A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling.

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling.

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal (PP) and pericentral (PC) axis. How these mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combined intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We found that PP and PC mitochondria are morphologically and functionally distinct; beta-oxidation was elevated in PP regions, while lipid synthesis was predominant in the PC mitochondria. In addition, comparative phosphoproteomics revealed spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifted mitochondrial phenotypes in the PP and PC regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

Association of Race With Post-operative Complications After Spinal Fusion in Children With Cerebral Palsy.

INTRODUCTION: Neuromuscular scoliosis in children with cerebral palsy (CP) can lead to debilitating difficulties with pain, ambulation, sitting, and respiratory or cardiac compromise. Spinal fusion can halt deformity progression, though the decision to undergo surgery involves an individualized risk-benefit assessment. The purpose of this study was to evaluate whether race is a risk factor for patients with CP to experience post-operative complications after spinal fusion. METHODS: This is a retrospective cohort analysis of a national database. Analyses methods include univariate analyses, multivariate regression models, and other ad-hoc tests. RESULTS: There were 3,081 pediatric patients with CP who underwent spinal fusion. Black patients had an increased risk of experiencing any post-operative complication compared to Caucasians (OR 1.322, 95% CI 1.099-1.590). Both Caucasian(p=0.005) and Black (p<0.001) races were risk factors for experiencing medical complications; Black patients had an increased risk compared to Caucasians (OR 1.373, 95% CI 1.130-1.667). Other races had a greater length of ICU stay than Caucasians (median {Mdn}=3.00 days vs Mdn=2.00, p=0.029), and longer total hospital stays than Caucasian and Black patients (Mdn=9.00 days vs Mdn=6.00 days vs Mdn=6.00 days, p<0.001). CONCLUSION: Race is an independent risk factor for pediatric patients with CP to experience medical complications following spinal fusion surgery, with Black patients having an increased risk compared to Caucasians. Further, other races were found to have significantly longer ICU and total hospital length of stay. This study is the first to present race as a risk factor for children with CP to experience increased post-operative complications following spinal fusion and will be valuable in understanding their individualized peri-operative courses and risks.

Race Is Associated With Risk of Salvage Procedures and Postoperative Complications After Hip Procedures in Children With Cerebral Palsy.

BACKGROUND: Despite the many surgical interventions available for spastic hip dysplasia in children with cerebral palsy, a radical salvage hip procedure may still ultimately be required. The purpose of this study was to assess whether race is an independent risk factor for patients with cerebral palsy to undergo a salvage hip procedure or experience postoperative complications for hip dysplasia treatment. METHODS: This is a retrospective cohort analysis utilizing the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Pediatric database from 2012 to 2019. International Classification of Diseases, 9th and 10th Revisions, Clinical Modifications (ICD-9-CM, ICD-10-CM), and current procedural terminology (CPT) codes were used to identify patients with cerebral palsy undergoing hip procedures for hip dysplasia and to stratify patients into salvage or reconstructive surgeries. RESULTS: There was a total of 3906 patients with cerebral palsy between the ages of 2 and 18 years undergoing a procedure for hip dysplasia, including 1995 (51.1%) White patients, 768 (19.7%) Black patients, and 1143 (29.3%) patients from other races. Both Black ( P =0.044) and White ( P =0.046) races were significantly associated with undergoing a salvage versus a reconstructive hip procedure, with Black patients having an increased risk compared to White patients [adjusted odds ratio (OR) 1.77, confidence interval (CI) 1.02-3.07]. Only Black patients were found to have an increased risk of any postoperative complication compared to White patients, with an adjusted OR of 1.26 (CI 1.02-1.56; P =0.033). Both White ( P =0.017) and black ( P =0.004) races were found to be significantly associated with medical complications, with Black patients having an increased risk (adjusted OR 1.43, CI 1.12-1.84) compared to White patients. There were no significant findings between the race and risk of surgical site complications, unplanned readmissions, or reoperations. CONCLUSION: This study demonstrates that patient race is an independent association for the risk of pediatric patients with cerebral palsy to both undergo a salvage hip procedure and to experience postoperative medical complications, with Black patients having an increased risk compared to White. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

Orthopedic Surgery Residency Program Website Content and Accessibility During the COVID-19 Pandemic: Observational Study.

BACKGROUND: The exceptional competitiveness of the orthopedic surgery specialty, combined with the unclear impact of the COVID-19 pandemic on residency recruitment, has presented significant challenges to applicants and residency program directors. With limited in-person opportunities in the 2020-2021 application cycle, applicants have been pressed to gauge chances and best fit by browsing program websites. OBJECTIVE: The aim of the study was to assess the accessibility and content of accredited orthopedic surgery residency program websites during the COVID-19 pandemic. METHODS: Using the online database of the Electronic Residency Application Service (ERAS), we compiled a list of accredited orthopedic surgery residency programs in the United States. Program websites were evaluated across four domains: program overview, education, research opportunities, and application details. Each website was assessed twice in July 2020, during a period of adjustment to the COVID-19 pandemic, and twice in November 2020, following the October ERAS application deadline. RESULTS: A total of 189 accredited orthopedic surgery residency programs were identified through ERAS. Of these programs, 3 (1.6%) did not have functional website links on ERAS. Data analysis of content in each domain revealed that most websites included program details, a description of the didactic curriculum, and sample rotation schedules. Between the two evaluation periods in July and November 2020, the percentage of program websites containing informative videos and virtual tours rose from 12.2% (23/189) to 48.1% (91/189; P<.001) and from 0.5% (1/189) to 13.2% (25/189; P<.001), respectively. However, the number of programs that included information about a virtual subinternship or virtual interview on their websites did not change. Over the 4-month period, larger residency programs with 5 or more residents were significantly more likely to add a program video (P<.001) or virtual tour (P<.001) to their websites. CONCLUSIONS: Most residency program websites offered program details and an overview of educational and research opportunities; however, few addressed the virtual transition of interviews and subinternships during the COVID-19 pandemic.