Citations

ABSTRACT Introduction A novel therapy for heavily pretreated triple‐class–exposed multiple myeloma (TCE MM) is B‐cell maturation antigen (BCMA)‐targeted immunotherapy. While the number of TCE+BCMA‐exposed patients is growing, real‐world data for this group are limited. Methods We present real‐world data from patients with TCE+BCMA‐exposed MM who initiated a subsequent line of therapy (LOT) using a US‐based claims database, Komodo's Healthcare Map. Results We identified 656 TCE+BCMA‐exposed patients; mean age was 66.5 years. Time from MM diagnosis to index was 5.4 years; mean number of prior LOTs was 5.9. The most prevalent prior therapy received within each drug class was daratumumab (98.5%), pomalidomide (86.0%), carfilzomib (85.8%) and belantamab mafodotin (74.5%). A total of 137 different subsequent treatment regimens were observed following TCE+BCMA exposure; the most common regimen was teclistamab (10.4%). The top three targeted agents within the subsequent regimen were carfilzomib (20.2%), pomalidomide (20.1%) and bortezomib (16.6%). Among this TCE+BCMA‐exposed population who received subsequent treatment, the median time to next treatment or death was 6.8 (95% CI, 6.1–7.5) months; time to treatment discontinuation or death was 3.5 (95% CI, 3.2–3.7) months. Conclusion This first real‐world analysis of patients with heavily pretreated TCE+BCMA‐exposed MM shows poor clinical outcomes, frequent therapy retreatment and no standard‐of‐care, highlighting the need for novel treatments. Clinical Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Spinal cord stimulation (SCS) is effective for some pain syndromes, but inappropriate referrals can frustrate patients and misuse resources. This retrospective study reviewed 370 patients referred to a Neuromodulation for Pain Program (NPP) from July 2022 to June 2024. Of these, 241 were deemed appropriate for SCS. The SCS-appropriate group had higher pain intensity, more neuropathic pain, and lower opioid use. Inappropriate referrals were often from family physicians. Key factors associated with inappropriateness included low pain intensity, lack of neuropathic features, and high opioid use. Enhancing referral quality through targeted education may improve care and system efficiency.

A three year old male neutered mixed breed dog presented with a mass on the right carpus and accompanying lameness. A Jamshidi bone biopsy was performed, and histopathology results were consistent with a sarcoma. The dog received oncolytic virotherapy (OV) with vesicular stomatitis virus (VSV) as part of a clinical trial in dogs with osteosarcoma (OSA). Ten days after VSV treatment, the affected limb was amputated, and histopathology was consistent with intramedullary HSA. Considering the new diagnosis, standard doxorubicin chemotherapy was prescribed. With this combination of therapies, the dog had an extended survival of more than seven years and remains alive at the time of writing. This is the first case report documenting OV given in conjunction with the standard of care for canine appendicular HSA.

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.

AbstractBackgroundVEXAS syndrome is an autoinflammatory disease caused by somatic UBA1 mutations on the X chromosome, predominantly affecting men.ObjectiveTo characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes.MethodsWe conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally.ResultsClinical features, age at onset, UBA1 mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional UBA1‐mutated women without typical inflammation are described separately.ConclusionVEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.

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.