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Background: Atopic dermatitis (AD), also known as eczema, is a highly prevalent, chronic inflammatory skin condition. The perioperative outcomes of patients with AD after total knee arthroplasty (TKA) have not been characterized., Methods: Adult patients who underwent TKA were identified in the PearlDiver administrative database. After matching based on patient characteristics, 90-day adverse events and 5-year revisions were compared by multivariable analyses and log-rank tests, respectively. Patients with atopic dermatitis were then stratified by medication status for repeated analysis between resultant subcohorts., Results: Relative to age, sex, and comorbidity matched patients without AD, those with AD had increased odds of aggregated adverse events (OR = 1.36), pneumonia (OR = 2.07), urinary tract infection (UTI, OR = 1.77), and emergency department (ED) visits (OR = 1.70) (P < 0.0001 for each). Those on medication for moderate-to-severe disease had similar associations as the primary analysis. Those not on medications were similar, but not found to have elevated odds of pneumonia. 5-year revisions were not markedly different., Conclusion: TKA patients with AD were at increased odds of pneumonia, UTI, and ED visits, but these risks were not exacerbated by immunosuppressive medications. Surgeons who are managing patients with AD for TKA should be vigilant but reassured by overall similar 5-year survival to revision., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Atopic dermatitis (AD) has been associated with psychiatric comorbidities., Objectives: To characterize the association between AD and bipolar disorder (BPD) with a case-control study of the NIH All of Us Research Program., Methods: Utilizing Systemized Nomenclature of Medicine diagnostic codes, we identified cases of AD. Four age, sex, and race/ethnicity matched controls were found for each case using propensity score matching. After controlling for age, sex, race/ethnicity, income, smoking status, and depression, the relationship between AD and BPD was evaluated using logistic regression., Results: We identified 13,431 AD cases with 53,724 matched controls. Participants with AD were more likely than controls to have BPD (7.8% vs. 4.6%, P<.001). After adjusting for demographics and comorbidities, we observed a significant association (OR 1.49, 95%CI 1.37-1.62, P<.001)., Conclusion: Compared to individuals without AD, individuals with AD have 1.49-fold increased odds of having BPD. Further investigation is needed to further understand this association., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: South Asians (SA) represent the fastest growing US immigrant group, and previous studies have indicated that they face disproportionately high burden of cardiometabolic disease. Cardiometabolic disease manifests as a syndemic or synergistic epidemic encompassing multiple disease clusters influenced by biological, social, and psychological factors stemming from the acculturative process. This process may exacerbate morbidity within immigrant subgroups. Our aim was to identify cardiometabolic risk profiles among SA using indicators of acculturation., Methods: We conducted a latent class analysis on data from the Mediators of Atherosclerosis in South Asians Living in America study ( N =771). A composite cardiometabolic disease outcome was constructed using prevalent hypertension, type 2 diabetes, and body mass index. Acculturation indicators included years living in the US, English language proficiency, dietary behaviors, preservation of cultural traditions, social and neighborhood support, maintenance of social relationships (i.e., friendships), and experiences of discrimination, along with proxies of acculturative stress (i.e., depressive symptomology, trait anxiety and anger). Social and environmental determinants of health, health behaviors, religiosity and spirituality served as covariates to further assess latent class membership., Results: Four cardiometabolic risk profiles emerged: (1) lowest risk [73.8% of sample] characterized by high integration into both SA and US cultures; (2) the modest risk [13.4% of sample], exhibiting elevated levels of mental health distress and experiences of discrimination, and distancing themselves from both cultures; and the (3) moderate risk [8.9% of sample] and (4) highest risk [3.9% of sample], demonstrating greater assimilation into US culture. Compared to the lowest risk profile: the modest risk profile was associated with low-income and conflicting attitudes about religion/spirituality, while the moderate risk profile was characterized by lower income and educational attainment with positive behaviors and attitudes toward religion/spirituality., Conclusion: Findings expand our understanding of immigrant cardiometabolic health as a syndemic issue wherein multiple co-occurring and interacting processes synergize to produce negative outcomes in already at-risk subpopulations. Furthermore, acculturation emerges as a crucial factor in understanding health disparities among immigrant and refugee groups in the US., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Montiel Ishino, Canenguez, Cohen, Kent, Villalobos, Needham, Kandula, Kanaya, Shields and Williams.)

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis. Neuromyelitis optica, systemic lupus erythematous, neurosarcoidosis, infections, and cerebrovascular conditions (eg, hypertension) should be considered in the differential diagnosis of multiple sclerosis for people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia. The diagnosis of multiple sclerosis in people from a minority ethnic or racial background in these regions requires a comprehensive approach that considers the complex interplay of immigration, diagnostic inequity, and social determinants of health., Competing Interests: Declaration of interests LA has received research support from the National Multiple Sclerosis Society, National Institutes of Health National Institute of Neurological Disorders and Stroke, Bristol Myers Squibb Foundation, Race to Erase MS Foundation, and Biogen Idec; is a local Principal Investigator for commercial trials funded by Genentech, Sanofi, and Genzyme; and declares consulting fees from Biogen Idec, Novartis, Genentech, and EMD Serono. DR has received research support from MS Canada, the National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, University of Toronto Division of Neurology, and Roche Canada; and has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Horizon Therapeutics, Novartis, Roche, and Sanofi Aventis. OC is a member of the data and safety monitoring board for Novartis, has served on one advisory board for Biogen, and has received a speaker honorarium from Merck. DO has received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis; and has received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Genzyme, Janssen, Novartis, and Merck. MM has served on scientific advisory boards for Sanofi, Novartis, and Merck; and received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. VR has received honoraria from the Autonomous University of Barcelona, Roche, Corne Neurosciences, and the Multiple Sclerosis Association of America; and is a consultant (Expert Opinion Program) for Teladoc Health International. DK has served as a consultant for CVS Health. RD has received research support from the UK MS Society, National Multiple Sclerosis Society, BMA Foundation, Horne Family Charitable Foundation, Biogen, and Merck; and has received honoraria for advisory boards and educational activities from Biogen, Novartis, Sandoz, Roche, Janssen, and Merck. MW is a co-investigator for a study funded by Genentech; has received honoraria and consulting fees from Alexion, Biogen Idec, Novartis, Genentech, Horizon Therapeutics, EMD Serono, Octave Biosciences, TG Therapeutics, and Sanofi/Genzyme; and has participated in speakers bureau for Biogen Idec, Genentech, EMD Serono, and TG Therapeutics. RAM is a co-investigator on a study funded in part by Biogen and Roche (no funds to her or her institution). JAC has received personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI; and serves as an Editor for Multiple Sclerosis. BB served as a consultant for Novartis, Roche, and UCB; and is funded by the National Multiple Sclerosis Society and National Institutes of Health for work unrelated to this paper. BH served on scientific advisory boards for Novartis; and has served as a data and safety monitoring board member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; and his institution has received institutional research grants from Roche. BH has received honoraria for counselling for the Gerson Lehrmann Group; and holds part of two patents: (1) the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, and (2) genetic determinants of neutralising antibodies to interferon. SDN reports grants or contracts from Biogen, Roche, Genentech, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; reports personal compensation for consulting for Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and participates on a data safety monitoring board and advisory board for MedDay Pharmaceuticals; and reports support from the Stiff Person Syndrome Research Foundation. AJS reports grant funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Bristol Myers Squibb; is contracted for research with Sanofi, Biogen, Novartis, Actelion, and Genentec; has received personal compensation for consulting from EMD Serono and Octave Bioscience; has received payment or honoraria for lectures for EMD Serono; has been called for expert testimony by The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; participates on a data safety monitoring board for Patient Centered Outcomes Research Institute and Yale University; participates on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is content Chair for the American Academy of Neurology Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. WR3rd has research grant support from the National Institutes of Health and the Veterans Administration; reports honoraria, consulting fees, and support for advisory activities for the Consortium of Multiple Sclerosis Centers, the University of Maryland, the University of Calgary, Temple University, Thomas Jefferson University, the Chan Zuckerberg Initiative, the American Association for Cancer Research, and the Alzheimer's Association of Georgia; and receives compensation for serving as Director of specialty programming for Mediflix. AS and BT declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe., Competing Interests: Declaration of interests JC declares receiving grants or research contracts from Biogen and Merck; personal compensation for consulting from Merck; payment or honoraria for lectures from Biogen, Merck, Bristol Myers Squibb, Novartis, and Roche; and support for attending meetings and travel from Merck. JC is a deputy chair International Medical and Scientific Board of Multiple sclerosis International Federation (MSIF), unpaid; and has received equipment, materials, drugs, medical writing, gifts, or other services from Novartis (Investigator initiated award). AJS declares receiving grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health and Bristol Myers Squibb (investigator initiated award); has done contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech; has received personal compensation for consulting from Emmanuel Merck, Darmstadt, Serono and Octave Bioscience; has received payments or honoraria for lectures from Emmanuel Merck, Darmstadt, Serono; has received expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; is a participant on a Data Safety Monitoring Board for the Patient Centered Research Institute, and Yale University; declares participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is a content Chair for the American Academy of Neurology (AAN) Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. JAC declares personal compensation for consulting from Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an editor of Multiple Sclerosis Journal. BLB is funded by the National Multiple Sclerosis Society, and National Institute of Health; is a consultant for Roche, and Sanofi; and is a Board Director AAN (unpaid). TG has served as a consultant and received compensation from Genentech, Horizon, Sanofi, Alexion, and Greenwich Biosciences. BH declares grants from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; received personal compensation for consulting from Sandoz, Novartis, and GLG consulting; holds patents for antibodies against KIR4·1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralising antibodies to interferon (filed 2010); and participated in a Data Safety and Monitoring Board for Novartis, Allergy Care DSMB, TG Therapeutics, and Polpharma, and Advisory Board for Novartis. HJK declares a research grant from the National Research Foundation of Korea and research support from Aprilbio, UCB, and Eisai; has received consultancy fees from Altos Biologics, AstraZeneca, Biogen, Daewoong, Kaigene, Kolon Life Science, MDimune, Merck Serono, and Roche; declares honoraria for lectures from Alexion, Eisai, GCPharma, Handok, Mitsubishi Tanabe Pharma, and Sanofi Genzyme; has received personal compensation for participation on a Data Safety Monitoring Board from Sanofi-Genzyme; has received compensation as Co-editor for the Multiple Sclerosis Journal and Associate Editor for the Journal of Clinical Neurology; and is a Vice President of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (unpaid). RAM declares grants or contracts from Biogen, Idec, and Roche. FM has received research funding to her institution from Sumaira Foundation, Genentech, Biogen, Horizon Therapeutics, US National Histitute Institute of Health, US Department of State, Foundation Pierre Fabre, and Novartis; has received consulting fees from Alexion, EMD Serono, Genentech, TG Therapeutics, and Horizon Therapeutics; and declares shares of the startup company Brain Capture (not related to the content of this manuscript). SDN declares grants or contracts (paid directly to institution) from Biogen, Roche, Genentech, National MS Society, Department of Defense, and Patient Centered Outcomes Research Institute; has received personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and is a study lead principal investigator for a Roche clinical trial programme. MAS declares personal honoraria for lectures from Roche, Biogen, Cinnagen, NanoAlvand, Merck, Novartis, and Abidi. DKS declares grants or research contracts from CNPq / Brazil 425331/2016–4 and 308636/2019–8, and Brazilian National Council for Scientific and Technological Development; has received investigator initiated awards from TEVA, Merck, and Biogen; has received personal compensation for consulting from Roche, and Alexion; declares personal honoraria for lectures from Roche, Alexion, Horizon, Merck, Americas Health Foundation; and is a member of International Society of Neuroimmunology, International Advisory Board (unpaid), and Academia Brasileira de Neurologia, Educational Committee (unpaid). DS declares a pilot research grant from the National MS Society paid to the Institution; declares receipt of personal honoraria for lecturing from Roche Pharmaceuticals; declares travel support from Roche Pharmaceutical; and is a Committee member and chair of Multiple Sclerosis International Federation (unpaid). AS has received grants or contracts from the Turkish MS Society, Istanbul University-Cerrahpasa Research Support Funds, and The Scientific and Technological Research Council of Türkiye Health Sciences Research Grants; has received consulting fees from Roche, Merck-Serono, Biogen Idec/Gen Pharma of Turkey , Sanofi-Genzyme, Novartis, and Alexion; has received honoraria for lectures from Sanofi-Genzyme, Novartis, TEVA, and Roche; and has received support for attending meetings from Sanofi-Genzyme, Roche, Merck-Serono, and Alexion. KT declares personal consulting fees from Merck and Eisai; declares payment for lectures from Merck, Eisai, Roche, and Terumo Blood and Cell Technology; and is a member of the Organizing Committee Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid). MW has received publication royalties from Springer and Elsevier; has received consultancy honoraria from Icometrix, Imcyse, Novartis, Sanofi, Merck, and Biologix; declares personal compensation for lectures or presentations from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, Icometrix, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; and declares support for attending meetings from Merck-Serono. BGW declares royalties from RSR, Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR , and Oxford University; declares personal consulting fees from Roche, Horizon Therapeutics, Cambridge Pharmaceuticals, and Mitsubishi Tanabe; has received payments for lecture presentations from Roche and Horizon; has a patent planned for NMO-IgG for diagnosis of neuromyelitis optica; and declares participation on a Data Safety Monitoring Board and Advisory borads for Alexion MedImmune/VielaBio/Horizon, and UCB Biosciences. KF declares grants from Ministry of Education, Culture, Sports, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan; has received personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; has received payment or honoraria forlectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; declares participation in an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB; serves as President of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid), President of the Japanese Society of Neuroimmunology (unpaid), is a Board Member of the Japan Multiple Sclerosis Society (unpaid), is a board member of theEuropean Charcot Foundation (unpaid), and is a Member of the International Medical and Scientific Board, MSIF (unpaid). All other authors declared no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration., Methods: In part 2, participants received natalizumab (Tysabri ® ) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire., Results: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified "requires less time in the clinic" as the reason for the SC preference., Conclusion: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration., Clinicaltrials: GOV: NCT03689972. INFOGRAPHIC., (© 2024. The Author(s).)

Spiritual wellbeing is known to be a predictor of increased patient coping in hospital settings. Therefore, access to a valid and reliable measure of spiritual wellbeing amongst general hospital patients is highly recommended. The aim of this study was to investigate the dimensionality, reliability, and validity of the Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale (FACIT-Sp-12) in a heterogeneous cohort of hospital patients. A cross-sectional survey was administered to 897 adult patients across six hospitals in Sydney, Australia. Confirmatory factor analysis for the three-factor FACIT-12-Sp indicated a poor fit, but after removal of Item 12, the three-factor FACIT-11-Sp presented a good fit to the data. Reliability testing indicated acceptable to good internal consistency. Validity was supported by statistically significant differences between patients who considered themselves 'both spiritual and religious' and 'not religious or spiritual'. While some caution should be taken when using the FACIT-Sp due to several limitations, nevertheless, in a general hospital population in Australia, the three-factor FACIT-11-Sp indicated good dimensionality, reliability, and validity., (© 2024. The Author(s).)

Background: Immunologic heterogeneity is known to exist within both eczematous dermatitis and psoriasis; however, selection of molecularly targeted therapies for individual patients generally does assess for or incorporate such information about patient-specific immune changes., Objective: We sought to develop a rapid, non-invasive method for obtaining and analyzing epidermal protein biomarkers from skin and utilize this methodology to dissect immunologic heterogeneity in both psoriasis and eczematous dermatitis., Methods: We optimize and evaluate detergent-based immune profiling system (DIPS) which utilizes a combination of two detergents to solubilize full-thickness epidermis when applied to the skin with an applicator. Downstream proteomic profiling of this material allows high-throughput immunologic characterization of immune biomarkers., Results: DIPS was performed on 43 patients with psoriasis and 27 patients with eczematous dermatitis. This approach was found to be painless, nonscarring, and enabled rapid turnaround from sample collection to data output. We used this approach to accurately differentiate psoriasis and eczema using a limited set of proteins and to identify cases of eczema/psoriasis overlap with non-canonical molecular profiles. Additionally, we measured patient-specific cytokine profiles in eczema that correlated with response to IL-4Rα blockade., Conclusion: DIPS is a promising new non-invasive cutaneous immune profiling approach that can deconvolute immune heterogeneity amongst patients with both psoriasis and eczematous dermatitis., Clinical Implication: DIPS has potential applications in both research and day-to-day dermatologic practice and may help personalize diagnosis and medication selection in patients with inflammatory skin diseases., Capsule Summary: Detergent-based immune profiling system (DIPS), a novel non-invasive approach for molecular evaluation of skin disease, is described and evaluated in psoriasis and eczematous dermatitis.

Study Objectives: We investigated profiles of community support and challenges in relation to insomnia symptoms among the Bhutanese living in the United States., Methods: Using data from the pilot Bhutanese Community of Central Ohio Health Study (N = 495; 51.5% men, 69.8% aged 18-44years), we used latent class analysis to identify distinct profiles of neighborhood social cohesion, social support, and community challenges (e.g., limited access to healthcare services and transportation, crime and safety issues, substance use, intimate partner violence) and their associations with insomnia symptoms. Insomnia symptoms were self-reported as difficulty falling and staying asleep and dichotomized as "not at all" vs. "some to always." Identified classes/profiles were further differentiated by self-reported sociodemographic, socioeconomic, health, acculturative, and discrimination factors., Results: Latent class analysis revealed four distinct classes/profiles. The High Cohesion (class 1) profile (30.1% of sample) had the lowest likelihood of insomnia symptoms at 6.5%, followed by class 2 or High Support (23.6%) with a 15.3% likelihood. Class 3 or High Challenges profile (11.5%) had a moderate likelihood of insomnia symptoms at 49%. Class 4 or the Low Cohesion/Support profile (34.7%) had a 100% likelihood of reporting insomnia symptoms. Class 4 when compared to class 1 was more likely to report cardiometabolic conditions, experiences of everyday discrimination, limited English linguistic proficiency, and not using telehealth., Conclusion: Community social cohesion and support may play an important role in mitigating insomnia symptoms among Bhutanese refugees. Further investigations are warranted., Competing Interests: Declaration of conflicts of interest The authors declare no conflict of interest., (Published by Elsevier Inc.)

Importance: While the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed., Observations: There are unique biological factors in children younger than 18 years and in adults older than age 50 years compared to typical adult-onset MS. These biological differences, particularly immunological and hormonal, may influence the clinical presentation of MS, resilience to neuronal injury, and differential diagnosis. While mimics of MS at the typical age at onset have been described, a comprehensive approach focused on the younger and older ends of the age spectrum has not been previously published., Conclusions and Relevance: An international committee of MS experts in pediatric and adult MS was formed to provide consensus guidance on diagnostic approaches and key clinical and paraclinical red flags for non-MS diagnosis in children and older adults.

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2., Competing Interests: JIC has a Collaborative Research and Development Agreement with Sanofi Pasteur for a clinical trial of a replication-defective herpes simplex virus (HSV) vaccine. DMK has been a consultant for Curevo, MaxVax LLC, and Gilead concerning HSV or varicella-zoster virus infections, has received research funding from Sanofi related HSV vaccines, and has received royalties from his employer from the licensing of institutionally-owned patents concerning HSV vaccine candidates on which he is a co-inventor., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background and Objectives: Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA., Methods: In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity., Results: In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%., Discussion: Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice., Trial Registration Information: ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03-3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35-1.32]; P = .26). These findings underscore the complexity of virus-host interactions and emphasize the need for further investigations into their role in EBV-associated diseases., Competing Interests: Potential conflicts of interest. Z. L. is currently an employee at Merck & Co, Inc, Rahway, New Jersey. The views and opinions expressed in this article do not represent the views and opinions of any public or private entity (e.g. agency, government, organization, institution, or company). All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists., Methods: Two patients with inborn errors of immunity, X- linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T cell (NST) response, B cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant setting (HSCT) before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing., Results: The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in one patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-vs-host-disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T cell compartments which recognized multiple norovirus structural and non-structural viral antigens. T cell responses were minimal during active CNI but detectable after resolution. Mapping of norovirus-specific T cell responses between the patient with DOCK8 and his matched sibling donor were nearly identical. B cell reconstitution or new endogenous antibody production for IgA or IgG were not observed., Conclusion: This report is the first to demonstrate reconstitution of norovirus-specific T cell immunity after HSCT closely temporally aligned with clearance of CNI suggesting that cellular immunity is sufficient for norovirus clearance., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background and Objectives: Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup., Methods: ASCLEPIOS I/II were identical, double-blind, double-dummy, active-controlled, multicenter, phase 3 trials. Participants were randomized (1:1) to receive ofatumumab 20 mg every 4 weeks or teriflunomide 14 mg once daily for up to 30 months. Pooled data were used to determine the efficacy/safety of ofatumumab vs teriflunomide in participants who self-identified as non-Hispanic Black, non-Hispanic Asian, Hispanic/Latino, or non-Hispanic White. Participants who did not self-identify into one of these groups were classified as other/unknown., Results: Of the 1,882 participants, 64 (3.4%) self-identified as non-Hispanic Black, 71 (3.8%) as non-Hispanic Asian, 145 (7.7%) as Hispanic/Latino, and 1,538 (81.7%) as non-Hispanic White. Baseline participant demographics/characteristics were largely balanced across subgroups, aside from minor variations in sex, disease duration, and MRI lesions. From months 0 to 24, the proportion of ofatumumab vs teriflunomide-treated patients achieving NEDA-3 (odds ratio [95% CI]) was as follows: non-Hispanic Black, 33.3% vs 3.4% (15.9 [1.67-151.71; p = 0.0162]); non-Hispanic Asian, 42.9% vs 21.9% (3.18 [0.95-10.59; p = 0.06]); Hispanic/Latino, 36.6% vs 18.6% (3.21 [1.32-7.79; p = 0.01]); and non-Hispanic White, 37.4% vs 16.6% (3.57 [2.73-4.67; p < 0.0001]). Rates of AEs were generally similar between treatment groups and across race/ethnicity subgroups; no new or unexpected safety signals were identified., Discussion: Ofatumumab was associated with greater proportions of NEDA-3 achievement than teriflunomide across race/ethnicity subgroups in the ASCLEPIOS trials. Within each treatment group, the proportion of patients achieving NEDA-3 from months 0 to 24 was similar across the subgroups and overall pooled population. Both ofatumumab and teriflunomide were well tolerated. Future MS trials should include ethnically diverse groups to better inform treatment decisions and improve real-world patient outcomes., Trial Registration Information: ClinicalTrials.gov: NCT02792218 (clinicaltrials.gov/ct2/show/NCT02792218), NCT02792231 (clinicaltrials.gov/ct2/show/NCT02792231). Submission date: June 2, 2016. First enrollment: August 26, 2016., Classification of Evidence: This study provides Class II evidence that among patients aged 18-55 years with RMS, the improvement in NEDA-3 with ofatumumab was comparably better than with teriflunomide among patients self-identified as non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, Hispanic/Latino, and other/unknown.

Competing Interests: Conflicts of interest Dr Feng has served as a consultant for AbbVie. Dr Cohen serves on a data and safety monitoring board for Advarra and has served as a consultant for Novartis and Takeda. Author Sun has no conflicts of interest to declare.

Purpose of Review: Increasing awareness and earlier diagnosis of autoimmune encephalitis (AE) have led to a greater number of patients being cared for longitudinally by neurologists. Although many neurologists are now familiar with the general approach to diagnosis and acute immunosuppression, this review aims to provide neurologists with guidance related to management beyond the acute phase of disease, including long-term immunosuppression, monitoring, potential biomarkers of disease activity, outcome measures, and symptom management., Recent Findings: Observational studies in AE have demonstrated that early diagnosis and treatment is associated with improved neurologic outcomes, particularly in AE with antibodies targeting neuronal cell surface/synaptic proteins. The literature regarding long-term management is evolving. In addition to traditional immunosuppressive approaches, there is emerging use of novel immunosuppressive therapies (ISTs) in case series, and several randomized controlled trials are planned. Novel biomarkers of disease activity and methods to measure outcomes and response to treatment are being explored. Furthermore, it is increasingly recognized that many individuals have chronic symptoms affecting quality of life including seizures, cognitive impairment, fatigue, sleep disorders, and mood disorders, and there are emerging data supporting the use of patient centered outcome measures and multidisciplinary symptom-based care., Summary: This review aims to summarize recent literature and offer a practical approach to long-term management of adult patients with AE through a multidisciplinary approach. We summarize current knowledge on ISTs, potential biomarkers of disease activity, outcome measures, and long-term sequelae. Further research is needed to answer questions regarding optimal IST, biomarker validity, and sequelae of disease., Competing Interests: A.Z. Mahadeen has received fellowship grant funding by the National MS Society, CF-2006-36618; A.K. Carlson has received fellowship funding (Grant 16696-P-FEL) from Biogen and institutional clinical training award (ICT-1805-31154) from the National MS Society, has received research support from Biogen, has served on scientific advisory boards for Sanofi, and has served as a consultant for Vigil Neuro; J.A. Cohen has received personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI and serving as an Editor of Multiple Sclerosis Journal; R. Galioto has no disclosures; J.R. Abbatemarco has served on scientific advisory boards for EMD Serono, Genentech, Horizon, and TG Therapeutics and has received research support from Horizon; A. Kunchok has received compensation for consulting for Genentech, Horizon, EMD Serono, and Alexion. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The optimal treatment approach for low-risk prostate cancer (LRPC) remains controversial. While active surveillance is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study aimed to evaluate the survival outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB)., Methods: We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using the NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local treatment (NLT). Only patients with Charlson-Deyo comorbidity scores of 0 or 1 were included to ensure comparability. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups., Results: After a median follow-up of 70.8 months, 24,545 deaths occurred, resulting in an all-cause mortality rate of 13%. RP demonstrated a survival benefit compared with NLT, particularly in patients younger than 74 years of age. In contrast, radiation treatments (EBRT and PSI) did not improve survival in the younger age groups, except for patients older than 70 years for EBRT and older than 65 years for PSI. Notably, EBRT in patients younger than 65 years was associated with inferior outcomes., Conclusion: This study highlights the differences in survival outcomes among LRPC treatment modalities. RP was associated with improved survival compared to NLT, especially in younger patients. In contrast, EBRT and PSI showed survival benefits primarily in the older age groups. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. These findings emphasize the importance of individualized treatment decisions for LRPC management., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Immune checkpoint inhibitors (ICIs) are effective antitumor agents but are associated with immune-related adverse events. ICI-induced psoriasis commonly presents in patients with a history of psoriasis but may occur de novo, and it has a significant physical and psychosocial impact. ICI-induced and non-ICI-induced psoriasis are likely mediated by similar cytokines, and similar treatments are employed. Topical treatment often suffices, and when needed, several systemic treatments appear to be effective without impacting antitumor response. Development of psoriasis may indicate a superior response to ICIs. Thus, recognition and management of ICI-induced psoriasis is essential to avoid ICI interruption and maximize therapeutic potential., Competing Interests: Disclosure Dr J. Leventhal serves on the advisory boards of La Roche-Posay and Sanofi and Regeneron Pharmaceuticals and receives clinical trial funding from Azitra, Inc and OnQuality. Dr J.M. Cohen serves on a data and safety monitoring board (DSMB) for Advarra Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cytokine blocking therapies have revolutionized the management of psoriasis and atopic dermatitis but can lead to the development of paradoxic psoriasis (PP). Patients treated with biologics should be closely monitored for the development of PP and other paradoxical eruptions (including inflammatory joint disease, inflammatory bowel disease, eczematous eruptions, lupus like eruptions, sarcoidal eruptions, and others) and occasionally the development of cutaneous T-cell lymphoma. Further understanding the immunologic mechanism of these processes will ultimately drive our understanding of and ability to predict and manage PPs., Competing Interests: Disclosure There are no funding sources. M. Abdelghaffar, S. Kottilil, and M.J. Murphy have nothing to disclose. J.M. Cohen serves on a data and safety monitoring board for Advarra and has received consulting fees from Novartis. W. Damsky has received research support from Pfizer, United States, Advanced Cell Diagnostics/Bio-techne, AbbVie, United States, Incyte, United States, and Bristol-Myers Squibb, United States; receives consulting fees from Eli Lilly, TWI Biotechnology, Incyte, Epiarx Diagnostics, Bristol Myers Squibb, and Boehringer Ingelheim; and receives licensing fees from EMD/Millipore/Sigma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience., Methods: This two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes., Conclusion: The results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions., Trial Registration: NCT05660187., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marisa McGinley has received research support from the National Institutes of Health, Novartis, Biogen, and Genentech. She has also received consulting fees from Genentech, EMD Serono, and Octave. Josh Carlson has received research support from the National Institutes of Health and the Institute for Clinical and Economic Review. He has also received consulting fees from Genentech, Pfizer, and Takeda. Jennifer Reihm reports no disclosures. Matthew Plow has received research support from the NIH, American Heart Association, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, Consortium of Multiple Sclerosis Centers, Department of Defence, Seibyl Foundation. Megan Roser reports no disclosures. Nikki Sisodia reports no disclosures. Jeffrey A. Cohen has received personal compensation for consulting for Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiNS Therapeutics, INMune, and Sandoz; and serving as an Editor of Multiple Sclerosis Journal. Anita D. Misra-Hebert has received research support from the Patient-Centered Outcomes Research Institute, National Institutes of Health, Agency for Healthcare Research and Quality, Ohio Department of Medicaid, Bayer, Novo Nordisk and Merck. Ann Lazar has received research support from the PCORI, NIH, DOD, and the University of California Office of the President Historically Black Colleges and University Initiative. She serves on NIH funded Data and Safety Monitoring Board (DMSB). She also receives funding for her role as the Statistical Editor for World Journal of Surgery and International Journal of Radiation Oncology, Biology, Physics. Riley Bove has received research support from NIH, DOD, National Multiple Sclerosis Harry Weaver Award, and from Biogen, Novartis, Eli Lilly and F Hoffman-LaRoche. She has received personal advisory board or consulting fees from EMD Serono, Horizon, Janssen, and TG Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The prevalence of multiple sclerosis (MS) and aging MS patients is increasing worldwide. There is a need to better understand this MS sub-population, which historically is underrepresented in the literature. This narrative review examines the evolving demographics, disease course, and treatments for older adults with MS (OAMS) to address current knowledge gaps and highlight areas critical for future research., Observations: OAMS populations require special consideration by clinicians. Older individuals have different care needs than individuals with adult onset MS who are mid-life or younger. Comorbidities, an aging immune system, increasing neurodegeneration, decreasing neurologic reserve, changing benefit/risk relationship for disease modifying therapies (DMTs), and wellness require special attention to provide holistic comprehensive care. Active areas of research include potential cessation of DMTs and novel disease targets., Conclusions and Relevance: This review highlights both the current knowledge and information gaps in the literature that are critical to understanding and properly managing OAMS. The aims are to inform MS clinicians in their current practice, as well as inspire future studies which are critical to providing quality and evidence-based care for OAMS., (© 2024. The Author(s).)

Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors., Competing Interests: Disclosure J.M. Cohen serves on a data and safety monitoring board for Advarra. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Multidisciplinary clinics (MDCs) provide benefits to patients with amyotrophic lateral sclerosis (ALS) and their caregivers, but MDC visits are information-heavy and can last 4 hours, with patients and caregivers meeting with multiple specialists within each MDC visit. There are questions about the effectiveness of current methods of sharing information from MDCs with patients. Video recordings are a promising new method of sharing information that may allow patients and caregivers to revisit the MDC and remind them of clinical recommendations and conversations., Objective: The objective of this trial is to determine the feasibility and acceptability of sharing information through video recordings of ALS MDC visits with patients and caregivers., Methods: This study was a randomized, controlled pilot trial with 3 months of follow-up from April 2021 to March 2022 in a rural multidisciplinary neurology clinic. We recruited patients with ALS, their caregivers, and their clinicians. Patients and their caregivers were randomized to either receive their normal after-visit summary (treatment as usual) or to receive their normal after-visit summary and a video recording of their MDC visit (video). Each specialist visit had its own recording and was accessible by patients and caregivers using a secure web-based platform called HealthPAL over a 3-month follow-up period. Primary study outcomes were feasibility and acceptability of the video intervention measured by recruitment rate (target: 70%), percentage of participants watching videos (target: 75%), and the Feasibility of Intervention Measure and Acceptability of Intervention Measure (targets: 3/5). We hypothesized that video recording would be feasible and acceptable to patients and their caregivers., Results: Of the 30 patients approached, 24 were recruited, while all caregivers (n=21) and clinicians (n=34) approached were recruited. A total of 144 specialist visits were recorded, approximately 12 specialist visits at a median of one MDC visit per patient. Of the recorded patients, 75% (9/12) viewed videos. High median intervention feasibility (4, SD 0.99) and acceptability (4, SD 1.22) of intervention measures were reported by patients and caregivers in the intervention arm. High median intervention feasibility (5, SD 0.21) and acceptability (4.88, SD 0.4) were reported by clinicians. Of the 24 patients, 50% (n=12) did not complete a 3-month follow-up, primarily due to death (n=10)., Conclusions: Video recording is highly feasible and acceptable for patients, caregivers, and clinicians at a rural ALS clinic. Our level of attrition is a useful benchmark for future studies in MDC populations. Despite high rates of patient death, 1-week assessments highlight the value of recordings for both patients and caregivers., Trial Registration: ClinicalTrials.gov NCT04719403; https://clinicaltrials.gov/study/NCT04719403., (©Reed W R Bratches, Jeffrey Cohen, Elizabeth Carpenter-Song, Lisa Mistler, Paul J Barr. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.06.2024.)

Background: Functional T-cell responses are essential for virus clearance and long-term protection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas certain clinical factors, such as older age and immunocompromise, are associated with worse outcome., Objective: We sought to study the breadth and magnitude of T-cell responses in patients with coronavirus disease 2019 (COVID-19) and in individuals with inborn errors of immunity (IEIs) who had received COVID-19 mRNA vaccine., Methods: Using high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor β repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and healthy controls, we quantified HLA class I- and class II-restricted SARS-CoV-2-specific responses and also identified several HLA allele-clonotype motif associations in patients with COVID-19, including a subcohort of anti-type 1 interferon (IFN-1)-positive patients., Results: Our analysis revealed that elderly patients with COVID-19 with critical disease manifested lower SARS-CoV-2 T-cell clonotype diversity as well as T-cell responses with reduced magnitude, whereas the SARS-CoV-2-specific clonotypes targeted a broad range of HLA class I- and class II-restricted epitopes across the viral proteome. The presence of anti-IFN-I antibodies was associated with certain HLA alleles. Finally, COVID-19 mRNA immunization induced an increase in the breadth of SARS-CoV-2-specific clonotypes in patients with IEIs, including those who had failed to seroconvert., Conclusions: Elderly individuals have impaired capacity to develop broad and sustained T-cell responses after SARS-CoV-2 infection. Genetic factors may play a role in the production of anti-IFN-1 antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEIs., (Published by Elsevier Inc.)

Research investigating the impact of barriers to care on health-related quality of life (HRQoL) among US adults with chronic inflammatory skin diseases (CISDs) is limited. In this study, we utilize multivariable-adjusted logistic regression to analyze the associations between cost barriers (e.g., delaying specialist and mental health care due to cost) and non-cost barriers (e.g., delaying care due to transportation issues and the lack of provider diversity) with HRQoL among US adults with several common CISDs in the National Institutes of Health's All of Us Research Program (AoURP). Among the 19,208 adults with CISDs included in our analysis, the prevalence of poorer HRQoL(i.e., "fair" or "poor" HRQoL) was significantly higher among adults with CISDs who experienced cost (aOR, 2.39;95% CI, 2.10-2.73) and non-cost barriers (aOR, 2.52; 95% CI, 2.20-2.88) than those with CISDs who did not experience those barriers. Since dermatologists are often the only physician caring for patients with CISDs, this study reinforces the critical role dermatologists have in addressing social determinants of health and advocating to reduce cost and non-cost barriers for their patients with CISDs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Herpesviruses establish latent infections, and most reactivate frequently, resulting in symptoms and virus shedding in healthy individuals. In immunocompromised patients, reactivating virus can cause severe disease. Persistent EBV has been associated with several malignancies in both immunocompromised and nonimmunocompromised persons. Reactivation and shedding occur with most herpesviruses, despite potent virus-specific antibodies and T cell immunity as measured in the blood. The licensure of therapeutic vaccines to reduce zoster indicates that effective therapeutic vaccines for other herpesviruses should be feasible. However, varicella-zoster virus is different from other human herpesviruses in that it is generally only shed during varicella and zoster. Unlike prophylactic vaccines, in which the correlate of immunity is antibody function, T cell immunity is the correlate of immunity for the only effective therapeutic herpesvirus vaccine-zoster vaccine. While most studies of therapeutic vaccines have measured immunity in the blood, cellular immunity at the site of reactivation is likely critical for an effective therapeutic vaccine for certain viruses. This Review summarizes the status of therapeutic vaccines for herpes simplex virus, cytomegalovirus, and Epstein-Barr virus and proposes approaches for future development.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.P.M. reports research support from the National Institutes of Health (NIH), Agency for Healthcare Research and Quality (AHRQ), Genentech, Novartis, and Biogen and consulting fees from Genentech and EMD Serono. J.A.C. reports personal compensation for consulting for Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INmune, and Sandoz and serving as an Editor of Multiple Sclerosis Journal.

We present a case of subacute onset progressive encephalomyelopathy in a 77-year-old man with symmetric lateral column signal abnormalities on spinal MRI. We discuss the differential and presumptive final diagnosis along with a review of the postulated disease immunopathogenesis.

Immunization via the respiratory route is predicted to increase the effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate the immunogenicity and protective efficacy of one or two doses of a live-attenuated murine pneumonia virus vector expressing SARS-CoV-2 prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally to male rhesus macaques. A single dose of MPV/S-2P is highly immunogenic, and a second dose increases the magnitude and breadth of the mucosal and systemic anti-S antibody responses and increases levels of dimeric anti-S IgA in the airways. MPV/S-2P also induces S-specific CD4 + and CD8 + T-cells in the airways that differentiate into large populations of tissue-resident memory cells within a month after the boost. One dose induces substantial protection against SARS-CoV-2 challenge, and two doses of MPV/S-2P are fully protective against SARS-CoV-2 challenge virus replication in the airways. A prime/boost immunization with a mucosally-administered live-attenuated MPV vector could thus be highly effective in preventing SARS-CoV-2 infection and replication., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Cognitive bias may lead to medical error, and awareness of cognitive pitfalls is a potential first step to addressing the negative consequences of cognitive bias (see Part 1). For decision-making processes that occur under uncertainty, which encompass most physician decisions, a so-called "adaptive toolbox" is beneficial for good decisions. The adaptive toolbox is inclusive of broad strategies like cultural humility, emotional intelligence, and self-care that help combat implicit bias, negative consequences of affective bias, and optimize cognition. Additionally, the adaptive toolbox includes situational-specific tools such as heuristics, narratives, cognitive forcing functions, and fast and frugal trees. Such tools may mitigate against errors due to cultural, affective, and cognitive bias. Part 2 of this two-part series covers metacognition and cognitive bias in relation to broad and specific strategies aimed at better decision-making., (Copyright © 2024. Published by Elsevier Inc.)

Cognitive bias may lead to diagnostic error in the patient encounter. There are hundreds of different cognitive biases, but certain biases are more likely to affect patient diagnosis and management. As during morbidity and mortality rounds, retrospective evaluation of a given case, with comparison to an optimal diagnosis, can pinpoint errors in judgment and decision-making. The study of cognitive bias also illuminates how we might improve the diagnostic process. In Part 1 of this series, cognitive bias is defined and placed within the background of dual process theory, emotion, heuristics, and the more neutral term judgment and decision-making bias., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Conflicts of interest JMC serves on a data and safety monitoring board (DSMB) for Advarra. The remainder of the authors have no conflicts of interest to declare.

Competing Interests: Conflicts of interest Dr Cohen serves on a data and safety monitoring board (DSMB) for Advarra. The remaining authors have no conflicts of interest to declare.

Competing Interests: Conflicts of interest J.M.C. serves on a data and safety monitoring board for Advarra. W.D. has served as a consultant for AbbVie, Boehringer Ingelheim, CSL Behring, Eli Lilly, EPIARX DIAGNOSTICS, Fresenius Kabi, Pfizer, Sanofi and TWi Biotechnology; he has been provided research support from AbbVie, Advanced Cell Diagnostics/Bio-Techne, Bristol Myers Squibb, Incyte and Pfizer; and he receives licensing fees from EMD/Millipore/Sigma. M.Z.J. declares no conflicts of interest.

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines., Competing Interests: Declaration of interests W.B., N.L.B., K.D., and J.I.C. are named as inventors on a patent application describing mAbs A10 and 4C12 in this paper, which has been filed by the National Institutes of Health., (Published by Elsevier Inc.)

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed the therapeutic landscape of MS through robust efficacy on clinical manifestations and MRI lesion activity, and the currently available anti-CD20 mAb therapies for use in MS are a cornerstone of highly effective disease-modifying treatment. Ocrelizumab is currently the only therapy with regulatory approval for primary progressive MS. There are currently few data regarding the relative efficacy of these therapies, though several clinical trials are ongoing. Safety concerns applicable to this class of therapeutics relate primarily to immunogenicity and mechanism of action, and include infusion-related or injection-related reactions, development of hypogammaglobulinemia (leading to increased infection and malignancy risk), and decreased vaccine response. Exploration of alternative dose/dosing schedules might be an effective strategy for mitigating these risks. Future development of biosimilar medications might make these therapies more readily available. Although anti-CD20 mAb therapies have led to significant improvements in disease outcomes, CNS-penetrant therapies are still needed to more effectively address the compartmentalized inflammation thought to play an important role in disability progression., (© 2024. The Author(s).)