RESUMO
Neutrophils are the most abundant immune cells that first respond to insults in circulation. Although associative evidence suggests that differences in neutrophils may be linked to the sex-specific vulnerability of inflammatory diseases, mechanistic links remain elusive. Here, we identified extensive sex-specific heterogeneity in neutrophil composition under normal and auto-inflammatory conditions at single-cell resolution. Using a combination of single-cell RNA sequencing analysis, neutrophil-specific genetic knockouts and transfer experiments, we discovered dysregulation of two unconventional (interferon-α responsive and T cell regulatory) neutrophil subsets leading to male-biased incidence, severity and poor prognosis of auto-inflammatory Behçet's uveitis. Genome-wide association study (GWAS) and exosome study revealed that male-specific negative effects of both genetic factors and circulating exosomes on unconventional neutrophil subsets contributed to male-specific vulnerability to disease. Collectively, our findings identify sex-specifically distinct neutrophil subsets and highlight unconventional neutrophil subsets as sex-specific therapeutic targets to limit inflammatory diseases.
RESUMO
BACKGROUND: Bile leakage is a common and serious complication of open hepatectomy for the treatment of biliary tract cancer. AIM: To evaluate the incidence, risk factors, and management of bile leakage after open hepatectomy in patients with biliary tract cancer. METHODS: We retrospectively analyzed 120 patients who underwent open hepatectomy for biliary tract cancer from February 2018 to February 2023. Bile leak was defined as bile drainage from the surgical site or drain or the presence of a biloma on imaging. The incidence, severity, timing, location, and treatment of the bile leaks were recorded. The risk factors for bile leakage were analyzed using univariate and multivariate logistic regression analyses. RESULTS: The incidence of bile leak was 16.7% (20/120), and most cases were grade A (75%, 15/20) according to the International Study Group of Liver Surgery classification. The median time of onset was 5 d (range, 1-14 d), and the median duration was 7 d (range, 2-28 d). The most common location of bile leakage was the cut surface of the liver (70%, 14/20), followed by the anastomosis site (25%, 5/20) and the cystic duct stump (5%, 1/20). Most bile leaks were treated conservatively with drainage, antibiotics, and nutritional support (85%, 17/20), whereas some required endoscopic retrograde cholangiopancreatography with stenting (10%, 2/20) or percutaneous transhepatic cholangiography with drainage (5%, 1/20). Risk factors for bile leakage include male sex, hepatocellular carcinoma, major hepatectomy, blood loss, and blood transfusion. CONCLUSION: Bile leakage is a frequent complication of open hepatectomy for biliary tract cancer. However, most cases are mild and can be conservatively managed. Male sex, hepatocellular carcinoma, major hepatectomy, blood loss, and blood transfusion were associated with an increased risk of bile leak.
