Heightened Epstein-Barr virus immunity and potential cross-reactivities in multiple sclerosis.

BACKGROUND: Epstein-Barr virus (EBV) is a likely prerequisite for multiple sclerosis (MS) but the underlying mechanisms are unknown. We investigated antibody and T cell responses to EBV in persons with MS (pwMS), healthy EBV-seropositive controls (HC) and post-infectious mononucleosis (POST-IM) individuals up to 6 months after disease resolution. The ability of EBV-specific T cell responses to target antigens from the central nervous system (CNS) was also investigated. METHODS: Untreated persons with relapsing-remitting MS, POST-IM individuals and HC were, as far as possible, matched for gender, age and HLA-DRB1*15:01. EBV load was determined by qPCR, and IgG responses to key EBV antigens were determined by ELISA, immunofluorescence and Western blot, and tetanus toxoid antibody responses by multiplex bead array. EBV-specific T cell responses were determined ex vivo by intracellular cytokine staining (ICS) and cross-reactivity of in vitro-expanded responses probed against 9 novel Modified Vaccinia Ankara (MVA) viruses expressing candidate CNS autoantigens. RESULTS: EBV load in peripheral blood mononuclear cells (PBMC) was unchanged in pwMS compared to HC. Serologically, while tetanus toxoid responses were unchanged between groups, IgG responses to EBNA1 and virus capsid antigen (VCA) were significantly elevated (EBNA1 p = 0.0079, VCA p = 0.0298) but, importantly, IgG responses to EBNA2 and the EBNA3 family antigens were also more frequently detected in pwMS (EBNA2 p = 0.042 and EBNA3 p = 0.005). In ex vivo assays, T cell responses to autologous EBV-transformed B cells and to EBNA1 were largely unchanged numerically, but significantly increased IL-2 production was observed in response to certain stimuli in pwMS. EBV-specific polyclonal T cell lines from both MS and HC showed high levels of autoantigen recognition by ICS, and several neuronal proteins emerged as common targets including MOG, MBP, PLP and MOBP. DISCUSSION: Elevated serum EBV-specific antibody responses in the MS group were found to extend beyond EBNA1, suggesting a larger dysregulation of EBV-specific antibody responses than previously recognised. Differences in T cell responses to EBV were more difficult to discern, however stimulating EBV-expanded polyclonal T cell lines with 9 candidate CNS autoantigens revealed a high level of autoreactivity and indicate a far-reaching ability of the virus-induced T cell compartment to damage the CNS.

Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection.

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a abundant extracellular matrix component. HS facilitates fibril formation in vitro, yet how HS impacts fibrillar plaque growth within the brain is unclear. Here we found that prion-bound HS chains are highly sulfated, and that the sulfation is essential for accelerating prion conversion in vitro. Using conditional knockout mice to deplete the HS sulfation enzyme, Ndst1 (N-deacetylase / N-sulfotransferase) from neurons or astrocytes, we investigated how reducing HS sulfation impacts survival and prion aggregate distribution during a prion infection. Neuronal Ndst1-depleted mice survived longer and showed fewer and smaller parenchymal plaques, shorter fibrils, and increased vascular amyloid, consistent with enhanced aggregate transit toward perivascular drainage channels. The prolonged survival was strain-dependent, affecting mice infected with extracellular, plaque-forming, but not membrane bound, prions. Live PET imaging revealed rapid clearance of recombinant prion protein monomers into the CSF of neuronal Ndst1- deficient mice, neuronal, further suggesting that HS sulfate groups hinder transit of extracellular prion protein monomers. Our results directly show how a host cofactor slows the spread of prion protein through the extracellular space and identify an enzyme to target to facilitate aggregate clearance.

Tau seeds occur before earliest Alzheimer's changes and are prevalent across neurodegenerative diseases.

Tau neurofibrillary tangles are a hallmark of Alzheimer's disease neuropathological change. However, it remains largely unclear how distinctive Alzheimer's disease tau seeds (i.e. 3R/4R) correlate with histological indicators of tau accumulation. Furthermore, AD tau co-pathology is thought to influence features and progression of other neurodegenerative diseases including Lewy body disease; yet measurements of different types of tau seeds in the setting of such diseases is an unmet need. Here, we use tau real-time quaking-induced conversion (RT-QuIC) assays to selectively quantitate 3R/4R tau seeds in the frontal lobe which accumulates histologically identifiable tau pathology at late disease stages of AD neuropathologic change. Seed quantitation across a spectrum of neurodegenerative disease cases and controls indicated tau seeding activity can be detected well before accompanying histopathological indication of tau deposits, and even prior to the earliest evidence of Alzheimer's-related tau accumulation anywhere in the brain. In later stages of AD, 3R/4R tau RT-QuIC measures correlated with immunohistochemical tau burden. In addition, Alzheimer's tau seeds occur in the vast majority of cases evaluated here inclusive of primary synucleinopathies, frontotemporal lobar degeneration and even controls albeit at multi-log lower levels than Alzheimer's cases. α-synuclein seeding activity confirmed synucleinopathy cases and further indicated the co-occurrence of α-synuclein seeds in some Alzheimer's disease and primary tauopathy cases. Our analysis indicates that 3R/4R tau seeds in the mid-frontal lobe correlate with the overall Braak stage and Alzheimer's disease neuropathologic change, supporting the quantitative predictive value of tau RT-QuIC assays. Our data also indicate 3R/4R tau seeds are elevated in females compared to males at high (≥ IV) Braak stages. This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer's disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define disease subtypes.

The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies.

BACKGROUND AND PURPOSE: Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection. METHODS: Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13). RESULTS: Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine. CONCLUSION: These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.

How Does Orthopaedic Surgeon Gender Representation Vary by Career Stage, Regional Distribution, and Practice Size? A Large-Database Medicare Study.

BACKGROUND: Orthopaedic surgery has the lowest proportion of women surgeons in practice of any specialty in the United States. Preliminary studies suggest that patients who are treated by physicians of the same race, ethnicity, cultural background, or gender feel more comfortable with their care and may have better outcomes. Therefore, understanding the discrepancies in the diversity of the orthopaedic surgeon workforce is crucial to addressing system-wide healthcare inequities. QUESTIONS/PURPOSES: (1) Does a difference exist in gender representation among practicing orthopaedic surgeons across geographic distributions and years in practice? (2) Does a difference exist in gender representation among practicing orthopaedic surgeons with regard to rural-urban setting, group practice size, and years in practice? METHODS: Orthopaedic surgeons serving Medicare patients in 2017 were identified in the Medicare Physician and Other Supplier Public Use File and Physician Compare national databases. This dataset encompasses more than 64% of practicing orthopaedic surgeons, providing a low proportion of missing data compared with other survey techniques. Group practice size, location, and Rural-urban Commuting Area scores were compared across physician gender and years in practice. Linear and logistic regressions modeled gender and outcomes relationships adjusted by years in practice. Least-square means estimates for outcomes were calculated by gender at the median years in practice (19 years) via regression models. RESULTS: According to the combined Medicare databases used, 5% (1019 of 19,221) of orthopaedic surgeons serving Medicare patients were women; this proportion increased with decreasing years in practice (R 2 0.97; p < 0.001). Compared by region, the West region demonstrated the highest proportion of women orthopaedic surgeons overall (7% [259 of 3811]). The Midwest and South regions were below the national mean for proportions of women orthopaedic surgeons, both overall (5% [305 of 6666] and 5% [209 of 4146], respectively) and in the first 5 years of practice (9% [54 of 574] and 9% [74 of 817], respectively). Women worked in larger group practices than men (median [interquartile range] 118 physicians [20 to 636] versus median 56 [12 to 338]; p < 0.001, respectively). Both genders were more likely to practice in an urban setting, and when controlling for years in practice, there was no difference between men and women orthopaedic surgeons practicing in rural or urban settings (respectively, R 2 = 0.0004 and 0.07; p = 0.89 and 0.09). CONCLUSION: Among orthopaedic surgeons, there is only one woman for every 20 men caring for Medicare patients in the United States. Although gender representation is increasing longitudinally for women, it trails behind other surgical subspecialties substantially. Longitudinal mentoring programs, among other evidenced initiatives, should focus on the more pronounced underrepresentation identified in Midwestern/Southern regions and smaller group practices. Gender-based equity, inclusion, and diversity efforts should focus on recruitment strategies, and further research is needed to study how inclusion and diversity efforts among orthopaedic surgeons improves patient-centered care. LEVEL OF EVIDENCE: Level III, therapeutic study.

Does the Number of Preoperative Corticosteroid Injections Affect Clinical and Radiographic Outcomes of Trapeziectomy and Suspensionplasty?

PURPOSE: This study aimed to determine whether an increasing number of preoperative corticosteroid injections is associated with greater radiographic subsidence of the thumb metacarpal at long-term follow-up after abductor pollicis longus suspensionplasty, secondary to steroid-induced pathologic weakening of capsuloligamentous restraints surrounding the thumb carpometacarpophalangeal joint and greater extension of the lunate, but neither affect patient-reported outcomes nor revision rates. METHODS: A retrospective chart review was performed of patients who underwent primary trapeziectomy and abductor pollicis longus suspensionplasty by a single surgeon over a 10-year period. The number of preoperative corticosteroid injections in the trapeziometacarpal joint was documented, and patients were separated into 4 subgroups: 0, 1, 2, or 3 or more injections. Preoperative and final radiographs were evaluated for a change in the distance between the base of the thumb metacarpal and the distal pole of the scaphoid as a measure of thumb metacarpal subsidence and radiolunate angle as a measure of nondissociative carpal instability, which has been reported as a complication after basal joint arthroplasty. Additionally, the final patient-reported outcomes (Quick Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation) and revision rates were also assessed. RESULTS: Of a total of 60 patients with an average age of 64 years that were included in the study, 16 (26.7%) received 0, 19 (31.7%) received 1, 12 (20%) received 2, and 13 (21.7%) received 3+ preoperative injections. The median postoperative follow-up was 92 months. The mean distance between the base of the thumb metacarpal and the distal pole of the scaphoid decreased by 2 mm, and the mean radiolunate angle increased by 4° across the entire cohort. When comparing subgroups, no differences were observed in either parameter or the final Patient-Rated Wrist Evaluation and Quick Disabilities of the Arm, Shoulder, and Hand scores. CONCLUSIONS: This study demonstrates no apparent detrimental effect of an increased number of preoperative corticosteroid injections on radiographic thumb metacarpal subsidence, increase in extension of radiolunate angle (nondissociative carpal instability), patient-reported outcomes, or revision rates at an average of almost 8 years after trapeziectomy and abductor pollicis longus suspensionplasty. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Same-day Discharge Is Safe and Effective After Implant-Based Breast Reconstruction.

BACKGROUND: Same-day discharge after mastectomy is a recently described treatment approach. Limited data exist investigating whether same-day discharge can be successfully implemented in patients undergoing mastectomy with immediate implant-based breast reconstruction (IBR). METHODS: Patients having mastectomy with IBR from 2013 to 2019 were reviewed. Enhanced recovery with same-day discharge was implemented in 2017. Patient characteristics, oncologic treatments, surgical techniques, and 90-day postoperative complications and reoperations were analyzed comparing enhanced recovery patients with historical controls. RESULTS: A total of 363 patients underwent nipple-sparing (214, 59%) or skin-sparing (149, 41%) mastectomy with 1-stage (270, 74%) or tissue expander (93, 26%) IBR. Enhanced recovery was used for 151 patients, with 79 of these patients (52%) discharged same-day. Overall, enhanced recovery patients experienced a significantly lower rate of 90-day complications (21% vs 41%, P < 0.001), including hematoma (3% vs 11%, P = 0.002), mastectomy flap necrosis (7% vs 15%, P = 0.02), seroma (1% vs 9%, P < 0.001), and wound breakdown (3% vs 9%, P = 0.05). Postoperative complication rates did not significantly differ among enhanced recovery patients discharged same day. Postoperative admissions significantly decreased after enhanced recovery implementation (100% to 48%, P < 0.001), and admitted enhanced recovery patients experienced a lower length of stay (1.2 vs 1.8, P < 0.001). Enhanced recovery patients experienced a lower incidence of ≥1 unplanned reoperation (22% vs 33%, P = 0.01); overall average unplanned and total reoperations did not significantly differ between groups. CONCLUSIONS: In conjunction with enhanced recovery practices, same-day discharge after mastectomy with IBR is a safe and feasible treatment approach.

Midterm Patient-Reported Outcomes in Wrist Denervation for Post-Traumatic Arthritis.

PURPOSE: To analyze patient-reported outcomes and range of motion in a cohort of patients who underwent wrist denervation for advanced wrist osteoarthritis. We hypothesized that improvements in pain and function would be seen with preserved range of motion. METHODS: Thirty patients underwent wrist denervation for symptomatic stage 1-4 scapholunate advanced collapse (SLAC) arthritis. Patient-Rated Wrist Evaluation, Quick Disabilities of the Arm, Shoulder, and Hand score, and range of motion measurements were assessed preoperatively and at final follow-up. RESULTS: The mean follow-up duration was 47 months (range, 24-92 months). The mean age at surgery was 65 years, and 96% of the patients were men. The dominant hand was involved in 66% of cases. The SLAC grades of patients involved were as follows: 10% (n = 3) grade 1, 27% (n = 8) grade 2, 60% (n = 18) grade 3, and 3% (n = 1) grade 4. Two patients required conversion to a wrist fusion and were considered failures. In the remaining 28 patients, the mean Patient-Rated Wrist Evaluation total score decreased 22 points (82.4 to 60.9) and the mean Quick Disabilities of the Arm, Shoulder, and Hand score decreased 8 points (32.4 to 24.8). Total arc of wrist flexion-extension showed an average 5° improvement. CONCLUSIONS: This method of wrist denervation was a viable salvage option for patients with symptomatic SLAC wrist osteoarthritis to preserve motion, decrease pain, and increase function with a low absolute failure rate at mid- to long-term follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Same-Day Discharge After Mastectomy: Breast Cancer Surgery in the Era of ERAS®.

BACKGROUND: Enhanced recovery after surgery (ERAS®) principles have been beneficial in major abdominal surgery. ERAS® was instituted in our breast surgery practice in 2017. The goal of this study was to evaluate the feasibility of outpatient mastectomies before and after ERAS®. METHODS: A retrospective review of all mastectomies between 1/2013 and 6/2018 was performed. Patients receiving autologous flap reconstruction were excluded. The institution-specific ERAS® pathway began on February 1, 2017. Patient characteristics, operative intervention, and postoperative outcomes were compared between pre-ERAS® and post-ERAS® groups and between outpatient and inpatient subgroups. Continuous and categorical variables were compared using Wilcoxon rank-sum and Chi-square analyses. RESULTS: A total of 487 patients were analyzed. Three hundred and forty-seven (71%) were prior to ERAS® and 140 after (29%). The two groups were not significantly different in background characteristics. Same-day discharge occurred in 58.6% of post-ERAS® patients versus 7.2% of pre-ERAS® patients (p < 0.001). Liposomal bupivacaine block was used for pain control more in the post-ERAS® group, 62.1% versus 6.1% (p < 0.001). Reconstruction type differed with 45.7% of the post-ERAS® group undergoing direct-to-implant reconstruction versus 34.3% of pre-ERAS® patients (p < 0.001) and with higher rates of submuscular implant and tissue expander placement in the pre-ERAS® versus post-ERAS® group (p < 0.001). Complications rates were lower in the post-ERAS® group versus pre-ERAS® group, 32.9% versus 52.4% (p < 0.001). The outpatient subgroup had higher rates of liposomal bupivacaine administration 74.4% versus 44.8% (p < 0.001). Baseline characteristics and complication rates did not differ between outpatient and admitted subgroups. CONCLUSION: ERAS® principles can be applied to breast cancer patients and allow for outpatient mastectomies with no increase in postoperative morbidity.

Factors associated with cytomegalovirus serostatus in young people in England: a cross-sectional study.

BACKGROUND: Human cytomegalovirus (CMV) is a common herpesvirus which is estimated to infect 83% of the global population. Whilst many infections are asymptomatic, it is an important cause of morbidity and mortality, particularly for immunocompromised people and for infants who are congenitally infected. A vaccine against CMV has been stated as a public health priority, but there are gaps in our understanding of CMV epidemiology. To guide potential future vaccination strategies, our aim was to examine risk factors for CMV seropositivity in young people in England. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected through questionnaires, and blood samples are taken. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for CMV antibodies. We undertook descriptive and regression analyses of CMV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals, of whom 175 (23.7%) were CMV-seropositive. CMV seroprevalence was associated with age, with 18.3% seropositive at 11-14 years compared to 28.3% at 22-24 years. CMV serostatus was also higher in people of non-white ethnicity (adjusted odds ratio [aOR] 6.22, 95% confidence interval [CI] 3.47-11.14), and in adults who were seropositive for EBV (aOR 2.08 [1.06-4.09]). There was no evidence that smoking status, occupation, body mass index and region of England were associated with CMV serostatus. CONCLUSIONS: CMV seroprevalence is strongly associated with ethnicity, and modestly increases with age in 11-24-year-olds. A greater understanding of the transmission dynamics of CMV, and the impact of this on CMV-associated morbidity and mortality, is necessary to inform effective vaccination strategies when a vaccine for CMV becomes available.

Predictors of Epstein-Barr virus serostatus in young people in England.

BACKGROUND: Epstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11-14 year olds throughout adolescence (68.6% in 15-18 year olds) and stabilising by early adulthood (93.0% in those aged 22-24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13-4.78]). Smoking was less strongly associated with EBV seropositivity. CONCLUSIONS: By the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies.

Association between pediatric asthma care quality and morbidity and English language proficiency in Ohio.

OBJECTIVE: Limited English proficiency can be a barrier to asthma care and is associated with poor outcomes. This study examines whether pediatric patients in Ohio with limited English proficiency experience lower asthma care quality or higher morbidity. METHODS: We used electronic health records for asthma patients aged 2-17 years from a regional, urban, children's hospital in Ohio during 2011-2015. Community-level demographics were included from U.S. Census data. By using chi-square and t-tests, patients with limited English proficiency and bilingual English-speaking patients were compared with English-only patients. Five asthma outcomes-two quality and three morbidity measures-were modeled using generalized estimating equations. RESULTS: The study included 15 352 (84%) English-only patients, 1744 (10%) patients with limited English proficiency, and 1147 (6%) bilingual patients. Pulmonary function testing (quality measure) and multiple exacerbation visits (morbidity measure) did not differ by language group. Compared with English-only patients, bilingual patients had higher odds of ever having an exacerbation visit (morbidity measure) (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.2-1.6) but lower odds of admission to intensive care (morbidity measure) (aOR, 0.3; 95% CI, 0.2-0.7), while patients with limited English proficiency did not differ on either factor. Recommended follow-up after exacerbation (quality measure) was higher for limited English proficiency (aOR, 1.8; 95% CI, 1.4-2.3) and bilingual (aOR, 1.6; 95% CI, 1.3-2.1), compared with English-only patients. CONCLUSIONS: In this urban, pediatric population with reliable interpreter services, limited English proficiency was not associated with worse asthma care quality or morbidity.

Reducing emergency department visits utilizing a primary care asthma specialty clinic in a high-risk patient population.

OBJECTIVE: Asthma is a leading cause of pediatric emergency department (ED) use. Optimizing asthma outcomes is a goal of Nationwide Children's Hospital (NCH) and its affiliated Accountable Care Organization. NCH's Primary Care Network, comprised of 12 offices serving a predominantly Medicaid population, sought to determine whether an Asthma Specialty Clinic (ASC) operated within a single primary care office could reduce ED asthma rates and improve quality measures, relative to all other network offices. METHODS: An ASC was piloted with four components: patient monitoring, provider continuity, standardized assessment, and multi-disciplinary education. A registry was established to contact patients at recommended intervals. At extended-length visits, a general pediatrician evaluated patients and a multi-disciplinary team provided education. Novel educational tools were utilized, guideline-based templates recorded and spirometry obtained. ED asthma rate, spirometry utilization, and controller fills by intervention office patients were compared to all other network offices before and after ASC initiation. RESULTS: At baseline, asthma ED visits by intervention and usual care populations were similar (p = 0.43). After, rates were significantly lower for intervention office patients versus usual care office patients (p < 0.001), declining in the intervention population by 26.2%, 25.2%, and 31.8% in 2013, 2014, and 2015, respectively, from 2012 baseline, versus increases of 3.8%, 16.2%, and 9.5% in the usual care population. Spirometry completion, controller fills, and patients with favorable Asthma Medication Ratios significantly increased for intervention office patient relative to the usual care population. CONCLUSIONS: A primary care-based asthma clinic was associated with a significant and sustainable reduction in ED utilization versus usual care. What's new: This study describes a comprehensive, multi-disciplinary, and innovative model for an asthma management program within the medical home that demonstrated a significant reduction in ED visits, an increase in spirometry utilization, and an increase in controller fills in a high-risk asthma population versus comparison group.

There and Back Again: A Forty-Year Perspective on Physician Nutrition Education.

Medical education faces an urgent need for evidence-based physician nutrition education. Since the publication of the 1985 National Academies report "Nutrition Education in the United States Medical Schools," little has changed. Although several key efforts sought to increase nutrition content in undergraduate medical education over the past 40 y, most medical schools still fail to include the recommended minimum of 25 h of nutrition training. Without foundational concepts of nutrition in undergraduate medical education, graduate medical education unsurprisingly falls short of meeting patient needs for nutritional guidance in clinical practice. Meanwhile, diet-sensitive chronic diseases continue to escalate, although largely preventable and treatable by nutritional therapies and dietary lifestyle changes. Fortunately, recent recognition and adoption of Food is Medicine programs across the country increasingly connect patients with healthy food resources and nutrition education as core to their medical care, and physicians must be equipped to lead these efforts alongside their dietitian colleagues. Filling the gap in nutrition training will require an innovative and interprofessional approach that pairs nutrition with personal wellness, interprofessional practice, and community service learning. The intersectional benefits of connecting these domains will help prepare future physicians to address the social, behavioral, and lifestyle determinants of health in a way that recognizes nourishing food access as a core part of clinical practice. There are numerous strategies to integrate nutrition into education pathways, including didactic and experiential learning. Culinary medicine, an evidence-based field combining the culinary arts with nutritional science and medicine, is 1 promising educational framework with a hands-on, interprofessional approach that emphasizes community engagement. Advancing the critical need for widespread adoption of nutrition education for physicians will require support and engagement across societal stakeholders, including co-leadership from registered dietitian nutritionists, health system and payor reform, and opportunities for clinical innovation that bring this essential field to frontline patient care.

Culinary Medicine: Needs and Strategies for Incorporating Nutrition into Medical Education in the United States.

In the past decade, medical education has increasingly incorporated evidence-based lifestyle interventions as primary strategies for preventing and managing noncommunicable diseases. This shift embraces the growing recognition of the significant impact of lifestyle on health outcomes, driving diseases including obesity, diabetes, heart disease, and cancer. Now deemed "food is medicine" (FIM), diet-related interventions witnessed integration into healthcare systems and recognition in the United States' White House Conference on Hunger, Nutrition, and Health in 2023. As FIM gains traction, investigating optimal strategies for team-based education becomes essential. Healthcare teams need the necessary knowledge and tools to effectively administer FIM services and collaborate across disciplines, ultimately enhancing disease prevention, chronic disease management, health quality, value, and overall wellness. Culinary medicine (CM), a vital component of FIM, bridges nutrition education, pragmatic culinary skills, and conventional strategies to improve chronic disease management. CM involves experiential learning, imparts practical skills, and encourages behavior change by addressing food-related determinants of health and promoting equitable access. Teaching kitchens serve as physical or virtual learning spaces and as a didactic and experiential method (skills lab), playing a crucial role by integrating culinary, lifestyle, integrative, and conventional medicine. A growing number of medical schools in the United States and globally offer CM education via diverse methods including interest groups, electives, and specialty tracks, encompassing didactic sessions, hands-on kitchen education, and virtual teaching methods. Given the rising demand for CM programs, this article aims to describe, map, and compare existing CM education types in medical education. It provides actionable recommendations for medical schools to establish and expand CM programs by fostering service-learning partnerships, clinical innovation, and interdisciplinary research. As FIM gains prominence, cultivating a robust foundation of educational strategies is vital to ensure seamless integration into both medical education and collaborative medical practice.

Culinary Medicine or Culinary Nutrition? Defining Terms for Use in Education and Practice.

Examination of how terms such as culinary nutrition, culinary nutrition science, culinary medicine, culinary nutrition professional, culinary nutrition intervention, culinary nutrition activity, and culinary nutrition competency are used in practice, and the creation of consensus definitions will promote the consistent use of these terms across work areas and disciplines. Thirty leading practitioners, academics, and researchers in the fields of food and nutrition across Australia, the United States, Canada, United Kingdom, Europe, and Asia were approached by investigators via email to submit definitions of key terms using a Qualtrics survey link. Further participants were reached through snowball recruitment. Initial emails were sent in October and November 2021 with subsequent reminders between November 2021 and March 2022. Two researchers undertook content analysis of the text answers for each of the terms and generated definitions for discussion and consensus. Thirty-seven participants commenced the survey and twenty-three submitted one or more definitions. Agreed definitions fell into two categories: practice concepts and practitioners. Further discussion amongst investigators led to the creation of a visual map to demonstrate the interrelationship of terms. Culinary nutrition science underpins, and interprofessional collaboration characterizes practice in this area, however, further work is needed to define competencies and model best practice.

Mimicking the brain: Epstein-Barr virus and foreign agents as drivers of neuroimmune attack in multiple sclerosis.

T cells have an essential role in adaptive immunity against pathogens and cancer, but failure of thymic tolerance mechanisms can instead lead to escape of T cells with the ability to attack host tissues. Multiple sclerosis (MS) occurs when structures such as myelin and neurons in the central nervous system (CNS) are the target of autoreactive immune responses, resulting in lesions in the brain and spinal cord which cause varied and episodic neurological deficits. A role for autoreactive T cell and antibody responses in MS is likely, and mounting evidence implicates Epstein-Barr virus (EBV) in disease mechanisms. In this review we discuss antigen specificity of T cells involved in development and progression of MS. We examine the current evidence that these T cells can target multiple antigens such as those from pathogens including EBV and briefly describe other mechanisms through which viruses could affect disease. Unravelling the complexity of the autoantigen T cell repertoire is essential for understanding key events in the development and progression of MS, with wider implications for development of future therapies.

Epstein-Barr virus and multiple sclerosis: moving from questions of association to questions of mechanism.

The link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) has puzzled researchers since it was first discovered over 40 years ago. Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS. Early MS disease is characterised by episodic neuroinflammation and focal lesions in the central nervous system (CNS) that over time develop into progressive neurodegeneration and disability. Risk of MS is vanishingly low in EBV seronegative individuals, history of infectious mononucleosis (acute symptomatic primary infection with EBV) significantly increases risk and elevated antibody titres directed against EBV antigens are well-characterised in patients. However, the underlying mechanism - or mechanisms - responsible for this interplay remains to be fully elucidated; how does EBV-induced immune dysregulation either trigger or drive MS in susceptible individuals? Furthermore, deep understanding of virological and immunological events during primary infection and long-term persistence in B cells will help to answer the many questions that remain regarding MS pathogenesis. This review discusses the current evidence and mechanisms surrounding EBV and MS, which have important implications for the future of MS therapies and prevention.