[Posted 23/May/2023]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted.

BACKGROUND: Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD.

DETAILS: To test associations between protein carbamylation and the primary outcome of progression to ESKD, authors measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2-4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study. The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m², and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8-10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb <=5.80 mmol/mol), those in quartile 4 (C-Alb >10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR.

Copyright © American Society of Nephrology. All rights reserved.

Source: Kalim, S., Zhgao, S., Tang, M., et al. (2023). Protein Carbamylation and the Risk of ESKD in Patients with CKD.. Journal of the American Society of Nephrology. 2023; 34(5): 876-885. Published: May, 2023. DOI: 10.1681/ASN.0000000000000078.

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

[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 Retrospective Chart Review

[Posted 5/Mar/2026]

AUDIENCE: Hospice & Palliative Nursing, Nephrology

KEY FINDINGS: Hospice-eligible patients frequently have renally cleared medications prescribed and at doses too high for their renal function. Analgesics, over-the-counter antihistamines, anticoagulants, anticholinergics have potential for significant adverse effects and higher vigilance is needed.

BACKGROUND: Hospice-eligible patients are vulnerable to adverse medication effects given their advanced illnesses and general older age. It is not known how often medications are not renal dose adjusted in hospice-eligible patients and which are frequently problematic. This study aims to identify commonly prescribed medications with significant renal clearance that are dosed too high and patient characteristics that increase the likelihood of occurrence.

DETAILS: This is a retrospective chart review of adult patients admitted to hospice care. Data collected included clinical/demographic data, renally cleared medications taken at time of hospice admission, and calculated renal function using several formulas. Descriptive statistics and binomial logistic regression were used to analyze data. Of 283 included charts, 27% had >=1 medication dosed too high for renal function. The most common medications prescribed and not renal dose adjusted included tramadol, gabapentin, duloxetine, loratadine, cetirizine, famotidine, apixaban, rivaroxaban, metformin, trospium, and most antimicrobials. Increasing serum creatinine values and increasing number of renally cleared medications were associated with a higher likelihood of a medication dosed too high [OR, 1.702, 95% CI (1.257, 2.305), P < 0.001] and [OR, 1.856, 95% CI (1.517, 2.271), P < 0.001] respectively. Residing at home vs a facility was associated with a reduced likelihood of having a medication dosed too high [OR, 0.30, 95% CI (0.134, 0.673), P = 0.003.].

Copyright © SAGE Publications. All rights reserved.

Source: Latuga, N. M. and Levy, K. Medications Not Dosed Within Recommended Range for Renal Function in Patients With Chronic Kidney Disease Identified upon Hospice Admission: A Retrospective Chart Review. American Journal of Hospice and Palliative Medicine. 2026; 43(3): 234-241. Published: March, 2026. DOI: 10.1177/10499091251323284.

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