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David A Isaacs,1,2 Kemberlee Bonnet,3 Michelle R Eckland,1 Kimberly Markowitz,4 Maria Pena,5 David G Schlundt3 1Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; 2Department of Pediatrics, Division of Pediatric Neurology, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA; 3Department of Psychology, Vanderbilt University, Nashville, TN, USA; 4Department of Neuroscience, Vanderbilt University, Nashville, TN, USA; 5College of Nursing, University of Florida, Gainesville, FL, USACorrespondence: David A Isaacs, Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave South, A-0118 MCN, Nashville, TN, 37232, USA, Tel +1 615 936.2025, Fax +1 615 936 1229, Email david.a.isaacs@vumc.orgPurpose: Adults with Tourette syndrome (TS) have worse mental health, physical health, and quality of life than the general population. The factors contributing to negative outcomes across multiple health domains in adults with TS remain uncertain, in part due to a lack of longitudinal studies in this population. In attempt to address these knowledge gaps, our center has initiated development of a regional registry for adults with TS. During the goal-setting and design phase of registry development, we conducted focus groups with adults with TS to identify research issues of greatest importance to this population and to obtain feedback on design and implementation of an adult TS registry.Patients and Methods: Participants were recruited from a tertiary care adult TS clinic and from institutional research registries. Focus groups were conducted online and were moderated by a qualitative research expert. Qualitative data analysis was performed using an iterative inductive/deductive approach.Results: Across four focus groups, adult TS participants (n=22) expressed a variety of research priorities, including developing more effective treatments for tics, identifying risk factors for tic persistence into adulthood, clarifying the interaction between TS symptoms and women’s health, clarifying the relationships between TS and other mental and physical health disorders, and addressing day-to-day living issues. Focus group participants were generally enthusiastic about creation of an adult TS registry. They indicated that adults with TS are more likely to engage with a registry that logistically accommodates participants (eg, by offering a wide range of visit times, by providing telehealth options) and that fosters bidirectional interaction (eg, by disseminating results regularly, by involving participants in registry design and implementation, by notifying participants of support resources).Conclusion: Focus group input clarifies the research priorities of adults with TS and will inform the ongoing development of an adult TS registry.Keywords: tic disorder, patient registry, neurodevelopmental disorder, movement disorder

Objective: Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS., Methods: We conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS)., Results: The prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (p = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (p = 0.003). In a regression analysis, controlling for significant patient-level covariates and income-level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (p = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (p < 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (p = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability., Interpretation: BA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Oral disease interventions primarily focus on behavioral changes like dietary improvements and ensuring better oral hygiene. However, recognizing the influence of biological factors, including genetics and early-life nutrition, is crucial. Iron deficiency (ID) and its advanced form, iron deficiency anemia (IDA), affect nearly two billion people globally, especially children and pregnant women. We conducted a comprehensive search using Medline via EndNote and Web of Science, employing keywords related to iron deficiency anemia (IDA), and we identified 36 studies deemed relevant for inclusion in this literature review. IDA prevalence is notably high among pregnant women and young children. Both IDA and early-childhood caries (ECC) disproportionately affect impoverished populations, highlighting the socioeconomic dimension of this issue. IDA presents with various oral mucosal changes and is closely linked to candidiasis. Additionally, IDA can hinder tooth development and weaken the immune response. Multiple population surveys have revealed a significant association between ECC and IDA. While some studies have explored the IDA-periodontal disease link, the current evidence is relatively limited in its robustness. In conclusion, more comprehensive longitudinal studies are essential to deepen our understanding of the IDA-oral disease connection. Investigating the underlying biological mechanisms is critical to developing effective interventions, particularly for vulnerable populations affected by IDA.

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors. Loss of STAT3 in hepatocytes or SAA remodeled the tumor microenvironment with infiltration by CD8 + T cells, while interleukin-6 overexpression in hepatocytes and SAA signaling via Toll-like receptor 2 reduced the number of intratumoral dendritic cells and, in doing so, inhibited T cell tumor infiltration. Genetic ablation of SAA enhanced survival after tumor resection in a T cell-dependent manner. Likewise, in individuals with pancreatic ductal adenocarcinoma, long-term survivors after surgery demonstrated lower serum SAA levels than short-term survivors. Taken together, these data define a fundamental link between liver and tumor immunobiology wherein hepatocytes govern productive T cell surveillance in cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII + glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed. Secondary outcomes included median progression-free survival (5.2 months; 90% confidence interval (CI), 2.9-6.0 months) and median overall survival (11.8 months; 90% CI, 9.2-14.2 months). In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Microbes are an integral component of the tumor microenvironment. However, determinants of microbial presence remain ill-defined. Here, using spatial-profiling technologies, we show that bacterial and immune cell heterogeneity are spatially coupled. Mouse models of pancreatic cancer recapitulate the immune-microbial spatial coupling seen in humans. Distinct intra-tumoral niches are defined by T cells, with T cell-enriched and T cell-poor regions displaying unique bacterial communities that are associated with immunologically active and quiescent phenotypes, respectively, but are independent of the gut microbiome. Depletion of intra-tumoral bacteria slows tumor growth in T cell-poor tumors and alters the phenotype and presence of myeloid and B cells in T cell-enriched tumors but does not affect T cell infiltration. In contrast, T cell depletion disrupts the immunological state of tumors and reduces intra-tumoral bacteria. Our results establish a coupling between microbes and T cells in cancer wherein spatially defined immune-microbial communities differentially influence tumor biology., Competing Interests: Declaration of interests W.J.H. reports royalties from Rodeo/Amgen; grants from Sanofi, NeoTX, and Circle Pharma; and prior consulting fees from Exelixis. G.L.B. reports prior and active roles as a consultant/advisory board member for Seattle Genetics (now Seagen), Adicet Bio, Aduro Biotech, AstraZeneca, BiolineRx, BioMarin Pharmaceuticals, Bristol-Myers Squibb, Cantargia, Cour Pharmaceuticals, Boehinger Ingelheim, Genmab, Hibercell, HotSpot Therapeutics, Incyte Corporation, Janssen, Merck, Molecular Partners, NanoGhost, Pancreatic Cancer Action Network, Shattuck Labs, and Verastem and reports receiving commercial research grants from Incyte Corporation, Bristol-Myers Squibb, Verastem, Halozyme, Biothera, Newlink, Novartis, Arcus Biosciences, and Janssen. G.L.B. is an inventor of intellectual property related to chimeric antigen receptor (CAR) T cells that is licensed by the University of Pennsylvania to Novartis and Tmunity Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)