Publications by Year: 2026

BACKGROUND: Asthma remission has emerged as a potential therapeutic goal. However, definitions of remission have primarily focused on adult populations, with limited consensus on how remission should be defined in children.

OBJECTIVE: To comprehensively review how asthma remission has been defined in children and to evaluate consistency and applicability of these definitions.

METHODS: This scoping review was conducted following PRISMA-ScR guidelines. PubMed MEDLINE was searched for studies published between January 2010 and February 2024. Eligible studies included children with asthma and reported definitions of remission. Key remission criteria were extracted and categorized, and hierarchical cluster analysis was used to identify key patterns.

RESULTS: Twenty-nine studies met the inclusion criteria. Most (79.3%) defined paediatric asthma remission based on the absence of clinical symptoms. The most common remission timeframe ranged from 1 to 2 years. A medication-free criterion was used in 68.9% of studies. On-treatment remission was reported in the minority of studies, but it is increasingly acknowledged as a valid outcome. Objective assessments, such as normal lung function (21%) and absence of bronchial hyperresponsiveness (10.3%), were infrequently included. Cluster analysis revealed 3 main patterns for remission definition: symptom-based, event-based, and 1 including objective criteria.

CONCLUSION: Current definitions of asthma remission in paediatric populations are predominantly symptom-based, with limited inclusion of objective physiological measures. Establishing consensus-based definitions for remission tailored to paediatric populations is essential to ensure clinical relevance and alignment with real-world disease patterns.

OBJECTIVE: Assess current drive times to the nearest pre-exposure prophylaxis (PrEP) provider in each county in the contiguous United States (US) and examine changes since the last analysis (2017).

METHODS: PrEP provider data were obtained from PrEPLocator.org in March 2025. Geospatial analyses calculated one-way drive times from population-weighted county centroids to the nearest provider. Counties with drive times >30 min were defined as PrEP deserts. Linear regression assessed variation in drive times by urbanicity and region, adjusting for median income, small-area population estimates of men who have sex with men (MSM), and proportion of racial/ethnic minority populations.

RESULTS: In 2025, median drive time was 30.2 min, increasing with decreasing urbanicity (p < 0.05). Half of counties were PrEP deserts, accounting for 36 million residents and 4 % of PrEP-eligible MSM. Drive times in micropolitan/non-core counties were 5-8 times higher than in large metro counties. Between 2017 and 2025, the US South had the largest relative reduction in drive time: however, relative changes did not significantly differ by urbanicity.

CONCLUSIONS: While PrEP access has improved nationally, important geographic disparities remain. Programs and policies must prioritize expanding access to PrEP to less urban areas to end the HIV epidemic in the US.

•AI-driven tools and multimodal biomarkers emerged as key for early VCID detection.•Novel neuroimaging, fluid, and retinal markers show promise for precision diagnostics.•BBB leakage and inflammation could early drive small vessel disease and VCID.•Clinical trials explore drug repurposing and hybrid lifestyle-pharmacological interventions.•Genetic insights into CADASIL reveal shared pathways with sporadic SVD.

BACKGROUND: The triple-negative breast cancer (TNBC) microenvironment undergoes progressive reprogramming, transitioning from an early immune-active state to a late immune-suppressed state. While tumor cell plasticity has been extensively studied, the temporal molecular remodeling of T cells in vivo remains poorly defined.

RESULTS: Transcriptional analysis of T cells within 4T1 TNBC tumors, harvested at one-, three-, and six-weeks post-tumor implantation in the mammary fat pads of BALB/c mice, revealed a decline in transcriptomic signatures associated with T cells from 194 at one week to 156 at six weeks, with a significant late-stage loss or reduction of transcripts related to T cell receptors (TCR), natural killer T, and gamma delta T cells. Furthermore, changes in various temporal signature genes specific to T cell cytokines and transcription factors reflected temporal T cell polarization to CD4+ type 1 T helper and type 1 CD8+ cytotoxic T cell responses at one week, CD8+ cytotoxic follicular T cell skewing at three weeks, and interleukin 17/22 producing CD8+ T cell transition at six weeks. The antigen-presenting cell (APC) transcripts deteriorated at six weeks, characterized by reduced expression of co-stimulatory and APC genes. Despite an early dominance of M1-like macrophage genes (e.g., IL-12α/β), persistent expression of arginase 1 (ARG1) and other M2-associated genes indicated a stable tolerogenic niche.

CONCLUSIONS: The temporally coordinated immune shifts, such as progressive decline in transcripts associated with T cell functions, TCRs, APCs, and sustained macrophage-driven immunosuppression, suggest tumor-driven adaptation toward immune evasion and identify potential windows for stage-specific immunotherapeutic intervention.

BACKGROUND: Vaccines are an evidence-based intervention that mitigates the impact of infections, yet many Americans indicate hesitancy toward receiving vaccines. One of the most common reasons for this is the potential for experiencing adverse reactions when receiving vaccines. The current literature shows that clinical decision support (CDS) tools have been utilized to improve vaccine coverage.

OBJECTIVE: Our aim was to assess specialist physician experiences, practices, and levels of comfort with evaluating adverse and allergic reactions to vaccines, as well as with addressing secondary vaccine hesitancy, using CDS tools.

METHODS: Researchers conducted 10 semistructured interviews with physicians in Mass General Brigham's Infectious Diseases and Allergy/Immunology units. The interview guide consisted of 11 questions divided into 4 sections: vaccine conversations, vaccine allergies/reactions, CDS, and structural facilitators/barriers. The interview responses were evaluated by using rapid thematic analysis.

RESULTS: Specialist physicians were generally comfortable talking to patients about vaccine hesitancy but were also open to CDS tools that effectively and efficiently contribute to improved conversations around secondary vaccine hesitancy to increase vaccine uptake. Desired CDS tool features include sharing educational visuals and videos with patients. The risks involve operational delays and lack of real-time data and accountability structures. Clinic modifications such as longer appointment times or group appointments were considered as other ways to help address vaccine hesitancy.

CONCLUSION: Specialist physicians expressed interest in using CDS tools to improve vaccine-related conversations with their patients. Future CDS tools must account for timely vaccine information and workflow efficiency issues. Future research should include generalist physicians, other health care team members, and patients.

BACKGROUND: Carpal tunnel release (CTR) is a common surgery with a well-described complication profile, but it is unclear whether patients' self-reported risk acceptance is higher than, equal to, or lower than actual surgical risks. We aimed to investigate patients' self-reported levels of risk acceptance for complications of CTR, factors associated with higher risk acceptance, and whether PROMIS Upper Extremity, PROMIS Pain Interference, and PROMIS Pain Intensity scores correlate with risk acceptance.

METHODS: A prospective, cross-sectional study was conducted of 47 adult patients with idiopathic carpal tunnel syndrome (CTS) who were indicated for mini-open CTR using a standard published technique with a well-described complication profile. A standardized questionnaire was used to survey patients about the highest acceptable risk of infection, persistent or recurrent symptoms, and nerve or vessel injury as a percentage from 0 % to 100 %. Our explanatory variables included PROMIS Upper Extremity, PROMIS Pain Interference, PROMIS Pain Intensity, and other patient-related factors.

RESULTS: The median patient-reported risk acceptance for infection after CTR surgery was 30 % (interquartile range 10 %-50 %), for persistent or recurrent symptoms was 40 % (interquartile range 20 %-50 %), and for nerve or vessel injury was 20 % (interquartile range 10 %-50 %). Diabetes mellitus was associated with higher risk acceptance for nerve or vessel injury during CTR. Lower PROMIS Upper Extremity scores were weakly correlated with higher risk acceptance for nerve or vessel injury during CTR. Higher PROMIS Pain Interference scores were weakly correlated with higher risk acceptance for persistent or recurrent symptoms after CTR.

CONCLUSIONS: The actual risks of common complications after CTR are much lower than most patients' self-reported risk acceptance. The severity of preoperative CTS symptoms affects patients' acceptance of the risk of surgical complications and symptom persistence after CTR.

Atopic dermatitis (AD) is a chronic skin disease marked by pruritus and barrier disruption. Though topical corticosteroids are standard, prolonged use may cause adverse effects. This updated meta-analysis assesses the efficacy and safety of ruxolitinib cream, a topical JAK1/JAK2 inhibitor, versus vehicle in AD treatment. PubMed, Embase, and Cochrane were searched up to April 2025 for RCTs evaluating ruxolitinib versus vehicle, following Cochrane and PRISMA guidelines. Primary outcomes included Investigator's Global Assessment-Treatment Success (IGA-TS) and 75% improvement in the Eczema Area and Severity Index (EASI75) at weeks 4 and 8; secondary outcomes included ≥4-point improvement in pruritus Numeric Rating Scale (NRS) at week 8 and incidence of at least one treatment-emergent adverse event (TEAE). Five RCTs (n = 1912) were included. Ruxolitinib significantly improved IGA-TS at 4 weeks (RR 4.56; 95% CI 3.01-6.92; p < .001) and 8 weeks (RR 4.00; 95% CI 2.97-5.38; p < .001), and EASI75 at 4 weeks (RR 3.10; 95% CI 1.79-5.38; p < .001) and 8 weeks (RR 3.16; 95% CI 2.21-4.51; p < .001). Benefits were consistent across age groups and dosages. Trial sequential analysis confirmed results' robustness. Pruritus NRS improved (RR 2.39; 95% CI 1.62-3.53; p < .001). TEAE risk was similar (RR 0.87; 95% CI 0.74-1.03; p = .10), though adolescents/adults had fewer events (RR 0.83; 95% CI 0.69-1.00; p = .04); children showed no significant increase (RR 1.14; 95% CI 0.74-1.75; p = .55). Ruxolitinib cream significantly improves IGA-TS, EASI75, and pruritus, with a comparable safety profile to vehicle.

BACKGROUND: Primary immune diseases (PI) encompass over 550 disorders that are associated with substantial risk of mortality and morbidity. Emerging evidence demonstrates significant survival disparities in PI among racial minoritized populations. However, published national data on treatment patterns are lacking.

OBJECTIVE: We investigated variations in the use of immunoglobulin replacement therapy (IgGRT) across different geographic regions (Midwest, West, Northeast, South, and other/unknown) and racial groups (Black, Asian, White, and other/unknown) in the United States.

METHODS: This study analyzed a subset of the Optum deidentified electronic health record dataset, focusing on 3 cohorts of PI patients: common variable immunodeficiency, hypogammaglobulinemia, and combined immunodeficiency (CID). The study compared the treatment status of IgGRT across regional and racial subgroups within each cohort.

RESULTS: Regional differences in IgGRT status were observed among common variable immunodeficiency patients, with treatment rate highest in the West (53.8%) and Midwest (49.9%) and lowest in the South (41.1%) (P < .005). Among patients with hypogammaglobulinemia, a higher proportion of patients in the West (55.8%) received IgGRT than in the South (40.3%) (P < .005). Among patients with CID, those residing in the Midwest (44.4%) had a significantly higher rate of IgGRT utilization compared to the South (32.5%) (P < .005). A greater proportion of White patients with CID (41.3%) received IgGRT compared to African American patients with CID (25.8%) (P < .008).

CONCLUSION: Our results show differences in IgGRT utilization rates across regional and racial categories within each disease cohort, suggesting potential disparities.

PURPOSE: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

METHODS: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We expressed the reference and variant RAPGEF2 in PDZ-GEF mutant background to conduct "humanization" studies.

RESULTS: Our experiments show that PDZ-GEF is expressed in the central nervous system. Loss of PDZ-GEF leads to severe locomotion defects, aberrant microtubular stability in motor neuron axons, and synaptic overgrowth at neuromuscular junctions in third instar larvae. Mutant animals are lethal at various developmental stages. Importantly, the neurodevelopmental phenotypes can be rescued by expression of the human RAPGEF2 reference cDNA but not by any of the variants.

CONCLUSION: Our findings provide functional evidence that the tested RAPGEF2 variants are loss-of-function alleles and that the RAPGEF2 variants are associated with a neurodevelopmental disorder.

INTRODUCTION: It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD), both of which are genetic forms of Alzheimer's disease (AD).

METHODS: We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed-models.

RESULTS: Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO -7. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD.

DISCUSSION: ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.