A Novel Unconventional T Cell Population Enriched In Crohn's Disease
Identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population.
KEY FINDINGS: Identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.
BACKGROUND: One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls.
DETAILS: Bulk TCR repertoire profiling of both the TCR alpha and beta chains was performed using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. It was further characterised specific T cell clonotypes via single-cell RNAseq. Identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs.
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Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
Source: Rosati, E., Rios Martini G., Pogorelyy, M. V., et al. (2022). A Novel Unconventional T Cell Population Enriched In Crohn's Disease. Gut. 2022; 71(11): 2194-2204. Published: November, 2022. DOI: XXXXXXXX.
Longitudinal Analysis of Liver Chemistry Trajectories and Risk of Type 2 Diabetes in Children With Metabolic Dysfunction-Associated Steatotic Liver Disease
Longitudinal increases in GGT and AST are strongly associated with an elevated risk of incident type 2 diabetes in children with MASLD, highlighting their value as dynamic biomarkers of metabolic dysfunction. Systematic tracking of these markers could help clinicians identify high-risk children earlier, facilitating timely intervention to mitigate type 2 diabetes progression.
KEY FINDINGS: A 30-unit increase in GGT over time was associated with a substantially higher risk of developing type 2 diabetes in children with MASLD. Together with AST, GGT may provide clinicians with concrete, routinely available parameters to monitor for early risk stratification. Further validation in independent cohorts is needed to confirm these findings and inform clinical application.
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children and is linked to type 2 diabetes. This study evaluates whether longitudinal changes in liver chemistries - γ-glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) - can serve as biomarkers of increased type 2 diabetes risk in children with MASLD.
DETAILS: This multicenter longitudinal cohort study followed 1,035 children with biopsy-confirmed MASLD, without type 2 diabetes at baseline, for a mean of 3.9 years. Liver chemistries were measured annually, and type 2 diabetes was diagnosed based on fasting glucose, HbA1c, and clinical diagnosis. Extended Cox models with inverse probability weighting were used to evaluate associations between liver enzyme trajectories and type 2 diabetes risk. The cumulative incidence of type 2 diabetes was 12.3%. Increases in GGT (hazard ratio [HR] 1.55; 95% CI 1.34-1.80), AST (HR 1.31; 95% CI 1.20-1.43), and ALT (HR 1.13; 95% CI 1.07-1.20) were associated with a higher risk of developing type 2 diabetes in the independent models. In the mutual model with all three liver chemistries, only GGT and AST remained significant.
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Copyright © American Diabetes Association. All rights reserved.
Source: Thai, N. Q. N., Chun, L. F., Newton, K. P., et al. Longitudinal Analysis of Liver Chemistry Trajectories and Risk of Type 2 Diabetes in Children With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Multicenter Cohort Study. Diabetes Care . 2026; 598-606. 49(4): Published: April, 2026. DOI: 10.2337/dc25-1532
The Tissue Systems Pathology Test Predicts Risk of Progression in Patients With Barrett's Esophagus
Study demonstrated mean effect estimates for ORs and HRs that were consistent with previously published performance metrics for the TSP-9 test in individual studies, with minimal heterogeneity across studies from both common-effect and random-effects models.
Summary
Systematic Review and Meta-Analysis
[Posted 31/Mar/2026]
AUDIENCE: Gastroenterology, Internal Medicine
KEY FINDINGS: Effect estimates of TSP-9 performance demonstrate that the test provides risk stratification for BE patients. The TSP-9 test can provide clinically impactful results to enable escalation of care for high-risk patients or to identify low-risk patients who can be safely managed with routine surveillance.
BACKGROUND: A systematic review and meta-analysis of published clinical validity studies was conducted to evaluate the predictive performance of the TSP-9 test. Identifying patients with Barrett’s esophagus (BE) who will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is challenging. The tissue systems pathology (TSP-9) test can predict risk of progression to HGD/EAC in BE patients.
DETAILS: Databases were searched for studies that assessed the clinical validity of TSP-9, and data describing progressors, non-progressors, TSP-9 results, and hazard ratios (HR) with 95% confidence intervals (CIs) were extracted. Odds ratios (OR), sensitivity, specificity, and prevalence-adjusted positive and negative predictive values (PPVadj/NPVadj) were calculated and used for meta-analysis. Six studies met eligibility criteria, comprising 699 patients. ORs and HRs for TSP-9 had mean common effect size estimates of 6.52 (95% CI: 4.40-9.66, P<0.0001, I2=33%) and 6.66 (95% CI: 4.59-9.66, P<0.0001, I2=0%), respectively, for predicting progression to HGD/EAC. Mean common effect size estimates were 61% (95% CI: 54%-68%) for sensitivity, 81% (95% CI: 78%-84%) for specificity, 28% (95% CI: 17%-42%) for PPVadj (high risk), 14% (95% CI: 9%-21%) for PPVadj (high/int risk), and 97% (95% CI: 96%-98%) for NPVadj with minimal inter-study heterogeneity (I2=79%, 21%, 0%, 0%, and 0%, respectively).
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Source: Houghton, C. C., Ditah, I., Leggett, C. L., et al. The Tissue Systems Pathology Test Predicts Risk of Progression in Patients With Barrett's Esophagus: Systematic Review and Meta-Analysis. Journal of Clinical Gastroenterology. 2026; 60(4)): 299-308. Published: April, 2026. DOI: 10.1097/MCG.0000000000002255
Microbial Dominance in Diabetic Foot Osteomyelitis Determined With Nanopore Sequencing Techniques Predicts Positive Response to Surgical Intervention
In patients with surgically treated OM, nanopore sequencing can generate interpretable metagenomic data from bone specimens that are culture concordant and associated with clinical response. These findings support the feasibility and plausibility of using real-time metagenomic sequencing to improve the clinical management of OM.
KEY FINDINGS: In patients with surgically treated OM, nanopore sequencing can generate interpretable metagenomic data from bone specimens that are culture concordant and associated with clinical response. These findings support the feasibility and plausibility of using real-time metagenomic sequencing to improve the clinical management of OM.
BACKGROUND: Tools to predict successful response to surgery for the treatment of diabetic foot osteomyelitis (OM) are currently lacking. Recent studies in nonbone infections have revealed that nanopore sequencing can provide real-time metagenomic identification of pathogens. In a cohort of patients with diabetic foot OM, we tested the feasibility of generating interpretable metagenomic data from surgically acquired osseous tissue, comparing bacterial community features (pathogen dominance) with clinical outcomes (resolution of infection). Researchers hypothesized that nanopore-generated microbial data can be feasibly generated from surgically acquired bone, aligns with conventional culture results, and is predictive of clinical response.
DETAILS: Researchers performed a pilot feasibility study of 10 consecutive patients hospitalized with diabetic foot OM who underwent surgery for OM. We performed metagenomic sequencing of surgical bone samples using the MinION (Oxford Nanopore). The primary metagenomic index was community dominance (relative abundance of most abundant species). The primary clinical end point was the clinical response to surgery, adjudicated at 1 year. Authors successfully generated interpretable metagenomic data from all 10 specimens, including 2 with negative culture growth. Among culture-positive specimens, the culture-identified pathogen was either the first or second most abundant organism in all cases. Patients with favorable clinical response exhibited greater pathogen dominance than those with unfavorable response (P = .002).
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Copyright © The Authors. Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Source: Schmidt, B. M., Ranjan, P., Erb-Downward, J., et al. Microbial Dominance in Diabetic Foot Osteomyelitis Determined With Nanopore Sequencing Techniques Predicts Positive Response to Surgical Intervention. The Journal of Infectious Disease. 2026; 233(3): 458-464. Published: March 15, 2026. DOI: 10.1093/infdis/jiaf617
Risk of Dyslipidemia Associated With Oral Janus Kinase Inhibitors
The meta-analysis found that all four JAKi drugs examined - baricitinib, upadacitinib, tofacitinib, and decernotinib - were associated with measurable increases in both HDL and LDL cholesterol compared to placebo. Notably, LDL elevations ranged from approximately 9 to 16 mg/dL depending on the drug, raising potential cardiovascular concerns. The authors conclude that dyslipidemia is a meaningful risk associated with JAKi therapy, and recommend that clinicians conduct routine lipid monitoring and regular cardiovascular risk assessments for patients on these medications to ensure long-term safety.
Summary
A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials
[Posted 16/Mar/2026]
AUDIENCE: Dermatology, Oncology
KEY FINDINGS: This systematic review and meta-analysis highlight the risk of dyslipidemia during treatment with JAKi, which could pose cardiovascular risks. Thus, regular assessments of cardiovascular risk factors and routine lipid monitoring in patients undergoing JAKi therapy may be essential for managing dyslipidemia and evaluating long-term cardiovascular safety.
BACKGROUND: Janus kinase inhibitors (JAKi) have sparked a new era in the treatment of immune-mediated diseases. While some studies have reported an increased incidence of dyslipidemia in JAKi-treated patients, the full extent of this adverse event is not established. The study aimed to assess the association between treatment with oral JAKi and dyslipidemia in phases 2 and 3 placebo-controlled randomized clinical trials (RCTs).
DETAILS: Janus kinase inhibitors (JAKi) have sparked a new era in the treatment of immune-mediated diseases. While some studies have reported an increased incidence of dyslipidemia in JAKi-treated patients, the full extent of this adverse event is not established. The study aimed to assess the association between treatment with oral JAKi and dyslipidemia in phases 2 and 3 placebo-controlled randomized clinical trials (RCTs). A systematic review and meta-analysis were conducted, encompassing phase 2 and 3 RCTs. The Embase, PubMed, and Web of Science databases were searched up to March 9, 2025. Only RCTs reporting lipid levels before and after treatment with JAKi were included. Data were extracted for changes in high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG) with values reported in mg/dL. A total of 13 studies were included in the analysis, comprising nine studies on rheumatoid arthritis, two on atopic dermatitis, one on Crohn's disease, and one on psoriasis. The studies encompassed a total of 3978 patients treated with JAKi and 1680 controls. Across all indications, the mean difference between JAKi and placebo for individual drug, was increased by 6.07 mg/dL (95% confidence interval [CI], 5.01-7.14) for HDL and 9.05 mg/dL (95% CI, 7.78-10.32) for LDL for baricitinib; HDL 5.4 mg/dL (95% CI, 3.2-7.7) and LDL 12.4 mg/dL (95% CI, 8.9-15.9) for upadacitinib; HDL 7.0 mg/dL (95% CI, 5.7-8.3) and LDL 15.7 mg/dL (95% CI, 12.9-18.6) for tofacitinib; and lastly HDL 3.0 mg/dL (95% CI, 0.2-5.8) and LDL 14.9 mg/dL (95% CI, 3.6-26.3) for decernotinib.
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Source: Isufi, D., Javanmardi, N., Jense, M. B., et al. Risk of Dyslipidemia Associated With Oral Janus Kinase Inhibitors: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. International Journal of Dermatology. 2026; 65: 737-745. Published: March, 2026. DOI: 10.1111/ijd.70122
Long-Term Control of Human Papillomavirus-Related Focal Epithelial Hyperplasia in an Human Immunodeficiency Virus-Positive Patient Using Methylene Blue-Mediated Photodynamic Therapy
Topical MB-mediated PDT successfully managed HPV-related FEH in an immunocompromised individual with history of valve disease. This outcome supports the need for further validation through clinical trials.
KEY FINDINGS: PDT mediated by MB is an effective and affordable approach for treating FEH associated with HPV in immunosuppressed patients, offering favorable outcomes and improved quality of life.
BACKGROUND: Human papillomavirus (HPV) infections are a major cause of oral lesions, and in individuals living with HIV, lesions such as focal epithelial hyperplasia (FEH) may persist or exhibit atypical features, potentially progressing to more severe conditions if untreated. Managing oral HPV lesions in immunocompromised patients is challenging, as conventional therapies may carry higher risks or show limited efficacy.
DETAILS: This study reports the case of a 49-year-old HIV-positive male with valve disease and arthritis, requiring crutches for mobility. He presented with multiple painless oral lesions, diagnosed as FEH associated with oral HPV, and had previously undergone unsuccessful treatments. Photodynamic therapy (PDT) using methylene blue (MB) and a red laser was proposed as a treatment. Topical MB-mediated PDT successfully cleared the FEH lesions, with no recurrence observed over 24 months.
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Source: de Araújo, J. C., Paiva, H. C., Faara, P. M. M., et al. Long-Term Control of Human Papillomavirus-Related Focal Epithelial Hyperplasia in an Human Immunodeficiency Virus-Positive Patient Using Methylene Blue-Mediated Photodynamic Therapy. A Case Report. Lasers in Surgery and Medicine. 2026; 58(2): 70-73. Published: February, 2026. DOI: 10.1002/lsm.70091
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