EUS-TTNB with micro-forceps in PCL is feasible, safe, and has a high diagnostic yield. Future prospective studies are needed to better assess the clinical impact of EUS-TTNB on the management of PCL.

Importance: Liver transplantation (LT) is a life-saving therapy for patients with end-stage liver disease and with acute liver failure, and it is associated with excellent outcomes and survival rates at 1 and 5 years.The incidence of biliary complications (BCs) after LT is reported to range from 5% to 20%, most of them occurring in the first three months, although they can occur also several years after transplantation.Objective: The aim of this review is to summarize the available evidences on pathophysiology, risk factors, diagnosis and therapeutic management of BCs after LT.Evidence Review: a literature review was performed of papers on this topic focusing on risk factors, classifications, diagnosis and treatmentFindings: Principal risk factors include surgical techniques and donor's characteristics for biliary leakage and anastomotic biliary strictures and vascular alterations for non-anastomotic biliary strictures. MRCP is the gold standard both for intra-and extrahepatic BCs, while invasive cholangiography should be restricted for therapeutic uses or when MRCP is equivocal. About treatment, endoscopic techniques are the first line of treatment with success rates of 70-100%. The combined success rate of ERCP and PTBD overcome 90% of cases. Biliary leaks often resolve spontaneously, or with the positioning of a stent in ERCP for major bile leaks Conclusions and Relevance: BCs influence morbidity and mortality after LT, therefore further evidences are needed to identify novel possible risk factors, to understand if an immunological status that could lead to their development exists and to compare the effectiveness of innovative surgical and machine perfusion techniques.

Objectives Endoscopic ultrasound through‐the‐needle biopsy (EUS‐TTNB) is a useful tool for differential diagnosis among pancreatic cystic lesions (PCLs). Cystic fluid cytology (CFC) is recommended by guidelines, but its diagnostic accuracy is about 50%. The aim of this meta‐analysis is to assess the clinical impact of EUS‐TTNB in terms of technical success (TS), histological accuracy (HA) and diagnostic yield (DY). Methods Original studies in English language on EUS‐TTNB were searched in MEDLINE and EMBASE until October 2019. Diagnostic accuracy of EUS‐TTNB for identification of mucinous PCLs was calculated using individual diagnostic data of patients who underwent CFC and surgery. Results Nine studies, including 454 patients who underwent EUS‐TTNB, met the inclusion criteria for the meta‐analysis. TS and HA of EUS‐TTNB were, respectively, 98.5% (95% Confidence Interval [CI] 97.3%–99.6%) and 86.7% (95%CI 80.1–93.4). DY was 69.5% (95%CI 59.2–79.7) for EUS‐TTNB and 28.7% (95%CI 15.7–41.6) for CFC. Heterogeneity persisted significantly high in most of subgroup analyses. In the multivariate meta‐regression, cyst size was independently associated with higher DY. Sensitivity and specificity for mucinous PCLs were 88.6 and 94.7% for EUS‐TTNB, and 40 and 100% for CFC. Adverse events rate was 8.6% (95%CI 4.0–13.1). Conclusions This meta‐analysis shows that EUS‐TTNB is a feasible technique that allows a high rate of adequate specimens to be obtained for histology; in about two‐thirds of patients a specific histotype diagnosis could be assessed. The number of adverse events is slightly higher respect to standard EUS‐FNA, but complications are very rarely severe.

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. Discrimination and calibration were assessed by the area under the receiver operating characteristic curve (AUC) and by Brier score in both the derivation and validation cohorts. Seven variables were independent risk factors for in-hospital mortality: age (Hazard Ratio [HR] 1.08, 95% Confidence Interval [CI] 1.07–1.09), male sex (HR 1.62, 95%CI 1.30–2.00), duration of symptoms before hospital admission <10 days (HR 1.72, 95%CI 1.39–2.12), diabetes (HR 1.21, 95%CI 1.02–1.45), coronary heart disease (HR 1.40 95% CI 1.09–1.80), chronic liver disease (HR 1.78, 95%CI 1.16–2.72), and lactate dehydrogenase levels at admission (HR 1.0003, 95%CI 1.0002–1.0005). The AUC was 0.822 (95%CI 0.722–0.922) in the derivation cohort and 0.820 (95%CI 0.724–0.920) in the validation cohort with good calibration. The prediction rule is freely available as a web-app (COVID-CALC: https://sites.google.com/community.unipa.it/covid-19riskpredictions/c19-rp). Conclusions A validated simple clinical prediction rule can promptly and accurately assess the risk for in-hospital mortality, improving triage and the management of patients with COVID-19.

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e64. Learning Objective-Upon completion of this activity, successful learners will be able to choose critically the exams that should be performed to diagnose autoimmune pancreatitis; recognize, diagnose, and describe possible other organ involvement in patients with IgG4-related autoimmune pancreatitis; and select the most appropriate test in the evaluation of suspected exocrine pancreatic insufficiency. BACKGROUND & AIMS:Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse. METHODS:Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS:Thirty-six studies met the inclusion criteria for meta-analysis. The median follow-up time was 40.8 months. Fifty-two percent of patients were classified as having type 1 AIP. The pooled estimate of relapse rate was 33% (95% CI, 30%-37%). A higher proportion of patients with type 1 AIP had a relapse compared with patients with type 2 AIP (37.5% vs 15.9%; P < .001). We found significant heterogeneity among studies (P < .01). Long-term maintenance therapy with steroids and study quality were associated independently with AIP relapse, after we adjusted for year of publication by multivariate meta-regression. CONCLUSIONS:In a systematic review and meta-analysis, we found that a large proportion of patients with AIP treated successfully with steroid induction therapy had a relapse (33%)-particularly patients with type 1 AIP (37%). Maintenance steroid therapy lasting longer than 1 year could reduce risk of relapse. However, the data characterizing relapse rates are of limited quality, indicating the need for randomized controlled trials and new immunosuppressive drugs.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

Background Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. Objectives The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. Methods Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. Results One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. Conclusions In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Background and Objectives: There is no clear evidence of a negative impact of biliary stents on the diagnostic yield of EUS-guided fine-needle biopsy (EUS-FNB) for diagnosing pancreatic head lesions. We aimed to evaluate the association between the presence of biliary stents and the diagnostic accuracy of EUS-FNB. Materials and Methods: A multicenter retrospective study including all jaundiced patients secondary to pancreatic head masses was performed. Patients were divided into two groups according to the presence of a biliary stent placed before EUS-FNB. Pathological results were classified according to the Papanicolaou classification and compared against the final diagnosis. Diagnostic measures in the two groups were compared. Multivariate logistic regression analyses including potential factors affecting EUS-FNB accuracy were performed. Results: Overall, 842 patients were included, 495 (58.8%) without and 347 (41.2%) with biliary stent. A plastic or a metal stent was placed in 217 (62.5%) and 130 (37.5%) cases, respectively. Diagnostic sensitivity and accuracy were significantly higher in patients without biliary stent than in those with stent (91.9% and 92.1% vs . 85.9% and 86.4%, P = 0.010 At multivariate analyses, lesion size (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.02–1.09, P = 0.01) and presence of biliary stent (OR: 0.51, 95% CI: 0.32–0.89, P = 0.01) were independently associated with diagnostic accuracy. In the subgroup of patients with biliary stent, the type of stent (plastic vs . metal) did not impact EUS-FNB yield, whereas the use of larger bore needles enhanced diagnostic accuracy (OR: 2.29, 95% CI: 1.28–4.12, P = 0.005). Conclusions: In this large retrospective study, an indwelling biliary stent negatively impacted the diagnostic accuracy of EUS-FNB. Preferably, EUS-FNB should precede endoscopic retrograde cholangiopancreatography, especially in the case of small tumors.