Glucose Intolerance In Pregnancy and Risk Of Early-Onset Type 2 Diabetes
Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood.
KEY FINDINGS: Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy.
BACKGROUND: The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood.
DETAILS: For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. Researcghers included 177,241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7.8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5.3 mmol/L) or higher in the fasting state; 180 mg/dL (10.0 mmol/L) or higher at 1 h; 155 mg/dL (8.6 mmol/L) or higher at 2 h; and 140 mg/dL (7.8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. During a cumulative follow-up of 1,882,647 person-years, and with a median follow-up of 10.8 (IQR 5.2-16.4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2.6 (95% CI 2.4-2.9) per 10,000 person-years in women with gestational normoglycaemia, 8.9 (7.4-10.6) per 10,000 person-years in women with an abnormal GCT and normal OGTT, 26.1 (22.4-30.1) per 10,000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71.9 (66.0-78.3) per 10,000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3.39 [95% CI 2.77-4.16]; p<0.0001), in women with one abnormal OGTT value (9.11 [7.64-10.86]; p<0.0001), and in women with gestational diabetes (24.84 [21.78-28.34]; p<0.0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11.81 [95% CI 8.58-16.25]; p<0.0001), and in women with gestational diabetes and an abnormal fasting glucose (38.02 [32.41-44.61]; p<0.0001).
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Source: Bardugo, A., Bendor, C. D., Rotem, R. S., et al. (2023). Glucose Intolerance In Pregnancy and Risk Of Early-Onset Type 2 Diabetes: A Population-Based Cohort Study. The Lancet. 2023; 11(5): 333-344. Published: May, 2023. DOI: 10.1016/S2213-8587(23)00062-1.
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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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
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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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
Oral Itraconazole Versus Oral Voriconazole for Treatment-Naive Patients With Chronic Pulmonary Aspergillosis in India (VICTOR-CPA Trial)
Voriconazole was not superior to itraconazole for treating chronic pulmonary aspergillosis and was associated with a significantly higher incidence of adverse events. Our findings support the continued use of itraconazole as the preferred therapy for chronic pulmonary aspergillosis, although voriconazole remains a reasonable alternative. The choice between the two agents should be guided by factors such as patient tolerance, drug availability, and cost considerations.
Summary
A Single-Centre, Open-Label, Randomised, Controlled, Superiority Trial
[Posted 28/Feb/2026]
AUDIENCE: Infectious Disease
KEY FINDINGS: Voriconazole was not superior to itraconazole for treating chronic pulmonary aspergillosis and was associated with a significantly higher incidence of adverse events. Our findings support the continued use of itraconazole as the preferred therapy for chronic pulmonary aspergillosis, although voriconazole remains a reasonable alternative. The choice between the two agents should be guided by factors such as patient tolerance, drug availability, and cost considerations.
BACKGROUND: Both itraconazole and voriconazole are used to treat chronic pulmonary aspergillosis. However, treatment success with itraconazole is only around 65-70%. Voriconazole, with its lower minimum inhibitory concentrations and better oral bioavailability, might offer improved outcomes, but no head-to-head comparison has been conducted to date. We aimed to evaluate whether oral voriconazole is superior to itraconazole in treating chronic pulmonary aspergillosis.
DETAILS: This single-centre, prospective, open-label, superiority trial was conducted at the chest clinic of a tertiary care hospital in Chandigarh, India. We enrolled treatment-naive adults aged 18 years or older with chronic cavitary pulmonary aspergillosis or chronic fibrosing pulmonary aspergillosis. We excluded those who denied consent, received any antifungal azoles for more than 3 weeks in the previous 6 months, or had other forms of aspergillosis. Participants were randomly assigned 1:1 to receive 200 mg twice daily of oral itraconazole or oral voriconazole for 6 months, using a computer-generated randomisation sequence with variable block sizes (4-8). Participants, staff administering the interventions, clinical outcome assessors, and data analysts were not masked to treatment assignment; a radiologist masked to clinical details and treatment allocation evaluated chest images. The primary outcome was the proportion of participants achieving a favourable response (clinical and radiological stability or improvement) at 6 months in the modified intention-to-treat population, which included all participants who received at least one dose of the allocated treatment. The safety analyses (a secondary outcome) were also performed in the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04824417) and is complete. Between April 15, 2021, and May 31, 2024, 150 individuals were screened, and 116 were randomly assigned to receive itraconazole (n=58) or voriconazole (n=58). Of the 116 participants, 74 (64%) were men, 42 (36%) were women, and the mean age was 45.9 years (SD 14.4). All participants received at least one dose of the study drug and were included in the primary analysis. The proportion of participants achieving a favourable response at 6 months was similar in both groups (69% [40 of 58] receiving voriconazole vs 67% [39 of 58] receiving itraconazole; absolute risk reduction -0.02 [95% CI -0.2 to 0.15], p=0.84). Voriconazole was associated with significantly more treatment-related adverse events than itraconazole (55% [32 of 58] of participants receiving voriconazole vs 34% [20 of 58] receiving itraconazole, p=0.025). There were four deaths, all in the voriconazole group; none were directly attributable to the treatment.
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Source: Sehgal, I. S., Agarwal, R., Dhooria, S., et al. Oral Itraconazole Versus Oral Voriconazole for Treatment-Naive Patients With Chronic Pulmonary Aspergillosis in India (VICTOR-CPA Trial): A Single-Centre, Open-Label, Randomised, Controlled, Superiority Trial. The Lancet Infectious Diseases. 2026; 26(3): 239-249 Published: March, 2026. DOI: 10.1016/S1473-3099(25)00537-7.
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