SGLT-2 inhibitors are now used beyond type 2 diabetes (T2DM) in heart failure (HF) and chronic kidney disease (CKD), where glucose is monitored less routinely. Whether their established ketoacidosis signal-particularly euglycaemic diabetic ketoacidosis (euDKA)-is maintained as the indications expand, and whether it reproduces across independent reporting systems, is untested. We analysed the US FAERS (2020Q1-2026Q1) and Japanese JADER using one pipeline. Signals required consensus across four methods (ROR, PRR, IC, EBGM/EB05). Analyses were run overall, within report-level indication strata [T2DM, HF, CKD, off-label type 1 diabetes (T1DM)] and against an active comparator (DPP-4 inhibitors), with two pre-specified negative controls, time-to-onset modelling and sensitivity analyses. The DKA signal met four-method consensus within every indication stratum, including HF and CKD, and was highest in off-label T1DM; it was therefore maintained, not diluted, as indications expanded. Overall RORs were 67.4 (95% CI 65.7-69.2) in FAERS and 112.3 (104.8-120.3) in JADER. SGLT-2 inhibitors accounted for 85.8% (FAERS) and 91.7% (JADER) of all euDKA reports, though euDKA was only 4.1% and 7.8% of SGLT-2 inhibitor reports. Both negative controls were null in both databases. Median time-to-onset was 60 days (Weibull β=0.48, 95% CI 0.46-0.50). Across two independent reporting systems, the SGLT-2 inhibitor ketoacidosis signal was maintained across the expanding cardiorenal indications, with euDKA concentrated within this class and early onset. Ketone-based assessment is warranted when ketoacidosis is suspected, particularly soon after initiation. As a disproportionality analysis, these are hypothesis-generating signals that cannot establish incidence, relative risk, or causality.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease of childhood and the hepatic component of a systemic metabolic and endocrine disorder linked to obesity and insulin resistance. Its psychological and social dimensions, however, remain under-recognized relative to its metabolic features. Affected children carry a substantial mental-health burden: elevated rates of depression, anxiety, disordered eating, and impaired quality of life that both reflect and aggravate the underlying disease. This mini review uses the biopsychosocial model to summarize current understanding of this burden in pediatric MASLD. We outline the bidirectional neuroendocrine and inflammatory mechanisms that link metabolic dysfunction with psychological distress, including cytokine signalling, leptin and adipokine dysregulation, hypothalamic-pituitary-adrenal axis activation, and the gut-brain axis. We then consider the social determinants and system-level barriers that shape outcomes, practical approaches to screening and integrated multidisciplinary management, and the psychosocial considerations raised by emerging pharmacotherapies such as glucagon-like peptide-1 receptor agonists. We highlight areas of ongoing debate: notably the tension between weight-centred intervention and the risk of precipitating disordered eating, and the neuropsychiatric monitoring of new pharmacological agents, together with the principal research gaps and likely future directions. Recognizing pediatric MASLD as a biopsychosocial condition, and embedding mental-health assessment within routine metabolic care, may improve both hepatic and psychological outcomes in this growing population.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that needs to be addressed through holistic management of metabolic, hormonal, and lifestyle factors. This research study, a cross-sectional examination, reports on clinical and psychological aspects of PCOS and PCOD in a group of 75 educated women analyzed with descriptive statistics, non-parametric tests, and binary logistic regressions. To carry out this analysis, we integrated the symptom severity index (SSI) and a binary measure of past sexual trauma history. The study observed irregular menstruation in 85.3% and weight gain in 84.0% of affected participants, representing a high prevalence of these core physical symptoms. The diagnostic status shows a psychological decline: post-diagnostic changes including feeling undesirable and being more introverted (p<0.001). Sexual molestation or abuse was reported by 72% of participants. Binary logistic regression showed that higher SSI scores (Odds Ratio = 1.72; 95% Confidence Interval [CI]: [1.28,2.30]; p<0.001) and a positive history of sexual trauma (OR = 3.58; 95% CI: [1.55,8.26]; p=0.003) were independent predictors of negative self-perception at diagnosis. The study argues that biomedical interventions are not enough and there needs to be a shift to integrated trauma-informed models of care. Human Design Education and Development can provide holistic support that promotes emotional inclusion by applying the principle of Listen and Share. In addition to reproductive and metabolic characteristics, PCOS/PCOD has a major psychological impact, which is clearly observed in this research of 75 educated women. There is a high symptom intensity and immediate decline in self-concept at diagnosis, which can result in negative body image and individuals feeling compelled to isolate themselves from society as a defense mechanism. This shows statistical significance (p=0.003). The number of people with higher symptom intensity and decline in self-concept due to negative body image and defensive social connection was recorded (p<0.001). Additionally, 72% of individuals self-reported sexual trauma, indicating a critical vulnerability that independently increased the likelihood of poor self-perception, irrespective of the intensity of physical symptoms (OR = 3.58, p=0.003).This study results in the immediate need for integrated trauma-informed multidisciplinary care paradigms in PCOS management and assesses the limitations of emphasizing interventions in biomedical management.
Osteoporosis is a common age-related skeletal disorder characterized by low bone mass, deterioration of bone microarchitecture, and increased susceptibility to fragility fractures. Although antiresorptive and anabolic therapies have substantially improved fracture prevention, current treatments do not fully address the aging-related biological processes that disrupt skeletal homeostasis. Increasing evidence from osteoimmunology, immunosenescence, and cellular senescence research suggests that inflammaging contributes to age-related bone loss by reshaping the bone marrow immune microenvironment. Immune cells with senescence-associated features may promote bone remodeling imbalance through excessive production of senescence-associated secretory phenotype factors, including interleukin-1β, interleukin-6, tumor necrosis factor-α, chemokines, matrix-degrading enzymes, and receptor activator of nuclear factor-κB ligand. These mediators enhance osteoclast differentiation and survival, impair osteoblast function, suppress osteogenic differentiation of bone marrow mesenchymal stromal cells, and propagate paracrine senescence within the bone marrow niche. Senolytics are pharmacological agents that selectively induce apoptosis in senescent cells by targeting senescent-cell anti-apoptotic pathways. Preclinical studies, including those using dasatinib plus quercetin, fisetin, and bone-targeted delivery platforms, have demonstrated the capacity to reduce global senescent-cell burden, attenuate SASP-related inflammation, and improve certain skeletal parameters in models of aging, postmenopausal osteoporosis, and radiotherapy-associated bone loss. However, it remains unclear whether these benefits arise from the elimination of immune cells with senescence-associated features, stromal cells, osteocytes, or a combination thereof. Critically, direct evidence that currently available senolytics selectively eliminate senescence-associated immune-cell subsets within the osteoporotic bone marrow is lacking. Early clinical evidence supports feasibility and hypothesis generation but does not yet establish senolytics as routine osteoporosis therapy. This narrative review synthesizes the mechanistic links among immunosenescence, inflammaging, immune cells with senescence-associated features, and bone remodeling imbalance; critically evaluates current preclinical and clinical evidence for senolytics in osteoporosis; and proposes a structured research roadmap—centered on fate-mapping, lineage-specific depletion, and single-cell multi-omics—to convert the prevailing hypothesis into experimentally testable and clinically actionable evidence, while delineating the translational challenges that must be overcome to achieve precision senolytic therapy.
International andrology guidance discusses refeeding after starvation as a clinical setting associated with gynaecomastia, based on reports from starvation-refeeding settings outside anorexia nervosa (AN). A targeted search of PubMed, PsycINFO, and Google Scholar, last conducted on 27 July 2026, identified no indexed reports in male patients recovering from AN. We therefore advance the testable hypothesis that transient glandular breast tissue may occasionally occur but remain unrecognised during nutritional recovery; the available evidence does not establish occurrence, prevalence, or clinical significance in AN. Five endocrine transitions provide biological plausibility: non-uniform recovery of the hypothalamic-pituitary-gonadal axis, expansion of the adipose tissue compartment in which aromatase is expressed, a transient leptin rise, possible preservation of adrenal androgen precursor availability, and recovery of insulin-like growth factor 1. Direct human data in male AN support parts of the endocrine trajectory, whereas the proposed link to breast tissue relies largely on indirect human evidence and preclinical studies. Potential under-recognition could arise from misclassification as pseudogynaecomastia, patient-side under-reporting, and follow-up that ends before later endocrine recovery; no clinical detection window has been established. We propose retrospective review, prospective surveillance extending beyond acute refeeding, targeted endocrine evaluation of confirmed glandular tissue, and multicentre studies of prevalence, risk factors, natural history, psychological effects, and treatment engagement.
BackgroundHypothyroidism is a common endocrine disorder with multisystem involvement and is increasingly recognized as a potentially reversible contributor to renal dysfunction. However, renal impairment related to thyroid hormone deficiency is frequently overlooked or misclassified as chronic kidney disease in clinical practice.MethodsIn this single-center retrospective observational study, 40 hospitalized adults with newly diagnosed hypothyroidism were included. Renal dysfunction was defined by elevated serum creatinine and reduced estimated glomerular filtration rate at admission. All patients received levothyroxine replacement therapy as part of routine care. Biochemical parameters were assessed at three timepoints: admission (T0), normalization of thyroid-stimulating hormone (T1), and normalization of serum creatinine (T2). Serum creatinine was the primary renal outcome, whereas estimated glomerular filtration rate was evaluated as a supportive calculated indicator. Secondary outcomes included thyroid hormones and other biochemical markers.ResultsAt baseline, mean serum creatinine was 114.88 ± 25.61 μmol/L and estimated glomerular filtration rate was 51.42 ± 16.32 mL/min/1.73 m². Following treatment, serum creatinine decreased significantly to 85.13 ± 21.01 μmol/L at T1 and 79.92 ± 5.64 μmol/L at T2 (both P < 0.01). Estimated glomerular filtration rate improved to 74.48 ± 32.56 and 75.04 ± 14.52 mL/min/1.73 m², respectively. Free thyroid hormone levels increased, while other biochemical parameters showed no consistent changes. Analyses at T1 and T2 were based on responder subgroups that achieved predefined biochemical targets.ConclusionThyroid hormone replacement was associated with significant short-term improvement in creatinine-based renal indices, suggesting that renal dysfunction in hypothyroidism may be at least partially functional and potentially reversible in some patients. These findings should be interpreted cautiously given the small sample size, retrospective design, responder-based subgroup analyses, absence of a comparison group, and potential residual confounding.
Introduction:Fasting during Ramadan poses specific challenges for children and adolescents with diabetes and may adversely affect glycemic control and the risk of acute complications. Data on the safety of Ramadan fasting among Arab youth with diabetes and adherence to guideline-based care remain limited. This study aimed to evaluate the experiences of Ramadan fasting among Arab children, adolescents, and youths with diabetes. Methods:In this cross-sectional study, we used an expert-reviewed and pilot-tested questionnaire distributed through social media to recruit a non-probabilistic online convenience sample of children, adolescents, and young adults with diabetes across Arab countries. All demographic, clinical, counseling, and fasting-related outcomes were self-reported. Results:In total, 242 (53.7% female) patients participated in this study. The most common age group was 13-17 years (50.8%), and 95.9% of the patients had type 1 diabetes. Before Ramadan, 11.5% reported diabetic ketoacidosis (DKA), 5.0% reported severe hypoglycemia during the previous 3 months, and 26.0% had hypoglycemia unawareness. Nearly half (45.5%) of the participants reported being permitted to fast by their physicians. During Ramadan, DKA and severe hypoglycemia occurred in 6.2% and 2.5% of the patients, respectively. The median number of completed fasting days was 22 (range 0-30). Older patients (aged 13-25 years) were more likely to be allowed to fast (p = 0.033) and complete more fasting days (p < 0.001). In multivariate regression, older age independently predicted fasting allowance (AOR = 1.951, 95% CI: 1.132 - 3.363, p = 0.016). Multiple daily injections decreased the likelihood of being allowed to fast (AOR = 0.444, 95% CI: 0.230 - 0.860, p = 0.016). The most common cause of fasting interruption was hypoglycemia (67.4%), followed by hyperglycemia (24.8%). A weak positive correlation was observed between pre-Ramadan counseling scores and the number of completed fasting days (Spearman's rho = 0.144; p = 0.025). Conclusion:Almost half of the participating Arab children, adolescents, and young adults with diabetes reported being permitted to fast during Ramadan. Older patients were more likely to be permitted to fast and completed more fasting days, and insulin pump users were more likely to be permitted to fast than those on multiple daily injections. A weak positive association was observed between counseling scores and the number of completed fasting days.
Objectives:In order to identify the factors related to osteoporosis in patients with type 2 diabetes, it is necessary to establish a visual risk classification model to evaluate the current risk and verify its effectiveness. Methods:This retrospective observational study included 2,265 patients with type 2 diabetes who were admitted to the First People's Hospital of Neijiang City between January 2021 and December 2025. All these patients underwent dual-energy X-ray absorptiometry (DXA) examinations during the same admission or physical examination visit. They were divided into the training group and the validation group in a ratio of 7:3. A predictive model was established using multivariate Logistic regression analysis and the Least Absolute Shrinkage and Selection Operator (Lasso) regression. A nomogram for clinical application was also established and its discrimination ability, calibration, and clinical practicability were verified. Results:Multivariate Logistic regression analysis revealed that age, gender, BMI, Triglyceride, Monocyte count, TyG and AISI were independent risk factors for osteoporosis in patients with type 2 diabetes. The nomogram model showed a reliable predictive effect, with an area under the curve (AUC) of 0.847 (95% CI, 0.821-0.874) in the training cohort and 0.833 (95% CI, 0.791-0.875) in the validation cohort. Decision curve analysis (DCA) confirmed that the nomogram model had strong clinical practical value. Conclusion:The risk factor assessment chart for osteoporosis in patients with type 2 diabetes established in this study has good discriminative ability and provides an objective tool for clinical personnel to conduct early assessment.
Background:Osteoporotic hip fractures often require immediate inpatient care and impose a substantial financial burden. Previous studies mainly focused on overall costs for patients with refractures, without disaggregating hospitalization costs by episode, leaving the determinants of first- and second-admission costs unclear in this subgroup. This study aimed to examine factors associated with hospitalization costs for each episode and to identify factors characterizing cost differences between the two hip-fracture hospitalizations in patients with subsequent osteoporotic hip fractures. Methods:Data were obtained from the Shanghai Health Statistics Center, covering all medical institutions in Shanghai, China, from January 1, 2013, to December 31, 2022. Multilevel models were used to identify factors related to hospitalization costs for the first and second fractures. Hospitalization variations and cost differences between the two fracture episodes were examined, and multivariable quantile regression was used to explore factors associated with cost differences. Results:Of 43,963 patients hospitalized for their first osteoporotic hip fracture, 1,152 experienced a subsequent hip fracture and required rehospitalization during the study period. At the first fracture, most patients were female (78.73%) and aged ≥80 years (57.47%). Grade-A tertiary hospitals represented 27.59% (n = 24) and 24.04% (n = 25) of treating hospitals for the first and second fractures, respectively, but admitted 55.64% (n = 641) and 51.39% (n = 592) of patients. For both episodes, fourth-degree surgery had the highest median costs ($9,787.15 and $9,726.55, respectively), whereas unoperated patients had the lowest ($1,147.75 and $1,133.36). Costs rose substantially with longer length of stay (LOS), reaching $11,197.72 and $11,729.95 for stays of ≥31 days. Null multilevel models of hospitalization costs revealed ICCs of 0.333 and 0.338 for the first and second fractures, respectively, both indicating significant hospital-level variance (all P < 0.001). Random-intercept models showed that grade-A tertiary hospitals showed higher adjusted costs than grade-B secondary hospitals for both fractures, and that higher surgery levels and longer LOS were positively associated with costs across both episodes (all P < 0.001). For the second fracture, an interval of 1 to 1.5 years between hospitalizations was associated with significantly lower costs compared with an interval of ≤1 year (exp(β) = 0.899; 95%CI, 0.824 to 0.980; P < 0.05). Quantile regression showed that a higher hospital level and longer LOS during the second hospitalization were associated with increased relative costs across quantiles (all P < 0.05). Conversely, a higher surgery level in the second hospitalization was associated with reduced relative costs at the 25th and 50th percentiles (all P < 0.05), indicating heterogeneous associations across different quantiles of the cost distribution. Conclusions:Among patients with subsequent osteoporotic hip fractures, grade-A tertiary hospitals were associated with higher adjusted costs than grade-B secondary hospitals for both fracture episodes, and inpatient costs increased progressively with higher surgery levels and longer LOS. Between-episode variations in hospital level, surgery level, and LOS exhibited heterogeneous effects on cost differences across quantiles. These findings highlight the need for episode-specific cost-control strategies that also account for variations between the two hospitalizations.
Objective:This study examined the association between the remnant cholesterol inflammation index (RCII) and handgrip strength in patients receiving maintenance hemodialysis (MHD). Methods:This single-center cross-sectional study included 117 maintenance hemodialysis patients. Baseline characteristics, laboratory variables, and maximal handgrip strength were collected. Remnant cholesterol (RC) was calculated as total cholesterol minus LDL-C minus HDL-C, and RCII was calculated as [RC (mg/dL) × hs-CRP (mg/L)]/10. Because RCII was markedly right-skewed and included three verified negative calculated values, negative values were truncated to zero and ln(RCII + 1) was used as the primary exposure. The fully adjusted linear regression model included sex, age, BMI, creatinine, triglyceride, fasting plasma glucose, and albumin. Sensitivity analyses evaluated alternative treatments of negative and extreme RCII values, and restricted cubic spline analysis assessed potential non-linearity. Results:In the fully adjusted complete-case model (N = 116), each 1-unit increase in ln(RCII + 1) was associated with a 1.585-kg lower handgrip strength (B = -1.585, 95% CI -2.790 to -0.379; P = 0.010). The coefficient remained negative after excluding negative RCII values, using the original RCII scale, truncating negative values to zero, excluding extreme values, and fitting Huber robust regression. Statistical significance was attenuated after P1-P99 and 1.5×IQR exclusions. RCS analysis showed a significant overall association (P = 0.019) without evidence of non-linearity (P = 0.245). Conclusion:Higher ln(RCII + 1) was associated with lower handgrip strength in maintenance hemodialysis patients after adjustment for seven clinically relevant covariates. The inverse direction was broadly consistent across sensitivity analyses, although estimates were less precise after excluding upper-tail RCII observations.
AimsDespite growing evidence implicating FN3K in the pathogenesis of cancer and diabetes, its precise role in modulating renal tubular injury within the context of diabetic nephropathy has yet to be fully elucidated.Materials and methodsFN3K expression was examined in DKD model mice, human kidney biopsy samples, and high glucose-treated HK-2 cells via immunohistochemistry (IHC) and Western blotting. Associations between serum FN3K levels and DKD risk were analyzed in the Kidney Precision Medicine Project cohort via multivariable logistic regression, restricted cubic spline modelling, and receiver operating characteristic (ROC) analysis. Regional proteomics, single-cell RNA sequencing, untargeted metabolomics, and joint pathway analyses were integrated to delineate FN3K-associated pathways and cell type-specific metabolic alterations. The effect of FN3K on mitochondrial function was evaluated using Mitochondrial respiratory chain activity assays.ResultsFN3K expression was significantly reduced in the renal tubular compartments of DKD mice and patients and was downregulated by high glucose in HK-2 cells. Low circulating FN3K levels were independently associated with increased DKD risk and improved diagnostic performance when combined with conventional biomarkers. Proteomic and single-cell analyses revealed the activation of PI3K/AKT signaling and the suppression of mitochondrial metabolic pathways in DKD tubules, whereas FN3K-high proximal tubule cells presented increased oxidative phosphorylation and reduced inflammatory and apoptotic signaling. Metabolomic profiling demonstrated that FN3K overexpression restored the levels of mitochondrial- and nitrogen-related metabolites and attenuated injury-associated lipid remodeling. Joint pathway analysis highlighted nitrogen and glutathione metabolism as convergent FN3K-related signatures. Over-expression of FN3K would improves the function of mitochondrial respiratory chain I and III activity.ConclusionsFN3K deficiency is associated with tubular injury and DKD progression, potentially through increased glycation stress, mitochondrial metabolic dysfunction.
Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders worldwide, affecting 6–13% of reproductive-aged women and exerting a profound metabolic, reproductive and psychological toll. Emerging evidence suggests that the gut microbiome may be a potentially critical, yet under-recognized, contributor to the pathophysiology of PCOS. Alterations in microbial composition and function appear to influence hormonal imbalance, metabolic dysfunction and inflammatory processes that characterize the condition. However, much of the current evidence remains associative or derived from preclinical models, and the causal nature of these relationships is only beginning to be established through approaches such as Mendelian randomization. This literature review examines the evolving relationship between the gut microbiome and PCOS through a mechanism-guided, evidence-stratified framework, with particular focus on how microbiota-targeted interventions — including prebiotics, probiotics, synbiotics, dietary modifications and fecal microbiota transplantation, may modulate gut health and mitigate symptom severity. Across the reviewed studies, microbiome-targeted supplementation was associated with improvements in insulin sensitivity, reductions in systemic inflammation and favorable hormonal changes, although the strength of evidence varies across outcomes and intervention types. Importantly, PCOS heterogeneity, including differences in body mass index (BMI), insulin resistance status and phenotype, may influence both gut microbiota composition and therapeutic response, underscoring the need for phenotype-stratified research. These findings suggest that targeting the gut microbiome may serve as a promising adjunct to conventional PCOS management. Though further rigorous, long-term clinical trials are needed to advance both understanding and clinical translation.
Artificial intelligence (AI) models are increasingly reported in endocrine disease management, but clinical value cannot be inferred from discrimination, model complexity, or explainability alone. This narrative review synthesizes evidence from diabetes and diabetic kidney disease (DKD), thyroid disease, polycystic ovary syndrome (PCOS; with attention to the proposed polyendocrine metabolic ovarian syndrome, PMOS, terminology transition), and obesity/GLP-1-based metabolic management through an actionability framework. We define clinical actionability as the link between a meaningful endocrine prediction and transparent reporting, bias and applicability appraisal, external or temporal validation, calibration, threshold-based utility, interpretable output, workflow integration, fairness assessment, and post-deployment monitoring. Diabetes/DKD provides a comparatively broad evidence base, including decision-support examples, non-invasive triage, calibration, decision-curve analysis, and early deployment-oriented work. Thyroid AI increasingly reports validation and clinical-utility metrics for nodule triage, biopsy decisions, and risk prediction, but prospective workflow evidence remains limited. PCOS/PMOS AI addresses diagnostic and reproductive-endocrine gaps, yet requires broader phenotype alignment, fairness analysis, and multi-setting validation during the PMOS terminology transition. Obesity/GLP-1 evidence now includes response-prediction, benefit-stratification, treatment-intensification, persistence, and remote-care examples, but it does not establish AI-guided treatment selection, adherence/tolerability prediction, or monitoring. Across modules, differences lie less in headline discrimination metrics, including the area under the receiver operating characteristic curve (AUC), than in validation, utility, workflow, fairness, and monitoring evidence. Endocrine AI should move from explainable prediction toward decision support that can be interpreted, thresholded, acted on, monitored, and revised in clinical workflows.
BackgroundDiabetic foot (DF) represents a severe and disabling complication of diabetes, closely linked to ulceration, amputation, functional impairment, and an elevated risk of death. Sarcopenia is a syndrome marked by progressive declines in muscle mass and function. Emerging evidence suggests a possible link between DF and sarcopenia. Nonetheless, a systematic evaluation of the influence of sarcopenia on adverse clinical outcomes in individuals with DF remains unavailable. The present investigation aims to systematically assess and quantitatively synthesize the association of sarcopenia and muscle attenuation with clinical outcomes in those with DF.MethodsA systematic search of Embase, Cochrane, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was conducted from their inception through December 2025. Observational studies enrolling DF individuals aged ≥ 18 years and comparing clinical prognoses between those with and without sarcopenia and muscle attenuation were included. The primary outcomes comprised rates of mortality and amputation. Secondary outcomes encompassed ulcer severity. The NHLBI was adopted for risk-of-bias evaluation. Given substantial between-study heterogeneity, a narrative synthesis was prioritized, with meta-analyses implemented for outcomes amenable to quantitative pooling.ResultsEighteen studies (9 cross-sectional, 4 prospective cohort, 4 retrospective cohort, and 1 retrospective case-control studies) comprising 2,888 individuals were included, of which 9 contributed to the meta-analysis. The meta-analysis revealed that, relative to those without sarcopenia and muscle attenuation, DF individuals with comorbid sarcopenia exhibited an elevated risk of all-cause mortality (HR = 2.38, 95% CI: 1.63–3.48), an association with amputation (OR = 2.11, 95% CI: 1.32–3.38), and a higher proportion of severe ulcers (Wagner grade 4–5) (RR = 1.69, 95% CI: 1.31–2.17).ConclusionsImpaired muscle health was associated with a higher risk of all-cause mortality, higher odds of amputation, and a greater prevalence of severe ulcers in patients with DF. Because the available evidence is observational and heterogeneous, these findings should be considered hypothesis-generating and should not yet be used to support prognostic screening or clinical risk-stratification decisions. Future prospective cohort investigations are necessary to further clarify the temporal relationship and underlying mechanisms.Funding and registrationThis study was supported by the Ningxia Natural Science Foundation (Grant Number: 2025AAC030725). This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420251247873).Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251247873.
BackgroundGraves’ disease is an organ-specific autoimmune disorder driven by thyrotropin receptor antibody (TRAb) and accompanied by persistent immune and inflammatory activation. Peripheral blood inflammatory indices are readily available and have been increasingly used to assess inflammation in autoimmune diseases. However, their clinical significance in Graves’ disease across different thyroid functional states is unknown.MethodsIn this retrospective study, 687 patients with Graves’ disease were enrolled. Five peripheral blood inflammatory indices were calculated, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Patients were stratified and compared according to thyroid functional status. Because sex distribution differed among the groups, sex-adjusted median regression models were additionally fitted, and group-by-sex interactions were examined. Correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were used to evaluate associations of these indices with clinical characteristics, liver biochemical abnormalities, and hyperthyroid relapse. The outcome models were internally validated using bootstrap resampling and repeated 10-fold cross-validation.ResultsSex distribution differed significantly among the thyroid functional groups. After adjustment for sex, MLR, SIRI, and PIV remained significantly higher in the overt hyperthyroid group than in the subclinical hyperthyroid and euthyroid groups. In patients with overt hyperthyroidism, MLR was positively correlated with age, FT3, FT4, ALT, and AST (rs = 0.152–0.206, all P < 0.05). Multivariable logistic regression identified TRAb, hemoglobin, and standardized MLR as independent factors associated with liver biochemical abnormalities, and the resulting model showed limited-to-moderate discrimination (apparent AUC, 0.703; optimism-corrected AUC, 0.692; cross-validated AUC, 0.680). Among the five inflammatory indices, PIV showed the highest individual discrimination for hyperthyroid relapse (AUC, 0.734). The TRAb–PIV model showed relatively good internal discrimination (apparent AUC, 0.815; optimism-corrected AUC, 0.805; cross-validated AUC, 0.788).ConclusionCompared with NLR and SII, the monocyte-containing indices MLR, SIRI, and PIV showed clearer differences across thyroid functional states in Graves’ disease and may provide complementary inflammation-related information. Among them, MLR was associated with liver biochemical abnormalities, whereas PIV showed potential adjunctive value for hyperthyroid relapse risk assessment.
ObjectiveFalls are a leading cause of morbidity among older adults with osteoporosis. While traditional risk assessment focuses on biological factors such as bone mineral density (BMD), psychological factors—particularly kinesiophobia—have received increasing attention. However, most studies conceptualize kinesiophobia as a continuous construct, potentially overlooking clinically meaningful heterogeneity. This study aimed to identify kinesiophobia phenotypes and examine their association with fall history in older adults with osteoporosis.MethodsThis cross-sectional study included 306 older adults with osteoporosis recruited from a tertiary hospital. Kinesiophobia was assessed using the Tampa Scale for Kinesiophobia (TSK-17) and the Kinesiophobia Causes Scale (KCS). Latent profile analysis (LPA) was performed to identify distinct kinesiophobia phenotypes based on standardized KCS scores. Multivariable logistic regression was used to evaluate the association between phenotypes and fall history, adjusting for age, body mass index (BMI), BMD, prognostic nutritional index (PNI), and the log-transformed systemic immune-inflammation index (log-SII). Model performance was assessed using the area under the receiver operating characteristic curve (AUC) with bootstrap validation.ResultsAmong 306 participants (mean age, 74.9 years; 77.1% women), 232 (75.8%) exhibited kinesiophobia and were included in the LPA. Three phenotypes were identified: sensitized, resilient, and frail. The frail phenotype was independently associated with a significantly higher odds of prevalent falls (OR, 2.93; 95% CI, 1.44–5.96; P = .003), whereas the sensitized phenotype was not. Notably, bone mineral density was not independently associated with fall history after adjustment (P = .735). The predictive model demonstrated moderate discrimination (AUC = 0.693; bootstrap AUC = 0.692), with improved performance after inclusion of kinesiophobia phenotypes.ConclusionKinesiophobia is a heterogeneous construct in older adults with osteoporosis. The frail kinesiophobia phenotype is associated with a substantially higher odds of prevalent falls, independent of traditional biological markers. These findings suggest that psychological and behavioral phenotyping may enhance fall history stratification and support more targeted prevention strategies in geriatric populations.
