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Interleukin 6 Receptor Blockade for Relapse Prevention in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease
Vilaseca, Andreu; Bilodeau, Philippe A; Gakis, Georgios; Savransky, Andrea; Mahler Ferreira Oliveira, Joao; Nguyen, Linda; Hooshmand, Sam I; Satyanarayan, Sammita; Moseley, Carson E; Haley, Leah; Roy-Hewitson, Chantal; Marrodan, Mariano; Casallas, Adriana; Manin, Analisa; Chen, Haiwen; Hoshina, Yoji; Grzezulkowska, Aniela; Carnero Contentti, Edgar; Galleguillos, Lorna; Upchurch, Margaret; Jackson-Tarlton, Caitlin S; Chu-Yueh Guo, Joanne; Fabian, Michelle; Virupakshaiah, Akash; Arrambide, Georgina; Caparó-Zamalloa, César; Paterno, Rafael; Waubant, Emmanuelle; Ordoñez Boschetti, Laura; Correale, Jorge; Villa, Andres M; Banwell, Brenda; Marignier, Romain; Pittock, Sean J; Greenberg, Benjamin; Bennett, Jeffrey L; Cho, Tracey; Clardy, Stacey; Solomon, Andrew J; Kister, Ilya; Zamvil, Scott S; Gelfand, Jeffrey M; Repovic, Pavle; Obeidat, Ahmed Z; Blackburn, Kyle; Tenembaum, Silvia; Chen, John J; Sotirchos, Elias S; Levy, Michael; Flanagan, Eoin P; ,; Murillo, Fabian; Syc-Mazurzek, Stephanie B; Cacciaguerra, Laura; Jiang, Mulan; da Silva Rezende, Nathane Braga; Wingerchuk, Dean M; Horsman, Susan E
IMPORTANCE/UNASSIGNED:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. OBJECTIVE/UNASSIGNED:To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. EXPOSURES/UNASSIGNED:Tocilizumab or satralizumab. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. RESULTS/UNASSIGNED:A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.
PMCID:13366257
PMID: 42440328
ISSN: 2168-6157
CID: 6066382
Single lag screw cephalomedullary nail angle-anatomy mismatch is associated with immediate postoperative malreduction after intertrochanteric hip fracture fixation
Fisher, Nina; Hammond, Benjamin; Lashgari, Alexander; Goldstein, Amelia; Ganta, Abhishek; Egol, Kenneth; Konda, Sanjit
PURPOSE/OBJECTIVE:To determine whether cephalomedullary nail (CMN) angle was associated with malreduction after intertrochanteric (IT) fracture fixation. Secondarily, to explore if CMN angle was associated with fixation failure (FF). METHODS:A retrospective comparative review was conducted of patients ≥ 65 years old with low energy falls and OTA/AO 31-A fractures treated with a CMN from 12/01/2016-06/30/2024 at a single academic institution (four hospitals). The primary outcome was immediate postoperative malreduction (IPM)-the absolute difference between post-fixation neck-shaft angle (NSA) and native contralateral NSA being ≥ 3°. The secondary outcome was FF. Univariate analyses compared IPM between 125° and 130° CMNs. Multivariable regression was performed to determine if CMN angle was associated with IPM, and as an exploratory analysis, FF. RESULTS:A total of 277 patients were included with follow-up of 18.2 ± 15.1 months. The 125° CMN group had significantly greater age, body mass index (BMI), and American Society of Anesthesiologists score (ASA). There was a higher incidence of IPM with 125° CMNs (p = 0.02). Among patients with native NSA ≥ 130°, those treated with a 125° nail had significantly higher IPM incidence (p = 0.01). Mean IPM did not differ by CMN angle. Logistic regression found that BMI (OR 1.06, p = 0.04) and 125° CMN angle (OR 1.82, p = 0.05) were associated with IPM. FF rates were similar between CMN angle groups, but failures had greater varus IPM than non-failures (p = 0.02). In the exploratory FF regression model, CMN angle and varus IPM were not associated with failure, while larger native NSA was associated with FF (OR 1.16, p < 0.001). CONCLUSION/CONCLUSIONS:125° and 130° nails achieved similar mean fracture alignment, yet 125° nails were more frequently associated with varus malreduction, especially with native valgus neck-shaft angles. After adjusting for confounders, higher BMI and 125° nails were associated with malreduction but not with fixation failure.
PMID: 42439991
ISSN: 1432-1068
CID: 6066352
Toward personalized medicine for mal de débarquement syndrome
Maruta, Jun; Cho, Catherine; Yakushin, Sergei B
BACKGROUND/UNASSIGNED:Mal de débarquement syndrome (MdDS) is a chronic vestibular disorder of non-spinning vertigo, with various somatic, cognitive, and affective symptoms. The manifestation of MdDS is often only subjective, and different symptoms are variably emphasized when patients appraise the severity of their illness. The etiology of MdDS remains unclear but may lie in improperly sustained neuroplasticity in the velocity storage mechanism of the central vestibular system. Two broad approaches targeting velocity storage-one focusing on correcting velocity storage's maladapted behavior and the other on attenuating its contribution to higher-order processing-have yielded varying degrees of treatment success. METHODS/UNASSIGNED:We conducted a secondary analysis of data from our recent study contrasting the outcomes of the above two approaches. We examined the variations in individual emphases of separate symptoms by correlating the subjective ratings of overall MdDS severity with those of specific symptoms across time points for each subject. We also explored the possibility that variations in symptom presentation influence the responsiveness to the two approaches of treatment. RESULTS/UNASSIGNED:Many symptoms correlated with the overall severity rating, but even those that showed strong correlation among many subjects, such as dizziness, fatigue, and brain fog, were endorsed variably across subjects. A moderate unfavorable dependence on visual sensitivity was found for the responsiveness to the velocity storage attenuation treatment, which distinguished the two treatment approaches. CONCLUSION/UNASSIGNED:Results provide a glimpse into the complexity of MdDS manifestations. Individual variations in what contributes to their perceived overall symptom severity may aid the choice of treatment approach.
PMCID:13333527
PMID: 42440785
ISSN: 1664-2295
CID: 6066392
Plasticizing Diabetes Care: The Metabolic Threat of Plastic-Associated Endocrine Disruptors and Micro-/Nanoplastics in Clinical Medicine
Sargis, Robert M; Reutrakul, Sirimon; Trasande, Leonardo; Nadal, Angel
PURPOSE OF REVIEW/OBJECTIVE:Diabetes care is characterized by the widespread use of plastics. With plastic-associated endocrine-disrupting chemicals (EDCs) implicated in diabetes pathogenesis, this review examines how medical plastics relate to diabetes and related disorders and proposes interventions to improve the situation. RECENT FINDINGS/RESULTS:Plastic-associated EDCs and micro-/nanoplastics (MNPs) are linked to metabolic dysfunction. Medical care exposes patients to these agents; however, the precise contribution of diabetes care to these exposures and their associated adverse health effects remains poorly defined. Diabetes care is an increasingly important contributor to plastic pollution and climate change, yet inadequate systems exist to mitigate its environmental impact. Plastic-associated EDCs and MNPs remain an underappreciated metabolic health threat. Mitigating the deleterious impacts of plastics on human and planetary health requires concerted actions from manufacturers, scientists, policymakers, professional organizations, healthcare providers, and patients. Doing so has the potential to improve metabolic health and promote health equity.
PMCID:13364795
PMID: 42440155
ISSN: 1539-0829
CID: 6066362
Upstream Overdose Prevention: Why the US Should Pilot a Safer, Regulated Drug Supply
Rife-Pennington, Tessa L; Hill, Katherine; Zagorski, Claire M; Butner, Jenna L; Sue, Kimberly L; Davis, Corey S; Incze, Michael A
The United States overdose crisis is driven in large part by an increasingly unpredictable and contaminated drug supply, including fentanyl and its analogs and emerging adulterants such as xylazine and nitazenes. Drug checking interventions such as fentanyl test strips and Fourier Transform Infrared Spectroscopy are essential for harm reduction, yet they also highlight a central policy failure: they place the burden of safety on people who use drugs (PWUD) and frontline programs after drugs have already entered an unregulated market. We argue for a more pragmatic upstream public health response, authorizing pilots of a safer, regulated drug supply ("safer supply"), broadly defined as legal and regulated access to psychoactive substances or close pharmaceutical alternatives intended to reduce reliance on the unregulated drug market. International experience, particularly models in Switzerland, Canada, and the United Kingdom, demonstrates feasibility and suggests potential benefits, including improved health and social stability, reduced reliance on unregulated supply, and reduced acute care utilization in some settings. For the United States context, we propose a portfolio approach: near-term, healthcare-based pilots leveraging existing controlled-substance infrastructure (eg, opioid treatment programs, clinics, pharmacies, and tech-enabled dispensing) while preserving space for community-governed models with legal protections and longer-horizon, state-regulated pathways. We address predictable concerns (secondary sharing, youth initiation, community impact, mixed population-level findings) and outline guardrails and evaluation strategies that are PWUD-led, nonpunitive, and methodologically rigorous. We conclude with concrete policy actions to authorize pilots, establish legal protections, fund independent evaluation, and scale models that demonstrably reduce harm while integrating with harm reduction and treatment services.
PMID: 42444078
ISSN: 2976-7350
CID: 6066482
Integrating Clinical Decision Support Systems in CKD Management
Cervantes, C Elena; Thiessen Philbrook, Heather; Bitzel, Jack; Patel, Dipal M; Menez, Steven; Srialluri, Nityasree; Sang, Yingying; Scott, John; Jaar, Bernard G; Grams, Morgan E; Parikh, Chirag R
PMCID:13355604
PMID: 42436698
ISSN: 2468-0249
CID: 6066232
Digital and computational innovations for posttraumatic stress disorder: How digital technologies can improve diagnosis, risk stratification, and individualized treatment
Hilberdink, Charlotte E; Huibregtse, Megan E; Hinojosa, Cecilia A; Dean, Grace S; van Zuiden, Mirjam; Schultebraucks, Katharina
Understanding trauma-related psychopathology increasingly requires tools capable of capturing how symptoms and underlying mechanisms unfold across real-world contexts. Traditional assessments, which depend on retrospective recall and intermittent clinical contact, are limited in their ability to reflect the dynamic and context-sensitive processes that shape trauma-related mental health outcomes. Emerging digital health technologies and computational approaches address this gap by enabling the continuous measurement of behavior and physiology, whereas biological markers provide mechanistic insights into processes such as stress-related neuroendocrine, autonomic, immune, and sleep-wake functioning that reflect the biological embedding of trauma over time. This review integrates recent advances in digital and biological measurement in posttraumatic stress disorder (PTSD) and outlines principles for combining these approaches within computational frameworks. We emphasize the importance of grounding digital proxies in established biological theory; modeling intraindividual dynamics rather than relying solely on cross-sectional group differences; and integrating multimodal behavioral, physiological, and contextual data. We further highlight essential considerations for ethical, inclusive, and methodologically rigorous implementation, including privacy-by-design, data quality, and clinical interpretability. Together, these approaches support a more mechanistic, dynamic, and personalized understanding of trauma-related risk and recovery, with the potential to enhance early risk stratification and guide preventive and individualized models of care.
PMID: 42438276
ISSN: 1573-6598
CID: 6066312
Trichophyton indotineae: Rise, Diagnosis, Treatment, and Future Directions
Cox, Victoria R V; Zuluaga, Tatiana; Gupta, Aditya K; Lipner, Shari R; Saunte, Ditte Marie Lindhardt; Nenoff, Pietro; Galili, Eran; Khurana, Ananta; Elewski, Boni; Jabet, Arnaud; Caplan, Avrom S
Dermatophytoses (synonymous with tinea) are superficial fungal infections of the skin, hair, and nails, typically caused by dermatophytes in the genera of Trichophyton and Microsporum. Dermatophyte infections are common and are estimated to affect roughly 20-25% of the global population. Historically, tinea infections have been treated with short courses of topical and/or oral antifungal therapies, however, the last decade has seen increasing antifungal treatment failure. Trichophyton (T.) indotineae (previously termed Trichophyton mentagrophytes-genotype VIII) has emerged as the primary species driving antifungal treatment failure worldwide. Clinically, T. indotineae infection may present as a typical dermatophyte infection, or atypically may mimic eczema, psoriasis, or other inflammatory dermatoses. Patients are often strikingly itchy and may be using topical steroid creams inappropriately in combination with antifungal and antibiotic agents. Terbinafine, once considered a first-line oral agent for tinea infections, often fails against T. indotineae, for which prolonged courses of itraconazole (often at higher than typical dermatophyte dosing) are now regarded as the treatment of choice. Fluconazole and griseofulvin demonstrate limited efficacy. Antifungal susceptibility testing may guide treatment choices but is not well established for dermatophytoses. Dermatologists should be aware of an approach to evaluating and treating refractory dermatophyte infections. Increased awareness among clinicians, including in infectious diseases, primary care, and the emergency room, is also important to facilitate early recognition, appropriate management, and timely referral. Dermatologists may play a key role in promoting antifungal stewardship and educating other clinician groups about emerging dermatophyte infections. In this review, we detail T. indotineae with a focus on clinical presentation, diagnostic confirmation, and treatment.
PMID: 42207393
ISSN: 1179-1888
CID: 6066222
The social environment and cognitive aging over the life course: laying out critical concepts and research gaps
Hicken, Margaret T; DeAngelis, Reed; Rigby, David; Burnside, Lindsey; Adar, Sara; Burgard, Sarah; Davis, Brigette A; Donnelly, Rachel; Finlay, Jessica M; Hajat, Anjum; Lee, Jinkook; Perry, Brea L; Thorpe, Lorna E; Umberson, Debra
The social environment refers to our interpersonal relations, workplaces, and neighborhoods, towns, or cities in which we live. A growing literature indicates that social environments are related to cognitive aging and risk of Alzheimer's disease and related dementias (AD/ADRD). Still, relatively little is known about how social-environmental exposures affect cognitive function over the life course and into older ages. Addressing this limitation, our paper outlines key features of the social environment and recommends priority areas of research on the social environment and cognitive aging. We divide our discussion into three subdomains: social connections, residential context, and work context. We then identify important gaps in the conceptual and empirical literature before outlining avenues for future research to strengthen our understanding of how social-environmental exposures over the life course link with cognitive function and AD/ADRD risk in late life.
PMCID:13358813
PMID: 42439047
ISSN: 1552-5279
CID: 6066322
Treatment-Resistant Fibrosing Alopecia in a Pattern Distribution Showing Clinical Improvement With Home Low-Level Light Therapy [Case Report]
Maas, Derek; Spindler, Archie; Zappi, Isabella; Lo Sicco, Kristen I; Shapiro, Jerry
PMID: 42444065
ISSN: 1346-8138
CID: 6066472