Jordi Gordillo

Transfusion Strategies for Acute Upper Gastrointestinal Bleeding

BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. RESULTS A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. CONCLUSIONS As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).

Secondary bacterial peritonitis in cirrhosis: A retrospective study of clinical and analytical characteristics, diagnosis and management

BACKGROUND & AIMS Secondary bacterial peritonitis in cirrhotic patients is an uncommon entity that has been little reported. Our aim is to analyse the frequency, clinical characteristics, treatment and prognosis of patients with secondary peritonitis in comparison to those of patients with spontaneous bacterial peritonitis (SBP). METHODS Retrospective analysis of 24 cirrhotic patients with secondary peritonitis compared with 106 SBP episodes. RESULTS Secondary peritonitis represented 4.5% of all peritonitis in cirrhotic patients. Patients with secondary peritonitis showed a significantly more severe local inflammatory response than patients with SBP. Considering diagnosis of secondary peritonitis, the sensitivity of Runyons criteria was 66.6% and specificity 89.7%, Runyons criteria and/or polymicrobial ascitic fluid culture were present in 95.6%, and abdominal computed tomography was diagnostic in 85% of patients in whom diagnosis was confirmed by surgery or autopsy. Mortality during hospitalization was higher in patients with secondary peritonitis than in those with SBP (16/24, 66.6% vs. 28/106, 26.4%) (p<0.001). There was a trend to lower mortality in secondary peritonitis patients who underwent surgery (7/13, 53.8%) than in those who received medical treatment only (9/11, 81.8%) (p=0.21). Considering surgically treated patients, the time between diagnostic paracentesis and surgery was shorter in survivors than in non-survivors (3.2+/-2.4 vs. 7.2+/-6.1 days, p=0.31). CONCLUSIONS Secondary peritonitis is an infrequent complication in cirrhotic patients but mortality is high. A low threshold of suspicion on the basis of Runyons criteria and microbiological data, together with an aggressive approach that includes prompt abdominal computed tomography and early surgical evaluation, could improve prognosis in these patients.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: A multicenter study

Background: Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch–anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. Methods: A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short‐term IFX efficacy was evaluated at week 8 and mid‐term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Results: Thirty‐three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21–67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. Conclusions: IFX was effective in the short‐ and mid‐term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. (Inflamm Bowel Dis 2011;)

Role of Albumin Treatment in Patients With Spontaneous Bacterial Peritonitis

BACKGROUND & AIMS Intravenous administration of albumin decreases the incidence of renal failure and mortality among patients with spontaneous bacterial peritonitis (SBP). However, it is unclear whether it should be given to all patients with SBP; we evaluated its efficacy. METHODS We analyzed data from all episodes of SBP (n = 216) during a 7-year period that occurred in a nonselected series of 167 patients with cirrhosis. Low-risk episodes (urea <11 mmol/L and bilirubin <68 μmol/L) were not treated with albumin, whereas high-risk episodes (urea >11 mmol/L and/or bilirubin >68 μmol/L) were or were not given albumin at the discretion of the attending physician. RESULTS Sixty-four episodes of SBP (29.6%) were low risk and not treated with albumin, whereas 152 (70.4%) were high risk; 73 of these (48%) were treated with albumin and 79 (52%) were not. Renal failure before SBP resolution was less frequent after low-risk episodes than high-risk episodes (4.7% versus 25.6%; P = .001), in-hospital mortality was lower (3.1% versus 38.2%; P < .001), and the 3-month probability of survival was higher (93% versus 53%; P < .001). In an analysis of only the high-risk group, patients who received albumin had lower in-hospital mortality than those not treated with albumin (28.8% versus 46.8%; P = .02) and a greater 3-month probability of survival (62% versus 45%; P = .01). CONCLUSIONS Albumin therapy increases survival of patients who have high-risk episodes of SBP, although it does not seem to be necessary for patients with low risk of death.

Long-term outcome of ulcerative colitis in patients who achieve clinical remission with a first course of corticosteroids.

BACKGROUND Although the early outcomes of ulcerative colitis after a first course of corticosteroids are well known, data on long-term disease evolution in patients responding to a first corticosteroid course are scarce. AIMS To evaluate the long-term clinical evolution in ulcerative colitis patients responding to a first course of corticosteroids and to identify those factors associated with a poorer outcome. METHODS Retrospective review of 114 patients diagnosed with ulcerative colitis who responded to the first corticosteroid course, and did not start thereafter maintenance therapy with thiopurines were included. RESULTS Corticosteroids were prescribed because of a moderate (78%) or a severe flare (22%). All but two patients followed maintenance treatment with mesalazine after corticosteroid discontinuation. After a median follow-up of 83 months (7-156), 72% of patients suffered new relapses leading to corticosteroid reintroduction in 65% of patients. The earlier corticosteroids were introduced in the course of ulcerative colitis, the higher the risk of relapse and corticosteroid reintroduction. Thiopurines were started in 51%, and infliximab in 19%. Eleven percent of patients underwent colectomy. No predictors of thiopurine use or colectomy were found. CONCLUSIONS Half of the ulcerative colitis patients responding to a first course of corticosteroids will require immunosuppressors mainly because of steroid-dependence.

Efficacy of different therapeutic options for spontaneous abdominal abscesses in Crohn's disease: are antibiotics enough?

Background: Management of abdominal abscesses (AA) in Crohns disease (CD) always includes antibiotics, and some type of drainage is added according to the response and other considerations. Our aim was to assess the efficacy of different therapeutic approaches to spontaneous AA in CD. Methods: All cases of AA in CD were identified from the databases of five university hospitals. Postoperative cases were excluded. Therapeutic success was defined as abscess resolution and nonreappearance within 1 year of follow‐up. Results: We identified 128 cases in 2236 patients (cumulative incidence 5.7%). Initial therapy included medical therapy with antibiotics alone (42.2%), antibiotics plus percutaneous drainage (23.4%), and antibiotics plus surgical drainage (34.4%). The highest final efficacy corresponded to surgery (91%) as compared with antibiotic therapy alone (63%) or percutaneous drainage (30%). Failure of initial therapy was predicted by immunomodulators at diagnosis (odds ratio [OR] 8.45; 95% confidence interval [CI] 1.16–61.5; P = 0.03), fistula detectable in imaging techniques (OR 5.43; 95% CI 1.18–24.8; P = 0.02), and abscess size (OR 1.65; 95% CI 1.07–2.54; P = 0.02) only for patients treated with antibiotic therapy alone. Percutaneous drainage was associated with 19% of complications (enterocutaneous fistulas 13%); surgery was associated with 13% of postoperative complications (enterocutaneous fistulas 7.7%). Following abscess resolution, 60% of patients were started on thiopurines, 9% on biologics, and in 31% baseline therapy was not modified. Conclusions: Management of spontaneous AA in CD with antibiotics alone seems to be a good option for small abscesses, especially those without associated fistula and appearing in immunomodulator‐naïve patients. Surgery offers better results in the remaining clinical settings, although percutaneous drainage can avoid operative treatment in some cases. (Inflamm Bowel Dis 2012)

Decision tree for early introduction of rescue therapy in active ulcerative colitis treated with steroids

Background: Corticosteroids are the treatment of choice for moderate‐to‐severe active ulcerative colitis (UC) but up to 30%–40% of patients fail to respond. It has been reported that early clinical‐biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate‐to‐severe attacks of UC. Methods: Consecutive patients treated with prednisone 1 mg/kg/day for moderate‐to‐severe attacks of UC were prospectively included. Clinical and biological parameters at 3 and 7 days after starting steroids were recorded. Response was defined as mild or inactive UC activity at day 7 (as assessed by the Montreal Classification of severity) together with no need for rescue therapies (cyclosporin, infliximab, or colectomy). A logistic regression analysis was performed to identify those independent predictors of response. In addition, a decision‐tree analysis was also performed. Results: Sixty‐eight percent of patients (64 out of 94) responded to steroids. In the univariate analysis the number of bowel movements, rectal bleeding, platelet count, and C‐reactive protein (CRP) levels at day 3 were associated with response at day 7, but only rectal bleeding was found to be an independent predictor in the logistic regression analysis. Conversely, the classification and regression tree (CART) model included these four variables. The decision‐tree model showed a higher sensitivity in predicting a rapid response to steroids than the logistic regression one. Conclusions: Rapid response to steroids in active UC attacks can be predicted after 3 days of treatment by simple clinical and biological parameters. A decision‐tree model for early introduction of rescue therapies is provided.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry

BACKGROUND AND AIMS Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. METHODS All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. RESULTS A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. CONCLUSIONS The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias.

Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment

BACKGROUND AND AIMS Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. METHODS In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. RESULTS We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. CONCLUSIONS Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe.

Fecal Calprotectin Levels Are Closely Correlated with the Absence of Relevant Mucosal Lesions in Postoperative Crohnʼs Disease

Background:Fecal calprotectin (FC) is the best noninvasive biomarker of disease activity in inflammatory bowel disease. Its correlation with endoscopic mucosal lesions could save inconvenient, expensive, and repeated endoscopic examinations in particular clinical settings. Patients and Methods:To assess the correlation between FC and the existence and severity of endoscopic postoperative recurrence (POR), a group of clinically stable outpatients with Crohns disease for whom an ileocolonoscopy was routinely planned to assess POR were invited to collect a stool sample before starting bowel cleansing to measure FC. POR was graded by means of Rutgeerts endoscopic score. Results:One hundred nineteen ileocolonoscopies were included, 42% with endoscopic POR. FC was significantly lower in the absence of endoscopic POR and in the absence of any endoscopic lesion. The area under the receiver operating characteristic curve was 0.76 (95% confidence interval, 0.68–0.85) for the diagnosis of the absence of lesions and 0.75 (95% confidence interval, 0.66–0.84) for endoscopic POR. Better sensitivity and negative predictive value were observed when combining FC and serum C-reactive protein (CRP), leading to a sensitivity of 82%, a specificity of 53%, and negative and positive predictive values of 81% and 54%, respectively, for the prediction of endoscopic POR with a combination of FC 100 &mgr;g/g and CRP 5 mg/L cutoff values. Conclusions:FC correlates closely with endoscopic POR in clinically stable postoperative patients with Crohns disease and, when used in combination with CRP, might save endoscopic examinations and allow for a high-grade suspicion of endoscopic POR in the long-term monitoring of these patients.