Improved Survival for Patients With Acute Upper Gastrointestinal Bleeding While on Antithrombotic Therapy: A Multicenter Prospective Cohort Study.

GOALS: Aim of the study was to determine if patients with acute upper gastrointestinal bleeding (AUGIB) while on antithrombotic agents (ATs) are at higher risk for worse outcomes. BACKGROUND: ATs are risk factors of AUGIB, but their impact on clinical outcomes is uncertain. STUDY: Patients with AUGIB (nonvariceal, NV-AUGIB or variceal, V-AUGIB) in 50 Italian hospitals were prospectively enrolled from January 1, 2014 to December 31, 2015. Clinical data, laboratory tests, comorbidities, prognostic scores, received therapies, and outcomes (death, rebleeding, surgery/radiology, transfusions, length of hospitalization) were analyzed. RESULTS: A total of 3324 patients (2764 NV-AUGIB, 83.2% and 560 V-AUGIB, 16.8%) were enrolled, 1399 (42.1%) on ATs. Patients taking ATs were older (75.4 vs. 62.8 y, P <0.001), had higher American Society of Anesthesiologists (ASA), Rockall and Glasgow-Blatchford scores ( P <0.001). At multivariate analysis considering comorbidities, ATs use resulted an independent protective factor against death [odds ratio (OR): 0.63, 95% confidence interval (CI): 0.45-0.87, P =0.006]. Rebleeding (5.5% vs. 5.8%, P =0.71) and need for salvage surgery/radiology (4.2% vs. 4.8%, P =0.41) were similar in the 2 groups. Considering specific ATs, low-dose aspirin was the most powerful factor lowering the death risk (OR: 0.51, 95% CI: 0.33-0.81, P =0.004). While the generic use of AT therapy did not emerge as a statistically significant independent protective factor considering separately NV-AUGIB (OR: 0.80, 95% CI: 0.56-1.13, P =0.21) and V-AUGIB (OR: 0.40, 95% CI: 0.15-1.07, P =0.068), the protective effect of low-dose aspirin was confirmed for NV-AUGIB (OR: 0.62, 95% CI: 0.41-0.94, P =0.025). CONCLUSIONS: ATs use is an independent protective factor against death in AUGIB. The protective effect is mainly derived from low-dose aspirin.

Derivation and validation of Re.Co.De death score risk in patients with acute nonvariceal upper GI bleeding.

BACKGROUND AND AIMS: Scores in upper GI bleeding (UGIB) are used to stratify death risk and need for hospitalization at admission, but a tool that incorporates dynamic changes during the hospital stay is lacking. We aimed to develop a death risk score that considers changes in clinical status during hospitalization and compare its performance with existing ones. METHODS: A multicenter cohort study enrolling patients with UGIB in 50 Italian hospitals from January 2014 to December 2015 was conducted. Data were collected and used to develop a risk score using logistic regression analyses. Performance curves (area under the receiver-operating characteristic [AUROC] curves), sensitivities, specificities, positive and negative predictive values, and outcomes classified as low, intermediate, and high death risk were calculated. The score's performance was externally validated and then compared with other scores. RESULTS: We included 1852 patients with nonvariceal UGIB in the development cohort and 912 in the validation cohorts. The new score, which we named the Re.Co.De (rebleeding-comorbidities-deteriorating) score, included 10 variables depicting the changes in clinical conditions while in the hospital. The mortality AUROC curves were .93 (95% confidence interval, .91-.96) in the derivation cohort and .94 (95% confidence interval, .91-.98) in validation cohort. In a comparison of AUROC curves with other scores, the new score showed a significant performance compared with pre- and postendoscopy scores. Patients with low and high scores had 30-day mortality rates of .001% and 48.2%, respectively. CONCLUSIONS: The Re.Co.De score has a higher performance for predicting mortality in patients with UGIB compared with other scores, correctly identifying patients at low and high death risk while in the hospital through a dynamic re-evaluation of clinical status.

Efficacy of Helicobater pylori eradication in patients with diffuse large B-cell lymphoma of the stomach: A systematic review.

OBJECTIVES: The role of Helicobater pylori eradication in the treatment of high-grade diffuse large B-cell lymphoma (DLBCL) of the stomach is unclear. METHODS: We performed a systematic review and meta-analysis of currently available data. DLBCL-remission rate after eradication therapy, post-remission maintenance, and response rate in the case of additional oncological therapy were extracted. RESULTS: By considering data of seven studies, the DLBCL remission was achieved in 81 (53.3%; 95% CI = 45.3-61.2) out of 152 H. pylori eradicated patients. The regression rate did not differ between pure DLCBL and DLCBL with MALT component, between stage I and stage II disease, and between Caucasians and Asians. Disease regression was maintained in all patients after at a median of 63 months (range: 46-29) follow-up. In those non-responders, DLBLC remission after additional chemo-immunotherapy was achieved in 63 (98.4%; 95% CI = 95.4-100) out of 64 patients. CONCLUSIONS: Data this systematic review suggest considering H. pylori eradication as first-line therapy to treat infected patients with early-stage, high-grade gastric lymphoma.

Comparison of assessment tools in acute upper gastrointestinal bleeding: which one for which decision.

BACKGROUND: Upper GI bleeding (UGIB) remains a common emergency with significant mortality. Scores help triage patients, but it is still unclear which score should be used in the different decision-making moments to identify patients at high or low death risk. We aimed to compare the overall performances of the most validated scores and their cut-off performance to identify patients at low and high death risk. The secondary outcome was to compare the scores' performance for predicting therapeutic endoscopy, the need for transfusion(s), rebleeding, and surgery/interventional radiology. METHODS: We conducted a prospective multicenter cohort study, including consecutive UGIB patients admitted to 50 Italian hospitals. We collected information to calculate the Rockall, the Progetto Nazionale Endoscopia Digestiva (PNED), the AIMS65, the Glasgow-Blatchford (GBS), and the Age, Blood tests, Comorbidities (ABC) scores, together with demographic figures, clinical data, and outcomes. RESULTS: We obtained complete data of 2307 outpatients, including 1887 non-variceal and 420 variceal bleeders. Our cohort's mean age was 67.5 years, with a prevalence of male gender (69%). The GBS has the best overall performance (ROC 0.74) compared to the other scores in identifying low-risk patients (p < .001). At the cut-off 0-1, both GBS and ABC scores provide the highest PPV (100%) for low-risk patients. ABC and PNED scores are the most useful ones (for AUC >80) to assess the high-risk patients for mortality. CONCLUSIONS: At admission, GBS and ABC scores identify low-risk patients suitable for outpatient management, while PNED and ABC scores identify high-risk patients. During hospitalization, the PNED score should be used to re-assess the mortality risk if a modification of clinical status occurs.

ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study.

OBJECTIVES: Existing scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB. DESIGN AND SETTING: International cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score's performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk. PARTICIPANTS AND RESULTS: We included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81-84) than existing scores (AUROCs: 0.65-0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4-7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; p<0.001). In LGIB, patients with low, medium and high ABC scores had in-hospital mortality rates of 0.6%, 6.3% and 18%, respectively. CONCLUSIONS: In contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.

Clinical outcomes in cirrhotics with variceal or nonvariceal gastrointestinal bleeding: A prospective, multicenter cohort study.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is associated with a distinct mortality in cirrhotics. We evaluated whether the rate of mortality and other outcomes differs between variceal and nonvariceal UGIB. METHODS: This was a prospective, multicenter, cohort study on UGIB cirrhotics observed in 50 hospitals. Variceal or nonvariceal UGIB were diagnosed at endoscopy. The 6-week mortality rate, need of blood transfusion, intensive care unit (ICU) admission, radiologic or surgical intervention, rebleeding rate, and length of stay in hospital were the main clinical outcomes compared. Data were analyzed at univariate and multivariate analysis, and odds ratio (OR) with their 95% confidence interval (CI) was calculated. RESULTS: The study enrolled 706 cirrhotics, including 516 (73%) variceal and 190 (27%) nonvariceal UGIB. There were 78 (11%; 95% CI = 8.7-13.4) deceases, without any difference between variceal (11.0%) and nonvariceal (11.0%) groups. Child-Pugh score C (OR: 6.99; 95% CI = 2.58-18.95), and development of either hepatorenal syndrome (OR: 16.5; 95% CI = 7.02-38.9) or hepatic encephalopathy (OR: 2.38; 95% CI = 1.25-4.5) were independent predictors of mortality. Transfusions and onset of hepatic encephalopathy were significantly more frequent in variceal, whereas ICU admission rate was higher in nonvariceal bleedings. Overall, antibiotic prophylaxis was eventually administered in only 392 (55.5%) patients. CONCLUSIONS: Data found that the overall mortality rate in cirrhotics with UGIB seems to be reducing and that the value did not differ between variceal and nonvariceal types. Prevention of both hepatorenal syndrome and hepatic encephalopathy and implementation of antibiotic prophylaxis could improve survival in these patients.

Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high-dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta-analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management. METHODS: A literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30-day mortality. RESULTS: There were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) -0.03, 95% CI -0.26, 0.19; P = 0.76], duration of hospital stay (MD -0.61, 95% CI -1.45, 0.23; P = 0.16) or 30-day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration. CONCLUSIONS: Oral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs.

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

Development and validation of an endoscopic classification of diverticular disease of the colon: the DICA classification.

BACKGROUND: A validated endoscopic classification of diverticular disease (DD) of the colon is lacking at present. Our aim was to develop a simple endoscopic score of DD: the Diverticular Inflammation and Complication Assessment (DICA) score. METHODS: The DICA score for DD resulted in the sum of the scores for the extension of diverticulosis, the number of diverticula per region, the presence and type of inflammation, and the presence and type of complications: DICA 1 (≤ 3), DICA 2 (4-7) and DICA 3 (>7). A comparison with abdominal pain and inflammatory marker expression was also performed. A total of 50 videos of DD patients were reassessed in order to investigate the predictive role of DICA on the outcome of the disease. RESULTS: Overall agreement in using DICA was 0.847 (95% confidence interval, CI, 0.812-0.893): 0.878 (95% CI 0.832-0.895) for DICA 1, 0.765 (95% CI 0.735-0.786) for DICA 2 and 0.891 (95% CI 0.845-0.7923) for DICA 3. Intra-observer agreement (kappa) was 0.91 (95% CI 0.886-0.947). A significant correlation was found between the DICA score and C-reactive protein values (p = 0.0001), as well as between the median pain score and the DICA score (p = 0.0001). With respect to the 50 patients retrospectively reassessed, occurrence/recurrence of disease complications was recorded in 29 patients (58%): 10 (34.5%) were classified as DICA 1 and 19 (65.5%) as DICA 2 (p = 0.036). CONCLUSIONS: The DICA score is a simple, reproducible, validated and easy-to-use endoscopic scoring system for DD of the colon.

Optimal bowel cleansing for colonoscopy: split the dose! A series of meta-analyses of controlled studies.

BACKGROUND: Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate preparation is crucial for an effective colonoscopy, but definitive data on the optimal preparation are lacking. OBJECTIVE: Our aim was to assess the efficacy of split-dose versus non-split-dose preparations, the rate of adequate preparation according to type and dose of laxatives, the role of "runway time" (the interval time between the last drink of purgative and the beginning of colonoscopy), and to evaluate compliance as an additive risk factor for colon cleansing. DESIGN: A series of meta-analyses of controlled studies. SETTING: Randomized clinical trial of split dose regimen versus entire dose taken on the day preceding colonoscopy. PATIENTS: Published trials (1960-2013) comparing split-dose versus non-split-dose preparations in adults undergoing colonoscopy were selected by using MEDLINE, the Cochrane Central Register of Controlled Trials, clinicaltrial.gov, ISI Web of Science, and Scopus. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Rate difference of the degree of colon cleansing between split dose and whole dose was the primary measure of treatment effect. RESULTS: We included 29 studies. Overall, an adequate preparation was obtained in 85% of patients in the split-dose group and in 63% of the non-split-dose group (rate difference 22%). The heterogeneity was caused by 5 factors: the runway time (the longer, the worse the cleansing), type of diet, male sex, use of polyethylene glycol 4 L, and the Jadad score. Compliance was significantly higher in the split-dose group. LIMITATIONS: Average quality of the included studies and publication bias. CONCLUSION: We provided further evidence of the superiority of a split-dose regimen over a non-split-dose regimen and showed that, regardless of type and dose, the superiority of split-dose regimens remains valid if the "golden 5 hours" rule is preserved.

Predicting mortality in patients with in-hospital nonvariceal upper GI bleeding: a prospective, multicenter database study.

BACKGROUND: Nonvariceal upper GI bleeding (NVUGIB) that occurs in patients already hospitalized for another condition is associated with increased mortality, but outcome predictors have not been consistently identified. OBJECTIVE: To assess clinical outcomes of NVUGIB and identify predictors of mortality from NVUGIB in patients with in-hospital bleeding compared with outpatients. DESIGN: Secondary analysis of prospectively collected data from 2 nationwide multicenter databases. Descriptive, inferential, and multivariate logistic regression models were carried out in 338 inpatients (68.6 ± 16.4 years of age, 68% male patients) and 1979 outpatients (67.8 ± 17 years of age, 66% male patients). A predictive model was constructed using the risk factors identified at multivariate analysis, weighted according to the contribution of each factor. SETTINGS: A total of 23 Italian community and tertiary care centers. PATIENTS: Consecutive patients admitted for acute NVUGIB. INTERVENTIONS: Early endoscopy, medical and endoscopic treatment as appropriate. MAIN OUTCOME MEASUREMENTS: Recurrent bleeding, surgery, and 30-day mortality. RESULTS: The mortality rate in patients with in-hospital bleeding was significantly higher than that in outpatients (8.9% vs 3.8%; odds ratio [OR] 2.44; 95% confidence interval [CI], 1.57-3.79; P < .0001). Hemodynamic instability on presentation (OR 7.31; 95% CI, 2.71-19.65) and the presence of severe comorbidity (OR 6.72; 95% CI, 1.87-24.0) were the strongest predictors of death for in-hospital bleeders. Other independent predictors of mortality were a history of peptic ulcer disease and failed endoscopic treatment. Rebleeding was a strong predictor of death only for outpatients (OR 5.22; 95% CI, 2.45-11.10). Risk factors had a different prognostic impact on the 2 populations, resulting in a significantly different prognostic accuracy of the model (area under the receiver-operating characteristic curve = 0.83; 95% CI, 0.77-0-93 vs 0.74; 95% CI, 0.68-0.80; P < .02). LIMITATIONS: Study design not experimental, no data on ward specialty, potential referral bias. CONCLUSIONS: In-hospital bleeders have a significantly higher risk of death because they are sicker and more often hemodynamically unstable than outpatients. Predictors of death have a different impact in the 2 populations.

The interaction of patients' physical status and time to endoscopy on mortality risk in patients with upper gastrointestinal bleeding: A national prospective cohort study.

BACKGROUND AND AIM: The correct time to perform an upper endoscopy is decisive in acutely GI bleeding patients. However, patients' physical status may affect mortality. We speculated that the physical status and procedural time could be the principal factors accountable for death-risk. The primary aim was to verify the interaction between physical status and time to endoscopy on mortality; the secondary aim was to verify the interaction of the physical status and time to endoscopy on the length of stay (LOS). METHODS: Consecutive patients admitted to 50 Italian hospitals were included. Clinical and endoscopic data were recorded. A multiple logistic regression analysis was performed and the interaction of adjusted clinical physical status and time to endoscopy on mortality was calculated. RESULTS: Complete data were available for 3.190 patients. The time frames did not interfere with outcomes but influenced LOS. Conversely, the ASA score correlated with mortality, LOS, need for transfusions and rebleeding risk. CONCLUSION: Endoscopy time should be tailored to the patient's physical. In our experience, ASA 1-2-3 patients can be safely submitted to endoscopy to reduce the LOS; on the contrary, keen attention should be paid to ASA4 patients, following the 'not too early-not too late' rule (12-24 h from admission).

Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection.

BACKGROUND & AIMS: Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. METHODS: We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n = 90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n = 90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. RESULTS: Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%-95.8%) and sequential therapies (93.3%; 95% CI, 86.9%-97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%-99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%-98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; -7.6% to 9.8%) and -1.0% in the per-protocol analysis (95% CI; -8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. CONCLUSIONS: Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

Comparison of assessment tools in acute upper gastrointestinal bleeding: Which one at which time point?

BACKGROUND: Decisions on managing bleeders remain a critical issue due to the high death risk. The Glasgow-Blatchford score (GBS) correctly identifies low-risk patients but none of the existing scores precisely assess the high risk patients. AIMS: To evaluate bleeding scores' prognostic performances in predicting mortality risk. SECONDARY OUTCOMES: To compare the scores in low and high-risk patients and identify the "best performing cut-off" (if different from the standard one) in discriminating survivors from deceased. METHODS: prospective multicenter cohort study including consecutive UGIB patients admitted to 50 Italian hospitals. We collected information to calculate Rockall, PNED, AIMS65, GB, and ABC scores, together with demographic and clinical data, and outcomes. RESULTS: for low-risk patients, the GB and the ABC are the best performing scores; for high-risk patients, all scores showed weak results, with the PNED score having the higher PPV. Searching for the "best performing cut-off", we found different points that determined a relevant numerical gain in terms of patients correctly assessed. CONCLUSIONS: we suggest using the GBS and the ABC score at admission, while the PNED appears to be more useful for high-risk. We also suggest using a new decisional cut-offs that, if validated, may increase the accuracy of current scores.

Defining Time in Acute Upper Gastrointestinal Bleeding: When Should We Start the Clock?

INTRODUCTION: The execution of upper endoscopy at the proper time is key to correctly managing patients with upper gastrointestinal bleeding (UGIB). Nonetheless, the definition of "time" for endoscopic examinations in UGIB patients is imprecise. The primary aim of this study was to verify whether the different definitions of "time" (i.e., the symptoms-to-endoscopy and presentation-to-endoscopy timeframes) impact mortality. The secondary purpose of this study was to evaluate the similarity between the two timeframes. METHODS: A post-hoc analysis was performed on a prospective multicenter cohort study, which included UGIB patients admitted to 50 Italian hospitals. We collected the timings from symptoms and presentation to endoscopy, together with other demographic, organizational and clinical data and outcomes. RESULTS: Out of the 3324 patients in the cohort, complete time data were available for 3166 patients. A significant difference of 9.2 h (p < 0.001) was found between the symptoms-to-endoscopy vs. presentation-to-endoscopy timeframes. The symptoms-to-endoscopy timeframe demonstrated (1) a different death risk profile and (2) a statistically significant improvement in the prediction of mortality risk compared to the presentation-to-endoscopy timeframe (p < 0.0002). The similarity between the two different timeframes was moderate (K = 0.42 ± 0.01; p < 0.001). CONCLUSIONS: The symptoms-to-endoscopy and presentation-to-endoscopy timeframes referred to different timings during the management of upper endoscopy in bleeding patients, with the former being more accurate in correctly identifying the mortality risk of these patients. We suggest that further studies be conducted to validate our observations, and, if confirmed, a different definition of time should be adopted in endoscopy.

New insight of human-IgH 3'regulatory regions in immunoglobulins switch.

BACKGROUND: Several studies in animal models have demonstrated the role of the 3' Regulatory Region (3'RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3'RR on the chromosome 14 (chr14). The classes' equilibrium can be altered during infections and in other pathological conditions. MATERIAL AND METHODS: We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3'RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects. RESULTS: In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3'RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels. CONCLUSION: The 3'RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3'RR1 and 3'RR2, also in physiological conditions.

Enteroscopy in diagnosis and treatment of small bowel bleeding: A Delphi expert consensus.

BACKGROUND: Enteroscopy plays an important role in the management of small bowel bleeding. However, current guidelines are not specifically designed for small bowel bleeding and recommendations from different international societies do not always align. Consequently, there is heterogeneity in the definitions of clinical entities, clinical practice policies, and adherence to guidelines among clinicians. This represents an obstacle to providing the best patient care and to obtain homogeneous data for clinical research. AIMS: The aims of the study were to establish a consensus on the definitions of bleeding entities and on the role of enteroscopy in the management of small bowel bleeding using a Delphi process. METHODS: A core group of eight experts in enteroscopy identified five main topics of small bowel bleeding management and drafted statements on each topic. An expert panel of nine gastroenterologists participated in three rounds of the Delphi process, together with the core group. RESULTS: A total of 33 statements were approved after three rounds of Delphi voting. CONCLUSION: This Delphi consensus proposes clear definitions and a unifying strategy to standardize the management of small bowel bleeding. Furthermore, it provides a useful guide in daily practice for both clinical and technical issues of enteroscopy.

Upper Gastrointestinal Endoscopy Quality in Italy: A Nationwide Study.

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.