BACKGROUND:Indoxyl sulfate (IS), a protein-bound uremic toxin derived from tryptophan metabolism, accumulates in patients with chronic kidney disease (CKD) and contributes to renal, vascular, and systemic injury. Conventional detection using LC-MS/MS is accurate but resource-intensive. To simplify IS quantification, Leadgene Biomedical developed a competitive enzyme-linked immunosorbent assay (ELISA) that employs anti-IS monoclonal antibodies capable of recognizing both free and protein-bound IS forms. METHODS:Serum samples from 188 participants -classified as low-risk (healthy or CKD ≤ stage 2, n = 79) and high-risk (CKD stage G3a and above (eGFR <60 mL/min/1.73 m2, n = 109) - were analyzed using the Leadgene® IS ELISA Kit. Diagnostic performance was assessed through ROC analysis, precision by nested-ANOVA (total %CV < 10%), and accuracy by comparison with LC-MS/MS. RESULTS:Mean age was higher in the high-risk group (65.17 ± 11.66 vs 57.96 ± 13.88 years, p < 0.001). The ELISA demonstrated excellent diagnostic performance with an area under the curve of 0.96 and an optimal cutoff of 2.233 µg/mL, yielding sensitivity 0.872 (95% confidence interval (CI) 0.816-0.912) and specificity 0.940 (95% CI 0.856-0.977). The Pearson correlation coefficient between the ELISA and LC-MS/MS results was 0.964, confirming high analytical concordance. CONCLUSION:The Leadgene® IS ELISA Kit provides a rapid and accessible platform for serum indoxyl sulfate quantification with validated analytical performance and significant association with higher-risk CKD classification.

Chronic kidney disease–mineral and bone disorder (CKD-MBD) confers a substantial fracture burden that is only partly addressed by therapies targeting phosphate, parathyroid hormone, and vitamin D. Redox dysregulation may represent a complementary mechanism: reactive oxygen species (ROS) are required for receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclastogenesis, whereas excessive ROS impair Wnt/β-catenin signalling in osteoblast precursors and promote osteocyte dysfunction. Uremic toxins, inflammation, and dialysis further increase oxidative stress. Molecular hydrogen (H2) is a highly diffusible redox modulator that has been proposed to limit damaging radical-chain reactions while preserving physiological oxidant signalling. In non-uremic skeletal models, H2 consistently suppresses osteoclast differentiation and bone loss, but evidence for osteoblast rescue is heterogeneous. In CKD and dialysis, H2-based interventions have shown signals of reduced oxidative stress and symptomatic benefit; however, human evidence is predominantly observational, and no study identified in this review assessed a bone-specific endpoint. We therefore integrate uremic bone redox biology with H2 pharmacology and propose a turnover-state-dependent model in which H2 may restrain excessive resorption in high-turnover disease, while its net effect in low-turnover adynamic bone remains uncertain because potential osteoblast rescue competes with anti-osteoclastic activity established only in non-uremic models. H2 should therefore be considered an experimental, mechanistically differentiated strategy requiring direct evaluation in uremic models and turnover-stratified clinical trials with parallel skeletal and vascular safety endpoints.

Healthcare systems increasingly depend on interoperable electronic health records, picture archiving and communication systems, cloud analytics, remote monitoring, and connected medical devices. These workflows create a long-lived confidentiality problem: clinical, genomic, pediatric, psychiatric, and family-linked data may remain sensitive for decades, whereas the public-key algorithms that protect current transport and identity systems are vulnerable to future cryptographically relevant quantum computers. Shor's algorithm threatens RSA, finite-field Diffie-Hellman, elliptic-curve Diffie-Hellman, and elliptic-curve signatures, while Grover's algorithm reduces the effective security margin of symmetric primitives. This review validates the post-quantum transition pathway for healthcare and distinguishes software-deployable post-quantum cryptography from hardware-specialized quantum key distribution. We summarize the standardized NIST primitives, correct the status of Falcon/FN-DSA as a FIPS 206 algorithm still in development, analyze deployment constraints in Internet of Medical Things environments, and map cryptographic migration to healthcare governance. A staged, hybrid, crypto-agile migration strategy is recommended: prioritize long-confidentiality data, inventory cryptographic dependencies, deploy hybrid key establishment at enterprise gateways, reserve QKD for selected high-value fixed links, and require vendor update pathways for clinical devices.

Aims:Chronic kidney disease (CKD) is a common and serious complication of type 2 diabetes, yet the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in non-obese or mildly overweight individuals remains uncertain. This study evaluated renal, cardiovascular, and systemic outcomes associated with GLP-1 RA therapy in adults with type 2 diabetes and body mass index (BMI) ≤ 30 kg/m². Materials and Methods:We conducted a real-world, target trial emulation, retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and BMI ≤30 kg/m² initiating GLP-1 RAs or dipeptidyl peptidase-4 inhibitors (DPP-4i) between 2016 and 2023 were identified. After exclusions, 23,103 GLP-1 RA and 44,156 DPP-4i users remained; 1:1 propensity score matching yielded two balanced cohorts of 20,928 patients. Outcomes-including major adverse kidney events (MAKE), progression to dialysis, cardiovascular events, hospitalization, and sepsis-were assessed over up to four years. Cox regression and Kaplan-Meier analyses estimated hazard ratios. Results:GLP-1 RA initiation was associated with lower risks of MAKE (14.8% vs. 16.8%; HR 0.93, p = 0.005) and progression to dialysis (HR 0.78, p < 0.001). Cardiovascular outcomes and all-cause mortality were similar between groups. GLP-1 RAs significantly reduced hospitalization (HR 0.84, p < 0.001) and sepsis (HR 0.88, p = 0.001). Benefits were consistent across BMI strata and clinical subgroups, with no evidence of effect modification. Conclusions:In adults with type 2 diabetes and BMI ≤ 30 kg/m², GLP-1 RAs confer clinically meaningful kidney protection and reduce hospitalization and sepsis, despite neutral cardiovascular effects. These findings support the use of GLP-1 RAs in non-obese or mildly overweight diabetic populations.

IgA nephropathy (IgAN) is an established autoimmune glomerular disease driven by mucosal tolerance failure, aberrant IgA1 glycosylation, and anti-glycan autoantibody formation. Mesangial deposition of galactose-deficient IgA1 (Gd-IgA1) complexes remains the central pathogenic event, though Gd-IgA1 alone is insufficient for disease, and emerging evidence implicates IgA2 deposition as an additional contributor. This review first outlines the classical, lectin, and alternative complement pathways and their predominant activation and regulatory mechanisms in IgAN, clarifying that the alternative pathway can initiate activation independently of the lectin pathway rather than acting solely as its amplifier. We then propose a compartment-based framework linking mesangial complement activation, endothelial and leukocyte responses, podocyte injury, and tubulointerstitial exposure to proteinuria, glomerulosclerosis, and fibrosis, while distinguishing complement-dependent mechanisms from complement-independent injury pathways at each site. We examine how complement biomarkers correspond to specific Oxford MEST-C lesions and discuss the current limitations of integrating these readouts with histology for risk stratification. Finally, we review pathway-selective therapies targeting mannan-binding lectin-associated serine protease (MASP)-2, factor B, C5aR, and C5, emphasizing that complement inhibition should complement rather than replace optimized supportive care and upstream IgA-axis modulation. This integrated view of autoimmune pathogenesis, complement biology, and pathway-selective therapeutics provides a foundation for precision-medicine approaches to progressive IgAN.

Chronic kidney disease (CKD) remains a leading cause of premature mortality and global disease burden, yet the molecular mechanisms underlying its progression are still incompletely understood. Accumulating evidence highlights circadian disruption as an underappreciated driver of CKD that warrants systematic re-examination. The kidney harbors an autonomous circadian oscillator, principally regulated by the CLOCK:BMAL1 transcription factor complex, which coordinates glomerular filtration, tubular electrolyte handling, blood pressure rhythmicity, inflammatory tone, and cellular repair. In CKD, retained uremic toxins, sustained oxidative stress, and persistent NF-κB activation collectively suppress this clock machinery, generating a self-reinforcing cycle of renal injury and circadian dysregulation. CKD is also accompanied by progressive attenuation of nocturnal melatonin secretion, weakening a central hormonal cue for peripheral clock entrainment and cytoprotection. Melatonin acts both as a chronobiotic and as a pleiotropic cytoprotective molecule. Through MT1/MT2 receptors, the nuclear receptor RORα, and receptor-independent antioxidant pathways, it may enhance Nrf2/HO-1 signaling, restrain NF-κB and NLRP3 inflammasome activity, suppress TGF-β1/Smad2/3-mediated fibrogenesis, preserve mitochondrial integrity, and engage SIRT1-linked clock regulation. Current clinical studies suggest that nightly melatonin supplementation can improve sleep quality and selected oxidative or circadian surrogate endpoints in hemodialysis patients; however, whether melatonin slows CKD progression or preserves renal function remains unproven. This review synthesizes the molecular interface between circadian dysregulation and CKD progression and articulates a rationale for adequately powered clinical trials evaluating melatonin as a candidate chronotherapeutic adjunct rather than an established renoprotective therapy.

Background:The increased incidence of herpes zoster (HZ) following coronavirus disease 2019 (COVID-19) suggests a period of immune dysregulation, but the associated long-term neuro-immunological risks remain unclear. Methods:Utilizing de-identified electronic health records from the TriNetX Global Collaborative Network, we established 1:1 propensity score-matched cohorts of COVID-19 survivors, comparing HZ-exposed and unexposed groups over a three-year follow-up. Primary endpoints included the incidence of peripheral nervous system disorders: Bell's palsy, Guillain-Barré syndrome (GBS), and myasthenia gravis (MG). Analyses included Cox proportional hazards models, landmark analyses, and multiple sensitivity analyses. Results:HZ reactivation was associated with increased three-year risks of all outcomes. The risk of Bell's palsy was elevated early and remained sustained (hazard ratio 3.625, 95% confidence interval 3.151-4.170). In contrast, the risks of GBS (hazard ratio 1.858, 95% confidence interval 1.243-2.779) and MG (hazard ratio 1.640, 95% confidence interval 1.178-2.284) showed delayed increases emerging after the first year. These associations remained consistent across sensitivity analyses and were more pronounced in individuals with metabolic comorbidities. COVID-19 vaccination was not associated with an increased risk of these outcomes, although subgroup findings should be interpreted with caution due to limited event counts. Conclusions:Post-COVID-19 HZ is associated with an increased risk of peripheral nervous system disorders, highlighting the need for symptom-based neurological awareness during both early and delayed post-infectious periods.

BACKGROUND/OBJECTIVES:Uremic pruritus and sleep disturbance commonly coexist in patients receiving maintenance hemodialysis. This analysis examined whether supplementation with Lactobacillus casei var. rhamnosus LCR35 was associated with changes in pruritus and sleep outcomes. METHODS:This 12-week randomized, open-label, controlled study included 78 patients receiving maintenance hemodialysis who were assigned to LCR35 supplementation (n = 38; three sachets daily) or usual care without probiotic supplementation (n = 40). No placebo was used. Outcomes were Pittsburgh Sleep Quality Index (PSQI) and 5-D Itch Scale results. We used analysis of covariance (ANCOVA) for between-group analyses, with the week-12 score as the dependent variable and the corresponding baseline score as a covariate. RESULTS:In the LCR35 group, descriptive improvements were observed in the 5-D Itch Scale and selected PSQI outcomes. However, none of the baseline-adjusted between-group differences was statistically significant: for 5-D Itch Scale, -1.48 (95% confidence interval (CI), -3.64 to 0.68; p = 0.176); for global PSQI, -0.80 (95% CI, -2.09 to 0.50; p = 0.225); for PSQI sleep disturbance, -0.07 (95% CI, -0.27 to 0.13; p = 0.482); and use of sleep medications, -0.28 (95% CI, -0.67 to 0.12; p = 0.163). In the LCR35 group, the exploratory association between changes in pruritus and the PSQI sleep-disturbances component was significant before, but not after, false-discovery-rate (FDR) correction (p = 0.007; FDR q = 0.055). CONCLUSIONS:Our preliminary findings raised the possibility that LCR35 might modestly influence pruritus and specific sleep disturbances. However, our results do not firmly establish a treatment effect, nor a patient phenotype most likely to benefit.

Introduction:Glaucoma is a progressive optic neuropathy associated with increased neurodegenerative risk. Vitamin D Deficiency (VDD) is a widespread systemic factor linked to neurobiological dysfunction. This study investigated the longitudinal association between VDD and the 5-year incidence of neurodegenerative outcomes in this glaucoma population. Methods:This retrospective cohort study used a large electronic health records (EHRs) network. Glaucoma patients were classified as VDD (< 30 ng/mL) or vitamin D adequate (VDA) (≥30 ng/mL). A 1:1 propensity score matching (PSM) procedure matched 10,881 patients per cohort based on 47 covariates. The primary endpoints were the 5-year incidence of unspecified dementia, Alzheimer disease (AD), and Parkinson disease (PD), analyzed using Cox proportional hazards models. Results:After PSM, VDD was associated with a higher 5-year risk of unspecified dementia (HR 1.241, 95% CI 1.066-1.446; p = 0.005), with greater risk in severe deficiency (< 20 ng/mL) (HR 1.493, 95% CI 1.179-1.890; p < 0.001). No association was found between VDD and AD or PD. Major predictors included advanced age (HR 6.84), hypertension (HR 2.70), hypoalbuminemia (HR 2.64), elevated CRP (HR 1.38), and diabetes (HR 1.29). Removing long-term NSAID users reduced the dementia risk to non-significant levels (HR 1.178, 95% CI: 0.998-1.391, p = 0.053), suggesting NSAID anti-inflammatory effects may not counteract VDD-related dementia risk in glaucoma patients. Conclusion:VDD is significantly associated with an increased risk of developing dementia in patients with glaucoma. These time-dependent and dose-response findings raise the possibility that correcting vitamin D deficiency may influence neurodegenerative outcomes, additional prospective studies are required to establish causality and clarify clinical implications.

BACKGROUND:Adynamic bone disease (ABD) is an increasingly prevalent form of low-turnover renal osteodystrophy in advanced chronic kidney disease (CKD). ABD was not recognized as a clinical entity prior to the widespread adoption of PTH-targeted therapeutic strategies, and sustained iatrogenic suppression of parathyroid hormone (PTH) activity is now understood as the primary and defining causal mechanism underlying the adynamic phenotype. Uremic toxins, FGF-23-Klotho dysregulation, impaired vitamin D signaling, chronic inflammation, calcium-phosphate imbalance, and osteocyte-mediated abnormalities function as modulatory contributors that amplify skeletal susceptibility within the context of sustained PTH suppression, rather than independent drivers of ABD. Clinically, ABD is associated with impaired bone quality, increased fracture risk, vascular calcification, and musculoskeletal frailty, abnormalities that are often not adequately reflected by areal bone mineral density measurements alone. SUMMARY:ABD in advanced CKD represents a PTH suppression-driven skeletal remodeling phenotype characterized by osteoblast, osteoclast, and osteocyte dysfunction together with disruption of osteoblast-osteoclast coupling. Suppression of Wnt/β-catenin signaling, elevated sclerostin expression, impaired mechanotransduction, skeletal resistance to PTH, and accumulation of uremic toxins collectively contribute to globally reduced remodeling activity and defective microdamage repair. In the context of markedly suppressed bone turnover, antiresorptive therapy is biologically unlikely to confer skeletal benefit and may exacerbate impairment of bone remodeling and renewal. By contrast, anabolic strategies aimed at restoring PTH1R-dependent bone formation and remodeling activation are mechanistically appropriate in CKD-associated ABD. Current evidence suggests that intermittent PTH analog therapy, particularly teriparatide, may improve bone formation markers, bone mineral density, and remodeling activity in selected CKD patients with low-turnover bone disease. Abaloparatide is mechanistically promising but clinically unvalidated in advanced CKD. Romosozumab should not be used in clinical practice for CKD-associated ABD given profound uncertainties regarding cardiovascular safety, vascular calcification, and calcium handling in this population. Practical considerations regarding patient selection, biochemical monitoring, prevention of ABD through avoidance of prolonged PTH suppression, and individualized treatment strategies are also discussed.

Chronic kidney disease (CKD) disrupts mineral metabolism, skeletal remodeling, vascular homeostasis, and immune regulation, producing the systemic phenotype of CKD-mineral and bone disorder (CKD-MBD) together with chronic inflammation and impaired host defense. Osteoimmunology provides a framework for understanding how bone cells, immune cells, and vascular cells interact through shared mediators such as RANKL, osteoprotegerin, NF-kappaB, NFATc1, inflammatory cytokines, fibroblast growth factor 23 (FGF23), Wnt inhibitors, and phosphate-dependent osteogenic signaling pathways. The calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor that regulates parathyroid hormone (PTH) secretion and can signal through Gαq/11, Gαi/o, Gα12/13, and beta-arrestin-dependent pathways. CaSR expression and/or calcium-sensing responses have been described in bone cells, selected immune-lineage cells, and vascular smooth muscle cells, suggesting that CaSR may participate in bone-immune-vascular communication. Calcimimetics, including cinacalcet, etelcalcetide, and evocalcet, are established CaSR-targeting therapies for secondary hyperparathyroidism in dialysis patients. Their best-validated actions are PTH suppression and improvement of calcium-phosphate biochemical control; clinical and experimental studies also support reductions in FGF23, selected bone-turnover markers, and vascular calcification measures. This review critically evaluates the pharmacology of calcimimetics and their potential osteoimmune relevance in CKD-MBD. We emphasize established clinical effects while distinguishing them from mechanistic hypotheses, including direct NLRP3 inflammasome suppression, Th17/Treg rebalancing, macrophage M1-to-M2 polarization, osteocyte connexin-43/DAMP regulation, and hematopoietic niche restoration, which remain insufficiently validated in human CKD. We propose an integrated bone-vascular-immune framework and identify biomarker-guided and precision-medicine strategies for future calcimimetic research.

Background: Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease (ESRD) receiving dialysis. Although calcimimetics (CAMs) and parathyroidectomy (PTx) are widely used for severe SHPT, their comparative effects on long-term clinical outcomes beyond mineral and bone disorder remain uncertain. Methods: We conducted a retrospective multicenter cohort study using the TriNetX research network (2010-2024). Adult dialysis patients with ESRD and severe SHPT, defined by at least one historical intact parathyroid hormone level >600 pg/mL prior to treatment initiation, were included. Patients receiving both therapies were excluded. After 1:1 propensity score matching for demographics, comorbidities, medications, and laboratory variables, outcomes including all-cause mortality, major adverse cardiovascular events (MACE), fracture, cognitive impairment, mild cognitive impairment (MCI), and sepsis were compared using Cox proportional hazards models. Results: After propensity score matching, 22,580 patients were included (11,290 in each group), with follow-up extending to 7 years. Compared with CAM therapy, PTx was associated with significantly lower risks of all-cause mortality (hazard ratio [HR] 0.914, 95% confidence interval [CI] 0.860-0.972), mild cognitive impairment (HR 0.646, 95% CI 0.436-0.955), and sepsis (HR 0.844, 95% CI 0.765-0.930). No significant differences were observed for MACE, fracture, hungry bone disease, overall cognitive impairment, or malignancy. Conclusion: In patients with ESRD and severe SHPT, parathyroidectomy was associated with lower risks of mortality, mild cognitive impairment, and sepsis compared with calcimimetic therapy, while cardiovascular and fracture outcomes were comparable. These findings suggest that PTx may confer broader systemic benefits beyond mineral and bone disorder control in selected dialysis patients.

Osteonecrosis of the jaw (ONJ) is a multifactorial disorder characterized by impaired bone remodeling, vascular compromise, immune dysregulation, and mucosal barrier disruption. Although these mechanisms have been extensively investigated, they are often discussed separately, limiting an integrated understanding of ONJ pathogenesis. Vitamin D has emerged as a biologically relevant factor across these interconnected pathways, yet its role in ONJ remains incompletely defined. This narrative and hypothesis-generating review synthesizes current mechanistic, preclinical, observational, and clinical evidence regarding vitamin D biology and ONJ and proposes a vitamin D-centered vulnerability model in which vitamin D deficiency acts as a context-dependent modifier rather than a primary causal driver. Mechanistically, vitamin D deficiency may impair osteoblast function and mineralization, disrupt angiogenic responses, promote pro-inflammatory immune signaling, and compromise mucosal integrity, collectively creating a microenvironment susceptible to impaired healing and osteonecrosis. These effects are likely to vary across clinical settings, particularly in patients receiving antiresorptive or antiangiogenic therapies. Clinical and epidemiological studies have reported associations between low vitamin D status and increased ONJ risk or severity, while some observational studies suggest that vitamin D supplementation may be associated with improved outcomes in selected populations. However, current human evidence remains predominantly observational and subject to substantial heterogeneity and residual confounding, and direct randomized evidence is lacking. Overall, this framework provides an integrated perspective linking vitamin D biology to ONJ-related pathogenic processes and may support future mechanistic research, risk stratification, and supportive multidisciplinary management strategies. Nevertheless, the proposed model should be interpreted cautiously as hypothesis-generating and requires further validation in well-designed prospective studies and randomized controlled trials.

Secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) is commonly interpreted as a compensatory response to disturbances in mineral metabolism, yet this view does not fully account for the biochemical instability and treatment resistance observed in advanced disease. Current therapeutic strategies primarily target individual regulatory pathways. Calcimimetics suppress parathyroid hormone (PTH) secretion through calcium-sensing receptor (CaSR) activation, whereas active vitamin D analogs reduce PTH synthesis via vitamin D receptor (VDR) signaling but are frequently associated with increased mineral load and elevated fibroblast growth factor 23 (FGF-23). Nutritional vitamin D (NVD) restores circulating 25-hydroxyvitamin D [25(OH)D] and supports tissue-level activation of vitamin D pathways without substantial increases in calcium or phosphate. When combined with calcimimetics, NVD provides complementary modulation of PTH regulation through distinct but interacting mechanisms. Experimental and clinical evidence suggests that this combination may enhance responsiveness of parathyroid tissue and contribute to improved biochemical control. At the system level, this approach has been associated with reduced PTH variability, relatively stable calcium balance, stabilization or modest reduction in phosphate, and reduction in FGF-23 compared with active vitamin D-based strategies. However, current evidence remains largely based on surrogate biochemical endpoints. The Evaluation Of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, the largest Randomized Controlled Trial (RCT) of cinacalcet in dialysis patients, demonstrated no significant reduction in the primary composite endpoint of all-cause mortality or major nonfatal cardiovascular events in the intention-to-treat analysis despite consistent biochemical improvements, and the extent to which combination calcimimetic-based therapy translates into improved long-term clinical outcomes therefore remains uncertain.

Secondary hyperparathyroidism (SHPT) is a major component of chronic kidney disease-mineral and bone disorder (CKD-MBD), reflecting progressive disturbances in mineral metabolism, endocrine signaling, skeletal remodeling, and parathyroid-gland biology. Traditionally, preoperative parathyroid hormone (PTH) has been used primarily as a biochemical threshold for surgical referral. However, persistent PTH elevation in advanced CKD-related SHPT may reflect more than isolated endocrine activity; available evidence suggests it integrates parathyroid-gland remodeling, receptor resistance, skeletal turnover, treatment refractoriness, and systemic CKD-MBD severity. This review summarizes key molecular and cellular mechanisms of progressive SHPT, including diffuse-to-nodular hyperplastic transition, downregulation of calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) signaling, disruption of the fibroblast growth factor 23 (FGF23)-Klotho axis, and activation of transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) proliferative pathways. Building on this mechanistic framework, we discuss how persistent PTH elevation has been linked to glandular remodeling, resistance to calcimimetic and vitamin D therapy, high-turnover renal osteodystrophy, hungry bone syndrome, altered intraoperative PTH kinetics, postoperative endocrine-skeletal remodeling, and long-term recurrence. Severe SHPT is also increasingly recognized as a systemic CKD-MBD phenotype associated with vascular calcification, cardiovascular risk, metabolic instability, and impaired quality of life. Within this framework, preoperative PTH is best interpreted as an integrated biomarker within a broader assessment of glandular remodeling, skeletal metabolic activity, endocrine resistance, and systemic CKD-MBD biology, rather than as an isolated biochemical threshold.

Background: Glaucoma is an age-related optic neuropathy frequently accompanied by systemic comorbidities. Vitamin D deficiency (VDD) has been associated with cardiovascular and renal diseases in the general population, yet its relationship with long-term systemic outcomes in glaucoma remains unclear. This study evaluated the association between baseline vitamin D status and subsequent mortality and cardiorenal events in patients with primary glaucoma. Methods: We conducted a retrospective cohort study using deidentified electronic health records from the TriNetX U.S. Collaborative Network, a federated network of participating healthcare organizations. Adults (≥18 years) with incident primary glaucoma (2005-2020) and a serum 25-hydroxyvitamin D (25(OH)D) test within 12 months prior to diagnosis were categorized as VDD (<30 ng/mL) or vitamin D adequacy (VDA; ≥30 ng/mL). After 1:1 propensity score matching across 47 demographic, clinical, medication, and laboratory variables, 11,855 patients per group were followed for up to 5 years. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), and renal function decline (eGFR < 60 mL/min/1.73 m2). Analyses incorporated Kaplan-Meier curves, Cox models, landmark tests, sensitivity analyses, and competing risk methods. Results: Among the 35,100 eligible patients, the matched cohorts demonstrated higher 5-year risks associated with VDD for all-cause mortality (HR 1.104; 95% CI 1.001-1.217), MACE (HR 1.151; 95% CI 1.078-1.229), and AKI (HR 1.154; 95% CI 1.056-1.261), whereas the risks of renal function decline did not differ (HR 0.972; 95% CI 0.907-1.042). Risk divergence emerged within the first year of follow-up and persisted through the 5-year observation period. Conclusions: In patients with primary glaucoma, vitamin D deficiency was associated with higher long-term risks of mortality and cardiorenal complications, but not renal function decline. Taken together, the results are consistent with vitamin D status serving as a marker of broader systemic vulnerability in glaucoma and highlight the need for prospective studies to further clarify its prognostic significance.

Background/Objectives: Migraine is associated with neurogenic inflammation, trigeminovascular activation, oxidative stress, and systemic metabolic changes. However, circulating antioxidant-related biomarkers in older adults with migraine remain insufficiently characterized. We examined whether self-reported migraine history was associated with serum uric acid (UA), albumin, and total protein levels in the Swedish Adoption/Twin Study of Aging (SATSA), including exploratory analyses in migraine-discordant twin pairs. Methods: This cross-sectional analysis used the first in-person testing wave of SATSA. Participants aged ≥50 years with complete migraine status and biomarker data were included. Serum UA was the primary outcome; albumin and total protein were secondary outcomes. Group differences were assessed using t-tests, Wilcoxon rank-sum tests, or chi-square tests, as appropriate. Linear regression models were adjusted for age, sex, and body mass index. Paired analyses were conducted in 13 migraine-discordant twin pairs. Results: Among 411 participants, 23 reported a migraine history. Participants with migraine had lower serum UA (4.39 vs. 5.15 mg/dL, p = 0.011), albumin (4.40 vs. 4.55 g/dL, p = 0.019), and total protein (7.16 vs. 7.43 g/dL, p = 0.008). These associations remained significant after adjustment. In discordant twin pairs, UA was lower in twins with migraine than in co-twins without migraine (4.34 vs. 4.72 mg/dL, p = 0.050), whereas albumin and total protein differences were not significant. Conclusions: Self-reported migraine history in older adults was associated with lower circulating UA, albumin, and total protein levels. These exploratory, cross-sectional findings should be interpreted as associative rather than causal and require confirmation in longitudinal studies.

Streptococcal toxic shock syndrome (STSS) is a fulminant manifestation of invasive group A Streptococcus infection characterized by superantigen-driven hyperinflammation, refractory shock, and rapidly progressive multiorgan dysfunction. Despite antimicrobial therapy, source control, intravenous immunoglobulin, and intensive organ support, some patients deteriorate rapidly, prompting interest in extracorporeal immunomodulation. This narrative review examines the biological rationale and clinical experience of hemoadsorption in STSS, supported by an illustrative case and comparison with published reports. Our patient developed vasopressor-dependent shock, acute kidney injury, thrombocytopenia, hepatic and myocardial injury, hyperlactatemia, and metabolic acidosis within 48 h. CytoSorb was integrated with continuous venovenous hemofiltration during ongoing deterioration, followed by hemodynamic and organ recovery; however, concurrent therapies preclude attribution of benefit to hemoadsorption. Published cases show a similar pattern, with extracorporeal escalation initiated during refractory shock and accumulating organ dysfunction rather than at a predefined biomarker threshold. Although experimental and observational evidence supports the biological activity of hemoadsorption, clinical evidence remains insufficient to establish a survival benefit. Current evidence does not support routine hemoadsorption for STSS. A rapidly progressive, multidimensional hyperinflammatory trajectory may instead provide a framework for future studies of patient selection and treatment timing.