Cholecystitis

ObjectiveTo investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.DesignPopulation based matched cohort study.SettingLinked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.PopulationAdults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling.Main outcome measuresThe main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding.ResultsCompared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).ConclusionsAntipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.

PurposeA systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.MethodsA systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.).ResultsA total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.ConclusionBased on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.

Background/purposeLaparoscopic cholecystectomy is one of the most commonly performed general surgical procedures. Difficult laparoscopic cholecystectomy is associated with increased operative time, hospital stay, complication rates, open conversion, treatment costs, and mortality. This study aimed to provide a comprehensive literature review on difficult laparoscopic cholecystectomy.MethodsA literature search was conducted for articles published in English up to June 2024 using common databases including PubMed/MIDLINE, Web of Science, Google Scholar, and ScienceDirect. Keywords included "safe laparoscopic cholecystectomy", "difficult laparoscopic cholecystectomy", "acute cholecystitis", "prevention of bile duct injuries", "intraoperative cholangiography," "bailout procedure," and "subtotal cholecystectomy". Only clinical trials, systematic reviews/meta-analyses, and review articles were included. Studies involving children, robotic cholecystectomy, single incision laparoscopic cholecystectomy, open cholecystectomy, and cholecystectomy for indications other than gallstone disease were excluded.Results/discussionEmergency laparoscopic cholecystectomy for acute cholecystitis is ideally performed within 72 h of symptom onset, with a maximum window of 7-10 days. Intraoperative cholangiography can help clarify unclear biliary anatomy and detect bile duct injuries. In the "impossible gallbladder", laparoscopic cholecystostomy or gallbladder aspiration may be considered. When dissection of Calot's triangle is deemed hazardous or impossible, the fundus-first approach allows for completion of the procedure with either total cholecystectomy or subtotal cholecystectomy. Subtotal cholecystectomy is effective in preventing bile duct injuries, can be performed laparoscopically, and is currently the best available bailout approach for difficult laparoscopic cholecystectomy.ConclusionDifficult laparoscopic cholecystectomy is a common clinical scenario that requires a judicious approach by experienced surgeons in appropriate settings. When difficult laparoscopic cholecystectomy is encountered, various bailout strategies are available. Currently, subtotal cholecystectomy is likely the most effective bailout approach.

BackgroundUltrasound-guided percutaneous cholecystostomy (US-PC) is widely used in high-risk surgical patients with acute cholecystitis. Still, success and safety rates specific to US guidance are not always distinguished within mixed 'image-guided' series.ObjectiveTo estimate technical success, clinical success, and major complication rates of US-PC.MethodsPrimary studies explicitly reporting US-PC or with separable data were included.Primary outcomestechnical success, clinical success (as defined by the study), and major adverse events (AEs). Single-arm meta-analysis using random-effects (logit, continuity correction); heterogeneity by I2 and prediction interval.ResultsFour eligible single-arm studies for technical success (N = 466). Pooled technical success 99.3% (95%CI 97.8-99.8; I2 = 0%). Three studies (N = 223) reported clinical success: pooled 97.6% (95%CI 83.4-99.7; I2≈64% due to varying definitions). Two studies (N = 293) reported major AEs: pooled 1.7% (95%CI 0.7-4.1; I2 = 0%). Thirty-day mortality is available from one large study (6.2%).ConclusionsIn high-risk patients, US-PC demonstrates very high technical success and low major complication rates; clinical success is high but variably defined across studies. Further direct comparisons and standardized definitions are warranted.