T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants.

Pathogenic mitochondrial DNA (mtDNA) single-nucleotide variants are a common cause of adult mitochondrial disease. Levels of some variants decrease with age in blood. Given differing division rates, longevity, and energetic requirements within haematopoietic lineages, we hypothesised that cell-type-specific metabolic requirements drive this decline. We coupled cell-sorting with mtDNA sequencing to investigate mtDNA variant levels within progenitor, myeloid, and lymphoid lineages from 26 individuals harbouring one of two pathogenic mtDNA variants (m.3243A>G and m.8344A>G). For both variants, cells of the T cell lineage show an enhanced decline. High-throughput single-cell analysis revealed that decline is driven by increasing proportions of cells that have cleared the variant, following a hierarchy that follows the current orthodoxy of T cell differentiation and maturation. Furthermore, patients with pathogenic mtDNA variants have a lower proportion of T cells than controls, indicating a key role for mitochondrial function in T cell homeostasis. This work identifies the ability of T cell subtypes to selectively purify their mitochondrial genomes, and identifies pathogenic mtDNA variants as a new means to track blood cell differentiation status.

Opioid Use After Inguinal and Ventral Hernia Repair.

BACKGROUND: Recent data on opioid consumption indicate that patients typically require far less than is prescribed. Prisma Health Upstate Hernia Center adopted standardized postoperative prescribing after hernia repair and began tracking patient-reported opioid utilization. The aim of this study is to evaluate patient opioid use after hernia repair in order to guide future prescribing. METHODS: All patients who underwent primary ventral (umbilical and epigastric), incisional, and inguinal hernia repair between February and May 2019 were reviewed. Patients reported the number of opioid pills taken at their first postoperative visit and documented either in the progress note or in the Americas Hernia Society Quality Collaborative (AHSQC) patient-reported outcomes (PRO) questionnaire. All demographic, operative, and outcomes data were captured prospectively in the AHSQC. Opioid use reported as milligram morphine equivalents (MME). RESULTS: A total of 162 surgeries were performed during the study period, and 107 had patient-reported opioid use for analysis. Inguinal hernia repair was performed in 36 patients, 10 primary ventral hernia repairs, and 61 incisional hernia repairs. No opioid use was reported in 63.9% of inguinal hernias, 60% of primary ventral hernias, and 20% of incisional hernias. Inguinal hernia patients consumed a mean of 10.5 MME, primary ventral patients 11 MME, and incisional hernia patients 78.5 MME. CONCLUSION: Patients require little to no opioid after primary ventral or inguinal hernia repair and opioid-free surgery is feasible. Incisional hernia is more heterogenous, but the majority of patients still required less opioid than previously thought.