The Impact of potential 'confounders' on the diagnostic sensitivity of circulating free DNA in management of FIT+ patients: a pilot study.

Cell-free DNA (cfDNA) has long been established as a useful diagnostic and prognostic tool in a variety of clinical settings, ranging from infectious to cardiovascular and neoplastic diseases. However, non-neoplastic diseases can act as confounders impacting on the amount of cfDNA shed in bloodstream and on technical feasibility of tumour derived free circulating nucleic acids selecting patients with cancer. Here, we investigated the potential impact of other pathological processes in the clinical stratification of 637 FIT+ patients. A single and multiple logistic regression yielded similar results. Crude sensitivity was 75.9% versus adjusted sensitivity of 74.1%, relative risk 0.9761 (0.8516 to 1.1188), risk difference 0.0181 (-0.0835 to 0.1199) and OR 0.9079 (0.5264 to 1.5658). Potential confounding effect from other source of cfDNA plays a pivotal role in the clinical stratification of FIT+ patients.

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Diverticular Inflammation and Complication Assessment classification, CODA score and fecal calprotectin in clinical assessment of patients with diverticular disease: A decision curve analysis.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.

Prevalence and Natural History of Segmental Colitis Associated With Diverticulosis.

INTRODUCTION: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis. METHODS: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients. RESULTS: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission. DISCUSSION: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course.

One-Day versus Three-Day Low-Residue Diet and Bowel Preparation Quality before Colonoscopy: A Multicenter, Randomized, Controlled Trial.

BACKGROUND: One-day low-residue diet (LRD) is recommended before colonoscopy, but only three single-center trials compared the 1-day versus 3-day LRD. The aim of this multicenter study was to compare the impact of a 3-day versus 1-day LRD on its ability to adequately and successfully prepare the bowel of outpatients that require a colonoscopy. The outpatients' tolerance and adherence to the LRD were also considered. METHODS: Consecutive outpatients were randomized to 1-day versus 3-day LRD at three open-access endoscopy units. The primary endpoint consisted of the proportion of patients with a satisfactory degree of bowel cleanliness (Score 2-3 on the Boston Bowel Preparation Scale [BBPS] in each segment). Secondary endpoints were patients' tolerance and adherence to the prescribed diet evaluated by a standardized questionnaire. RESULTS: 289 patients were included in the study (1-day LRD arm = 143, 3-day LRD arm = 146). BBPS ≥2 was not significantly different in the two dietary regimens in any of the three colonic segments (71% vs. 72%, p = 0.9). The percentage of patients with incomplete preparation was similar in the two arms (9% vs. 9%; p = 1.0). No significant differences were found among colonoscopy findings in terms of abnormalities (81% vs. 84%, p = 0.8). Both groups scored similarly in overall tolerance to LRD (48% vs. 49%, p = 1.0) and also in whether they would have adopted a different dietary regimen (p = 0.3). CONCLUSION: Our multicenter randomized study confirmed that optimal bowel cleansing is reached through a 1-day LRD.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria.

BACKGROUND: Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of 'harmonized' criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population. METHODS: In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 'harmonized' criteria. RESULTS: Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54-2.00] and cancer (OR: 1.92, 95% CI 1.42-2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated. CONCLUSIONS: MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.

Evaluation of a novel liquid biopsy-based ColoScape assay for mutational analysis of colorectal neoplasia and triage of FIT+ patients: a pilot study.

Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study. The assay was evaluated on 52 prospectively collected whole-blood samples obtained from FIT+ patients enrolled in the CRC screening programme of ASL NAPOLI 3 SUD, using colonoscopy as confirmation. The assay's sensitivity for advanced adenomas was 53.8% and the specificity was 92.3%. The PPV was 70.0% and negative predicitive value (NPV) was 85.7%. Workflow optimisation is essential to maximise sensitivity. Of note, four of the six positive cases missed by ColoScape had a less than suboptimal DNA input (data not shown). Had they been ruled out as inadequate, sensitivity would have increased from 53.8% to 69%. However, as stated previously, this is not a clinical trial, but rather an initial, preliminary technical evaluation. In conclusion this study shows that ColoScape is a promising tool and further studies are warranted in order to validate its use for the triage of FIT+ patients.

Clinical utility of the SMSA grading tool for the management of colonic neoplastic lesions.

BACKGROUND: Whilst polyp size has been traditionally used as a predictor of the complexity of endoscopic resection, the influence of other factors is increasingly recognised. The SMSA grading system takes into account polyp Site, Morphology, Size and Access, with higher scores correlating with increased technical difficulty. AIMS: To evaluate whether the SMSA grading tool correlates with endoscopic and clinical outcomes. METHODS: This retrospective study was conducted at two high volume centres in the United Kingdom and Italy. All polyps identified at colonoscopy were included in this study and classified as per the SMSA grading system. RESULTS: A total of 1668 lesions were resected in 1016 patients. There was a positive correlation between increasing SMSA level and the inability to resect lesions "en bloc" (p<0.001). Histologically complete clearance was higher in the lower SMSA groups (p<0.0001). Additional endoscopic therapies, were more commonly required with the higher SMSA groups to achieve histological clearance (p<0.0001). Moreover, advanced histology in resection specimens and procedural complications were significantly less common in SMSA level 1 lesions compared to level 3 or 4 lesions (p<0.0001). CONCLUSIONS: The SMSA grading tool is a useful predictor of outcome following the resection of colonic neoplastic lesions.

Surgery has a key role for quality assurance of colorectal cancer screening programs: impact of the third level multidisciplinary team on lymph nodal staging.

PURPOSE: From 2011 to 2013 in the area of the Naples 3 public health district (ASL-NA3), a colorectal cancer screening program (CCSP) was developed. In order to stress the need of quality assurance procedures for surgery and pathology, a third level oncologic pathway was added and set up at a referral colorectal cancer center (RC). Lymph nodal (LN) harvesting, as a process indicator, and nodal positivity were adopted for an interim analysis. METHODS: The program was implemented by a series of audit meetings and a double type of multidisciplinary team (MDT): "horizontal" and "vertical." Three hundred and forty colorectal cancer (CRC) patients underwent surgery: 119 chose to be operated at the RC (Gr In), 65 were operated at 22 district hospitals (DH) (Gr Out), and 156 symptomatic not screened patients were operated at the RC (Gr Sym). RESULTS: Statistical analysis revealed differences between Gr In and Gr Out colon groups both for LN harvesting (median of 26 and 11, respectively, P = 0.0001), and for nodal positivity after the first screening round (34.78 and 19.45%, respectively, P = 0.0169). Results were all the more significant in a subset analysis on early T stage colon subgroups (In vs Out) both for LN harvesting (P < 0.0001) and nodal positivity (P < 0.0001). CONCLUSION: xSignificant differences between RC and DHs were found, particularly for early-stage CRC patients. LN harvesting should be considered as a surrogate marker of quality assurance for at least screening hospitals for "minimum best" standard of care. This should lead to set up a third level in any CCSP.

Quality of bowel cleansing in hospitalized patients undergoing colonoscopy: A multicentre prospective regional study.

BACKGROUND: Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. AIMS: To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. METHODS: Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. RESULTS: Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time >12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67]). CONCLUSIONS: We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

Transition of gastroenterological patients from paediatric to adult care: A position statement by the Italian Societies of Gastroenterology.

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.

Prevalence and characteristics of serrated lesions of the colorectum in Italy: A multicentre prospective cohort study.

BACKGROUND: Serrated lesions are recognized as important contributors to colorectal cancer incidence. We aimed to prospectively assess the prevalence of serrated lesions and identify potential predictors of these lesions during colonoscopy in an Italian population. METHODS: Prospective cross sectional study involving 8 endoscopy units from February 1st to July 31st 2012. RESULTS: Out of 2468 colonoscopies, 886 precancerous lesions were detected in 567 patients. Of these, 173 SELs were diagnosed in 148 patients (140 serrated/hyperplastic polyps and 33 serrated adenomas). Prevalence was 7% (173/2468). Serrated lesions accounted for 19.5% of all precancerous lesions. Serrated polyps were prevalent in the left colon (42.1%) and serrated adenomas in the proximal colon (54.5%). Independent clinical predictors of serrated lesions were patient age (OR 0.98 [0.97-1.00]) and post-polypectomy surveillance (OR 1.87 [1.24-2.82]). Endoscopic predictors were right colon location (OR 2.65 [1.63-4.30] vs. rectum; and 1.53 [1.03-2.26] vs. left colon), polypoid shape (OR 0.41 [027-0.64]) and size <6 mm (OR 0.49 [0.33-0.72] vs. 6-10 mm; and 0.14 [0.07-0.28] vs. >10 mm). There was no independent predictor of serrated adenoma. CONCLUSION: In our Italian study population, the prevalence of colorectal serrated lesions was 7%. Their diagnosis is associated with younger age and surveillance colonoscopy, right-sided colorectal location, non-polypoid shape and size <6 mm.

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.

Predictors of favourable outcome in non-variceal upper gastrointestinal bleeding: implications for early discharge?

BACKGROUND: There is a lack of validated predictors on which to decide the timing of discharge in patients already hospitalized for upper nonvariceal bleeding. AIMS: Identify factors that appear to protect nonvariceal bleeders from the development of negative outcome (rebleeding, surgery, death). METHODS: Secondary analysis of two prospective multicenter studies. Multivariate analyses for each investigated outcome were performed; a single model was developed including all factors that were statistically significant in each sub-model. A final score was developed to predict favourable outcomes. Prognostic accuracy was tested with ROC curve analysis. RESULTS: Out of 2398 patients, 211 (8.8%) developed one or more adverse outcomes: 87 (3.63%) had rebleeding, 46 (1.92%) needed surgery and 107 (4.46%) died. Predictors of favourable prognosis were: ASA score 1 or 2, absence of neoplasia, outpatient bleeding, use of low-dose aspirin, no need for transfusions, clean-based ulcer, age <70 years, no haemodynamic instability successful endoscopic diagnosis/therapy, no Dieulafoy's lesion at endoscopy, no hematemesis on presentation and no need for endoscopic treatment. Overall prognostic accuracy of the model was 83%. The final score accurately identified 20-30% of patients that eventually do not develop any negative outcome. CONCLUSIONS: The "good luck score" may be a useful tool in deciding when to discharge a patient already hospitalized for acute non-variceal bleeding.

The "Prometeo" study: online collection of clinical data and outcome of Italian patients with acute nonvariceal upper gastrointestinal bleeding.

GOALS: To implement an online, prospective collection of clinical data and outcome of patients with acute nonvariceal upper gastrointestinal bleeding (UGIB) in Italy ("Prometeo" study). BACKGROUND: Epidemiology, clinical features, and outcomes of nonvariceal UGIB are mainly known by retrospective studies and are probably changing. STUDY: Data were collected by 13 Gastrointestinal Units in Italy from June 2006 to June 2007 (phase 1) and from December 2008 to December 2009 (phase 2): an interim analysis of data was performed between the 2 phases to optimize the online database. All the patients consecutively admitted for acute nonvariceal UGIB were enrolled. Demographic and clinical data were collected, a diagnostic endoscopy performed, with endoscopic hemostasis if indicated. RESULTS: One thousand four hundred thirteen patients (M=932, mean age±SD=66.5±15.8; F=481, mean age±SD=74.2±14.6) were enrolled. Comorbidities were present in 83%. 52.4% were treated with acetyl salicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs): only 13.9% had an effective gastroprotection. Previous episodes of UGIB were present in 13.3%. Transfusion were needed in 43.9%. Shock was present in 9.3%. Endoscopic diagnosis was made in 93.2%: peptic lesions were the main cause of bleeding (duodenal ulcer 36.2%, gastric ulcer 29.6%, gastric/duodenal erosions 10.9%). At endoscopy, Helicobacter pylori was searched in 37.2%, and found positive in 51.3% of tested cases. Early rebleeding was observed in 5.4%: surgery was required in 14.3% of them. Bleeding-related death occurred in 4.0%: at multivariate analysis, the risk of death was correlated with female sex [odds ratio (OR=2.19, P=0.0089)], presence of neoplasia (OR=2.70, P=0.0057) or multiple comorbidities (OR=5.04, P=0.0280), shock at admission (OR=4.55, P=0.0001), and early rebleeding (OR=1.47, P=0.004). CONCLUSIONS: Prometeo database has provided an up-to-date picture of acute nonvariceal UGIB in Italy: patients are elderly, predominantly males, and with important comorbidities. Gastroprotection is underutilized during NSAIDs treatment. With respect to previous studies, Prometeo shows a higher incidence of low-dose acetyl salicylic acid use and comorbidities, whereas no significant difference were found in other items (etiology of bleeding, NSAIDs use, need for endoscopic hemostasis, incidence of rebleeding, and overall mortality).

Mortality from nonulcer bleeding is similar to that of ulcer bleeding in high-risk patients with nonvariceal hemorrhage: a prospective database study in Italy.

BACKGROUND: Nonulcer causes of bleeding are often regarded as minor, ie, associated with a lower risk of mortality. OBJECTIVE: To assess the risk of death from nonulcer causes of upper GI bleeding (UGIB). DESIGN: Secondary analysis of prospectively collected data from 3 national databases. SETTINGS: Community and teaching hospitals. PATIENTS: Consecutive patients admitted for acute nonvariceal UGIB. INTERVENTIONS: Early endoscopy, medical and endoscopic treatment as appropriate. MAIN OUTCOME MEASUREMENTS: Thirty-day mortality, recurrent bleeding, and need for surgery. RESULTS: A total of 3207 patients (65.8% male), mean (standard deviation) age 68.3 (16.4) years, were analyzed. Overall mortality was 4.45% (143 patients). According to the source of bleeding, mortality was 9.8% for neoplasia, 4.8% for Mallory-Weiss tears, 4.8% for vascular lesions, 4.4% for gastroduodenal erosions, 4.4% for duodenal ulcer, and 3.1% for gastric ulcer. Frequency of death was not different among benign endoscopic diagnoses (overall P = .567). Risk of death was significantly higher in patients with neoplasia compared with benign conditions (odds ratio 2.50; 95% CI, 1.32-4.46; P < .0001). Gastric or duodenal ulcer significantly increased the risk of death, but this was not related to the presence of high-risk stigmata (P = .368). The strongest predictor of mortality for all causes of nonvariceal UGIB was the overall physical status of the patient measured with the American Society of Anesthesiologists score (1-2 vs 3-4, P < .001). LIMITATIONS: No data on the American Society of Anesthesiologists class score in the Prometeo study. CONCLUSIONS: Nonulcer causes of nonvariceal UGIB have a risk of death, similar to bleeding peptic ulcers in the clinical context of a high-risk patient.