Ten-year outcomes following ventral hernia repair: making the case for better post-market surveillance in the USA.

BACKGROUND: We sought to identify the 10-year complication and recurrence rates and associated sociodemographic and operative characteristics associated with non-mesh versus mesh-based ventral hernia repairs (VHRs). METHODS: This was an IRB-approved (2020H0317) retrospective longitudinal study of patients undergoing mesh or non-mesh VHR from 2009-2019 at a single tertiary-care institution. The electronic medical record was used to collect sociodemographic, clinical, and intraoperative details, and early (≤ 30 days) and long-term (> 30-day) postoperative complications. Up to ten-year follow-up was obtained for long-term complications, categorized as: hernia recurrence reoperation (HRR), major complications requiring emergency surgery (MCES) (defined as non-elective operations related to the abdominal wall), and non-recurrence procedural intervention (NRPI) (defined as any procedures related to the abdominal wall, bowel, or mesh). Kaplan-Meier survival curves were obtained for each long-term complication. RESULTS: Of the 645 patients identified, the mean age at index operation was 52.51 ± 13.57 years with 50.70% female. Of the index operations, 21.24% were for a recurrence. Procedure categories included: 57.36% incisional, 37.21% non-incisional umbilical, 8.22% non-incisional epigastric, 3.88% parastomal, 0.93% diastasis recti, and 0.47% Spigelian hernias. Operative approaches included open (n = 383), laparoscopic (n = 267), and robotic (n = 21). Fascial closure (81.55%) and mesh use (66.2%) were performed in the majority of cases. Median follow-up time was 2098 days (interquartile range 1320-2806). The rate of short-term complications was 4.81% for surgical site infections, 15.04% for surgical site occurrences, and 13.64% for other complications. At 10 years, the HRR-free survival probability was 85.26%, MCES-free survival probability was 94.44%, and NRPI-free survival probability was 78.11%. CONCLUSIONS: A high proportion of patients experienced long-term recurrence and complications requiring intervention after index VHR. For many patients, a ventral hernia develops into a chronic medical condition. Improved efforts at post-market surveillance of operative approaches and mesh location and type should be undertaken to help optimize outcomes.

Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.

Major myeloid cell functions from adhesion to migration and phagocytosis are mediated by integrin adhesion complexes, also known as adhesome. The presence of a direct integrin binding partner Kindlin-3 is crucial for these functions, and its lack causes severe immunodeficiency in humans. However, how Kindlin-3 is incorporated into the adhesome and how its function is regulated is poorly understood. In this study, using nuclear magnetic resonance spectroscopy, we show that Kindlin-3 directly interacts with paxillin (PXN) and leupaxin (LPXN) via G43/L47 within its F0 domain. Surprisingly, disruption of Kindlin-3-PXN/LPXN interactions in Raw 264.7 macrophages promoted cell spreading and polarization, resulting in upregulation of both general cell motility and directed cell migration, which is in a drastic contrast to the consequences of Kindlin-3 knockout. Moreover, disruption of Kindlin-3-PXN/LPXN binding promoted the transition from mesenchymal to amoeboid mode of movement as well as augmented phagocytosis. Thus, these novel links between Kindlin-3 and key adhesome members PXN/LPXN limit myeloid cell motility and phagocytosis, thereby providing an important immune regulatory mechanism.