Citations

Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes. We generated an inducible, muscle-specific SDH knockout mouse that demonstrates lower mitochondrial oxygen consumption, myofiber contractility, and exercise endurance. Respirometry analyses show that in vitro complex I respiration is unaffected by loss of SDH subunit C in muscle mitochondria, which is consistent with the pulmonary emphysema animal data. SDH knockout initially causes succinate accumulation associated with a down-regulated transcriptome but modest proteome effects. Muscle mass, myofiber type composition, and overall body mass constituents remain unaltered in the transgenic mice. Thus, while SDH regulates myofiber respiration in experimental pulmonary emphysema, it does not control muscle mass or other body constituents.

Purpose: To report the use of modified ex vivo renal artery (RA) reconstruction in a patient with 2 small right RAs (RRAs) in anticipation of planned fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysm (TAAA). Case Report: A staged hybrid repair was utilized in a patient with Extent II TAAA involving celiac axis (CA), superior mesenteric artery (SMA), single left RA (LRA), and 2 small (<3 mm) RRAs. The first-stage operation consisted of hepato-renal bypass using modified ex vivo renal reconstruction with single end-to-end anastomosis to both RAs using a saphenous vein graft. A second stage FB-EVAR was performed using patient-specific manufactured stent-graft with 3 fenestrations for the CA, SMA, and LRA 6 weeks later. The patient recovered with no complications. At 4 years, the patient had widely patent hepato-renal bypass and target vessels with normal renal function. Conclusion: The use of adjunctive hybrid procedures may optimize or facilitate FB-EVAR. In this patient, salvage of 2 small RAs was not ideally suited for branch stenting but was possible using modified ex vivo RA reconstruction with preservation of kidney parenchyma and function. Clinical Impact This case report illustrates a hybrid approach to overcome one of the most frequent limitations to total endovascular incorporation of renal arteries, eg small diameter, early bifurcation and multiple vessels. The modified ex vivo technique allows meticulous renal artery reconstruction without the deleterious effect of warm ischemia and without the cumbersome reconstruction of ureter and vein that is needed with traditional on table ex vivo auto transplantation. The technique is used in a minority of cases and adds the morbidity of open approach. Case selection is of paramount importance.

OBJECTIVE Common peroneal (fibular) neuropathy is the most common mononeuropathy of the lower extremity. Despite this, there are surprisingly few studies on the topic, and a knowledge gap remains in the literature. As one attempts to address this knowledge gap, a core outcome set (COS) is needed to guide the planning phases of future studies to allow synthesis and comparability of these studies. The objective of this study was to develop the COS–common peroneal neuropathy (CoPe) using a modified Delphi approach. METHODS A 5-stage approach was used to develop the COS-CoPe: 1) stage 1, consortium development; 2) stage 2, a literature review to identify potential outcome measures; 3) stage 3, a Delphi survey to develop consensus on outcomes for inclusion; 4) stage 4, a Delphi survey to develop definitions; and 5) stage 5, a consensus meeting to finalize COS and definitions. The study followed the COS–STAndards for Development (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-CoPe consisted of 31 data points/outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months. The consensus optimal time points for assessment were preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-CoPe should serve as a minimum set of data that should be collected in all future neurosurgical studies on common peroneal neuropathy. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

OBJECTIVES: This study seeks to evaluate the variability of Medicaid reimbursement and compare it with Medicare reimbursement using the 20 most commonly billed orthopaedic trauma Current Procedural Terminology (CPT) codes nationwide. The authors anticipate significant variability between states and hypothesize that Medicaid payment will be significantly less than Medicare payment. METHODS: The top 20 most common orthopaedic trauma surgery procedural codes were identified from a previous analysis performed by Haglin et al. The Centers for Medicare and Medicaid Services Physician Fee Schedule was used to determine reimbursement rates from Medicare, and state Medicaid fee schedules were used to determine reimbursement rates for Medicaid. State Medicaid rates were compared with their corresponding Medicare rates to determine a dollar difference. In addition, the dollar difference for each CPT code was divided by its respective physician relative value unit. This was used to acknowledge the possible variability in the complexity of orthopaedic procedures and the related physician effort. The Medicare Wage Index was used to adjust Medicaid rates based on the cost of living for the state as well. Coefficients of variation were calculated to represent overall variability in Medicaid and Medicare reimbursement rates. RESULTS: The mean reimbursement rates for Medicaid were lower for all 20 procedures compared with Medicare. On average, Medicaid reimbursed 16.0% less than Medicare and 29.6% less when adjusting for cost of living. MCD reimbursed at a higher rate than MCR for all procedures in only 9 states (Alaska, Arizona, Arkansas, Montana, Nebraska, New Jersey, New Mexico, North Dakota, and South Dakota) while 38 states reimbursed at a lower rate than MCR, on average. The coefficient of variation ranged from 0.24 to 0.34 for the Medicaid unadjusted group and from 0.35 to 0.46 for the Medicare Wage Index–adjusted group. By contrast, the Medicare group was consistent at 0.06 for all 20 procedures. The average dollar difference across the 20 CPT codes for Medicaid reimbursement compared with Medicare reimbursement ranged from −$76.89 to −$225.17, and the dollar difference per relative value unit ranged from −$5.96 to −$15.16. CONCLUSIONS: This study found a high amount of variation between state Medicaid reimbursement rates and average rates that were significantly lower than Medicare reimbursement rates for the top 20 most used orthopaedic trauma CPT codes as identified by Haglin et al. The discrepancy in reimbursement was increased when Medicaid rates were adjusted for state cost of living. LEVEL OF EVIDENCE: Prognostic, Level III. See Instructions for Authors for a complete description of levels of evidence.

AbstractINTRODUCTIONWell‐chosen biomarkers have the potential to increase the efficiency of clinical trials and drug discovery and should show good precision as well as clinical validity.METHODSWe suggest measures that operationalize these criteria and describe a general approach that can be used for inference‐based comparisons of biomarker performance. The methods are applied to measures obtained from structural magnetic resonance imaging (MRI) from individuals with mild dementia (n = 70) or mild cognitive impairment (MCI; n = 303) enrolled in the Alzheimer's Disease Neuroimaging Initiative.RESULTSVentricular volume and hippocampal volume showed the best precision in detecting change over time in both individuals with MCI and with dementia. Differences in clinical validity varied by group.DISCUSSIONThe methodology presented provides a standardized framework for comparison of biomarkers across modalities and across different methods used to generate similar measures and will help in the search for the most promising biomarkers.Highlights A framework for comparison of biomarkers on pre‐defined criteria is presented. Criteria for comparison include precision in capturing change and clinical validity. Ventricular volume has high precision in change for both dementia and mild cognitive impairment (MCI) trials. Imaging measures’ performance in clinical validity varies more for dementia than for MCI.

AbstractPhase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences. Some sequences require the latest hardware and software system upgrades and are continuously rolled out as they become available at each site. The main sequence additions/changes in ADNI4 are: (1) compressed sensing (CS) T1‐weighting, (2) pseudo‐continuous arterial spin labeling (ASL) on all three vendors (GE, Siemens, Philips), (3) multiple‐post‐labeling‐delay ASL, (4) 1 mm3 isotropic 3D fluid‐attenuated inversion recovery, and (5) CS 3D T2‐weighted. ADNI4 aims to help the neuroimaging community extract valuable imaging biomarkers and provide a database to test the impact of advanced imaging strategies on diagnostic accuracy and disease sensitivity among individuals lying on the cognitively normal to impaired spectrum.Highlights A summary of MRI protocols for phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI 4). The design and justification for the ADNI 4 MRI protocols. Compressed sensing and multi‐band advances have been applied to improve scan time. ADNI4 protocols aim to streamline safety screening and therapy monitoring. The ADNI4 database will be a valuable test bed for academic research.

Abstract BACKGROUND Our institution recently transitioned from paravertebral nerve blocks (PVB) to intercostal nerve cryoablation (INC) for pain control following minimally invasive repair of pectus excavatum (MIRPE). This study aimed to determine how INC affected the operative time, length of stay, complication rates, inpatient opioid use, and outpatient prescription of opioids at a single center. METHODS A retrospective review was performed at a single pediatric referral center of all patients who underwent MIRPE between 2018–2023. Patient demographics, operative details, and perioperative course were collected. The use of INC versus PVB was recorded. Univariate analyses were performed using Wilcoxon rank sum tests for continuous variables and chi-squared tests for categorical variables. RESULTS 255 patients were included with a median age of 15 years, median BMI of 18.50 kg/m2, and median Haller index of 4.40. INC was utilized in 41% (105/255), and 59% (150/255) received PVB. The two groups did not differ significantly in BMI, Haller index, or complications, though the INC patients were older by 1 year (15.0 vs 16.0, p = 0.034). INC was associated with an increased operative time (INC: 92 min vs. PVB: 67 min, p < 0.001), decreased length of stay (3 vs. 4 days, p = < 0.001), more than 2-fold decrease in inpatient opioids per day (INC: 16 (MME) vs PVB 41 (MME), p < 0.001), and a four-fold decrease in the amount of opioids prescribed at discharge (INC: 90 MME) vs PVB 390 MME, p < 0.001). CONCLUSION INC after MIRPE significantly decreased both the inpatient opioid utilization and our outpatient prescribing practices while also decreasing our overall length of stay without increasing complications. Level of Evidence: Level III

Abstract Purpose: Early detection of neurofibromatosis type 1 (NF1)–associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. Experimental Design: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. Results: The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration–based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Conclusions: Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.

Metabolic and bariatric surgery (MBS) is the most effective and durable therapeutic intervention for patients with obesity. In recent years, laparoscopic sleeve gastrectomy (SG) has become the most commonly performed primary MBS procedure owing to its technical feasibility and excellent short-term outcomes. Despite these favorable results and perceived advantages, SG is associated with several unique complications. Complications such as a postoperative leak or bleeding have been more commonly observed and reported than others, and their management approaches are well described. However, other complications following SG are far less familiar to surgeons, which may delay recognition and result in poor patient outcomes. Of these complications, we describe splenic injuries; esophageal perforation; staple line malformations; stapling of intraluminal devices; phytobezoar formation; gastro-colic, gastro-pleural and gastro-bronchial fistula; pancreatic leak; and portomesenteric venous thrombosis. It is paramount for surgeons to be aware of these underreported issues and have the resources to learn how to recognize and manage them when they arise. This review aims to describe rare (i.e., reported incidence <1%) and underdescribed complications after SG, focusing on causes, clinical presentation, prevention strategies, and management.

AbstractINTRODUCTIONAge‐related and Alzheimer's disease (AD) dementia–related neurodegeneration impact brain health. While morphometric measures from T1‐weighted scans are established biomarkers, they may be less sensitive to earlier changes. Neurite orientation dispersion and density imaging (NODDI), offering biologically meaningful interpretation of tissue microstructure, may be an advanced brain health biomarker.METHODSWe contrasted regional gray matter NODDI and morphometric evaluations concerning their correlation with (1) age, (2) clinical diagnosis stage, and (3) tau pathology as assessed by AV1451 positron emission tomography.RESULTSOur study hypothesizes that NODDI measures are more sensitive to aging and early AD changes than morphometric measures. One NODDI output, free water fraction (FWF), showed higher sensitivity to age‐related changes, generally better effect sizes in separating mild cognitively impaired from cognitively unimpaired participants, and stronger associations with regional tau deposition than morphometric measures.DISCUSSIONThese findings underscore NODDI's utility in capturing early neurodegenerative changes and enhancing our understanding of aging and AD.Highlights Neurite orientation dispersion and density imaging can serve as an effective brain health biomarker for aging and early Alzheimer's disease (AD). Free water fraction has higher sensitivity to normal brain aging. Free water fraction has stronger associations with early AD and regional tau deposition.