Differentially co-expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease.

BACKGROUND: Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD. METHODS: Forty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype. RESULTS: Abnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density. CONCLUSIONS: Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Health Insurance and Differences in Infant Mortality Rates in the US.

Importance: Health insurance status is associated with differences in access to health care and health outcomes. Therefore, maternal health insurance type may be associated with differences in infant outcomes in the US. Objective: To determine whether, among infants born in the US, maternal private insurance compared with public Medicaid insurance is associated with a lower infant mortality rate (IMR). Design, Setting, and Participants: This cohort study used data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research expanded linked birth and infant death records database from 2017 to 2020. Hospital-born infants from 20 to 42 weeks of gestational age were included if the mother had either private or Medicaid insurance. Infants with congenital anomalies, those without a recorded method of payment, and those without either private insurance or Medicaid were excluded. Data analysis was performed from June 2022 to August 2023. Exposures: Private vs Medicaid insurance. Main Outcomes and Measures: The primary outcome was the IMR. Negative-binomial regression adjusted for race, sex, multiple birth, any maternal pregnancy risk factors (as defined by the CDC), education level, and tobacco use was used to determine the difference in IMR between private and Medicaid insurance. The χ2 or Fisher exact test was used to compare differences in categorical variables between groups. Results: Of the 13 562 625 infants included (6 631 735 girls [48.9%]), 7 327 339 mothers (54.0%) had private insurance and 6 235 286 (46.0%) were insured by Medicaid. Infants born to mothers with private insurance had a lower IMR compared with infants born to those with Medicaid (2.75 vs 5.30 deaths per 1000 live births; adjusted relative risk [aRR], 0.81; 95% CI, 0.69-0.95; P = .009). Those with private insurance had a significantly lower risk of postneonatal mortality (0.81 vs 2.41 deaths per 1000 births; aRR, 0.57; 95% CI, 0.47-0.68; P < .001), low birth weight (aRR, 0.90; 95% CI, 0.85-0.94; P < .001), vaginal breech delivery (aRR, 0.80; 95% CI, 0.67-0.96; P = .02), and preterm birth (aRR, 0.92; 95% CI, 0.88-0.97; P = .002) and a higher probability of first trimester prenatal care (aRR, 1.24; 95% CI, 1.21-1.27; P < .001) compared with those with Medicaid. Conclusions and Relevance: In this cohort study, maternal Medicaid insurance was associated with increased risk of infant mortality at the population level in the US. Novel strategies are needed to improve access to care, quality of care, and outcomes among women and infants enrolled in Medicaid.

Reconstructive Management of Gunshot Wounds to the Frontal Sinus: An Urban Trauma Center's Perspective.

INTRODUCTION: In the last decade, we have seen a steady increase in the incidence of frontal sinus trauma due to gunshot wounds and a decrease in motor vehicle trauma. Penetrating gunshot wounds to the frontal sinus present a unique challenge to the reconstructive surgeon because they require careful consideration of the management principles of plastic surgery. Despite previous reviews on frontal sinus trauma, there are no studies examining the management techniques of frontal sinus fractures due specifically to gunshot wounds. In this study, we aim to retrospectively evaluate the use of a variety of tissue flaps in intervention and associated outcomes. METHODS: A retrospective chart review was completed on all patients with gunshot wound(s) to the frontal sinus from January 2010 to January 2018 at a single institution. The patients were classified based on the fracture pattern (anterior vs posterior table vs both), degree of displacement, presence of nasofrontal outflow tract injury, and evidence of cerebrospinal fluid leak. Patients were then stratified according to the type of reconstruction performed (cranialization, obliteration and need for free flap) and evaluated for major and minor complications after reconstruction. RESULTS: In this study, we present outcome data from 28 cases of frontal sinus trauma due to gunshot wounds. There was a statistically significant difference (P = 0.049) in the type reconstructive strategy employed with each type of flap, with pericranial flaps primarily used in cranialization, temporal grafts were more likely to be used in obliteration, and free flaps were more likely to be used in cranialization. The overall major complication rate was 52% (P = 0.248), with the most common acute major complication was cerebrospinal fluid leak (39%) and major chronic was abscess (23.5%). CONCLUSIONS: This report explores the management of frontal sinus trauma and presents short-term outcomes of treatment for penetrating gunshot wounds at a tertiary referral center.