Advances in understanding of autoimmune hyperthyroidism and neonatal Fc receptor (FcRn) biology have created an opportunity for a novel immunomodulatory treatment approach. This review is timely in evaluating newly emerged literature for FcRn blockers Batoclimab (IMVT-1401), Imeroprubart (IMVT-1402) and Efgartigimod (ARGX-113) in Graves' disease and thyroid eye disease.

Preliminary phase 2 clinical trial data of Batoclimab therapy in Graves' disease demonstrated rapid normalisation of thyroid hormone levels with the majority maintaining this after the treatment course. Rapid declines in anti-TSH receptor antibodies were observed with a subset of patients achieving sustained seroconversion. A case report described maintained remission of Graves' disease 23 months following short-course Batoclimab therapy. Batoclimab was well tolerated with no treatment-related adverse events. Phase 3 clinical trials of Efgartigimod therapy in thyroid eye disease were terminated early due to it unlikely achieving the intended clinical efficacy following interim analysis. Mid- and late-phase clinical trials for Imeroprubart and Batoclimab therapy in Graves' disease and thyroid eye disease are ongoing.

FcRn blockade is a promising new therapeutic approach for the management of autoimmune hyperthyroidism. Durability, cost-effectiveness and patient selection remain to be defined.

Individuals with chronic kidney disease (CKD) have twice the risk of peripheral arterial disease (PAD) and are more susceptible to arterial calcification. Diagnosing arterial abnormalities involves a combination of clinical assessment and noninvasive tests. The ankle-brachial index (ABI) is a cost-effective method for assessing arterial abnormalities and predicting mortality. Continuous Doppler ultrasound is the gold standard for ABI assessment due to its greater accuracy, and point-of-care ultrasound (POCUS) enables bedside measurement of this index.

To analyze the prevalence of arterial abnormalities in individuals undergoing hemodialysis using POCUS.

We conducted an observational, analytical, cross-sectional study of 85 patients on hemodialysis, using a clinical and sociodemographic questionnaire and calculating the ABI. The primary outcome was the analysis of the presence of arterial abnormalities through the measurement of ABI using the POCUS method..

The prevalence of ABI results suggestive of PAD and arterial calcification was 24.7% and 22.4%, respectively. Diabetes mellitus (p = 0.02) and advanced age (p = 0.01) were identified as the main risk factors for PAD.

The POCUS-assisted assessment identified a prevalence of 24.7% for PAD and 22.4% for arterial calcification among patients with CKD. Advanced age and diabetes mellitus were the main risk factors associated with PAD. The data suggest that POCUS is an innovative approach for the bedside diagnosis of arterial abnormalities in patients on hemodialysis.

Malnutrition, encompassing undernutrition, overnutrition, and micronutrient deficiency represents a global public health challenge with substantial implications for the development and clinical progression of type 2 diabetes mellitus (T2DM). The bidirectional relationship between nutritional status and glycemic regulation remains incompletely characterized across diverse geographic and socioeconomic settings worldwide, warranting a systematic synthesis of the available observational evidence.

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were conducted across PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL register from inception through December 2024. Twenty primary studies were included from multiple high-, middle-, and low-income countries across Asia, Europe, Africa, the Americas, and the Middle East, encompassing a total of more than 25,000 participants. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist; 45% of studies were assessed as high confidence and 55% as moderate confidence, following structured qualitative domain-level appraisal.

Malnutrition prevalence, assessed by multiple validated instruments, ranged substantially across study populations and settings. Nutritional risk, defined by Geriatric Nutritional Risk Index criteria, was identified in 30.3% of participants in one Chinese cross-sectional study (n=551). Malnutrition prevalence, assessed using heterogeneous validated instruments across clinically and geographically diverse populations, ranged from 18.5% to 83.8% across included studies; this wide range reflects substantial variation in assessment instrument, patient acuity, clinical setting, and population demographics rather than a uniform epidemiological estimate. Indicators of undernutrition - including hypoalbuminemia, low BMI, and micronutrient deficiency - were associated with impaired glycemic regulation, greater complication burden, and elevated mortality risk. Adjusted odds ratios for diabetic retinopathy associated with malnutrition ranged from 1.67 (95% CI: 1.04-2.70) to 2.24 (95% CI: 1.07-4.69) depending on nutritional index used. Severe malnutrition was associated with 8.91-fold higher adjusted mortality odds (95% CI: 1.04-76.18) compared with moderate malnutrition among hospitalized T2DM patients. Conversely, indicators of overnutrition including elevated BMI and increasing waist circumference - were consistently associated with incident T2DM and adverse cardiometabolic profiles across multiple prospective and cross-sectional studies. Early-life famine exposure was associated with elevated adjusted odds of hyperglycemia in adulthood (aOR range: 1.34-1.57), emphasizing the relevance of developmental nutritional programming to adult T2DM risk. A dual burden of malnutrition concurrent undernutrition and overnutrition within the same populations and study samples - was observed across multiple geographic settings, consistent with patterns documented during nutritional transition.

This systematic review identifies broadly consistent observational associations, with variability in association strength and direction by outcome domain and clinical context between malnutrition in both its under- and overnutrition forms and adverse clinical outcomes in T2DM across diverse global populations. These findings should be interpreted as associative rather than causal, given the predominance of observational cross-sectional and case-control designs, substantial heterogeneity in malnutrition definitions and outcome measures, and inherent risks of reverse causality and residual confounding. Future research should prioritize longitudinal and mechanistic study designs to clarify temporal pathways, and contextually appropriate nutritional screening should be integrated into T2DM prevention and management frameworks globally.

https://www.crd.york.ac.uk/prospero/, identifier, CRD42024559848.

This study aimed to investigate the effect of a 1-day outpatient intervention on insulin resistance in women with gestational diabetes mellitus (GDM), to explore its potential mechanisms, and to evaluate its impact on maternal and neonatal outcomes so as to optimize clinical intervention strategies and provide evidence for ensuring maternal and neonatal safety.

A total of 252 patients with GDM were included in this study, and they were divided into the GDM intervention group (receiving 1-day outpatient comprehensive management mode of diabetes) and the GDM group (routine nutrition consultation). All participants were followed up to 6-week postpartum. Variance analysis, chi-square test, and bivariate Pearson's correlation were used to analyze changes in blood glucose, stress hormones, iron metabolism, and oxidative stress markers, as well as their correlations.

After intervention, fasting insulin, HOMA-IR, and 2-h postprandial blood glucose were significantly decreased in the GDM intervention group (all p < 0.05). Levels of epinephrine (E), cortisol, MDA, and serum ferritin (SF) were also lower than in the GDM group (all p < 0.05). The rates of insulin use, postpartum glucose abnormality, preterm birth, and macrosomia were significantly reduced (all p < 0.05). E, cortisol, MDA, and SF were positively correlated with HOMA-IR (r = 0.457, 0.532, 0.324, 0.321, all p < 0.05).

One-day outpatient intervention can effectively alleviate insulin resistance, lower postprandial blood glucose, and improve maternal and infant outcomes in GDM patients. The mechanism may be associated with improved iron metabolism, reduced stress disorder, and oxidative stress injury in GDM patients.

Liver fibrosis is an important predictor of mortality in patients with type 2 diabetes mellitus (T2DM). Current clinical practice relies on total 25-hydroxyvitamin D, which does not distinguish between its two main circulating isoforms, 25(OH)D2 and 25(OH)D3, although these metabolites may differ in their associations with liver fibrosis and long-term prognosis.

We analyzed two independent T2DM cohorts: hospitalized Chinese patients with T2DM (n = 1,978) and US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 (n = 4,616). Serum 25(OH)D2 and 25(OH)D3 were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Isoform-specific associations with advanced fibrosis, defined by the NAFLD Fibrosis Score (NFS) and Fibrosis-4 index (FIB-4), were examined using multivariable logistic regression and restricted cubic spline (RCS) analyses. In NHANES, multivariable Cox proportional-hazards models were used to evaluate all-cause, cardiovascular, and diabetes-related mortality according to vitamin D status.

In both cohorts, lower serum 25(OH)D3 was non-linearly associated with a higher risk of advanced liver fibrosis. By contrast, 25(OH)D2 showed no protective association; in NHANES, the highest tertile was associated with a higher risk of NFS-defined fibrosis (OR = 1.41, P = 0.003). RCS analyses suggested cohort-specific apparent inflection regions for 25(OH)D3 at 11.88 ng/mL in the Chinese cohort and 23.86 ng/mL in NHANES; these exploratory estimates were not intended as clinical cut-offs. In longitudinal NHANES analyses, lower 25(OH)D3 was associated with higher cause-specific mortality among participants with advanced fibrosis; however, estimates within the FIB-4 high-risk stratum were based on sparse events and were therefore regarded as exploratory and interpreted with caution. Bioinformatic analysis implicated the AGE-RAGE and PI3K-Akt signaling pathways as candidate mechanisms.

Lower serum 25(OH)D3, but not 25(OH)D2, was associated with advanced liver fibrosis in T2DM after multivariable adjustment. Among participants with advanced fibrosis, lower 25(OH)D3 was also associated with higher cardiovascular mortality, although cause-specific estimates based on sparse events were exploratory. These findings may support further investigation of isoform-specific 25(OH)D3 assessment for risk stratification in this population.

The interplay between inflammation and coagulation is a central driver of thrombotic risk across various diseases. While mathematical models of blood coagulation are well established, there remains a critical gap in quantitative frameworks that capture inflammation-induced hypercoagulability. In this study, we develop a mathematical model that explicitly simulates the interaction between pro-inflammatory cytokines and the coagulation cascade. The model incorporates key mechanisms, including: (a) up-regulation of tissue factor by interleukin-1𝛽, interleukin-6, and tumor necrosis factor-α; (b) suppression of natural anticoagulants, namely, antithrombin III and tissue factor pathway inhibitor, by interleukin-6 and tumor necrosis factor-α; and (c) feedback amplification of pro-inflammatory cytokines by thrombin. By encoding the bidirectional feedback between inflammatory and coagulation pathways, the model captures essential features of inflammation-driven hypercoagulability and enables systematic quantification of how variability in inflammatory extent and duration result in heterogeneous thrombin generation (TG) dynamics. To evaluate its effectiveness, we integrate the model with TG assays and apply it to virtual patient cohorts representing 4 clinically distinct conditions: COVID-19, sickle cell disease, type 2 diabetes mellitus and hemophilia A. Model simulations predict that disease-specific inflammatory environments induce distinct shifts in TG dynamics. In COVID-19 and type 2 diabetes mellitus, elevated cytokine levels lead to shortened lag times and increased thrombin peak, whereas in sickle cell disease, shortened lag times are accompanied by a reduced thrombin peak. These effects are strongly modulated by both cytokine concentration and duration of exposure. These results demonstrate that the proposed computational model augments conventional TG assays by mechanistically linking inflammatory signaling to disease-specific coagulation responses. Collectively, the proposed computational framework extends conventional TG assays by considering the interplay between inflammation and coagulation, thereby providing a mechanistic exploratory platform for generating testable hypotheses regarding disease-specific thromboinflammatory regulation. This framework lays a foundation to support future clinical prediction or individualized therapeutic decision-making after validation using prospective patient-level longitudinal datasets.

Early-life gut microbiome assembly is a pivotal determinant of lifelong health; however, the integrated frameworks governing this process across developmental milestones remain insufficiently defined. This review establishes a multidimensional framework by delineating the crosstalk between the gut microbiome and the host throughout the preconception, prenatal, postpartum, and early childhood stages. We first highlight the emerging paradigm of biparental microbial contributions during the preconception period, detailing how paternal and maternal niches jointly prime offspring development. Moving into pregnancy, we examine the maternal reservoir, integrating the role of gut microbiota-derived metabolites across multiple trimesters in prenatal priming and vertical transmission. For the postpartum period, we discuss the development of the multikingdom gut microbiome and address the impacts of delivery modes and clinical interventions. Here, we articulate a critical knowledge gap: the discrepancy between taxonomic "catch-up" and true functional restoration, particularly in vulnerable cohorts such as preterm infants. Furthermore, we propose a "developmental synchronization" model within the maternal-infant-microbiome continuum. This model posits that early-life "windows of opportunity" are defined by the obligate temporal coupling of host physiological maturation with stage-specific microbial metabolic signals. From a translational perspective, we discuss how this framework informs the development of precision interventions, such as stage-specific probiotics, prebiotics, or metabolic modulators. These therapies aim to restore not only the microbial composition but also the synchronized functional dialog between the microbiome and host development. By mapping the "microbiota-metabolite-host target-physiological phenotype" network, we provide a systematic roadmap for precision-targeted interventions during the first 1000 days of life.

To investigate the changes, bidirectional relationships, and moderating factors of illness perception and intrinsic capacity in older adults with COPD and Type 2 Diabetes Mellitus (T2DM) during the hospital-to-home transition.

A prospective cohort study was conducted from April 2024 to September 2025, conveniently enrolling 232 older adults with COPD and T2DM from the Sixth People's Hospital of Nantong. Participants were assessed at three time points: at discharge (T0), 1 month (T1), and 3 months (T2) post-discharge, using the Brief Illness Perception Questionnaire (BIPQ) and a WHO framework-based intrinsic capacity assessment tool. A Random-intercept cross-lagged panel model (RI-CLPM) was used to analyze the dynamic cross-lagged relationships, a Latent growth model (LGM) was used to analyze the association of their change trajectories, and exploratory subgroup analyses were performed.

(1) Trajectory analysis: Illness perception total scores showed a consistent and significant decreasing trend across the three time points (p < 0.001), while intrinsic capacity total scores exhibited a slight but significant linear decline (p = 0.010). (2) Dynamic associations: The RI-CLPM revealed significant bidirectional negative associations between illness perception and intrinsic capacity during the T0-to-T1 phase (β = -0.21, β = 0.18, both p < 0.05). During the T1-to-T2 phase, only intrinsic capacity was positively associated with subsequent higher negative illness perception (β = 0.15, p = 0.047). (3) Trajectory association: The parallel process LGM indicated a moderate-to-strong positive correlation between the rate of improvement in illness perception and the rate of decline in intrinsic capacity (r = 0.32, p = 0.008). (4) Subgroup differences: Exploratory analyses showed that COPD severity (GOLD stage 3-4) and impaired baseline vitality significantly strengthened the negative association between illness perception and intrinsic capacity (between-group comparison p < 0.05).

During the hospital-to-home transition, illness perception and intrinsic capacity in older adults with COPD and T2DM exhibit a dynamic interaction, characterized by bidirectional influences in the early stage and a more sustained effect of intrinsic capacity on perception later. COPD severity and baseline vitality status are important clinical moderators of this relationship. The findings provide a basis for developing targeted transition care strategies that integrate psychological and functional interventions for high-risk subgroups.

To investigate the value of the C-reactive protein-triglyceride glucose index (CTI) and the controlling nutritional status score (CONUT) in predicting the risk of progression to severe sepsis or septic shock in patients with diabetes complicated by Enterobacteriaceae bloodstream infections.

A total of 236 patients with diabetes complicated by Klebsiella pneumoniae or Escherichia coli bloodstream infections from January 2023 to December 2025 were enrolled. Patients were grouped based on CTI quartiles (Q1-Q4) and CONUT scores (normal-low risk, moderate risk, high risk). Demographic, clinical characteristics, and laboratory indicators were collected to analyze intergroup differences and their association with severe clinical outcomes (severe sepsis or septic shock). Multivariate logistic regression models adjusted for confounding factors, and ROC curves evaluated the predictive ability of combined CTI and CONUT indices.

The study found that as the CTI quartile increased, the incidence of sepsis (p < 0.001) and in-hospital mortality (p = 0.009) significantly increased. The CONUT high-risk group exhibited a particularly high sepsis incidence of 89.8% (p < 0.001), with more pronounced trends toward elevated HbA1c levels and decreased platelet counts (p < 0.05). Significant correlations were observed between CTI and HbA1c levels. Within different CONUT score groups, the high-risk group demonstrated markedly higher HbA1c levels compared to the normal light exposure group. Multivariate regression analysis revealed that CTI Q4 (adjusted OR = 5.301, 95% CI: 2.054-13.679, p = 0.001) and moderate/high CONUT scores (adjusted OR = 3.379 and 5.099, respectively, p < 0.001) were independent predictors of severe outcomes. ROC analysis indicated that the area under the curve (AUC) for combined CTI and CONUT scores in predicting severe outcomes was 0.777 (95% CI: 0.716-0.837), outperforming either single indicator.

Both CTI and CONUT scores were effective indicators for predicting severe sepsis or septic shock in patients with diabetes complicated by Enterobacteriaceae bloodstream infections.

Dental implants are a predictable treatment for tooth loss; however, infections extending into deep fascial spaces are rare and potentially life-threatening. This case highlights the importance of early diagnosis and multidisciplinary management of an implant-related submental abscess in a diabetic patient. A 33-year-old female with type 2 diabetes mellitus (HbA1c: 8.1%) presented with submental swelling five months after anterior mandibular implant placement. Clinical examination revealed erythema, tenderness, and purulent discharge around implant #41. Cone-beam computed tomography (CBCT) showed complete resorption of the lingual cortical plate and a radiolucent tract extending into the submental space, indicating abscess formation. The implant system used was Megagen AnyOne® (4.0×10 mm). The patient was treated with amoxicillin-clavulanic acid 1 g every 12 hours for 5 days, and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control, followed by extraoral drainage with Penrose drain placement. The infected implant was removed surgically under local anesthesia, followed by thorough debridement of the cavity and local irrigation with rifamycin SV solution (250 mg/3 mL). The postoperative course was uneventful, and CBCT at the 3-month follow-up confirmed complete bone healing without recurrence. This case suggests that implant-related submental infections may result from a combination of surgical errors, anatomical factors such as lingual plate perforation, and systemic risk factors, including diabetes mellitus. CBCT plays a vital role in detecting cortical perforation and deep-space extension. Careful preoperative imaging, proper implant angulation, and timely combined medical-surgical management are critical for preventing serious complications and achieving favorable outcomes.