From Elective to Emergent Cholecystectomy: A Single-Center Experience.

BACKGROUND: Symptomatic cholelithiasis is a common disease in which the majority of patients are managed electively. There is an unknown proportion of patients who require emergency surgery for acute cholecystitis in this elective waiting period. Our study aimed to evaluate risk factors for requiring an emergency cholecystectomy during this waiting period. METHODS: This single-center retrospective observational study queried medical records for scheduled elective cholecystectomies from 2017 to 2022. We then evaluated these patients to determine who required emergency intervention via acute cholecystectomy. Patient demographics were analyzed. Patient cohort subgroups were created for patients who waited longer than 60 days and less than 60 days. RESULTS: 1086 patients from 2017 to 2022 were scheduled for an elective cholecystectomy. Of those, 48 required emergency cholecystectomy. Average wait times of those who required emergent cholecystectomy were found to be significantly higher at 60.3 d, compared to 47.3 d for the elective group (P = .03*). Subgroup analysis of patients with >60 d average wait time re-demonstrated significance with 92.1 d and 115.7 d (P = .004) for the elective and emergency subgroups, respectively. >60 d wait time showed increased odds ratio of 1.805 (P = .05) for requiring an emergency cholecystectomy. Logistic regression analysis identified >60 d waiting period (P = .01) and obesity (P = .0001) as predictors of needing emergency surgery. DISCUSSION: Wait time >60 d is associated with an increased risk of emergent cholecystectomy. Obesity was identified as a key risk factor which should be considered for stratifying patients for more urgent surgical intervention.

Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures.

OBJECTIVE: A common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine-induced seizures (PISs) remain unclear. Global M1 mAChR (M1 R) knockout mice are resistant to PISs, implying that M1 R activation disrupts excitation/inhibition balance. Parvalbumin-positive (PV) inhibitory neurons express M1 Rs, participate in cholinergically induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M1 Rs expressed on PV cells contributes to PISs. METHODS: CA1 PV cells in PV-CRE mice were visualized with a floxed YFP or hM3Dq-mCherry adeno-associated virus, or by crossing PV-CRE mice with the RosaYFP reporter line. To eliminate M1 Rs from PV cells, we generated PV-M1 knockout (KO) mice by crossing PV-CRE and floxed M1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200 µm). In behavioral experiments, locomotion and seizure symptoms were recorded in wild-type (WT) or PV-M1 KO mice during PISs. RESULTS: Pilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq-receptor signaling. Pilocarpine-induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV-M1 KO mice. Finally, compared to WT mice, PV-M1 KO mice were associated with reduced severity of PISs. SIGNIFICANCE: Pilocarpine can directly depolarize PV+ cells via M1 R activation, but a subset of these cells progress to DB. Our electrophysiologic and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV-mediated γ-aminobutyric acid (GABA)ergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs.