Molecular testing has emerged as a pivotal tool for the preoperative assessment of cytologically indeterminate thyroid nodules. In this cross-sectional study, we evaluated the diagnostic utility of a targeted next-generation sequencing (NGS) 4-gene panel, including BRAF^V600E, TERT promoter mutations, RET fusions, and NTRK3 fusion, for enhancing the cytological diagnosis of thyroid nodules prior to surgical intervention. A total of 827 thyroid nodules subjected to fine-needle aspiration and subsequent histopathological confirmation were analyzed, among which 773 (93.5%) were classified as malignant or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The observed prevalence of molecular alterations was: BRAF^V600E, 68.3% (526/770); TERT promoter mutations, 10.3% (79/770); RET fusions, 10.3% (79/770); and NTRK3 fusion, 3.9% (30/770). Notably, the 4-gene NGS panel demonstrated brilliant diagnostic performance for indeterminate cytological nodules (Bethesda categories III-V), achieving a sensitivity of 87.9%, specificity of 96.3%, positive predictive value (PPV) of 99.7%, negative predictive value (NPV) of 35.9%, and overall accuracy of 88.2%. These findings indicate that the targeted NGS 4-gene panel provides high diagnostic precision in distinguishing benign from malignant nodules. Its implementation offers a cost-effective, efficient molecular diagnostic strategy that may reduce unnecessary diagnostic procedures and facilitate optimized clinical management.

Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world settings. We retrospectively analyzed 1048 newly diagnosed MM patients from the National Longitudinal Cohort of Hematological Diseases in China (NICHE) between 2012 and 2023, with a total of 5406 MRD assessments. A longer time to best MRD response (> 6 months) was significantly associated with improved progression-free and overall survival, especially among those with persistent MRD positivity but stable low-level disease burden. Early responders were more likely to exhibit high tumor burden and high-risk cytogenetic abnormalities. Notably, a prolonged MRD duration (≥ 36 months) predicted favorable outcomes regardless of MRD negativity status. Integrating response timing and duration identified a "Late + Durable" MRD pattern consistently associated with the best prognosis, even in patients with persistent MRD positivity, high-risk cytogenetics, or without ASCT. These findings highlight the prognostic significance of longitudinal MRD monitoring beyond single-timepoint assessments. A slow but durable MRD response may overcome adverse biological features and support individualized risk stratification, therapeutic decisions, and long-term disease monitoring in MM.

Plant based protein consumption is increasingly recognized for its therapeutic potential in managing metabolic health and preventing chronic diseases. This review provides a comprehensive analysis of the physiological impact of plant proteins, including their roles in satiety regulation and weight management via the modulation of appetite regulating hormones. We examine how plant proteins optimize lipid metabolism and reinforce gut homeostasis by promoting diverse microbiota and increasing the production of short chain fatty acids. Furthermore, we dissect the mechanisms through which plant proteins and their digestion derived peptides attenuate the pathogenesis of cardiovascular disease, type 2 diabetes, and chronic kidney disease. Specific attention is given to the modulation of intracellular signaling pathways such as PI3K-Akt and the regulation of the renin angiotensin system. The review also highlights that the health efficacy of plant proteins is highly dependent on the food matrix, where synergistic interactions between proteins, fiber, and phytochemicals are critical. Finally, the impact of food processing on peptide bioaccessibility is examined, and a process-matrix function paradigm is proposed for future research. In conclusion, these insights underscore the role of plant proteins as functional components that are essential for developing sustainable and precise nutritional strategies to mitigate the global burden of non-communicable diseases.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.

This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.

The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.

Diabetes mellitus presents a growing public health challenge across geographies including Asia, particularly in countries where blood glucose monitoring (BGM)-referring to capillary finger-prick self-monitoring of blood glucose (SMBG) using a meter and test strips-is underutilized. Having evolved and improved over recent decades, glucose monitoring (GM)-including SMBG and continuous glucose monitoring (CGM)-has become an essential tool for effective diabetes management, yet remains underutilized because of systemic, economic, and educational barriers. This work synthesizes expert insights and published evidence to develop best practice recommendations for BGM.

A targeted literature review (TLR) was conducted across five thematic domains: monitoring practices, clinical decision-making, patient engagement and adherence, technology and innovation, and policy and reimbursement. Insights were complemented by a structured expert forum involving clinicians from seven Asian countries, underscoring larger implications in geographies where SMBG remains underutilized within the diabetes care continuum. The forum highlighted disparities in device access, affordability, and insurance coverage, and emphasized the need for structured diabetes self-management education (DSME) and digital integration.

Findings support the use of structured SMBG for non-insulin-treated type 2 diabetes and CGM for insulin-treated individuals and those at risk of hypoglycemia. Evidence from the literature review also highlighted the importance of proper SMBG technique, with common errors such as inadequate handwashing, repeated lancet use, and excessive finger squeezing contributing to inaccurate readings and finger-site injuries. Hybrid models combining CGM and SMBG for calibration or confirmation are pragmatic solutions balancing clinical utility and affordability. Digital platforms, AI-driven analytics, and mobile apps enhance patient engagement and glycemic control but face challenges of scalability and regulation.

Policy reforms, including inclusion of BGM in national health benefit packages, expanded insurance coverage, and public-private partnerships, are critical to improving access. The recommendations advocate for personalized, context-specific monitoring strategies that balance clinical efficacy with affordability and infrastructure realities. This consensus-based framework aims to guide healthcare professionals in optimizing BGM practices and improving long-term outcomes for people living with diabetes. FITTER BiG is a new extension of the long-standing FITTER initiative, which has provided insulin injection technique recommendations for more than two decades. FITTER BiG complements this work by focusing specifically on best practice recommendations for blood glucose monitoring. FITTER BiG will provide BGM-specific recommendations designed to complement the injection technique guidance outlined in the FITTER Forward consensus statement (Klonoff et al. Mayo Clin Proc 100:682-699, 2025 [1]).

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) effectively manage type 2 diabetes mellitus (T2DM). Recent medication shortages have impacted patient access to treatment. The objectives of this study were to evaluate the effect of incretin therapy shortages on glycemic control and adverse patient outcomes. This retrospective cohort study evaluated the impact of interruptions in therapy on patients receiving maintenance doses of incretin therapy for at least three months. Patients were excluded if they were not on adequate maintenance doses, had missing hemoglobin A1c (HbA1c) levels, discontinued therapy due to side effects or cost, or had a history of chronic glucocorticoid use or organ transplant. The primary outcome was HbA1c levels before and after therapy interruption. Secondary outcomes were the incidence of gastrointestinal issues, hyperglycemia, and hypoglycemia-related hospital/clinic visits. A total of 71 patients were included. The median therapy duration was 9 months. Patients had a baseline HbA1c of 6.9%. Following interruption, 25.4% of patients had glucose-lowering therapy additions to their regimen, 35.2% dosage adjustments, and 39.4% no changes. HbA1c increased significantly to 7.2% at 12 months (P < 0.001). No significant differences were observed in adverse events or clinic/hospital visits (P = 0.571 and P = 1.00). Shortages of incretin therapy significantly increased patients' HbA1c levels up to 12 months post interruption. Long-term shortages or restrictions of these agents are likely to lead to adverse clinical outcomes. Further studies are needed to assess the outcomes of prolonged shortages or restrictions of these therapies.

Introduction: Pancreaticoduodenectomy is a complex surgical procedure involving meticulous resection and reconstruction steps. Materials and Methods: We analyzed the first 15 laparoscopic pancreaticoduodenectomies performed for ampullary, periampullary, and cephalic pancreatic tumors at the Fundeni Clinical Institute, Bucharest, a high-volume center with extensive expertise in hepatopancreatobiliary surgery. Patient demographics, medical history, intraoperative parameters, early postoperative outcomes, and oncological results regarding radical resection were evaluated. Results: The mean patient age was 59.4 years, with 53.33% males. Cardiovascular comorbidities were present in 60% of patients, while 26.66% had controlled type 2 diabetes mellitus. Previous cholecystectomy was noted in 46.66% of cases, and 60% presented with jaundice at diagnosis. The mean operative time was 360 minutes. Pancreaticogastrostomy was performed in 66.66% of cases and pancreaticojejunostomy in 33.33%, with 26.66% of procedures being fully laparoscopic. Biochemical leakage occurred in 13.33% of cases, while grade B pancreatic fistula developed in 6.67% of cases and was managed conservatively. Moderate biliary fistula occurred in 13.3% of the patients, with remission under conservative treatment. All resections achieved negative margins (R0). The mean number of retrieved lymph nodes was 15.6, and the average hospital stay was 18.7 days. Discussions: Laparoscopic pancreaticoduodenectomy provides oncological outcomes comparable to the open approach and may improve postoperative recovery in experienced centers. Conclusions: Our results are encouraging, with potential for further improvement through careful patient selection and refinement of surgical technique.

Proximal lower extremity weakness in patients with diabetes mellitus presents a diagnostic challenge due to overlapping etiologies, including diabetic amyotrophy, lumbar radiculopathy, and chronic inflammatory demyelinating polyneuropathy (CIDP). This report presents the case of an 80-year-old male with a history of type 2 diabetes mellitus who experienced recurrent falls, progressive right thigh weakness, and muscle atrophy. Although the clinical presentation initially suggested diabetic amyotrophy, electrodiagnostic studies and imaging failed to support this diagnosis. Instead, findings were more consistent with peripheral neuropathy and possible focal L5 radiculopathy. This case highlights the limitations of current diagnostic frameworks for diabetic amyotrophy, particularly in atypical presentations that lack classic features such as pain and characteristic electromyographic abnormalities. The absence of standardized diagnostic criteria necessitated a diagnosis of exclusion, emphasizing the importance of clinical judgment. This report underscores a structured approach to evaluating diabetic patients with lower extremity weakness, including the role of a comprehensive workup, the exclusion of diagnoses with similar presentations, and the potential for recovery through supportive care.

Automated insulin delivery (AID) systems aim to safely optimize glycemic outcomes; however, data in the new-onset type 1 diabetes (T1D) period are limited. We evaluated safety and glycemic outcomes of Omnipod 5 AID System use in the new-onset period.

This was a retrospective observational analysis of youth at a single center who initiated Omnipod 5 within 90 days of T1D diagnosis. Safety outcomes included diabetic ketoacidosis (DKA) and severe hypoglycemia. Continuous glucose monitoring (CGM) metrics and insulin delivery data were analyzed across the first 3 months of use and between pediatric age groups (<6-year-olds, 6 to <12-year-olds, and 12 to <18-year-olds).

Among 74 youth initiating Omnipod 5 within 90 days of T1D diagnosis, there was no occurrence of DKA or severe hypoglycemia in the first 3 months of AID system use. The time-weighted average glucose target value on the device setting was 118.8 mg/dL (6.6 mmol/L) with a median of 97% time in Automated Mode over 3 months. Median total daily insulin was 7.4 units (45.5% basal) in <6-year-olds, 11.4 units (48% basal) in 6 to <12-year-olds, and 25.7 units (45% basal) in 12 to <18-year-olds. The median glucose management indicator (GMI) was 7.1% (54 mmol/mol) and time in range (70-180 mg/dL, 3.9-10.0 mmol/L) was 72.1% with minimal hypoglycemia: 1.0% Level 1 time below range (TBR, 54-69 mg/dL, 3.0-3.8 mmol/L) and 0% Level 2 TBR (<54 mg/dL, <3.0 mmol/L).

These real-world observational data from youth with new-onset T1D using a tubeless AID system indicate safety and favorable glycemic outcomes with AID system initiation early after diagnosis. Future studies should assess the long-term glycemic and quality of life impact of early AID system adoption.

Amyloidosis encompasses a spectrum of disorders characterized by the extracellular accumulation of insoluble amyloid fibrils in various tissues, with peripheral neuropathy emerging as one of the most significant clinical manifestations. Peripheral sensory neurons are highly susceptible to amyloid-induced injury due to their long axonal projections and the relatively weaker neurovascular barrier of the dorsal root ganglia compared with the blood-brain and plasma-nerve barriers. Resulting nerve damage contributes to painful and disabling peripheral neuropathy, which affects millions worldwide. While hereditary amyloidosis polyneuropathies and type 2 diabetes are well-recognized conditions linked to amyloid deposition and neuropathy, similar pathogenic mechanisms may also be implicated in certain autoimmune and chronic metabolic disorders. A unifying histopathological feature across these diverse conditions is the deposition of amyloidogenic proteins. These fibrillar aggregates, composed of self-assembled peptides and proteins, disrupt tissue homeostasis, impair cellular function, and promote progressive nerve damage. Both inherited and acquired forms of amyloidosis are capable of triggering neuropathic complications, suggesting that amyloid-related mechanisms represent a convergent pathway in neuropathy of varied etiologies. In particular, type 2 diabetes mellitus stands out as a common condition in which amyloid accumulation significantly contributes to peripheral nerve injury. Collectively, these observations highlight the molecular and cellular parallels between different forms of amyloid-associated neuropathies and emphasize the need for deeper investigation into shared mechanisms that link protein aggregation with neuronal dysfunction.