Prophylactic Biosynthetic Retrorectus Mesh Placement During Stoma Reversal Reduces the Rate of Stoma Site Incisional Hernia.

INTRODUCTION: Stoma site incisional hernias (SSIHs) are associated with substantial long-term morbidity, and the rate can be as high as 30% to 40%. Recent efforts using prophylactic mesh reinforcement (PMR) to reduce the development of hernias have shown encouraging outcomes. The objective of this study was to assess the use of prophylactic biosynthetic mesh at the time of stoma reversal on the overall SSIH rate. METHODS: This is an observational retrospective cohort study. A review of 101 consecutive patients who underwent PMR in the retrorectus plane from 2015 to 2020 was compared to 73 consecutive patients who underwent primary stoma closure without mesh from 2011 to 2014. The primary endpoint was the presence of SSIH on clinical examination or computed tomography after ostomy takedown. RESULTS: In total, 174 cases were analyzed with 101 patients in the treatment group (median follow-up 45.2 months) and 73 patients in the control group (median follow-up 43.2 months). There were no major differences in preoperative characteristics between the groups. Fourteen patients developed SSIHs with 1 (1.0%) in the treatment arm and 13 (17.8%) in the control arm (p = 0.001). The majority of stomas were loop ileostomies and end colostomies, and stoma type did not affect hernia rates. On univariate analysis, body mass index (p = 0.029) and chronic kidney disease < 3 (p = 0.003) were independent predictors of hernia formation, while mesh was significantly protective (p = 0.000057). DISCUSSION: PMR with biosynthetic mesh at the time of stoma reversal and closure is an effective procedure to reduce the incidence of SSIHs and does not seem to be associated with an increased risk of complications.

A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.

Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.

Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily.

C1q-like (C1QL) -1, -2, and -3 proteins are encoded by homologous genes that are highly expressed in brain. C1QLs bind to brain-specific angiogenesis inhibitor 3 (BAI3), an adhesion-type G-protein coupled receptor that may regulate dendritic morphology by organizing actin filaments. To begin to understand the function of C1QLs, we determined high-resolution crystal structures of the globular C1q-domains of C1QL1, C1QL2, and C1QL3. Each structure is a trimer, with each protomer forming a jelly-roll fold consisting of 10 ß strands. Moreover, C1QL trimers may assemble into higher-order oligomers similar to adiponectin and contain four Ca(2+)-binding sites along the trimeric symmetry axis, as well as additional surface Ca(2+)-binding sites. Mutation of Ca(2+)-coordinating residues along the trimeric symmetry axis lowered the Ca(2+)-binding affinity and protein stability. Our results reveal unique structural features of C1QLs among C1q/TNF superfamily proteins that may be associated with their specific brain functions.