newborns with PMRs obtained ? 72 hours after hospitalization were also true nosocomial cases. Of the 18 hospitalizations for a DIAG1 of 008.61 or 558.9, with PMRs and a prior hospitalization for a DIAG1 other than rotavirus, and with a discharge in the previous 72 hours, 5 turned out to have been community-acquired (of those, the 2 categorized as 558.9) while 13 were true nosocomial cases. The 11 cases thought to be possible nosocomial cases all had medical histories that were incompatible with NAGER and were thus classified as false nosocomial cases. We were thus able to categorize 67.1 % (n = 49) of the medical histories reviewed as true nosocomial cases (Fig. 1). Of these, 36.7% (n = 18) occurred in neonates (Table I). Overall, 51 % of these true nosocomial cases occurred in male patients, 90 % (n = 44) occurred under the age of 2, a 35 % (n = 17) occurred in newborns; and 30 % (n = 15, all pediatric patients) had been discharged within the previous 72 hours. According to the reference method, 5 of every 103 children hospitalized in the 2003-2009 period had contracted NAGER in hospital, with a 5 ‰ higher prevalence in neonatal patients (Table I) and a post-discharge attack rate of 2 ‰. A statistically significant difference was observed between the calculation method used and the prevalence of NAGER (p = 0.001). The sensitivity and PPV of method 1 in detecting NAGER were 67 % and 51 %, respectively, while for method 2 they were 100 % and 79 %, respectively. The LR+ and LR- of method 1 were 67 and 0.33, respectively, in contrast with 100 and 0 for method 2. The degree of positive agreement with respect to the reference method was 52 % greater for method 2 (Table II). The reliability of the MBDS was greater when contrasted with the microbiology results (kappa indices of 0.58 vs. 0.88) (Table II). For neonatal patients, the mean age of children with NAGER was 0 days (minimum = 0, maximum = 29) while for pediatric patients it was 10 months (minimum = 1, maximum = 89). The cumulative percentage in children under 1 year of age was 75.5 %, with a greater incidence between 7 and 11 months (Fig. 2). The illness was significantly associated with age, with children under 2 years of age having a 9-fold risk of infection by rotavirus compared to children being 2 and over (p < 0.001). The main reason for hospitalization in neonatal patients was "preterm or prematurely born newborn" (73 %) while for pediatric patients it was for bronchiolitis/bronchospasms (32 %) and lower respiratory tract infections (19 %). Cases of NAGER followed a seasonal pattern similar to that of AGE caused by community-acquired rotavirus, with higher peaks in the second half of autumn and the first half of winter (November-January), when a little over half of all the annual cases occurred, along with other minor peaks in spring (Fig. 3). The greatest amount of cases occurred in November. There were also summer outbreaks in 2005 and 2007. Between 2003 and 2009, the mean number of NAGER cases was 4.14 per 103 hospitalizations per year (Table I) The incidence rate was similar when calculated with method 2, and was much higher when calculated with method 1. The difference between methods 1 and 2 with respect to the reference method was found mostly in pediatric cases, where the two methods estimated 2 and 1 cases more per 103 hospitalizations/year, respectively, than the reference method (Table I). By the reference method, incidence reached 2 maximum peaks, one in 2004 and another lesser peak in 2007. Incidence decreased in 2008 and again, albeit not significantly, in 2009 (Fig. 4). The annual incidence distribution reflects a similarity among the different methods for assessing seasonal evolution (Fig. 4). The mean hospital stay for all hospitalizations in 2003-2009 was 4 days (interquartile range [IQR]= 3.7-4.3): Three (2.5-3.4) for pediatric cases and 7.9 (7.3-8.5) for neonates. For patients with NAGER, it was 9 days (IQR = 5-20): 7 (4-9) for pediatric cases and 25 (16-37.3) for neonates. In premature infants, it was 29 days (IQR = 20-39; minimum = 15, maximum = 44). In the period between 2007 and 2009 there was an overall decrease of 5 cases for every 103 hospitalizations (approx. 2.8 ‰ less frequent) with respect to the 2003-2005 period (p < 0.001). When measured with method 2, this decrease was even greater, at 3.6 ‰ (p < 0.001) (Table III). In contrast, no significant differences between the two three-year periods were observed when calculated with method 1 (p = 0.33). When the reference method was used, the IR went down by 9 cases for every 104 days of hospital stay (IRR2007-2009/2003-2005 = 0.55; 95 % CI 0.54-0.56; p < 0.001). The IRR between the two three-year periods with method 2 was 0.45 (95 % CI 0.44-0.46); when measured with the MBDS, it was 1.08 (95 % CI 1.06-1.10) (Table III). Discussion The DIAG2 taken from the MBDS detected 67 % of NAGER cases during the 2003-2009 period, with a safety of 51 % and a moderate power of agreement with respect to the clinical method. In contrast, the MBDS taken together with microbiology results produced maximum detection, with a 28 % higher safety and very good agreement. Although both methods showed an excellent level of diagnostic evidence (LR+ > 10), method 1 was only moderately effective for ruling out the illness (LR- = 0.33) when it was not detected. Throughout the study period, the mean incidence of NAGER showed high variability, with a range of 2.7-7.8 cases per 103 hospitalizations/year. This was also true for the mean IR, which ranged from 7.0 to 77.7 cases for every 104 days of hospital. The disease was 56 % more frequent in neonatal than in pediatric patients. On average, the hospital stay for children who contracted NAGER in the hospital was 4 days longer in pediatric cases and 17 days more for neonates. In the 2007-2009 period, the illness was almost 2 times less prevalent compared to 2003-2005, with the risk of contracting the illness per day of hospital stay decreasing almost by half. While in the three-year period in which privately funded vaccines were available, the number of cases/year showed a decrease of 55 %, universal vaccination programs in Europe in the same time period showed a prevention of up to 72 % of cases/year (25). The selected study period was selected for convenience, to evaluate the efficacy of vaccines before 2010, when the Spanish Agency for Medicines and Health Products interrupted the supply of Rotarix® and Rotateq® because of the detection of porcine circovirus in March and June of that year, respectively (18). Maximum vaccine coverage, despite the fact that the vaccines were not subsidized by the Spanish healthcare system, would have thus occurred when the drugs were first made available, from 2007 to 2009, a time when pediatricians were recommending the health benefits of vaccination during well child visits, thereby promoting their commercialization. Although in November, 2010, Rotateq® was re-released into the market, Rotarix® is still unavailable in Spain (17). We then decided to compare the 2007-2009 period with an immediately preceding period of equal length, leaving out the year 2006, as explained above in the methods section. Overall, the MBDS per se overestimated the incidence by 3 cases for every 103 hospitalizations and the mean IR by 6 cases for every 104 days of hospital stay. Besides, it did not detect the decrease during the 2007-2009 period. Together with microbiology results, the MBDS did indicate this decrease, although it overestimated it by 2 cases per 103, as well as the decrease in risk per day of hospital stay by 10 %. It is difficult to compare the incidence found in other Spanish studies due to the heterogeneity in the designs and methodologies used (3,4,6,8). In this context, the variability of the assessment methods would be an important source of error (26). Furthermore, the majority of previous studies have been retrospective, which supposes a lack of follow-up in the 72 hours after discharge and the exclusion of mild or asymptomatic cases (4,8,10). Previous studies based solely on hospital discharge data with the specific code of CIE-9-MC 008.61 have been shown to underestimate the real burden of the disease (4). To evaluate the validity and reliability of the MBDS, we took the patients' medical histories as a reference, as they contain more complete information on patient hospitalizations and, together with the PMRs, they offer more accurate data. The fact is, as mentioned above, that almost a third of identified as true nosocomial cases had been discharged less than 72 hours before being readmitted with NAGER as their DIAG1; that is, the disease became symptomatic after the first discharge. The difficulty in comparing different studies in this field is an even greater challenge in the European context, with discrepancies among public health systems and different epidemiological patterns (5,10). The changes observed between the two three-year periods under study, as well as any comparisons made between national and international results must be taken with caution given the low number of cases of NAGER and the low statistical power of the sample. The UHG was an ideal place to carry out this study because its microbiology lab is a place of reference throughout the region. Feces sample collection to check for rotavirus in children is routinely carried out if there is any suspicion of AGE whenever any symptoms of the disease are observed. Because of this, the date of the microbiology results was taken to be the start of symptomatic AGE in order to estimate probable nosocomial cases, possible nosocomial cases, and true nosocomial cases (Fig. 1). For those entries with PMRs within the first 72 hours after hospitalization, a community origin was assigned. Nevertheless, a PMR after this period did not necessarily indicate a nosocomial origin since there is sometimes a time lapse between the start of symptoms and a PMR. These cases were thus defined as probable nosocomial cases. Those in which a PMR was obtained within 72 hours of discharge were considered to be nosocomial, but even after this period, we could not entirely rule out a nosocomial origin since in cases with mild symptoms, outpatient feces sampling may be delayed or not performed. In order not to lose these cases, we reviewed all medical histories with PMRs obtained up to one month after hospital discharge with a DIAG2 of 00.861, and/or 558.9, and/or 787.03, and/or 787.91. As mentioned above, we identified 37 cases with PMRs on the third day after discharge, 36 with a DIAG2 of 008.61 and one with a DIAG2 of 558.9 (Fig. 1). In one month follow-up of hospitalizations due to rotavirus, readmitted patients usually are within three days after the initial discharge (27). Still, this would not have identified mild or asymptomatic cases after discharge with no DIAG2 entries of 558.9, and/or 787.03, and/or 787.91, and/or without microbiology sample collection. This has prompted a call to include in future a new label of "present on admission" (POA), which would accompany each diagnostic code to differentiate diagnoses made at the time of hospital admission (POA = Y, yes) from those appearing during the actual hospital stay (POA = N, no). The mean incidence of NAGER calculated through the DIAG2, namely 6.90 per 103, is higher than the national average (obtained by the same means) of 4.50 per 103 (8). Although the reliability of the MBDS is only moderate, this comparison reveals a high incidence of NAGER in the UHG. Moreover, the mean IR of 11.07 per 104 (IR: 7-77.72) obtained with the clinical method is double that described for Western Europe, which is 4.6 per 104 (range: 0-6.8 per 104) (13). Indeed, the mean IR reported for Europe as a whole is similar to those reported in prospective studies (1,11). In this context, the incidence observed in the UHG of 4.14 per 103 is quite low if we compare it with prospective studies carried out in Spain (3,6,28). This difference may be due to the aforementioned loss of mild or asymptomatic cases, especially in the absence of follow-up period, as well as to the loss of symptomatic cases that remain unclassified as such in the MBDS because they were not properly entered in the medical histories or for lack of microbiology results. This could be a possible source of selection bias in our study. Even in prospective studies which only record results of symptomatic infection, the observed prevalence is higher than in our study (3). Taking these considerations into account, the main limitation of this study is the type of information in the MBDS. Indeed, it has been estimated that post-discharge appearance of NAGER occurs in up to 11 cases for every 103 hospitalizations (29). Even so, it would be necessary to perform feces analyses both before and after discharge to identify asymptomatic cases (30). In addition to all the aforementioned, and with respect to the difficulty in making comparisons, it must be remembered that the incidence is influenced by the seasonal period followed (epidemic season vs. complete year) and the age range of the patients (14). Surveillance studies have determined a combined incidence of NAGER that can reach up to 8.1 cases during epidemic months (95 % CI 6.4-9.9) (31). The use of medical histories as a reference also presents several limitations such as interviewer bias. The form in which each clinic records the beginning and the course of digestive symptoms in each patient's medical history may differ depending on his or her particular interest the pathology observed or the severity of its evolution. For this reason, we chose to also review the nursing records, in which the number and consistency of stools is recorded with greater accuracy, as is the presence of vomiting. Further, as the medical records were all reviewed by the same person, interobserver agreement could thus not be calculated, which could produce observer bias (erroneous differential classification of disease). We attempted to minimize this by elaborating a systemized data collection form. But this same error could occur in the process of codification, depending on the experience of those applying the disease codes. To date, no studies have specifically evaluated the efficacy of the MBDS as a surveillance system for NAGER, although it has been used to monitor other nosocomial infections such as surgical site infections, catheter-associated urinary tract infection, central line-associated bloodstream infection, ventilator-associated pneumonia/events, postprocedure pneumonia, as well as infections caused by bacteria associated with hospital health care (methicillin-resistant Staphylococcus aureus and Clostridium difficile) (32). It has also been used to determine the prevalence of nosocomial infections (33) and its agreement with other data sources in detecting cancer (34), emergency pathologies (35), postoperative risk factors and secondary effects (36), cerebrovascular trauma (37), and surgical mortality (38) have been assessed. As in our study, other researchers have found a moderate sensitivity and high specificity of the MBDS in detecting Clostridium difficile and surgical site infection (32). Due to the low incidence of hospital infection, the PPV of registries like the MBDS are probably low. This is also the first published analysis of the effects of the commercialization of both vaccines against rotavirus on NAGER incidence in Spain. In countries with a nation-wide immunization schedule, the indirect benefits on the non-vaccinated public have previously been demonstrated (39,40), albeit not at the intrahospital level. Nevertheless, the decrease observed in the three-year study period after the vaccines had been made available may be due to herd immunity as well as to the "hand washing program" promoted by the UHG since 2008, a strategy that has proven effective in lowering the communicability of the virus within the hospital, which is found on the hands of 77 % of hospital health workers (5,41). Still, only 37 % of NAGER cases that we identified had actually been isolated, all of them in neonatal patients. Other researchers have estimated that the disease is isolated only in 50 % of patients (14). This study has analyzed for the first time the validity and reliability of the DIAG2 of the MBDS in estimating NAGER. The clinical method ruled out 25 % of the cases categorized by this system. The MBDS, taken together with microbiology results, equivalent to the Microbiology Information System, is more exact, safer and more reliable than the MBDS alone in estimating NAGER; and better at ruling out it. Nevertheless, because it offers a high level of diagnostic evidence, method 1 may be used to estimate nosocomial infection in contexts with various prevalences, always with caution. In this sense, future studies with larger sample sizes should be undertaken to bolster these findings. We should raise awareness among healthcare professionals about the importance of proper recording of clinical variables to improve the coding in Healthcare Information Systems. If we cannot validly and efficiently assess the quality of care, it will be impossible to design strategies to improve monitoring and control of nosocomial infections. The implementation of a specific code to register this pathology in the MBSD would be an important step forward in this regard. Artículo 10 New trends in the management of diverticulitis and colonic diverticular disease ABSTRACT Colonic diverticular disease is a chronic disorder presenting with a variety of abdominal symptoms and recurrent episodes of acute diverticulitis. It is close linked to age so its prevalence has risen notably during the last decades in western countries, increasing costs related to medical attention. Recently, several works have provided evidence to a series of measures that could improve the outcomes as well as reduce expenses associated to this process. The aim of the present review is to expose a view of the new trends in the management of diverticulitis and colonic diverticular disease, based on the highest clinical evidence available. Key words: Primary anastomosis. Colonic diverticular disease. Acute diverticulitis. Laparoscopic peritoneal lavage. Routine colonic evaluation. Abbreviations AD: Acute diverticulitis; C-AD: Complicated acute diverticulitis; CT-scan: Computed tomography scan; HP: Hartmann's procedure; NPV: Negative predictive value; PPV: Positive predictive value; RCT: Randomized clinical trial; Sn: Sensitivity; Sp: Specificity; UC-AD: Uncomplicated acute diverticulitis. Introduction Colonic diverticular disease is a chronic entity with a wide variety of abdominal symptoms that eventually may course with recurrent episodes of acute diverticulitis (AD). The prevalence of colonic diverticulosis is not influenced by genre and increases with age. In this sense, the rise of life expectancy explains the accumulation of cases in Western countries. It is estimated that the prevalence of this disease can exceed 60 % in subjects above 80 years old, of which, up to 25 % will suffer at least one episode of AD during their lifetime (1-3). The classic therapeutic algorithm is based on the Hinchey classification, the use of antibiotics and the Hartmann's procedure (HP) during the acute phase; and elective colectomy in recurrent cases (Fig. 1). In contrast, a large number of papers published in the last decade have led to open new horizons in the management of this entity. The aim of the present review is to expose an overview, based on the highest evidence available, of new trends in the management of diverticulitis and colonic diverticular disease. Material and methods A bibliographic search was conducted using "diverticulitis" as search term in PubMed.gov (NLM). The search was limited to the last five years (from December 2014) and no other limits were imposed. At first, references not related to colonic diverticulosis, as well as those that offered no modification to the example of classic algorithm (Fig. 1) were excluded. In a second time, we selected works with level of evidence 1 or 2, according to the criteria of the Oxford Centre for the Evidence-Based Medicine (OCEBM) (Table I), and classified them within the different sections of this manuscript. These references formed the core of each section. Since surgical approach should not influence therapeutic indication and there is plenty of evidence in the literature that laparoscopic surgery in experienced hands is comparable or even superior to open surgery in almost any scenario, the use of laparoscopy was not an objective of the present review. Results Bibliographic search diagram is shown in figure 2. In the following paragraphs, the findings and conclusions of papers exposing new trends in the management of AD and colonic diverticular disease are discussed. Diagnostic scores and severity scales The diagnosis of diverticulosis can be established by barium enema, colonoscopy or even computed tomography (CT-scan) (4); however, a majority of patients will be diagnosed with diverticular disease during the first episode of AD. In the diagnosis of AD, clinical signs and symptoms play a key role on the suspicion and request of complementary tests. In this regard, AD is a condition with a high rate of clinical misdiagnosis (between 34 % and 68 %) what has motivated the development of at least two diagnostic scores based on clinical parameters (5,6). Of these, the first one was published in 2010 by Laméris et al. who prospectively analyzed 1,021 patients with abdominal pain, identifying by logistic regression, three items associated with the diagnosis of AD (pain with tenderness in the left lower quadrant, absence of vomiting and C-reactive protein ? 50 mg/dL) (6). Likewise, based on data from the clinical history, physical examination and laboratory tests; Andeweg et al. identified seven variables (age ? 50 years, previous episode of AD, increased pain with movement, tenderness in the left lower abdomen, absence of vomiting and C-Reactive protein ? 50 mg/dL) from which constructed a diagnostic nomogram. According to these authors, this tool could discriminate up to 86 % of patients with AD, a figure similar to ultrasound (90 %) (5). Both diagnostic scores were externally validated in an independent cohort by Kiewiet et al., obtaining values of sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) as shown below: a) Laméris et al. (6) (PPV: 81 %-100 %; NPV: 47 %-66 %; Sn 24-37 %; Sp: 93 %-100 %); and b) Andaweg et al. (5) (PPV: 89 %-92 %; NPV: 47 %-76 %; Sn: 14-48 %; Sp: 98 %-99 %). However, commonly used diagnostic radiological imaging presents better diagnostic performance than these clinical tools. To this respect, although ultrasound has demonstrated good (Sn) and (Sp) (92 % and 90 %, respectively), at present, CT-scan shows better values (94 % and 99 %, respectively) and is considered the gold standard for the diagnosis of AD (7,8). Given the diagnostic performance of such scores, these would be particularly useful when they are positive. Their authors argue that the use of these scores might reduce the number of complementary tests requested for AD. However, from our point of view, shared by other authors (9), is precisely in patients with positive test in whom radiological imaging would be more useful since it could determinate the severity of the AD, an essential factor in the therapeutic approach. Finally, it has been proposed several alternatives to the Hinchey classification (10), some of which might even be useful to select patients candidates for outpatient treatment (11). Nonetheless, to date, this scale described for the first time in 1978 (12), subsequently modified by Wasvary et al. in 1999 (13), and adapted to the findings of CT-scan in recent years (4) continues to be the most widely used. Uncomplicated acute diverticulitis: Antibiotic therapy and outpatient treatment Traditionally, treatment of uncomplicated AD (UC-AD) has been based on intravenous antibiotics and digestive rest. However, in recent years, various authors have considered the possibility of manage this condition through treatment with oral antibiotic and liquid diet from the beginning (14-20). Biondo et al. (18) conducted a randomized clinical trial (RCT) in which 132 patients diagnosed with UC-AD received the same scheme of oral or intravenous antibiotic. After 60 days of follow-up, no difference in quality of life or rate of treatment failure (4.5 % vs. 6.1 %, respectively) was observed. In contrast, the average cost of inpatient treatment was 1,124 € higher than in the ambulatory group. These results are consistent, both in terms of safety and effectiveness (14,15,17,19,21), as well as efficiency (14,15,21), with other lower evidence studies previously published. Unlu et al. (17) reached the same conclusion after a re-trospective analysis of 312 patients with a median follow-up of 48 months. These authors highlight the importance of a rigorous analgesic control, since according to their findings; the main reason of hospital readmission is the persistence of pain without other type of complication. The results of these and other studies have been grouped and analyzed in a systematic review that reported up to 97 % of success with outpatient treatment for UC-AD (22). Another new trend in the management of UC-AD questions the need for antibiotic administration. Several publications have suggested this therapeutic approach (23-25). To date, the highest evidence to this respect has been published by Chabok et al. (26). These authors conducted a RCT involving 623 patients with UC-AD treated with or without antibiotic, concluding that there were no significant differences regarding complications of the inflammatory process (1 % vs. 1.9 %), recurrence (15.8 % vs. 16.2 %), need for resection (1.6 % vs. 2.3 %) and hospital stay (2.9 vs. 2.9 days), after one year of follow-up. Nevertheless, the rate of complication in the group without antibiotic could double that of those patients who were treated with antimicrobials (1.9 % vs. 1 %) (26). The sample size necessary to discriminate this difference as statistically significant is estimated on 5,000 patients approximately, hardly attainable in an RCT of these characteristics. Additionally, the clinical significance of that difference might not support the routine use of antibiotics in this scenario. It should be highlighted that the success of these measures, which could reduce the healthcare costs associated with the process up to 60 % (21), is strongly influenced by the selection of patients. The majority of works considered as factors of exclusion for outpatient treatment or antibiotics-free: Renal or cardiac failure, diabetes mellitus, immunosuppression states or the absence of almost immediate response to the first dose of analgesic and antibiotic. In brief, it could be concluded that outpatient treatment of UC-AD may be safe and effective in selected patients. However, further studies are necessary before leaving the routinary use of antibiotics in this entity. Peritoneal laparoscopic lavage The treatment of complicated AD (C-AD) has evolved over the years. Currently, there is consensus that C-AD Hinchey I should be initially treated with intravenous antibiotic, while Hinchey II can be managed safely and successfully by percutaneous drainage in those centers with availability (27-29). The controversy is generated in cases with Hinchey II and large abscesses or not accessible percutaneously, and Hinchey III/IV. In C-AD Hinchey IV almost all authors agree on the need to resect the affected colon, inflamed and perforated. However, regarding the surgical technique, some surgeons defend the creation of primary anastomosis and others of HP, discussion that will be objective in the next section. In the remaining cases, i.e. C-AD Hinchey II with gas or inaccessible percutaneously and Hinchey III, several authors have proposed the laparoscopic lavage and drainage from the peritoneal cavity as an alternative to the HP, even in elderly patients (30). The introduction of this strategy, which was first published in 1996 (31), is the result of numerous studies. In this regard, a systematic review that analyzed the outcomes of several studies on the use of peritoneal lavage in C-AD (321 patients from two prospective studies, nine retrospective and several case series) was published in 2010. The authors concluded that this strategy could control the systemic and abdominal sepsis in 95.7 % of cases, associating a morbidity and mortality of 10.4 % and 1.7 %, respectively (32). Furthermore, only 1.7 % of patients required a colostomy. In their results, the authors also expose that laparoscopic peritoneal lavage should not be considered in C-AD Hinchey IV, since up to half of these patients treated by peritoneal lavage and drainage presented residual pelvic abscesses. These results led to design two RCTs which are still in development: a) Ladies trial (33), a multicenter RCT that compares the laparoscopic lavage versus the resection plus primary anastomosis or HP in C-AD Hinchey III and IV, respectively; and b) the DILALA trial (34), a RCT focused on comparing the laparoscopic lavage versus the HP. Preliminary results of the latter (DILALA trial), after analyzing 83 patients, suggest that laparoscopic lavage is short term safe and feasible in C-AD Hinchey III; resulting in less surgical time and shorter hospital and resuscitation stays, without differences in terms of morbidity and mortality with respect to the HP (35). In the same line, the authors of "Ladies trial" have published one of the retrospective studies on peritoneal lavage with best sample size and design (36). In this work, after reviewing 38 patients with C-AD Hinchey II with free gas or Hinchey III, these authors report that laparoscopic peritoneal lavage may control abdominal septic focus after one intervention in 79 % of cases, and after a reoperation in 92.1 %. Mortality rate associated with this strategy is 5.2 %. In addition, a logistic regression analysis revealed that the presence of co-morbidities, very high levels of C-reactive protein and high scores in the Mannheim scale of peritonitis are predictive factors of failure of this therapeutic approach (36). In summary, peritoneal lavage and laparoscopic drainage, with the advantages inherent to a minimally invasive approach, could diminish the number of urgent laparotomies, bowel resections and stomas; therefore reducing the morbidity associated with the treatment of the urgent episode of C-AD Hinchey II/III. However, the final results of the RCTs currently ongoing are necessary for this approach to be generalized on daily practice. Primary anastomosis in urgent surgery Laparoscopic peritoneal lavage may be an alternative in cases of C-AD Hinchey III; however, other authors advocate by resection of the affected segment in both C-AD Hinchey III and IV. Traditionally, this scenario led invariably to HP; however, during the last years, several works have proposed as an alternative the realization of primary anastomosis with or without diversion stoma (37). In this regard, although some authors have published relatively low rates of postoperative complications without the use of diversion ileostomy (24 %-84 %), these works present significant selection bias by including patients with low surgical risk and C-AD Hinchey II/III (38-41). Thus, the current trend is to associate diversion ileostomy in cases in which primary anastomosis is performed. In this line, several retrospective studies published in recent years have pointed out that primary anastomosis plus diversion ileostomy may have similar outcomes to HP in terms of overall morbidity and mortality (37,38,42,43). In 2012, Oberkofler et al. presented the results of a RCT in which 62 patients with C-AD Hinchey III/IV were randomized to receive colon resection with primary anastomosis and diversion ileostomy, or HP (44). The analysis took into account the urgent procedure, the elective surgery for closure of stoma, and the global care process. When only the urgent intervention was considered, no difference between the two approaches was found in any variable (operative time, blood loss and number of transfusions, stay in ICU, hospital stay, complications, mortality and costs of the process). Conversely, when only the intervention for reversing the stoma was analyzed, the group presenting loop ileostomy (primary anastomosis) was favored with less surgical time (183 vs. 73 minutes), less hospital stay (9 vs. 6 days) and a lower rate of serious complications (3 vs. 0). Likewise, 90 % of the patients with ileostomy underwent surgery for reversing the stoma compared to 56 % in the group with colostomy. Finally, when evaluated both interventions together, only significant differences in operative time and overall number of complications, in favor of the group with primary anastomosis and diversion ileostomy were observed. In view of these results, it cannot be firmly concluded that the realization of primary anastomosis with diversion stoma be superior to the HP; however, this strategy should be taken into account at least in selected cases of young patients with high probabilities of reversing the stoma. Monitoring and prevention of recurrence Most of the current clinical guidelines recommended to do a routine colonoscopy six weeks after a first episode of AD, due to the possible existence of an underlying malignant disease. Nonetheless, the more and more frequent use of high resolution CT-scan in the diagnosis of the acute episode and the results of several series that have evaluated the incidence of cancer in these patients (45-48) have led to some clinical guidelines no longer recommend this attitude (4). Of those studies that have addressed this issue (45-54), the review with the largest number of patients has been published by Sharma et al. (55). These authors, after the analysis of 11 studies involving patients diagnosed of AD by CT-scan with subsequent colonoscopy (five retrospective studies and prospective the remaining; a total of 1,970 patients) estimated that globally these patients presented: a) underlying carcinoma in 1.6 % (CI 95: 0.9 %-2.8 %) cases; and b) non-malignant polyps in 16.5 % (CI 95: 11.2 %-23.8 %). When the analysis was subdivided into UC-AD and C-AD, the proportion of cancer in the group without complication decreased to 0.7 % (CI 95: 0.3 %-1.4 %), rising to 10.8 % (CI 95: 5.2 %-21 %) in the case of C-AD. These figures, inherently low for patients who suffered UC-AD, become still less relevant when compared with data from a meta-analysis involving 68,324 patients of a screening program for colon cancer in asymptomatic subjects without risk factors (56). In this latest work, the proportion of cancer was estimated at 0.78 % (CI 95: 0.13 %-2.97 %) and at 19 % (CI 95: 15 %-23 %) for non-malignant polyps. This comparison allowed Sharma et al. conclude what previously pointed out by other studies (45-54): In the absence of other signs or clinical symptoms of cancer, routine colonoscopy may not be necessary in patients who suffered from UC-AD diagnosed by CT-scan. These patients could simply be included in screening programs for colorectal cancer. Nevertheless, Choi et al., after a retrospective study with 149 patients, warn that patients older than 50 years perhaps should be taken in particular consideration by a possible increased risk of advanced neoplasia (57). On the other hand, from the 25 % of patients who are suffering symptomatic diverticular disease, between 7 % and 45 % of them will suffer recurrent episodes of AD. To this respect, special efforts are made to study measures for preventing recurrence of AD as well as improving chronic symptoms. To date, lifestyle measures (fiber intake, interruption of smoking, regular physical activity, and weight loss) and non-absorbable antibiotics as rifaximin have been proposed as possible effective measures on the reduction of the number of episodes of AD (4). Recently, based on the pathophysiological similarities that might share diverticular disease and inflammatory bowel disease, administration of other agents such as mesalamine, sodium butyrate, or probiotics have opened new horizons in the therapy of diverticular disease of the colon. Regarding mesalamine, still in 2002, an Italian group published that long-term treatment associating this to rifaximin was superior to rifaximin alone improving chronic symptoms and decreasing the number of acute episodes (58). More recently, the results of the DIVA trial, a RCT that evaluated the effect of mesalamine ± probiotics for twelve weeks after a first episode of AD, have been published (59). Although none of these two schemes was superior to placebo in terms of rate of recurrence, a slight effect on chronic symptoms was observed. Similarly, the recent results of the phase III RCTs PREVENT1 (n = 590) and PREVENT2 (n = 592) conclude that mesalamine is not superior to placebo preventing the recurrence of AD (60). Another molecule that due to its anti-inflammatory role and ability to regulate the intestinal microenvironment may decrease the episodes of AD is sodium butyrate. According to a RCT, the administration of this short-chain fatty acid on a daily basis for twelve months could reduce significantly the number of episodes of AD (31.8 % vs. 6.7 %) and improve chronic symptoms (61). Finally, the axiom that recommended elective surgery for resection after two episodes of AD is to date controversial, even in cases of C-AD (62). In 2006, the American Society of Colon and Rectal Surgeons stated that this indication should be made on a case-by-case basis and not taking into account only the number of episodes of AD (63). Other current clinical guidelines have adopted this trend (4), which is based on several facts: a) Elective surgery may present severe complications (64); b) the majority of patients with C-AD will do so in the first episode (64-66); c) only 5.5 % of patients with recurrent AD will require urgent surgery since the risk of perforation appears to decrease in this scenario (67); and d) even after resection, some patients will continue presenting discomfort and episodes of AD (65). On the contrary, patients with severe chronic symptoms or those with comorbid conditions such as chronic renal failure, collagenophaties or immunosuppression of any origin would constitute a group that could benefit from early elective surgery (4,68). Regarding elective surgery, current guidelines recommend to perform the most economic resection possible (63), which should extend at least to the proximal rectum in order to minimize the probability of postoperative recurrent AD (69,70). Discussion In view of the evidence in favor of the new trends in the management of AD and diverticular disease of the colon (Table II), we are witnessing a gradual change in the diagnostic-therapeutic algorithm of this pathology, which may be modified with the inclusion of these measures in the near future (Fig. 3). Nevertheless, this evidence in the majority of cases is based on only one RCT; therefore, new studies in the coming years must confirm the usefulness of these measures until they can be applied safely and efficiently in daily clinical practice.