Citations

Abstract Bioinformatics methods can be used to quantify mitochondrial DNA copy number from whole genome sequencing (WGS) data. We evaluated mitochondrial DNA copy number from human brain-derived WGS data using the fastMitoCalc tool. 341 Parkinson’s Disease cerebellum samples were compared with 74 age-matched controls from the North American Brain Expression Consortium. Parkinson’s Disease cerebellum had significantly higher mitochondrial DNA copy number compared with controls (P = 4.15e–7), and this effect was reproducible in four of five brain banks when analysis was restricted to each resource that contributed Parkinson’s Disease samples to this genetic dataset. Follow-on analyses of 128 Parkinson’s Disease cerebellum samples and 33 controls that had paired neuropathology data and clinical scores demonstrated a significant increase in mitochondrial DNA copy number with Unified Staging System for Lewy Body disorders stages and Unified Parkinson’s Disease Rating Scale (off meds) motor scores. Analysis of Lewy Body scores from ten brain regions showed cerebellum mitochondrial DNA copy number increased upon pathological infestation of α-synuclein aggregates in the brainstem and limbic system but did not increase after late-stage neocortical involvement. This genetics dataset supports previous observations of cerebellum activation in Parkinson’s Disease and suggests mitochondrial DNA copy number may increase to support this regional activation as a compensatory mechanism to pathology or motor symptoms.

Background: Patients with end-stage heart failure-related cardiogenic shock (HF-CS) are conclusively associated with a poor health-related quality of life (HRQL). Axillary mechanical circulatory support (aMCS), such as the Impella 5.5, is increasingly used in this population and may improve HRQL during hospitalization by providing enhanced left ventricular unloading. We aimed to assess changes in HRQL between admission and two weeks after Impella 5.5 placement in patients with HF-CS, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: We conducted a prospective longitudinal analysis on patients with the Impella 5.5 between May 2023 and July 2023. Participants completed the condensed KCCQ-12 at admission and again two weeks post-implantation. Changes in the scores were evaluated using the Wilcoxon signed-rank test. Results: Fifteen patients were enrolled. The median age was 59 years (50–63), and the median ejection fraction at implantation was 20% (15–30). On admission, most patients reported an overall HRQL of poor-to-fair (46.7%) according to the summary KCCQ-12 score. The median overall summary score increased significantly after Impella 5.5 support (50.52 vs. 28.13, p = 0.005). Symptom frequency (70.83 vs. 43.75, p = 0.009) and quality-of-life (50.00 vs. 12.50, p = 0.023) domains improved significantly, while physical limitation showed a positive trend and social limitation remained unchanged. These HRQL improvements occurred alongside a significant shift toward lower SCAI shock stages, marked increases in cardiac output and cardiac index, and no escalation in vasoactive-inotropic requirements. Conclusions: Impella 5.5 support in HF-CS patients was associated with early and clinically meaningful improvements in HRQL, particularly in symptom frequency and quality of life, during the critical pre-transplant or recovery period. These findings suggest that the Impella 5.5 may provide both physiological and patient-perceived benefits in this high-risk population.

This case describes a 74-year-old woman who developed post-surgical acute respiratory distress syndrome (ARDS) after Photodynamic Bone Stabilization System (PBSS) a balloon rupture with extravasation of approximately 20 mL of monomeric resin. The ARDS likely resulted from 2 possibilities: (1) displacement of fat or tumor embolism from PBSS insertion/inflation, displacement from bioinert monomers, or orthopedic screws; or (2) chemical inflammation/pneumonitis due to intravascular dissemination of bioinert monomeric resin. Though balloon rupture and/or fat embolism is a stated manufacturer risk, (IlluminOss. Accessed May 19, 2025. https://illuminoss.com/uploads/nuggets/60e47f517ee33862a5fcaab8/900356_T.pdf) this is the first published human case report of ARDS as a complication of PBSS balloon rupture.

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management.

Background: Fat grafting is a common procedure in plastic and reconstructive surgery. It is associated with several disadvantages and complications, especially in patients undergoing recurrent procedures. Researchers are exploring the implications of cryopreserving adipose tissue and stem cells in plastic surgery. This article aimed to evaluate whether autologous fatty tissue and adipose-derived stem cells obtained through liposuction can be safely stored via cryopreservation for future surgical use. Methods: A comprehensive literature search was conducted across 3 databases, including PubMed, ScienceDirect, and Ovid MEDLINE, using specific keywords, yielding 75 articles. Studies that were not written in English or conducted in vitro were excluded. Only studies published in English within the last 5 years, and focusing on the use of cryopreservation of adipose tissue, were included. After review, a total of 22 articles met the inclusion criteria and were analyzed. Results: Cryopreserving adipose tissue and adipose-derived stem cells shows great potential in plastic surgery. Patient factors such as harvesting site, age, and obesity significantly impact the yield. The highest yield was obtained by harvesting from the abdomen and thigh. Additionally, cryopreservation requires cryoprotective agents, among which a combination of dimethyl sulfoxide and human serum albumin was most effective. Despite the advancement in cryoprotective agents, thawing adipose tissue results in cell death and impaired extracellular matrix integrity. However, cryopreserved stromal vascular fraction gel demonstrated fewer complications and better retention. Conclusions: The cryopreservation of adipose tissue and stromal vascular fraction gel demonstrates promising advancements for future applications in plastic surgery and regenerative medicine.

Introduction: Mitral valve transcatheter edge-to-edge repair (M-TEER) has emerged as a minimally invasive option for high-risk surgical candidates with severe and symptomatic mitral regurgitation (MR), but post-procedure residual mitral valve (MV) dysfunction remains a significant concern. This study evaluates the clinical utility of combining artificial intelligence applied to electrocardiograms (ECG-AI) for diastolic dysfunction (DD) grading and the echocardiography-derived velocity time integral of the MV and left ventricular outflow tract ratio (VTIMV/LVOT) in predicting prognosis in patients post-M-TEER. Methods: A retrospective analysis of patients who underwent M-TEER between 2014 and 2021 was conducted. Patients were categorized based on VTIMV/LVOT and ECG-AI scores into three groups: both normal parameters, either abnormal parameter, or both abnormal parameters to compare outcomes (mortality, major adverse cardiovascular events [MACE], and the need for subsequent MV reintervention) using Kaplan–Meier analysis, multivariable Cox regression models, and net reclassification improvement. Results: Overall, 250 patients were included; the median age was 79.5 (IQR: 73.1, 84.6) and 66.4% were male. The combined abnormal VTIMV/LVOT (≥2.5) and ECG-AI score for DD (>1) was associated with higher risk of one-year mortality (adjusted HR: 4.56 [1.04–19.89], p = 0.044) and MACE (adjusted HR: 3.72 [1.09–12.72], p = 0.037) compared to patients with both normal parameters. Conclusions: This study highlights the potential additive value of integrating VTIMV/LVOT and ECG-AI scores as a prognostic tool for a personalized approach to the post-operative evaluation and risk stratification in M-TEER patients.

BACKGROUND AND OBJECTIVES: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS: The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2–4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION: VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

Objective Vacuoles E1 enzyme X‐linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality. Methods Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS. To address this gap, we formed an international multidisciplinary panel of VEXAS experts. Results Through formalized meetings and a voting process, the group developed consensus clinical guidance considerations for the management of VEXAS. These considerations offer practical advice on several key topics: (1) clinical features of VEXAS, (2) UBA1 screening methods, (3) the diagnosis of myelodysplastic syndromes (MDSs) in patients with VEXAS, and (4) prognosis and management. The aim is to provide expert guidance on which patients to test, how to test for VEXAS, how to approach MDS in the context of VEXAS, and considerations for management. Conclusion This work marks the first formal international consensus guidance for VEXAS and is intended to be used as a resource for clinicians seeking to understand the disease and its management.