Adolescent diabetic kidney disease (DKD) represents an early-onset microvascular complication characterized by prolonged metabolic exposure and accelerated renal decline. Elevated serum creatinine and blood urea nitrogen (BUN) are key biochemical indicators of impaired renal function.

This scoping review aims to systematically map and evaluate pharmacological strategies for slowing the rise of creatinine and BUN in adolescents (aged 10-19 years) with DKD, with emphasis on renoprotective mechanisms, therapeutic sequencing and the potential applicability of these therapies to adolescent populations.

A scoping review was conducted in accordance with PRISMA-ScR guidelines. A comprehensive literature search was performed using PubMed, Scopus and Google Scholar for studies published between 2020 and 2025. Eligible studies included clinical trials, observational studies, clinical guidelines and relevant reviews focusing on pharmacological interventions in adolescents (10-19 years) with diabetic kidney disease. Study selection was based on predefined inclusion and exclusion criteria.

A total of 35 studies and guideline-based references were included in the final synthesis. Intensive glycemic control (insulin for type 1 diabetes; metformin ± insulin for type 2 diabetes) was associated with improved metabolic control and favorable renal outcomes. Renin-angiotensin system blockers consistently reduced albuminuria and induced an acute hemodynamic reduction but stabilized the long-term decline in estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated additional renoprotective effects in type 2 diabetes; risks (euglycemic DKA) limit use in type 1. In adult studies, finerenone attenuated inflammatory and fibrotic pathways; no adolescent data exist. Glucagon-like peptide-1 receptor agonists improved metabolic control and reduced obesity-associated renal stress. However, pediatric-specific evidence remains limited, and much of the available evidence is derived from adult studies.

Adult data suggest potential benefits of early multi-target pharmacotherapy, but adolescent-specific evidence is needed to confirm a critical role in delaying renal deterioration. Whether integration of conventional and novel agents improves long-term renal outcomes in adolescents requires direct investigation. Further pediatric-focused research is required to establish safety, efficacy and optimal therapeutic strategies.

Diabetic peripheral neuropathy (DPN) involves Schwann cell injury closely linked to endoplasmic reticulum (ER) stress. Melatonin shows neuroprotective potential, but the specific regulatory mechanisms involving the COX2-IRE1α axis remain to be clarified.

To investigate the potential regulatory role of melatonin in attenuating DPN through the modulation of the COX2-IRE1α ER-stress signaling axis.

In-vitro, RSC96 Schwann cells were exposed to high glucose (HG) and treated with melatonin (MT), COX2 overexpression, or IRE1α knockdown. Cell viability, apoptosis, and ER stress markers were assessed. In-vivo, 30 rats were divided into control, DPN and MT-treated DPN groups (n=10). After 4 weeks of treatment, sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), sciatic nerve morphology and protein expression in nerve tissues were analyzed.

HG significantly reduced cell viability and upregulated ROS and ER-stress markers (P < 0.05). MT treatment dose-dependently mitigated these effects. COX2 overexpression partially reversed MT-mediated protection, while IRE1α knockdown attenuated the damage induced by COX2. In DPN rats, 4-week MT treatment significantly improved MNCV and attenuated nerve morphological degeneration compared to the DPN group (P < 0.05). MT administration was associated with a significant reduction in COX2 and IRE1α protein expression in sciatic nerve tissue, paralleling the in vitro findings.

Melatonin treatment is associated with improved nerve function and reduced ER stress in DPN models. These protective effects may be mediated via the modulation of the COX2-IRE1α signaling axis, suggesting a potential therapeutic target for DPN.

To characterize longitudinal changes in routine blood count-derived inflammatory indices throughout pregnancy and the early postpartum period in women with diet-controlled gestational diabetes mellitus (GDM A1) compared with normoglycemic controls.

This retrospective cohort study included 366 pregnant women, comprising 170 women with GDM A1 and 196 normoglycemic controls, who received antenatal care at Beijing Friendship Hospital. Routine complete blood count parameters were collected at seven clinically relevant time windows: 8-12, 16-20, 24-28, 28-32, and 36 weeks of gestation, immediately before delivery, and postpartum. The aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were calculated. Exploratory unadjusted between-group comparisons were performed using Mann-Whitney U-tests. Adjusted linear mixed-effects models were used to evaluate group-by-time interactions while accounting for within-subject correlation and baseline covariates.

Women with GDM A1 were older and had higher early-pregnancy BMI than normoglycemic controls. After adjustment for maternal age, early-pregnancy BMI, gravidity, parity, and history of macrosomia, significant group-by-time interactions were observed for all six inflammatory indices, including AISI (P < 0.001), SIRI (P < 0.001), SII (P = 0.017), LMR (P = 0.011), MLR (P = 0.011), and PLR (P = 0.022). In Holm-adjusted post hoc comparisons, SIRI was higher in the GDM A1 group during the postpartum period (adjusted ratio = 1.204, 95% CI: 1.066-1.360, P = 0.020), and PLR was higher immediately before delivery (adjusted ratio = 1.123, 95% CI: 1.036-1.217, P = 0.032).

Women with GDM A1 showed altered longitudinal trajectories of CBC-derived inflammatory indices, with the most robust adjusted time-specific differences involving postpartum SIRI and pre-delivery PLR. These indices may provide accessible research markers for characterizing stage-specific inflammatory patterns in diet-controlled GDM, but prospective studies incorporating direct inflammatory and metabolic measurements are required to establish clinical utility.

The accuracy of the FreeStyle Libre 2 system in critically ill patients needing insulin therapy remains inadequately evaluated.

To evaluate the clinical and numerical accuracy of continuous glucose monitoring (FreeStyle Libre 2) and capillary glucometry (StatStrip) compared with central laboratory glucose in critically ill patients requiring insulin therapy.

We conducted a diagnostic accuracy study, evaluating simultaneously two index tests, the FreeStyle Libre 2 and capillary glucose, compared to the central laboratory glucose (venous or arterial) as reference standard. The study included critically ill adult patients admitted to the intensive care unit (ICU) with diabetes or stress hyperglycemia, requiring insulin therapy, and ventilatory or vasopressor support. Numerical accuracy was assessed using ISO 15197:2013 criteria and Mean Absolute Relative Difference (MARD). Clinical accuracy was evaluated using Clarke and Parkes error grid analysis.

A total of 157 paired measurements were collected. FreeStyle Libre 2 showed a MARD comparable to capillary glucose (10.43% vs 7.58%; p=0.14). Neither method met ISO 15197:2013 numerical accuracy criteria. In the clinical accuracy analysis, FreeStyle Libre 2 classified 100% of measurements within zones A+B on both the Clarke and Parkes grids, whereas capillary glucose achieved 97.6% and 100%, respectively.

FreeStyle Libre 2 showed numerical accuracy comparable to capillary blood glucose and consistently reliable clinical performance in critically ill patients needing insulin therapy. These results support its potential as an alternative to capillary glucose monitoring in the ICU. More studies involving a greater number of hypoglycaemic events are required to confirm its effectiveness in this critical range.

Objectives The study aims to identify the microbiological characteristics, clinical features, and outcomes of adult patients with septic arthritis (SA) at Sultan Qaboos University Hospital (SQUH), Muscat, Oman, over a 10-year period from 2011 to 2020. Methods The study is an observational retrospective study that was conducted by retrospectively reviewing culture-positive SA cases treated at SQUH from 2011 to 2020. The data were collected from the hospital medical record (InterSystems TrakCare®; InterSystems Corporation, Cambridge, MA, USA) for patients whose ages were ≥18 years at the time of admission. The study was approved by the Medical Research and Ethics Committee of the College of Medicine and Health Sciences at SQU. Results A total of 57 adult patients (41 males, 71.9%) were identified to have native joint SA. The median age was 50 years. Among these patients, 24 patients (42%) had pre-existing joint disease, most commonly osteoarthritis (13 cases, 22.8%). Diabetes (23 patients, 40.4%) and sickle cell disease (SCD) (11 patients, 19.3%) were the most common comorbid conditions. A single joint was involved in 49 cases (86.0%). The most involved joints were the knee (34 cases, 59.6%), the hip (seven cases, 12.3%), and the shoulder (five cases, 8.8%). The most common causative pathogens were Staphylococcus aureus in 17 cases (29.8%), followed by Pseudomonas aeruginosa in nine cases (15.8%). Most patients underwent surgical interventions, including arthroscopic washout in 39 cases (68.4%) and arthrotomy in five cases (8.8%). The median duration of intravenous antibiotics was 14 days, and the median duration of oral antibiotics was 14 days. Seven cases were treated with antibiotics only without any surgical intervention. The mortality rate was 7%. Conclusion In this study, SA was more commonly observed among elderly patients and those with comorbidities, particularly diabetes mellitus and SCD. S. aureus was the most common organism.

Saprochaete capitata is a rare opportunistic yeast-like fungus increasingly recognized as a cause of invasive infections, predominantly in immunocompromised hosts. While most cases are reported in patients with hematological malignancies and neutropenia, infections in patients with chronic metabolic and renal disorders are uncommon and often underdiagnosed. Isolation of S. capitata from urine is particularly rare and poses diagnostic challenges in distinguishing colonization from invasive disease.

We report a fatal case of sepsis associated with Saprochaete capitata isolated from the urine of a 65-year-old male with type 2 diabetes mellitus, chronic kidney disease, and chronic lymphatic filariasis. The patient presented with fever, chills, tachycardia, cellulitis of the right lower limb, and features of systemic inflammatory response syndrome. Laboratory investigations revealed marked leukocytosis, elevated inflammatory markers, and acute-on-chronic renal failure. Despite clinical features of sepsis, repeated bacterial blood and urine cultures were sterile. Urine microscopy showed pyuria, and culture on CLED agar yielded dry, creamy-white, yeast-like colonies. A lactophenol cotton blue mount demonstrated hyaline septate hyphae with rectangular arthroconidia. The isolate was urease-negative and was definitively identified as Saprochaete capitata by MALDI-TOF mass spectrometry. Antifungal susceptibility testing revealed low minimum inhibitory concentrations (MICs) for voriconazole, itraconazole, and posaconazole, with elevated MICs for echinocandins, consistent with known resistance patterns. The patient was treated empirically with broad-spectrum antibacterial agents but did not receive early antifungal therapy. His clinical condition rapidly deteriorated, progressing to septic shock and multi-organ dysfunction syndrome, requiring intensive care support, mechanical ventilation, vasopressors, and hemodialysis. Despite maximal supportive care, the patient succumbed to his illness.

This case highlights the clinical significance of isolating Saprochaete capitata from urine in high-risk patients presenting with sepsis and negative bacterial cultures. It underscores the need for heightened clinical suspicion, prompt fungal identification using advanced diagnostic methods, and early initiation of appropriate antifungal therapy. Awareness of this rare but aggressive pathogen is crucial for improving outcomes in vulnerable patient populations.

The aim of the study is to integrate targeted transcriptomic analyses of previously identified biomarker proteins (proteomic findings) to better understand vascular complications (Cx) in Type 2 diabetes (T2D).

Total RNA was extracted from baseline citrate plasma samples of 543 individuals with T2D from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Among these, 224 participants had microvascular Cx, 142 had macrovascular Cx (51 had both types of Cx) and 228 had no Cx (control group). mRNA expression was quantified using the OpenArray platform and group differences were analysed using ΔΔct values. Neutrophil elastase (NE) protein levels were measured in baseline plasma by ELISA.

Eleven genes were retained for focused analysis. For microCx, the largest gene expression differences were observed for clusterin (~2-fold upregulation) and integrin alpha-IIb (~50% downregulation), compared with the control group. For macroCx, clusterin exhibited the strongest upregulation (~2.5-fold), whereas apolipoprotein F showed the greatest downregulation (~20%). Comparative analysis of proteomic and transcriptomic data across study groups revealed that only 32% of gene expression differences were mirrored at the protein level. NE levels were highest in the microCx group and were significantly elevated versus control only in that group; NE levels also correlated inversely with circulating actin protein expression (R² = 0.92).

Combining proteomic and targeted plasma transcriptomic data provides exploratory insights into biological processes associated with vascular complications in T2D and highlights NE as a candidate component of a proteolytic pathway for further investigation.

Relapse limits survival after allogeneic hematopoietic cell transplant. Although human leukocyte antigen-matched related donors (MRDs) are traditionally preferred, mismatched unrelated donors (MMUDs) using posttransplant cyclophosphamide may provide stronger graft-vs-leukemia effects, potentially altering donor selection strategies.

To compare outcomes between MRD and MMUD transplant in the posttransplant cyclophosphamide era and assess whether MMUD grafts are associated with lower relapse rates.

This retrospective cohort study (January 1, 2017, to August 31, 2024) assessed 1038 patients with acute leukemia or myelodysplastic syndromes and/or myeloproliferative neoplasms undergoing their first peripheral blood hematopoietic cell transplant using posttransplant cyclophosphamide. The MRD cohort was from a single tertiary center, and the MMUD cohort was from the Center for International Blood and Marrow Transplant Research. Data were analyzed between January 19, 2026, and April 2, 2026.

Transplant from MRD (n = 306) vs MMUD (n = 732).

Disease-free survival (DFS), overall survival (OS), relapse, nonrelapse mortality, and graft-vs-host disease (GVHD). The study used inverse probability of treatment weighting with overlap weights and bootstrapping to address structural confounding, particularly donor age. Cox proportional hazard models were used to compare outcomes between groups and confirm that phrasing with the author.

Among 1038 patients (526 [50.7%] female), donors in the MRD group were older (median [IQR] age, 57 [45-64] years) than in the MMUD group (median [IQR] age, 28 [24-35] years) (P < .001). Recipient age was similar (median [IQR] age, 60 [47-66] vs 58 [47-65] years; P = .40). In patients with a high or very high Disease Risk Index (DRI), MMUD transplant was associated with significantly lower relapse hazard vs MRD (weighted hazard ratio [HR], 0.56; 95% CI, 0.33-0.94; P = .03), although DFS (HR, 0.71; 95% CI, 0.46-1.11; P = .14) and OS (HR, 0.85; 95% CI, 0.53-1.37; P = .51) were similar. Conversely, in patients with low to intermediate DRIs, hazard estimates for DFS (HR, 1.24; 95% CI, 0.92-1.66; P = .16) and OS (HR, 1.36; 95% CI, 0.99-1.88; P = .06) lacked precision. MMUD was associated with lower risk of grade III to IV acute GVHD (HR, 0.56; 95% CI, 0.32-0.98; P = .04) but higher chronic GVHD (HR, 2.82; 95% CI, 2.02-3.95; P < .001).

In this cohort study, MMUD transplant was associated with lower relapse rates compared with MRD in patients with high-risk malignant tumors, potentially reflecting enhanced alloreactivity, although accompanied by increased chronic GVHD. These findings indicated that the immunologic role of human leukocyte antigen mismatch varies by disease risk, suggesting that MMUD grafts offered a distinct risk-benefit profile that warrants further investigation.

Radical cystectomy for bladder cancer is associated with high complication rates. Evidence supporting perioperative specialized immunonutrition for reducing complications is limited.

To determine whether perioperative specialized immunonutrition reduces 30-day complications compared with standard oral nutrition support among adults undergoing radical cystectomy.

This multicenter, randomized, double-blind, phase 3 clinical trial (SWOG S1600) conducted at 13 US academic and community sites within the National Cancer Institute National Clinical Trials Network and National Community Oncology Research Program enrolled patients from March 5, 2019, through October 19, 2023, with 30-day complications assessed through day 90 and survival outcomes through 2 years. Participants included adults with bladder cancer scheduled for radical cystectomy who could swallow oral liquids and did not have severe malnutrition. Statistical analysis was performed from January 2024 to December 2026.

Participants consumed drinks 3 times daily for 5 days before and after surgery. Both drinks used the same base formula. The immunonutrition product contained added l-arginine, ω-3 fatty acids, and dietary nucleotides. Adherence was 94.5% (52 of 55), measured using the plasma arachidonic acid to eicosapentaenoic acid biomarker.

Analysis was performed on a modified intent-to-treat basis. The primary outcome was any 30-day complication (Clavien-Dindo grade ≥1). A 65% complication rate and a 35% relative reduction were prespecified. Secondary outcomes included high-grade complications at 30 and 90 days, adverse events, and 2-year disease-free and overall survival.

Of the 203 participants enrolled, the median age was 68.8 years (range 32.0-95.2 years) and 162 (79.8%) were male. Of 203 randomized (99 immunonutrition, 104 standard), 17 withdrew, and 8 lacked 30-day data, yielding 178 evaluable participants (90 immunonutrition, 88 standard). Any 30-day complication occurred in 62.2% of patients (56 of 90) receiving immunonutrition and 58.0% of patients (51 of 88) receiving standard nutrition (odds ratio [OR], 1.18; 95% CI, 0.64-2.18). High-grade 30-day complications occurred in 11.1% of patients (10 of 90) receiving immunonutrition vs 12.5% of patients (11 of 88) receiving standard nutrition (OR, 0.86; 95% CI, 0.34-2.17). Two-year overall survival was 87.4% among patients receiving immunonutrition vs 78.2% among patients receiving standard nutrition, and disease-free survival was 77.0% among patients receiving immunonutrition vs 67.5% among patients receiving standard nutrition. Adverse events occurred for 34.1% of patients (31 of 91) receiving immunonutrition and 20.5% of patients (18 of 88) receiving standard nutrition, with nausea most common.

In this randomized clinical trial of adults undergoing radical cystectomy, perioperative specialized immunonutrition did not reduce 30-day complications compared with standard oral nutrition. Differences in 2-year survival favored immunonutrition but were not statistically significant. Further mechanistic evaluation and subgroup analyses are warranted.

ClinicalTrials.gov Identifier: NCT03757949.

Psychological distress in breast cancer survivors (BCS) is highly prevalent. Access to treatment is limited by barriers, including a lack of psychotherapists.

To evaluate the efficacy of a scalable, publicly accessible digital mental health treatment (DMHT) for reducing symptoms of depression and anxiety in BCS and the effect of human coaching on engagement among BCS with initially low engagement.

This randomized clinical trial followed the SMART (Sequential, Multiple Assignment, Randomized Trial) design and was conducted in the US between September 2021 and January 2024. Adult women who were within 5 years of receiving a breast cancer diagnosis (stage I-III), had a smartphone with a data plan, and had elevated symptoms of depression or anxiety were eligible for inclusion. Participants completed self-reported questionnaires at baseline, 8-week postintervention period, and 6-month and 12-month follow-up periods. Participants were randomized 2:1 to either the DMHT (IntelliCare) or the patient education program. Data analysis was based on intention-to-treat principle.

The DMHT program is an 8-week self-guided, fully automated suite of 5 clinically focused applications. Participants in the DMHT group were classified as having optimal or suboptimal engagement based on week 1 use. Those with suboptimal engagement were subsequently randomized 1:1 to receive additional coaching or no coaching. The patient education program is an active control condition consisting of 8 weeks of use of a psychoeducational application and no human support.

Primary outcomes were symptoms of anxiety (self-assessed using the 7-item Generalized Anxiety Disorder) and depression (self-assessed using the 8-item Patient Health Questionnaire). Secondary outcomes were number of days of application use and number of application sessions.

A total of 313 women (mean [SD] age, 51.62 [10.51] years) were enrolled and assigned to the DMHT program (n = 209) or the patient education program (n = 104). Primary analyses included 272 participants. Participants in both DMHT and patient education programs showed significantly reduced symptoms of both depression (Cohen d = -0.60 at the 8-week, -1.03 at the 6-month, and -1.13 at the 12-month assessment) and anxiety (Cohen d = -0.68 at the 8-week, -0.80 at the 6-month, and -0.85 at the 12-month assessment) from baseline. Compared with participants in the patient education group, those in the DMHT group showed significantly greater reductions in symptoms of anxiety (average marginal effect [AME] = -1.43; z = -2.65 [95% CI, -2.49 to -0.38]; P = .01) but not for symptoms of depression (AME = -0.98; z = -1.89 [95% CI, -1.99 to 0.04]; P = .06). Compared with participants with suboptimal engagement who did not receive coaching, those who received coaching used the intervention for a significantly greater number of days (mean [SD], 27.48 [0.94] vs 24.04 [1.16] days; P = .02).

This randomized trial found that BCS can benefit from a DMHT program, particularly for reducing anxiety. Coaching may promote consistent engagement with a DMHT for those with difficulty engaging initially.

ClinicalTrials.gov Identifier: NCT04583891.