[Posted 18/Mar/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: By using integrative scRNA-seq, spatial transcriptomic analysis and functional assays, authors have uncovered a stem-like cell cluster marked with PTPRO and ASCL2 as the metastatic culprit, whose subpopulations show further different liver or ovary organotropism.

BACKGROUND: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered.

DETAILS: Authors performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). Authors also conducted immunofluorescence staining and functional experiments to examine the mechanism. Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary.

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Li, R., Liu, X., Huang, X., et al. (2024). Single-Cell Transcriptomic Analysis Deciphers Heterogenous Cancer Stem-Like Cells in Colorectal Cancer and Their Organ-Specific Metastasis. Gut. 2024; 73(3): 470-484 .Published: March, 2024. DOI: 10.1136/gutjnl-2023-330243.

A Multicenter Cohort Study

[Posted 1/Apr/2026]

AUDIENCE: Endocrinology, Internal Medicine

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.

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

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 (PPV_adj/NPV_adj) 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 PPV_adj (high risk), 14% (95% CI: 9%-21%) for PPV_adj (high/int risk), and 97% (95% CI: 96%-98%) for NPV_adj with minimal inter-study heterogeneity (I2=79%, 21%, 0%, 0%, and 0%, respectively).

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

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

[Posted 24/Mar/2026]

AUDIENCE: Infectious Disease, Endocrinology

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).

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

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.

Copyright © John Wiley & Sons Ltd. All rights reserved.

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

A Case Report

[Posted 2/Mar/2026]

AUDIENCE: General Surgery, Infectious Disease

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.

Copyright © Wiley Periodicals LLC. All rights reserved

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