Citations

BACKGROUND: Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. We aimed to analyze transpulmonary gradients of proteins consumed or elaborated across the lungs to identify mediators of PVD by unbiased proteomics. METHODS: Overall, 21 controls and 160 patients with HF with reduced ejection fraction underwent pulmonary artery catheterization with blood sampling from postcapillary (wedged balloon) and precapillary (unwedged) position to obtain transpulmonary gradients. The samples from controls and HF from the highest (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using the proteomic proximity extension assay (Olink) of 275 proteins. Venous blood concentrations or transpulmonary gradients were analyzed to identify biomarkers or potential mediators of PVD. RESULTS: Comparison of Q1 and Q4 of PVR identified PSP-D (pulmonary surfactant-associated protein D) as a marker of PVD. Examination of gradients across the lungs in high PVR HF revealed significant uptake of 18 proteins, mostly associated with inflammation (chemokines, oncostatin-M, MMP9 [matrix metalloproteinase 9]) or with TGF (transforming growth factor)/activin pathway (GDF2 [growth differentiation factor 2]/BMP9 [bone morphogenic protein 9]), and release of 5 proteins, notably IL (interleukin) 6 and IL33. In contrast, these protein gradients were negligible in controls and low PVR patients with HF. Active pulmonary release of IL6 contributed to systemic elevation of IL6 and correlated with right ventricular function. CONCLUSIONS: The lungs of patients with HF with high PVR display abnormal uptake and release of proinflammatory cytokines from IL6/gp130 family (IL6, IL33, oncostatin-M), along with increased transpulmonary uptake of GDF2/BMP9. The study shows that proteins orchestrating inflammation or pulmonary vessel remodeling in group 1 pulmonary hypertension, are also operating in patients with PVD due to HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06331208.

Background: The COVID-19 pandemic brought profound changes to health care systems worldwide. This study examines the adaptive responses of a sleep medicine practice that successfully pivoted to telemedicine, remote diagnostics, and agile operations, resulting in sustained growth and improved patient accessibility. Methods: We analyzed organizational and cultural elements enabling responsiveness, including telemedicine infrastructure, adaptive leadership, quality-focused processes, and effective communication. Objective outcomes were assessed by analyzing patient demographics, telemedicine visits, and sleep testing patterns during three phases: pre-pandemic (June 1, 2018 to March 8, 2020), acute COVID-19 (March 9, 2020 to April 19, 2020), and post-acute COVID-19 (April 20, 2020 to December 31, 2021). Results: Across 105,199 encounters, monthly sleep medicine visits and testing declined ∼50% during acute COVID-19, but rebounded to surpass baseline in the post-acute phase. Virtual visits increased significantly, replacing many face-to-face encounters. Home sleep apnea test use rose sharply, driven by disposable WatchPAT tests, while polysomnography use decreased. Testing volumes increased overall post-acute compared with pre-pandemic. Patients served during acute and post-acute phases were younger, more often female, non-White, and postgraduate-educated (all p < 0.001). Nonlocal patients increased during the post-acute phase, reflecting telemedicine expansion. Conclusions: Proactive telemedicine investments, adaptive leadership, quality-focused processes, and effective communication enabled this practice to adapt successfully during the pandemic. These resilience strategies provide a model for navigating future health care challenges, underscoring telemedicine and e-health’s critical roles in maintaining care delivery during crises.

Background: Distal radius fractures involving the physis are among the most common upper extremity injuries in children and adolescents. Unlike transitional fractures of the distal tibia, known as Tillaux and triplane fractures, transitional fractures of the distal radius have not been well characterized. This study aims to evaluate Salter-Harris III and IV fractures of the distal radius in the pediatric transitional age population to determine if a characteristic fracture pattern exists analogous to the distal tibia. We hypothesized that pediatric transitional fractures of the distal radius would follow a pattern that would ultimately dictate treatment and predict outcomes. Methods: A retrospective chart review of pediatric patients with transitional fractures of the distal radius at a single institution was performed. Salter-Harris III and IV fractures of the distal radius with CT imaging were included. Two independent reviewers determined the metaphyseal fracture plane and the major intra-articular epiphyseal fracture fragments. Descriptive statistical analysis was performed. Results: Thirty patients who met inclusion criteria made the study cohort. There were 5 Salter-Harris III fractures and 25 Salter-Harris IV fractures. Mean age at the time of injury was 15±1.5 years. The metaphyseal fracture demonstrated a coronal fracture plane in all cases, and 20% had a sagittal plane component. The major epiphyseal fracture fragments were identified as dorsal ulnar corner in 70%, radial column in 43%, volar rim in 30%, and dorsal wall in 17%. Patients were treated with open reduction and internal fixation (N=12, 40%), closed reduction and percutaneous pinning (N=4, 13%), or cast immobilization (N=14, 47%). Most patients (N=24, 80%) did not demonstrate a growth disturbance after treatment. Angular deformity, however, was significantly higher in patients with a primary dorsal ulnar corner epiphyseal fragment (N=4, 19% vs. N=0%, P =0.03). Conclusion: Transitional fractures of the distal radius occurred on average at age 15. The injuries demonstrated a consistent pattern, with a coronal fracture plane in the metaphysis and a dorsal ulnar corner fragment in most epiphyses. The dorsal physis may be the strongest portion of the distal radius at the time of injury, though mechanism of injury may impact patterns as well. Level of Evidence: Level III.

The rapid advancement of nuclear and mitochondrial genomic editing tools has created an urgent need for efficient, nonlethal larval genotyping methods in zebrafish ( Danio rerio ) research. This study optimizes and validates a nondestructive proteinase K digestion method for mitochondrial and nuclear DNA genotyping while characterizing its impact on larval survival and gene expression. Using optimized protocol parameters, we demonstrate successful amplification of different mitochondrial and nuclear genetic loci with consistently high sensitivity. Molecular validation through PCR, restriction fragment length polymorphism analysis, and Sanger sequencing confirmed the specificity and reliability of the extracted DNA. The method successfully detected C-to-T base edits in the mt-tl1 gene introduced using the FusX TALE Base editor system, demonstrating its applicability to gene editing studies. Both 48-well and optimized 96-well formats were used, enabling this approach to be deployed at scale. This optimized method enables researchers to correlate genotypes with phenotypes in longitudinal studies while maintaining specimen viability, particularly valuable for investigating early-onset mitochondrial diseases, and utilizes standard laboratory equipment and reagents, facilitating widespread adoption in zebrafish research while adhering to ethical principles in reducing animal mortality.

The FAITH! (Fostering African-American Improvement in Total Health) Cardiovascular Health and Wellness Program is more than a decade-long community-based participatory research initiative aimed at addressing cardiovascular health disparities among African-Americans in Minnesota. Founded in 2013, the program employs a culturally tailored, community-driven approach by partnering with African-American faith communities to promote cardiovascular health through education, digital health tools, and multilevel interventions targeting the social determinants of health. Grounded in community-based participatory research principles, FAITH! prioritizes equitable academic-community partnerships, co-learning, community capacity building, and shared ownership in all aspects of research and implementation. The program’s exemplary innovations include the NIH-funded FAITH! Trial, a randomized clinical trial, testing a mobile health intervention (the FAITH! App) co-created with the African-American community, and the Techquity by FAITH! study. Techquity by FAITH! evaluates the effectiveness of a culturally relevant, community-informed mHealth intervention supported by a Digital Health Advocate network to improve overall cardiovascular health and digital health literacy. During its evolution, FAITH! has addressed emergent public health crises, including the COVID-19 pandemic, by adapting programming to provide emergency preparedness resources, health education, and vaccine outreach. Key outcomes include sustainable church-based health ministries, increased research participation, and successful translation of research into practice. The program has also contributed to research workforce development by mentoring and training diverse early-career scholars and community leaders in community-based participatory research and cardiovascular health equity research. Lessons learned highlight the transformative impact of community-based participatory research in building trust, facilitating culturally relevant dissemination, and sustaining health equity initiatives. The FAITH! model demonstrates a scalable, community-led strategy for advancing cardiovascular health in underserved populations and provides a blueprint for future initiatives aiming to reduce racial health disparities.

AbstractObjectiveTo evaluate the diagnostic performance of multiparametric MRI (mpMRI), mpMRI combined with PSA density (PSAd) and combined biopsy (CBx) in detecting clinically significant prostate cancer (csPCa) in men undergoing active surveillance, using radical prostatectomy (RP) specimens as the reference standard.Patients and MethodsIn this prospective single‐centre study, 91 patients with low‐risk prostate cancer under active surveillance underwent mpMRI, PSAd measurement, CBx and ultimately RP. mpMRI was reported using PI‐RADS v2.0, and PSAd was dichotomised at 0.12 ng/ml/cm3. Diagnostic accuracy was compared using ISUP grade ≥2 and ≥3 thresholds. Radical prostatectomy pathology served as the reference standard.ResultsFor detecting ISUP ≥3 cancer, mpMRI combined with PSAd achieved the highest sensitivity (93.3%) and negative predictive value (94.4%). CBx demonstrated the highest specificity (88.2%) and overall diagnostic balance (Youden index = 0.348). mpMRI alone showed intermediate performance. Differences in classification between strategies were statistically significant (McNemar p < 0.001).ConclusionsmpMRI combined with PSAd provides high sensitivity and negative predictive value for ruling out aggressive prostate cancer, supporting its use as a non‐invasive triage tool in active surveillance. CBx remains the most specific method for histological confirmation. These strategies should be used complementarily to optimise decision‐making in active surveillance protocols.

Summary We investigated the outcomes of patients with advanced systemic mastocytosis (AdvSM) undergoing allogeneic haematopoietic cell therapy (alloHCT) in the US. Twenty‐seven adult (median age, 58 years) patients with AdvSM received alloHCT from 2014 to 2021. Most patients were white (93%), male (63%) and had systemic mastocytosis (SM) with associated haematological neoplasm (SM‐AHN, 70%), received peripheral blood grafts (89%) and non‐myeloablative regimens. KIT mutation was detected in 14 of the reported 16 patients (87.5%). Post‐transplantation cyclophosphamide (PTCy) was used in approximately 50% of the cohort. Approximately 1 year after alloHCT, median bone marrow mast cell burden decreased from 15% pre‐alloHCT to 1.5% (range 0–8) at 1 year post‐alloHCT. The median serum tryptase decreased from 55 ng/mL (range 3–400 ng/mL) pre‐alloHCT to 18 ng/mL (range 0–481 ng/mL) at 1 year post‐alloHCT. At 1 year, progression‐free survival (PFS) and overall survival (OS) were 59% (95% confidence interval [CI], 41%–77%) and 74% (95% CI, 56%–89%) respectively. In the subset of patients with SM‐AHN, 1‐year PFS and OS were 74% (52%–91%) and 79% (95% CI, 58%–94%) respectively. The cumulative incidence of relapse/progression for the entire population of patients with SM ( n = 27) was 4% (95% CI, 0–14) at 100 days and 15% (95% CI, 4–31) at 1 year. For the subset of patients with AHN, the cumulative incidence was 11% (95% CI, 1–28) at 100 days and 21% (95% CI, 6–42) at 1 year. Relapse/progression was the cause of death in six of 12 patients (5 died of AHN and 1 died of SM progression). Eighteen and nine patients received a KIT inhibitor before alloHCT and after alloHCT respectively. In addition, six patients received a KIT inhibitor for the treatment of relapse/progression of SM after alloHCT. Although it is difficult to delineate the exact effect of alloHCT and KIT inhibitors because of the size of the study in this era, the use of alloHCT and KIT inhibitors pre‐ and post‐ alloHCT is increasing. In the near future, larger studies are required to provide further insights into this subject.

Individuals with obesity and endurance exercise-trained athletes both exhibit excess lipid content in their skeletal muscle compared with healthy, sedentary individuals, yet they experience vastly different health outcomes. Lipids taken up from the circulation contribute to lipid stored in muscle in both populations. Differences in the muscle uptake of plasma non-esterified fatty acids (NEFA) and fatty acids derived from plasma triacylglycerol (TG) between individuals with obesity and endurance-trained athletes have not been systematically examined. In athletes, muscle actively regulates the uptake of TG-derived fatty acids through upregulation of the activity of muscle lipoprotein lipase—the enzyme responsible for the intravascular hydrolysis of TG, a phenomenon evident in the fasting state. In contrast, in individuals with obesity, skeletal muscle functions as a passive recipient of TG-derived fatty acids, an event that becomes quantitively more important when the plasma TG concentrations increase during the postprandial state. Considerable differences in the muscle uptake of plasma NEFA between athletes and individuals with obesity are less evident. These observations indicate mechanistic differences in the regulation of plasma TG-derived fatty acids uptake in muscle between individuals with obesity and endurance-trained athletes in shaping the excess lipid content in their muscles. Moreover, this evidence highlights the need for targeting a reduction in plasma TG in the postprandial state when aiming to attenuate lipid accumulation in muscle in the pathophysiology of obesity.

BACKGROUND Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple seizure types, intellectual disability, and distinctive EEG findings. Deep brain stimulation of the centromedian nucleus (CM-DBS) is an emerging therapy for LGS, but pediatric experience remains limited. OBSERVATIONS The authors report a single-center experience with CM-DBS in 6 children and adolescents (ages 12–18 years) with LGS. One patient experienced infection-related device removal after 2 months. The remaining 5 received sustained stimulation for 2.5–5 years. All 5 showed caregiver-reported improvements in seizure burden and alertness, with corroborating Clinical Global Impression–Improvement scores. Three patients exhibited marked seizure reduction following targeted reprogramming toward a previously identified optimal target of stimulation in the anterolateral CM. Pre- and post-DBS scalp EEG recordings were available in 1 patient and showed a reduced burden of interictal discharges. LESSONS CM-DBS is a promising treatment for pediatric, medically refractory LGS when resective approaches are unsuitable. Benefits were sustained over years. Lead localization and direction of stimulation appear important to optimize clinical benefit. These findings support the feasibility and safety of pediatric CM-DBS and highlight the need for prospective trials incorporating EEG-based outcomes and patient-centered measures including comorbidities and quality of life. Early, network-targeted neuromodulation may improve long-term outcomes. https://thejns.org/doi/10.3171/CASE25478

BACKGROUND Septic facet cysts are a rare phenomenon reported in the literature among immunocompromised hosts and may require operative intervention for appropriate source and symptomatic control. OBSERVATIONS A 70-year-old male with a past medical history of immunoglobulin A lambda smoldering myeloma degenerative lumbar disease who presented with low back and radicular lower extremity pain was found to have a left L4–5 septic facet cyst with extension to the epidural space. Intraoperative cultures were positive for Nocardia species. Staging workup revealed progression to high-risk-profile multiple myeloma. LESSONS Patients with septic facet cysts may require operative intervention for appropriate source control. Nocardia spine infections and septic facet cysts are rare and require investigation of preexisting risk factors and any potential underlying immunocompromise. https://thejns.org/doi/10.3171/CASE25220