Citations

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset neurodegenerative brain iron accumulation, which is often recognized after clinical regression. Recent reports have described a few individuals with CRD who screened positive for carnitine palmitoyltransferase-I deficiency by newborn screening (NBS). However, heterogeneous clinical presentations, conflicting biochemical/molecular sequencing of CPT1A, and a lack of metabolic characterization have led to lengthy, costly diagnostic journeys. To address some of these aspects, this investigation retrospectively evaluated NBS acylcarnitine patterns in five CRD cases using Collaborative Laboratory Integrated Reports (CLIR). A total of 25 metabolites/ratios were identified to deviate significantly from reference ranges and were primarily composed of elevated free carnitine and reduced long-chain acylcarnitine levels. While low acylcarnitine concentrations are often not reported due to a lack of lower reference cutoffs, ratios involving these metabolites relative to short-chain acylcarnitines could aid in identifying CRD cases via NBS. When comparing this pattern to CPT-Ia cases, we confirmed a nearly identical acylcarnitine pattern between these, and thus support the need to consider CRD in cases with NBS results suggestive of CPT-Ia. This study is the first case series to characterize NBS patterns in patients with CRD and highlights the unique opportunity for early detection, particularly in cases that are neonatally asymptomatic and have unremarkable confirmatory biochemical results.

Abstract Human visual cortex comprises three interacting streams, but anatomy and correlated activity cannot determine the direction or reliability of interareal influence. Characterizing directional interactions among these streams can reveal the architecture through which activity can propagate across the visual system. Here, we used single-pulse electrical stimulation during intracranial EEG recordings in 17 patients to map directed causal influences among 22 atlas-defined visual cortical areas. The resulting effective connectivity matrix revealed a selective and asymmetric architecture of interareal influence. Feedforward influences from early visual areas to the dorsal, lateral, and ventral streams were more reliable and more prevalent than feedback influences. Cross-stream interactions favored temporal-to-parietal over parietal-to-temporal influence, with higher response reliability and a greater proportion of significant responses among sampled connections. Network-level profiles were consistent with source-like organization in early visual areas and the ventral stream, and integrator-like organization in the dorsal and lateral streams. Independent visual-task data collected in three of the same patients illustrated how stimulation-derived connectivity may relate to functional responses across connected visual regions. These findings reveal a directional architecture for activity propagation across the human visual cortex and provide empirical constraints for biologically grounded models of visual processing.

Abstract Problem The Association of American Medical Colleges has urged actions to promote inclusivity in medical education for historically underrepresented groups. Studies suggest that underrepresentation may be addressed through structured mentorship and workshops at the premedical level and generate interest in less familiar specialties including physical medicine and rehabilitation (PM&R). Approach The authors implemented a novel half-day multi-institutional workshop in spring 2024 featuring physicians and medical students from New York City medical centers. The workshop included structured mentorship and pertinent PM&R-related topics, including disability health and adaptive sports, to which premedical students often have limited exposure. Participants were invited to complete pre- and postworkshop surveys to evaluate the workshop’s impact. The authors collaborated with prehealth chapters of organizations such as the American Medical Women’s Association and the Minority Association of Pre-Medical Students to distribute surveys. Outcomes The preworkshop survey was completed by 147 premedical students, and 81 registered for the workshop. Ultimately, 55 attended the workshop, with 71% completing the postworkshop survey. Most participants had no previous exposure to PM&R (n = 77, 53.5%) and to adaptive sports (n = 116, 80.6%). Furthermore, although 76 (52.8%) had shadowed a physician, only 6 (4.2%) had experience shadowing a PM&R physician. The authors gathered a diverse representation of responses, including those identifying as female (n = 119, 81.0%) and underrepresented in medicine (n = 84, 57.1%). Pre–post comparative analysis showed a statistically significant rise in students’ motivation to apply to medical school (P = .018), along with a statistically significant increase in the interest and understanding of PM&R and adaptive sports (P < .001). Next Steps Future work will focus on developing longitudinal mentorship, improving accessibility through hybrid formats, and expanding the curriculum through interspecialty collaborations to support broader implementation and evaluation.

Abstract Objective: Outpatient parenteral antimicrobial therapy (OPAT) programs continue to evolve with increases in multidisciplinary teams, complex oral antibiotics, long-acting injectable antimicrobials, patients with substance use disorder (SUD) and telehealth. We sought to examine how OPAT programs are currently structured and identify barriers to safe care. Design: Cross-sectional survey. Participants: Physician, pharmacist, and advanced practice providers (APP) Emerging Infections Network (EIN) members. Methods: A survey was conducted between February and March 2025 to assess OPAT structure, expansion to complex outpatient antimicrobial therapy (COpAT), and barriers to safe OPAT care. Results: Of 1639 EIN members, 622 (38%) responded; 75% reported an active role in OPAT. Oversight of patients on COpAT was reported by 59%, and mandatory ID consultation for OPAT by 59%. Eighty-one percent reported >75% of OPAT patients were followed by ID. Most patients received OPAT at home (78%) followed by post-acute care facilities. Outpatient and inpatient ID physicians were responsible for laboratory test monitoring (75% and 30% respectively), while 37% reported a multidisciplinary OPAT team and 32% reported non-specialists. Respondents cited inadequate support in data analysis, administration, information technology and financial support for clinical staff. Common challenges were lack of leadership awareness (51%), difficulty managing patients with SUD (50%) and timely access to laboratory test results (48%). Conclusions: ID physicians were commonly involved in OPAT care, with many programs expanding to COpAT. Several barriers to the safe delivery of OPAT remain, including lack of institutional support, reimbursement and poor communication between stakeholders.

ABSTRACT Negative pressure wound therapy relies on suction, commonly set to −125 mmHg, to evacuate wound fluid, but dysvascular and pressure injuries often respond unpredictably. Newton's third law indicates that negative pressure applies an equal and opposite contact pressure on the wound surface, and this study quantified this contact pressure across dressing types, wound configurations and suction levels. Using a porcine explant model, central and peripheral contact pressure measurements were obtained beneath black reticulated open cell foam, white foam and a novel thermoplastic elastomer dressing across plexiglass, intact skin, shallow and deep wounds under −50, −75 and −125 mmHg. Contact pressure increased proportionally with negative pressure, and multivariable modelling demonstrated that dressing type, wound type and suction level significantly influenced pressure, with negative pressure explaining most of the variance (0.77 and 0.68). Thermoplastic elastomer at −50 mmHg in deep wounds produced the lowest contact pressure, whereas black reticulated open cell foam and white foam at −125 mmHg generated elevated contact pressures of approximately +125 to +195 mmHg. These findings show that black reticulated open cell foam at conventional −125 mmHg can create hypoperfusion conditions, whereas thermoplastic elastomer consistently produces the lowest pressures and may enhance perfusion at lower suction levels, offering a physiologic explanation for improved clinical outcomes in dysvascular and pressure injuries treated with reduced negative pressure.

Abstract Complete response (CR) is an important treatment goal in follicular lymphoma (FL). In relapsed or refractory (R/R) FL, CR rates decline, and disease progression accelerates with each treatment line, with particularly poor outcomes in patients with high‐risk features. Odronextamab, a CD20 × CD3 bispecific antibody, demonstrated deep, durable responses and generally manageable safety in R/R FL in the Phase 2 ELM‐2 study (NCT03888105); we present an exploratory analysis in patients who attained a CR. Patients received intravenous odronextamab with step‐up dosing in Cycle 1, 80 mg weekly in Cycles 2–4, then 160 mg once every 2 weeks until disease progression or other protocol‐defined reason for discontinuation. Patients with CR lasting ≥9 months switched to dosing once every 4 weeks. Overall, 73.4% (94/128) of patients attained CR, 93.6% (88/94) by first response assessment (~Week 12). Median time to CR was 2.7 months (range 2.3–7.9). Median duration of CR was 25.1 months (95% confidence interval [CI] 20.5–not evaluable [NE]) overall and 23.7 months (18.2–NE) in patients with high‐risk features. Overall, 79.5% (35/44) of patients who switched to Q4W dosing maintained CR at last assessment. Patients with low/undetectable CD20 expression by immunohistochemistry (<10% CD20 + cells) or RNA sequencing (messenger RNA < 500 transcripts per million) could achieve CR. Median progression‐free survival was 27.8 months (95% CI 23.0–NE) in patients with CR and not reached in those with undetectable circulating tumor DNA at Week 12. Treatment‐emergent adverse events (TEAEs) led to treatment discontinuation in 16.0% of patients with CR; the most common TEAE was cytokine release syndrome (56.4%). This generally manageable safety profile and the sustainability of CRs support odronextamab as a potential long‐term treatment for heavily pretreated R/R FL.