Trauma to the gallbladder is associated with concurrent injuries to the extra hepatic biliary system: A South African experience.

INTRODUCTION: Gallbladder trauma is a rare injury. This study aimed to describe the significance of these injuries and the appropriate management strategies. METHODS: A retrospective study was undertaken at a major trauma centre in South Africa and included all patients diagnosed with a gallbladder injury between January 2012 and October 2020. RESULTS: A total of 51 cases were included (88% male, mean age: 38 years), with 44 (86%) penetrating trauma cases [28 stab wounds (SW), 16 sustained gunshot wounds (GSW)]. Of the 7 (13%) blunt trauma cases, five were involved in a motor vehicle crash, and two were injured via assault. All patients underwent laparotomy. Full-thickness gallbladder laceration or perforation was the most common type of injury (84%) and all patients with a gallbladder perforation or laceration had a cholecystectomy at index operation. Two out of 5 patients with a gallbladder contusion were managed conservatively without a cholecystectomy and the remaining three had evidence of gallbladder necrosis which were managed with cholecystectomy. Associated extrahepatic bile duct injuries occurred in 4% of cases, and 18 cases (35%) required intensive care unit (ICU) admission. The overall mortality was 8%. CONCLUSION: Gallbladder injury is rare but when encountered implies a significant degree of trauma. Although cholecystectomy is usually definitive, there is an association with other occult extra-hepatic biliary tract injuries. The severity of the associated injuries usually determines patient outcomes.

FKBPs facilitate the termination of spontaneous Ca2+ release in wild-type RyR2 but not CPVT mutant RyR2.

FK506-binding proteins 12.6 (FKBP12.6) and 12 (FKBP12) tightly associate with the cardiac ryanodine receptor (RyR2). Studies suggest that dissociation of FKBP12.6 from mutant forms of RyR2 contributes to store overload-induced Ca(2+) release (SOICR) and Ca(2+)-triggered arrhythmias. However, these findings are controversial. Previous studies focused on the effect of FKBP12.6 on the initiation of SOICR and did not explore changes in the termination of Ca(2+) release. Less is known about FKBP12. We aimed to determine the effect of FKBP12.6 and FKBP12 on the termination of SOICR. Using single-cell imaging, in cells expressing wild-type RyR2, we found that FKBP12.6 and FKBP12 significantly increase the termination threshold of SOICR without changing the activation threshold of SOICR. This effect, dependent on the association of each FKBP with RyR2, reduced the magnitude of Ca(2+) release but had no effect on the propensity for SOICR. In contrast, neither FKBP12.6 nor FKBP12 was able to regulate an arrhythmogenic variant of RyR2, despite a conserved protein interaction. Our results suggest that both FKBP12.6 and FKBP12 play critical roles in regulating RyR2 function by facilitating the termination of SOICR. The inability of FKBPs to mediate a similar effect on the mutant RyR2 represents a novel mechanism by which mutations within RyR2 lead to arrhythmia.