While protein fibrillation represents a critical challenge in therapeutic insulin delivery, the structural determinants and immunological consequences of insulin-derived fibrils (IDFs) formed in the presence of phenolic preservatives remain poorly characterized. This study investigated the structural characteristics of IDFs formed with (IDF (+)) and without (IDF (-)) phenolic preservatives and elucidated their differential immunomodulatory mechanisms in bone marrow-derived macrophages (BMDMs). IDF structural properties were characterized using Thioflavin T fluorescence and nanoparticle tracking analysis (Spectradyne nCS1™). BMDMs were treated with IDF (+), IDF (-), or m-cresol. Cytotoxicity, reactive oxygen species (ROS) production, MIP-1α levels, and expression of signaling pathways were quantified. Structural analysis revealed similar aggregation states between IDF (+) and IDF (-). However, IDF (+) induced greater cytotoxicity and ROS production than IDF (-), which produced minimal ROS. Both fibrils increased MIP-1α levels. Additionally, IDF (-) upregulated NRF2 whereas m-cresol downregulated STAT6. Together, these results suggest distinct mechanisms of macrophage activation and suggest that protein aggregates can induce macrophage responses directly. Insulin fibrils activate macrophage inflammatory pathways through ROS-independent mechanisms. Phenolic preservatives enhance fibril cytotoxicity and likely ROS production while differentially modulating inflammatory signaling. These findings suggest that strategies to attenuate the effects of IDFs in insulin infusion therapy may increase longevity and biocompatibility of these devices.

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for managing patients with acute coronary syndromes (ACS) is the first major update since the 2013-2015 ST-elevation myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI) guidelines. It brings both conditions together into a single framework. This review covers the most important new and revised recommendations and points out where evidence is still lacking.

Rozanolixizumab (rozanolixizumab-noli; RYSTIGGO[®]), a humanised immunoglobulin G4P monoclonal antibody, is a subcutaneously administered neonatal Fc receptor (FcRn) inhibitor approved for the treatment of both acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) in adults. The pivotal, randomised, placebo-controlled phase III MycarinG trial demonstrated that a 6-week cycle of once-weekly rozanolixizumab ≈ 7 mg/kg or ≈ 10 mg/kg resulted in statistically significant and clinically meaningful improvements across all myasthenia gravis-specific scales assessed at day 43 versus placebo. Treatment benefits were rapid, sustained and consistent across repeated symptom-driven rozanolixizumab cycles. In a randomised, open-label, phase III crossover trial, self-administered rozanolixizumab improved MG symptoms regardless of whether manual push or infusion pump method was used. Rozanolixizumab was generally well tolerated with an acceptable safety profile; the most common adverse events were headache, diarrhoea, pyrexia and nausea. Thus, rozanolixizumab is an efficacious and generally well tolerated therapy for adults with AChR or MuSK Ab+ gMG, representing a convenient and valuable additional treatment option for these patients.

Effective diabetes management in adolescents with Type 1 diabetes is crucial to reduce the risk of long-term complications. However, adolescents show the poorest glycemic outcomes of all age groups. A bihormonal fully closed-loop (FCL) system, which requires no user input, may help address these challenges. In this trial, the performance and safety of a bihormonal FCL system (Inreda® AP) was evaluated in adolescents. The trial was a single-center, randomized, crossover trial in adolescents with Type 1 diabetes aged 12-18 years. The FCL system was compared with the participants' usual diabetes treatment in a home healthcare setting. The trial consisted of two study periods of 2 weeks, separated by a 2-week washout period. The primary endpoint was time in range (TIR; 3.9-10.0 mmol/L). In total, 20 individuals were enrolled and the data from 15 of them were analyzed. Glucose outcome parameters showed significant improvements during the FCL treatment period. Median TIR was 61.3% [interquartile range (IQR): 53.7%-68.2%] in the control period compared with 74.9% (IQR: 73.1-81.0) during the FCL period (p < 0.001). Additionally, other glucose outcomes including time above range (> 10.0 mmol/L) and median blood glucose were significantly improved in the FCL treatment period. To conclude, this trial provides preliminary evidence that treatment with the bihormonal FCL system may improve glucose outcome parameters, with no safety concerns observed in adolescents with Type 1 diabetes over the short study duration. However, future research should focus on long-term trials with larger study populations to confirm these findings and evaluate the long-term effects of bihormonal FCL treatment in adolescents.

This study aimed to evaluate the clinical efficacy and safety of hybrid closed-loop systems for glycemic control in children aged < 7 years with Type 1 diabetes. Relevant studies published up to July 30, 2025 were electronically retrieved from the PubMed, Cochrane Library, Embase, and Web of Science databases. Two investigators independently screened the literature, extracted valid data, and assessed the risk of bias of included studies, with a meta-analysis conducted via RevMan 5.4 software. Three randomized controlled trials, with 274 children enrolled, were incorporated into the analysis. The results indicated that 3 months of using the hybrid closed-loop system significantly increased the percentage of time in range (mean difference [MD] = 9.95%, 95% confidence interval [CI] [7.8, 12.09], p < 0.00001) and reduced glycated hemoglobin (MD = -0.51%, 95% CI [-0.64, -0.37], p < 0.00001). However, no significant difference was noted in the percentage of time below range between the two groups (MD = 0.56%, 95% CI [-0.13, 1.25], p = 0.11). A comparison of serious adverse events showed no statistically significant differences in the risk of diabetic ketoacidosis (p = 0.50) and severe hypoglycemia (p = 0.64) between the hybrid closed-loop system group and the conventional therapy group. The hybrid closed-loop system can effectively improve glycemic control in children under 7 years old with Type 1 diabetes without increasing the risk of adverse events. Further high-quality, large-sample clinical studies are still required to verify and supplement the present conclusions.

Open-source automated insulin delivery shows promise for managing type 1 diabetes, though pediatric efficacy and safety data remain limited. This study aimed to compare real-world glycemic outcomes of open-source automated insulin delivery systems with hybrid closed-loop systems in youth with type 1 diabetes. This retrospective cohort study included individuals aged ≤ 19 years with type 1 diabetes for at least one year who used either open-source automated insulin delivery systems (Loop, iAPS, or AndroidAPS) or hybrid closed-loop systems (Tandem t:slim) for at least six months between January 2015 and June 2024. Data were collected from one month before system initiation to 18 months after initiation or the last clinical visit. Glycated hemoglobin, time in range, and glucose management indicator were evaluated using regression analyses and adjusted linear mixed-effects models. A total of 198 participants (143 open-source automated insulin delivery and 55 hybrid closed-loop users) were included (mean age 13.8 years; 57% male). Over 18 months, glycated hemoglobin decreased from 7.40% to 6.96% in the open-source automated insulin delivery group and from 7.35% to 7.28% in the hybrid closed-loop group. Adjusted analyses showed no significant differences in glucose management indicator or time in range between groups across follow-up. Severe hypoglycemia occurred in one participant per group, and no diabetic ketoacidosis events were observed. Open-source automated insulin delivery systems demonstrated similar long-term glycemic outcomes and safety compared with hybrid closed-loop systems, supporting their use as a safe, non-inferior alternative.