Citations

Single-cell studies have defined immune states in inflammatory bowel disease (IBD), but how adaptive receptor histories organize circulating immunity remains unclear. We generated a single-cell transcriptomic atlas of peripheral blood from 249 participants with Crohn's disease, ulcerative colitis, or non-IBD control status, including 182 with productive TCR and BCR recovery. Expanded TCR clonotypes marked inflammatory-memory and cytotoxic states, while distinct but similar paired TCRs shared inflammatory programs across participants. BCR lineage maturation linked IgA-associated mucosal and plasma B cell programs to somatic mutation and class switching, distinguishing maturation-associated biology from clonal expansion. Helper, regulatory, and cytotoxic T-cell programs covaried with B-cell states, and inferred interactions nominated reciprocal antigen-presentation and helper pathways. Repertoire-based machine learning distinguished diagnosis, inflammation, and contemporaneous six-month treatment-response status. Together, this atlas connects receptor architecture to coordinated systemic immune remodeling, establishes a foundation for repertoire-informed patient stratification, and prioritizes candidate mechanisms of IBD pathogenesis.

Abstract Background and Aims Fibroblast–neutrophil interactions are implicated in ulcerative colitis (UC) treatment resistance, but whether fibroblasts modify neutrophil inflammatory activity remains unclear. We investigated responses to fibroblast exposure, stromal depletion, and α5β1-directed treatment. Methods We integrated human and mouse colonic single-cell RNA sequencing (scRNA-seq), spatial protein profiling (CODEX), fibroblast–neutrophil coculture, and dextran sulfate sodium (DSS) mouse colitis with fibroblast activation protein (FAP) ablation or α5β1-directed treatment. Readouts included cellular representation and protein fluorescence via flow cytometry, neutrophil extracellular trap (NET)-associated elastase activity, RNA programs and epithelial responses using scRNA-seq. Results Inflamed UC tissue contained higher fractions of inflammatory fibroblasts and oncostatin M (OSM)- and CXCR4-associated neutrophils. Inflammatory fibroblasts had higher FAP–α5β1 module scores, and proximity to FAP-high fibroblasts was associated with higher neutrophil OSM and CXCR4 fluorescence. UC fibroblasts increased neutrophil OSM, CXCR4 and myeloperoxidase (MPO) fluorescence and NET-associated elastase activity relative to control fibroblasts, while α5β1-directed treatment attenuated these responses. Both mouse FAP ablation and α5β1 blockade in DSS colitis reduced histologic inflammation and overall neutrophil frequency. Ablation broadly reduced recovered neutrophil representation, whereas blockade increased OSM-positive and PADI4-positive percentages within neutrophils despite lower MPO fluorescence within these subsets. Both interventions were associated with lower epithelial chemokine scores but distinct absorptive and mucus/secretory responses. Conclusions Fibroblast exposure modifies neutrophil inflammatory phenotype and effector-associated activity, identifying candidate therapeutic pathways in UC. Evaluating these responses alongside neutrophil representation and tissue inflammation could inform pharmacodynamic assessment of stromal-directed therapies. Graphical Abstract What You Need to Know Background and Context Fibroblast–neutrophil interactions are associated with treatment resistance in ulcerative colitis. Whether fibroblast exposure modifies neutrophil inflammatory phenotype and effector activity, beyond its established recruitment role, remains unclear. New Findings UC fibroblasts increased neutrophil inflammatory proteins and NET-associated elastase activity; α5β1-directed treatment attenuated these responses. FAP ablation and α5β1-directed treatment reduced colitis and overall neutrophil frequency. α5β1-directed treatment lowered MPO within OSM-positive and PADI4-positive neutrophils despite higher marker-positive percentages. Epithelial single-cell RNA sequencing revealed reduced chemokine programs with both interventions but distinct barrier-associated and regenerative expression patterns. Limitations Cellular drug targets remain unresolved. Spatial associations and elastase activity do not establish direct contact, NET formation, or clinical efficacy. Clinical Research Relevance Fibroblast-associated pathways offer candidate therapeutic opportunities to modify neutrophil inflammatory phenotype and effector activity in UC. Coculture responses were pharmacologically modifiable, and stromal interventions reduced experimental colitis. Measuring neutrophil frequency, subset proteins, and effector activity alongside tissue inflammation could guide pharmacodynamic assessment. Clinical efficacy and treatment-selection utility require validation. Basic Research Relevance Human coculture provides experimental evidence that fibroblast exposure modifies neutrophil inflammatory proteins and NET-associated elastase activity. FAP+ stromal ablation and α5β1-directed treatment produced distinct patterns of neutrophil representation and subset proteins in colitis. Epithelial single-cell RNA sequencing revealed reduced chemokine programs with both interventions but differing barrier-associated and regenerative expression patterns. Together, these findings motivate mechanistic studies of how stromal recruitment cues, soluble signals, and matrix-associated interactions regulate neutrophil responses, and whether these changes contribute to reduced epithelial inflammation and tissue repair. Lay Summary Fibroblasts, support cells in the intestine, increased inflammatory activity in immune cells called neutrophils. Blocking a pathway involved in cell attachment reduced these responses in cultures. Targeting fibroblast-associated pathways also reduced experimental colitis, with changes in intestinal lining gene activity related to inflammation, barrier function, and repair. These findings suggest potential approaches to treating ulcerative colitis.

Objective: Patients with limited English proficiency often face barriers to accessing timely care. We evaluated whether Spanish-language Fast Pass messaging, combined with two-way Short Message Service (SMS) functionality, increased appointment acceptance rates among Spanish-preferring patients while maintaining equitable outcomes for English-preferring patients. Methods: A pre/post-quality improvement project was conducted at Mayo Clinic from November 2023 to June 2025. Epic’s Fast Pass, an automated appointment waitlist system, was enhanced with Spanish-language templates and bidirectional SMS in lieu of patient portal utilization. The primary outcome was the Fast Pass acceptance rate for Spanish-preferring patients. Balancing measures included acceptance among English-preferring patients. Secondary outcomes included scheduler efficiency and cost savings. Results: Prior to implementation, Spanish-preferring patients accepted 4.69% of Fast Pass offers compared with 7.57% for English-preferring patients. Post-implementation, acceptance rates for Spanish-preferring patients increased from 4.69% to 8.05%, a 71.6% improvement in the acceptance rate, exceeding the initial target of a 7.57% acceptance rate. Acceptance rates for English-preferring patients also improved, rising from 7.57% to 9.5%, or a 25.5% improvement in the acceptance rate. The intervention resulted in 344 additional Spanish-language accepted appointments and 29,883 additional English-language accepted appointments, both measured by unique patient appointments. The intervention also improved operational efficiency, saving more than 4,000 hours of scheduler time and reducing scheduling-related costs. Conclusions: Spanish-language concordant and SMS-enabled Fast Pass messages improved patient equity in appointment access while increasing scheduling efficiency and reducing operational costs. Health systems should adopt language-concordant digital communication strategies. Future research should expand to include additional languages and explore artifical intelligence–based scheduling support.

ABSTRACT Objectives Lasers are integral to contemporary endourologic stone surgery; however, reported institutional practices regarding laser access, personnel requirements, and safety protocols vary. We sought to characterize respondent‐reported laser access models, operational requirements, safety practices, and perceived barriers to care. Materials and Methods A cross‐sectional, web‐based 25‐item survey was distributed between October 2024 and March 2025 through social media, professional organizations, and departmental contacts. The survey assessed practice characteristics, laser access, physician and technician responsibilities, institutional safety requirements, and perceived barriers to care. Responses were self‐reported, collected anonymously, and summarized using descriptive statistics. Results A total of 187 respondents completed the survey; 85.6% identified as endourologists and 61.5% practiced in academic settings. Most respondents reported institution‐owned laser equipment (70.1%), while 9.6% reported contracted equipment and 20.3% combination models. Among respondents addressing contracted equipment availability ( n = 58), 55.2% reported ready access after regular business hours and 46.6% on weekends. Among 182 evaluable responses, 65.4% reported that physicians could operate lasers without a technician present. Fifty‐two respondents perceived that technician availability could affect patient care; among these, 40 reported potential delays in definitive treatment and 33 reported potential multiple or staged procedures. Staff laser safety goggles could be deferred according to 78.4% of evaluable responses, and 18.3% reported a prior institutional laser safety incident. Conclusion This survey identified substantial respondent‐reported variation in laser access, staffing requirements, and safety practices. The findings describe perceived institutional practices and barriers and do not establish effects on treatment delays, workflow efficiency, patient outcomes, or comparative safety. Future studies should directly compare institutional models using objective measures of access, workflow, treatment delays, and safety outcomes.

Abstract Context. Thyroid nodule ultrasound findings are crucial in guiding management decisions for patients with thyroid nodules. However, the frequency with which ultrasound images are discussed and reviewed with patients during clinical visits is not well understood. Objective. To assess how often thyroid ultrasound images are shown and discussed with patients during consultations, and to identify predictors of image review during clinical visits. Design and setting. Secondary analysis of a multicenter pilot randomized clinical trial conducted at two academic medical centers in the United States. Participants. Adults undergoing evaluation for thyroid nodules. Intervention. Participants were randomized to receive either usual care or care enhanced with a conversation aid. Main Outcome Measures. The primary outcome was the frequency of thyroid nodule imaging review evaluated as a binary outcome. Secondary outcomes included evaluation of predictors of image discussion. Results. Eighty-five patients were evaluated. Most participants were women (80%), mean age (60 years, SD 16), and White (86%), undergoing new patient visits (84%). Thyroid nodule ultrasound images were reviewed with patients in 53% of visits (45/85), and in all cases, clinicians initiated the imaging discussion. Predictors of image review included type of consultation (new patient visit) (OR 10.6, 95% CI: 1.79, 62.3). Age, sex, study arm, thyroid nodule size or cancer risk and plan of care (e.g., completing a biopsy) were not statistically associated with review of clinical images. Conclusions. Review of thyroid ultrasound images during clinical visits is relatively common, with consultation type serving as significant predictor.

This cohort study evaluates the association between measured lipoprotein(a) level and incident venous thromboembolism.

ABSTRACT Background Primary Biliary Cholangitis (PBC) is an autoimmune cholangiopathy with polygenic architecture and unknown aetiology. Evidence links Neanderthal‐derived genetic variants to autoimmune conditions; however, their contribution to PBC susceptibility remains unexplored. Objective We investigate whether archaic alleles influence PBC risk. Design Genotype data from four PBC cohorts were analysed: CANUK (4615 cases, 9233 controls), OLD IT (444 cases, 901 controls), NEW IT (255 cases, 579 controls) and MAYO (891 cases, 621 controls). Association testing with 235 592 Neanderthal Informative Markers (NIMs) was performed, adjusting for population stratification. Heritability was estimated using RHE‐mc and temporal haplotype dynamics were assessed using ancient DNA data from Europe and Asia. Results A Neanderthal‐derived variant in TNPO3 (rs12531711), previously reported by Cordell et al. showed strong association in CANUK ( p = 2.04 × 10 −26 ) and replicated across all validation cohorts. This variant functions as an eQTL, upregulating IRF5 and downregulating TNPO3 in blood. It is rare in African populations but common both in Europeans and Asians. Temporal analysis of the haplotype carrying rs12531711 revealed frequency increased substantially during the Bronze Age (5000–3000 BP), rising from 2.0% to 7.7% in Europe and 3.4% to 17.4% in Asia, before stabilizing. Despite this strong single‐variant association, the heritability explained by NIMs was not significantly different from that of non‐NIM variants. Conclusion A Neanderthal‐derived variant contributes to PBC risk and its frequency increased in the Bronze Age, possibly due to pathogen‐driven selection. Archaic introgression overall has limited influence on PBC heritability. Functional studies are needed to elucidate the role of rs12531711.

OBJECTIVE The objective was to synthesize denominator-based evidence on indications, techniques, and postoperative outcomes of cervicomedullary decompression (CMD), spinal canal stenosis surgery, and cerebrospinal fluid (CSF) diversion for hydrocephalus in achondroplasia. METHODS This systematic review followed PRISMA 2020 and was prospectively registered (PROSPERO CRD42025626915). MEDLINE (via PubMed), Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception through November 2025. The authors included observational studies of patients with achondroplasia who underwent CMD, spinal canal stenosis surgery, or CSF diversion for hydrocephalus with extractable outcomes and definable denominators. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I. Random-effects single-arm meta-analyses were performed for prespecified endpoints (any improvement, complete resolution, and mortality) only in cohorts with fully categorizable symptom status. RESULTS The authors included 38 observational studies (1442 patients): 18 CMD studies with 600 patients, 18 spinal stenosis studies with 686 patients, and 4 hydrocephalus studies with 156 patients. No study was at low risk of bias. For CMD (mean age 3.5 years; mean follow-up 27.8 months), any improvement was observed in 93% (95% CI 84%–97%) of patients and complete resolution in 44% (95% CI 16%–77%), and pooled mortality was 0% (95% CI 0%–5%). For spinal stenosis (mean age 36.6 years; mean follow-up 53.1 months), any improvement was observed in 92% (95% CI 78%–97%) and complete resolution in 30% (95% CI 16%–51%), and pooled mortality was 1% (95% CI 0%–2%). Hydrocephalus management was predominantly ventriculoperitoneal shunting (74.4%), with endoscopic third ventriculostomy in 23.1%, but symptom outcomes were rarely classifiable (9.6%), precluding strategy-level inference. CONCLUSIONS CMD and spinal stenosis surgery were frequently followed by symptom improvement in published series, whereas complete resolution was variably defined and inconsistently reported. Hydrocephalus studies described practice patterns but lacked outcome reporting adequate for comparing diversion strategies. Validated patient-reported outcomes were rarely reported, limiting inference on health-related quality of life.

Objective: The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms (TAAAs) and complex abdominal aortic aneurysms (CAAAs) in patients actively smoking at the time of repair compared with previous smokers and non-smokers. Methods: Single-center retrospective review of elective FB-EVARs for TAAA and CAAAs between 2007 and 2023 was conducted. Demographics, comorbidities, aneurysm extent/ morphology, technical details, and peri-operative outcomes were collected. Patients were grouped into 1 of 3 groups: active smokers, prior smokers, and never smokers. Patients who stopped smoking within 6 weeks to surgery were considered active smokers. Rupture and symptomatic aneurysms were excluded. Endpoints included early (<30 days) mortality and major adverse events (MAEs). Results: There were 676 patients (73% male, mean age 74 ± 7.8). There were 141 (21%) active smokers, 455 (67%) prior smokers, and 80 (12%) never smokers. Active smokers were significantly younger than prior or never smokers (71 ± 6.7, 75 ± 6.9, and 76 ± 12, respectively; P < .001). Cardiovascular risk factors were similar, except active smokers were significantly more likely to have chronic obstructive pulmonary disease (60% vs 42% vs 6.2%, P < .001) and peripheral arterial disease (31% vs 24% vs 10%, P = .002) when compared to prior and never smokers, respectively. Patients who never smoked had significantly more extent II aneurysms (34%) than prior (18%) and active (15%) smokers, P = .001. Univariable and multivariable logistic regression analyses showed no statistically significant associations between smoking status and any specific peri-operative adverse events following surgery. Conclusion: Active smoking status does not appear to affect peri-operative outcomes after FB-EVAR for complex aortic aneurysms. Although smoking cessation must be strongly encouraged, repair should not be delayed due to active smoking status. Clinical Impact These data suggest that active smoking, in isolation, should not be considered a contraindication to elective FB-EVAR when anatomy is suitable and patients are otherswise optimized. This is particularly relevant for high-risk patients who may have limited alternative treatment options. Proceeding with FB-EVAR in active smokers does not appear to compromise early safety or procedural efficacy.

BACKGROUND Intraneural perineuriomas (INPs) are rare benign peripheral nerve sheath tumors with characteristic clinical and MRI features. Their 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appearance has not been characterized in a patient series. The authors evaluated FDG uptake patterns in INP. OBSERVATIONS The authors retrospectively reviewed that data of patients with confirmed INP who had MRI and FDG PET studies that included the affected nerve. Eight patients were included (5 male and 3 female; mean age 30.8 years, range 16–61 years). All lesions showed mildly increased FDG uptake relative to the contralateral nerve (lesion maximum standardized uptake value [SUVmax]: mean 1.5, median 1.2, range 1.1–3.5; contralateral nerve SUVmax: mean 0.9, median 0.9, range 0.8–1.0) and skeletal muscle background (SUVmean: mean 0.8, range 0.5–0.9). Six patients had denervation edema and/or fatty atrophy, without appreciably increased FDG uptake in the affected musculature. No additional abnormal hypermetabolic foci were identified. LESSONS INPs generally demonstrate low-level FDG uptake. PET is best regarded as a complementary test when already available or when metabolic characterization may refine the differential diagnosis; unexpectedly high uptake should prompt reconsideration of the diagnosis or additional evaluation. https://thejns.org/doi/10.3171/CASE26698