Sex differences in gallstone formation involve the gut microbiota, but the specific mediating mechanisms remain unclear. This study established gallstone and pseudo-germ-free mouse models and found that male mice maintained higher gut microbiota diversity, whereas females showed an increased Firmicutes/Bacteroidota ratio, with enrichment of Clostridium_sensu_stricto_13 and Lactobacillus. This shift led to increased production of toxic secondary bile acids-deoxycholic acid and lithocholic acid-resulting in elevated bile hydrophobicity and higher cholesterol saturation, which significantly increased gallstone susceptibility in females. Following antibiotic-induced microbiota depletion, male mice exhibited higher levels of glycodeoxycholic acid and taurodeoxycholic acid, along with reduced hepatic Cyp7a1 expression. These changes promoted cholesterol absorption and impaired bile acid synthesis, thereby increasing gallstone risk in males compared to females. Gut microbiota eradication further revealed that hepatic Abcc4, Sult2a5, Slco1a1, and Slco1a4 are regulated not only by sex hormones but also exhibit sex-specific responses to microbial modulation. Collectively, these results highlight gut microbiota-mediated bile acid metabolism as a key modifiable driver of sex differences in gallstone formation under a lithogenic diet.

A 37-year-old woman underwent laparoscopic bailout subtotal cholecystectomy at a county hospital on December 20, 2025, for acute cholecystitis with cholelithiasis. Dense Calot's triangle adhesions prevented safe ductal exposure. Suspected cystic-duct impaction prevented intraoperative cholangioscopic entry; the remnant was sutured (no clip/stapler documented), and no formal intraoperative cholangiography was performed. MRCP showed a long, low-inserting cystic duct, a 6-mm confluence calculus and upstream biliary dilatation. Tissue friability and persistent obstruction may have contributed to the subsequent leak.

BackgroundCompetition for urgent and emergent operating-room access is a significant challenge in many hospitals. Evidence-based benchmarks for early intervention are well established for emergencies like acute appendicitis or hip fracture. In contrast, laparoscopic cholecystectomy for acute cholecystitis or symptomatic cholelithiasis is often delayed. The purpose of this study was to evaluate the clinical and economic impact of delays in laparoscopic cholecystectomy across the US.MethodsThe Nationwide Readmissions Database was queried for patients aged ≥18 years admitted between 2021 and 2022 undergoing urgent or emergent laparoscopic cholecystectomy. Patients were stratified based on operative timing (<3 vs ≥ 3 days). The primary outcome was 30-day readmission. Secondary outcomes included VTE, SSI, and total cost. Propensity score matching (1:1) was performed using 46 covariates. Linear regression assessed the cost associated with each additional hospital day prior to surgery, with a subgroup analysis of safety-net hospitals.ResultsAmong 136,893 patients, 24,496 (17.9%) experienced delayed laparoscopic cholecystectomy. After matching (n = 48,992), delays were associated with increased odds of readmission (9.5%; OR 1.22 [1.15-1.29], P < 0.001) and VTE (1.5%; OR 1.51 [1.30-1.77], P < 0.001). SSI (0.2%) was not significantly different. The mean total cost was $25,957 ± $21,609 for delayed patients vs $20,784 ± $20,027 for early surgery. Linear regression revealed an incremental cost of $1,695 per additional hospital day prior to surgery, rising to $2071 per day in safety-net hospitals (P < 0.001).DiscussionDelays in laparoscopic cholecystectomy have significant clinical and economic impacts, underscoring the urgent need for national benchmarks to standardize operative timing and reduce disparities for patients in safety-net hospitals.

Hemolytic anemias in childhood comprise a heterogeneous group of hereditary and acquired diseases that may be associated with liver involvement through multiple mechanisms. Chronic hemolysis leads to a sustained increase in unconjugated bilirubin, with a risk of pigmentary cholelithiasis; ineffective erythropoiesis and repeated transfusions contribute to iron overload and the development of chronic liver disease. In certain conditions, such as sickle cell anemia, vaso-occlusive events can cause acute and chronic liver damage. Furthermore, there are well-documented associations between autoimmune hemolytic anemias and immune-mediated liver diseases. This review analyzes the main types of hemolytic anemia associated with liver disease in children, including thalassemias, hereditary spherocytosis and elliptocytosis, sickle cell anemia, pyruvate kinase deficiency, and autoimmune hemolytic anemias. The review describes pathophysiological mechanisms, clinical and biochemical manifestations, diagnosis, treatment, and follow-up. Early recognition of liver involvement allows for optimized treatment and the prevention of potentially serious complications.

Bouveret's syndrome, a rare cholelithiasis complication (gallstone impaction via cholecystoduodenal fistula causing gastric outlet obstruction), is reported in an 81-year-old male with chronic cholecystitis, coronary heart disease, and left nephrectomy. He presented with spasmodic epigastric pain, nausea, and vomiting of coffee-ground-like gastric contents. Multimodal imaging confirmed the diagnosis, and laparoscopic gallstone extraction was successful.

Background and objectives Cholelithiasis is a commonly encountered biliary disorder in the Asian subcontinent, with a substantial burden observed in the Indian population. A significant proportion of patients admitted with gallbladder stones also present with choledocholithiasis. In individuals with acute calculous cholecystitis who are discharged without surgical intervention, the likelihood of subsequent gallstone-related complications increases progressively over time. The objective of the present study was to evaluate the safety, efficacy, and perioperative outcomes of performing single-session endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) in the same operative setting. This combined approach, although less commonly adopted than the traditional two-session strategy, may provide meaningful benefits in the management of patients with concomitant gallbladder and common bile duct (CBD) stones. Methods A retrospective single-centre review from a tertiary care centre in South India was conducted between June 2014 and June 2024. Patients with gallbladder pathology and concomitant choledocholithiasis were evaluated and scheduled for ERCP and LC in the same session. Results A total of 147 patients were included in the study, with a median age of 49 years and a female predominance. Choledocholithiasis with cholelithiasis was the most common indication in the study. The majority of cases were cannulated within 10 minutes (51%) and in five or fewer attempts (95.9%). Stone extraction was successful in 136 cases (92.5%), with CBD clearance achieved in 130 cases. Open CBD exploration was performed in three cases, and laparoscopic CBD exploration was performed in one case. LC was performed during the same session. Conclusion Under careful patient selection, single-session ERCP plus LC will not only save time but also avoid repeated administration of anaesthesia. Therefore, whenever expertise is available, the single-session ERCP and LC strategy can be adopted.

The Chilaiditi sign is a rare radiographic finding characterized by the interposition of the colon between the liver and the right hemidiaphragm. Although typically asymptomatic, it may complicate upper abdominal procedures or mimic pneumoperitoneum. We present a 73-year-old male with symptomatic cholelithiasis whose preoperative computed tomography (CT) imaging incidentally revealed the Chilaiditi sign. Given this finding, the standard umbilical approach for peritoneal access was avoided, and pneumoperitoneum was instead established via left upper quadrant (LUQ) Veress needle insertion to reduce the risk of injury to the interposed colon. Port placement was similarly adjusted away from the right upper quadrant. The procedure was completed without complications, and the patient was discharged on postoperative day four. This case highlights the importance of recognizing the Chilaiditi sign on preoperative imaging, as identification of this anatomic variant can directly influence peritoneal entry technique, trocar positioning, and overall operative safety during laparoscopic procedures.

Drug Combinations offer increased therapeutic efficacy and reduced toxicity compared with single agents. Understanding a drug combination's mechanisms of action (MoA) can provide important insights into therapeutic efficacy. The MoA of many FDA-approved drugs, however, often remains unclear. To decipher the underlying molecular mechanisms of drugs used alone and in combination, we investigated the combination of a statin (atorvastatin or simvastatin) plus ezetimibe using drug-treated RNA-seq transcriptome data from the human hepatocyte-like SOAT2-only-HepG2 cells and from liver biopsies of non-obese normolipidemic patients with uncomplicated cholesterol gallstone disease in the Stockholm Study. We proposed a novel Boolean logical modeling framework to simulate the MoA of a drug combination using fourteen two-variable Boolean models. Thereafter, a pattern matching approach was applied to associate drug-induced differentially expressed genes with the idealized differential expression templates derived from Boolean models. We found 1560 and 565 genes differentially expressed in at least one treatment condition in SOAT2-only-HepG2 cells and liver biopsies, respectively. Our analysis revealed both expected and novel combinatorial modes of the statins and ezetimibe. We mapped the downstream genes of each combinatorial mode to the human protein-protein interactome and obtained underlying pathways, which are important for understanding the therapeutic effects of the drug combinations. Functional enrichment and disease-association analyses of the downstream genes also provide critical insights into the additional therapeutic actions of the drugs. Our study demonstrates that drug-induced transcriptomes, integrated with the human interactome, are informative in deciphering the MoA of drug combinations using Boolean logical modeling.