Soluble tumor necrosis factor receptor type 1 is an alternative marker of urinary albumin-creatinine ratio and estimated glomerular filtration rate for predicting the decline of renal function in subjects with type 2 diabetes mellitus.

BACKGROUND: Urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rates (eGFR) help predict worsening diabetic kidney disease (DKD) but have their limitations. Soluble tumor necrosis factor receptor type 1 (sTNFR1) is a biomarker of DKD. The predictive abilities of sTNFR1 and UACR plus eGFR have not been compared. METHODS: This prospective cohort study included patients with type 2 diabetes (T2D) to identify the risk factors of worsening DKD. Renal events were defined as > 30 % loss in eGFR based on consecutive tests after 6 months. The associations of sTNFR1, UACR, and eGFR levels and the risks of renal events were tested using a Cox regression model and the area under the curve (AUC) was compared between sTNFR1 levels and UACR plus eGFR using receiver-operating characteristic (ROC) analysis. The accuracy of stratification was evaluated using Kaplan-Meier analysis. RESULTS: Levels of sTNFR1 and UACR were associated with risks of > 30 % decline in eGFR after adjusting for relevant factors. The association between sTNFR1 levels and renal outcomes was independent of UACR and eGFR at baseline. The AUC of sTNFR1 level was comparable with that of combined UACR and eGFR (0.73 vs. 0.71, respectively, p = 0.72) and the results persisted for quartile groups of sTNFR1 and risk categories of Kidney Disease: Improving Global Outcomes (KDIGO) (0.70 vs. 0.71, respectively, p = 0.84). Both stratifications by sTNFR1 levels and KDIGO were accurate. CONCLUSION: sTNFR1 could be an alternative marker for identifying patients with diabetes at risk of declining renal function.

Recent progress in unraveling cardiovascular complications associated with primary aldosteronism: a succinct review.

This comprehensive review offers a thorough exploration of recent advancements in our understanding of the intricate cardiovascular complications associated with Primary Aldosteronism (PA). PA encompasses a spectrum of conditions characterized by hypertension and excessive production of aldosterone operating independently of the renin-angiotensin system. Given its association with an elevated risk of cardiovascular and cerebrovascular complications, as well as a higher incidence of metabolic syndrome in comparison to individuals with essential hypertension (EH), an accurate diagnosis of PA is of paramount importance. This review delves into the intricate interplay between PA and cardiovascular health and focuses on the key pathophysiological mechanisms contributing to adverse cardiac outcomes. The impact of different treatment modalities on cardiovascular health is also examined, offering insights into potential therapeutic approaches. By highlighting the significance of recognizing PA as a significant contributor to cardiovascular morbidity, this review emphasizes the need for improved screening, early diagnosis, and tailored management strategies to both enhance patient care and mitigate the burden of cardiovascular diseases. The findings presented herein underscore the growing importance of PA in the context of cardiovascular medicine and emphasize the potential for translating these insights into targeted interventions to improve patient outcomes.

The predictors of long-term outcomes after targeted therapy for primary Aldosteronism.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.

Systemic antibiotics adjuvants to scaling and root planing in type 2 diabetic and periodontitis individuals: Systematic review with network meta-analysis.

Targeting inflammatory pathways is considered a common strategy to control type 2 diabetes (T2D) and periodontitis. This overview was to validate systemic antibiotics as an adjuvant to scaling and root planing (SRP) for the treatments of periodontal patients with T2D. Literature searches were conducted using Web of Science, PubMed, Cochrane, and EMBASE. Randomized trials comparing SRP and systemic antibiotics on glycated hemoglobin (HbA1c) and probing pocket depth (PPD) in adults with T2D and periodontitis were analyzed using network meta-analysis and meta-regression. At 3-month postintervention, meta-analyses of 16 studies revealed that SRP and SRP plus systemic antibiotics (SRPa) had similar significant effects in reducing HbA1c levels of - 0.72% and - 0.96% respectively. While SRP and SRPa also, respectively, reduced PPD of - 0.67 and - 0.89 mm, SRPa showed a better reduction than SRP. At 6-month postintervention, meta-analyses of 7 trials revealed that only SRP was effective in reducing HbA1c levels (-0.29%) but not SRPa. Although both SRP and SRPa still significantly reduced PPD by - 0.56 and - 0.81 mm, respectively, there was no difference between them. The current overview suggested that routine SRP alone is highly recommended for patients with T2D and periodontitis, since systemic antibiotics as an adjuvant provide a rather short-term effect.

Soluble tumor necrosis factor receptor type 1 predicts cardiorenal outcomes and better associated with distinct cardiovascular or renal outcomes than precedential renal or cardiovascular events in type 2 diabetes mellitus.

Background: Inflammations are the crucial pathogenesis of chronic complications of type 2 diabetes mellitus (T2DM). Objectives: The timeline of cardiovascular and renal complications of T2DM and whether soluble tumor necrosis factor receptor type 1 (sTNFR1) levels predict cardiorenal outcomes were still elusive. Design: Prospectively observational study. Methods: Chinese patients with T2DM were enrolled. Cardiorenal composite events defined by either cardiovascular composite events (all-cause mortality, acute coronary syndrome, or non-fatal stroke) or renal composite events (a decline of >30% of renal function or worsening status of albuminuria) were followed. Associations of sTNFR1 levels and cardiovascular, renal, and cardiorenal composite events were analyzed in regression models presented by hazard ratio (HR) and 95% confidence interval (95% CI). Results: Among 370 subjects, 42 cardiovascular and 86 renal composite events occurred. Higher sTNFR1 levels were related to higher frequency and risks of cardiovascular composite events (HR 1.07, 95% CI 1.01-1.13, p = 0.009) and renal composite events (HR 1.05, 95% CI 1.02-1.09, p < 0.001). Occurrences of cardiovascular composite events were not predicted by precedential renal composite events. sTNFR1 levels were proved to be associated with risks of cardiorenal composite events in Cox regression sequential models (adjusted HR 1.04, 95% CI 1.00-1.08, p = 0.03). The results were consistent in all subgroup analyses. Conclusion: Levels of sTNFR1 were associated with cardiorenal complications of T2DM and the predictabilities of TNFR1 levels were better than precedential cardiovascular or renal events.

Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy.

BACKGROUND: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors. METHODS: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A2-2 (CA2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo. RESULTS: Incubation of murine macrophages with CA2-2 led to polarization into the M1 phenotype, and the CA2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently. CONCLUSION: In this study, CA2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments.

Follow-up care and assessment of comorbidities and complications in patients with primary aldosteronism: The clinical practice guideline of the Taiwan Society of aldosteronism.

Primary aldosteronism (PA) is the most common form of endocrine hypertension, characterized by excess aldosterone production that leads to an increased risk of cardiovascular events and target organ damage. Both adrenalectomy and medical treatment have shown efficacy in improving clinical outcomes and comorbidities associated with PA, including a specific subtype of PA with autonomous cortisol secretion (ACS). Understanding the comorbidities of PA and establishing appropriate follow-up protocols after treatment are crucial for physicians to enhance morbidity and mortality outcomes in patients with PA. Additionally, the screening for hypercortisolism prior to surgery is essential, as the prognosis of patients with coexisting PA and ACS differs from those with PA alone. In this review, we comprehensively summarize the comorbidities of PA, encompassing cardiovascular, renal, and metabolic complications. We also discuss various post-treatment outcomes and provide insights into the strategy for glucocorticoid replacement in patients with overt or subclinical hypercortisolism. This clinical practice guideline aims to equip medical professionals with up-to-date information on managing concurrent hypercortisolism, assessing treatment outcomes, and addressing comorbidities in patients with PA, thereby improving follow-up care.

Identifying KCNJ5 Mutation in Aldosterone-Producing Adenoma Patients With Baseline Characteristics Using Machine Learning Technology.

Background: Primary aldosteronism is characterized by inappropriate aldosterone production, and unilateral aldosterone-producing adenoma (uPA) is a common type of PA. KCNJ5 mutation is a protective factor in uPA; however, there is no preoperative approach to detect KCNJ5 mutation in patients with uPA. Objectives: This study aimed to provide a personalized surgical recommendation that enables more confidence in advising patients to pursue surgical treatment. Methods: We enrolled 328 patients with uPA harboring KCNJ5 mutations (n = 158) or not (n = 170) who had undergone adrenalectomy. Eighty-seven features were collected, including demographics, various blood and urine test results, and clinical comorbidities. We designed 2 versions of the prediction model: one for institutes with complete blood tests (full version), and the other for institutes that may not be equipped with comprehensive testing facilities (condensed version). Results: The results show that in the full version, the Light Gradient Boosting Machine outperformed other classifiers, achieving area under the curve and accuracy values of 0.905 and 0.864, respectively. The Light Gradient Boosting Machine also showed excellent performance in the condensed version, achieving area under the curve and accuracy values of 0.867 and 0.803, respectively. Conclusions: We simplified the preoperative diagnosis of KCNJ5 mutations successfully using machine learning. The proposed lightweight tool that requires only baseline characteristics and blood/urine test results can be widely applied and can aid personalized prediction during preoperative counseling for patients with uPA.

CXCL5 suppression recovers neovascularization and accelerates wound healing in diabetes mellitus.

BACKGROUND: Higher chemokine C-X-C motif ligand 5 (CXCL5) level was observed in type 2 diabetes mellitus (DM) patients; however, its role in diabetic vasculopathy was not clarified. This study aimed to explore the impacts and mechanistic insights of CXCL5 in neovasculogenesis and wound healing in DM. METHODS: Endothelial progenitor cells (EPCs) and human aortic endothelial cells (HAECs) were used in vitro. Streptozotocin-induced diabetic mice and Leprdb/JNarl mice were used as type 1 and type 2 DM models. Moreover, CXCL5 knockout mice were used to generate diabetic mice. Hindlimb ischemia surgery, aortic ring assays, matrigel plug assay, and wound healing assay were conducted. RESULTS: CXCL5 concentrations were increased in plasma and EPCs culture medium from type 2 DM patients. CXCL5 neutralizing antibody upregulated vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1) and promoted cell function in EPCs from type 2 DM patients and high glucose-treated EPCs from non-DM subjects as well as HAECs. CXCL5 directly up-regulated interleukin (IL)-1ß/IL-6/tumor necrosis factor-α and down-regulated VEGF/SDF-1 via ERK/p65 activation through chemokine C-X-C motif receptor 2 (CXCR2). CXCL5 neutralizing antibody recovered the blood flow after hindlimb ischemia, increased circulating EPC number, and enhanced VEGF and SDF-1 expression in ischemic muscle. CXCL5 suppression promoted neovascularization and wound healing in different diabetic animal models. The above observation could also be seen in streptozotocin-induced CXCL5 knockout diabetic mice. CONCLUSIONS: CXCL5 suppression could improve neovascularization and wound healing through CXCR2 in DM. CXCL5 may be regarded as a potential therapeutic target for vascular complications of DM.

Prognostic predictors of adrenocortical carcinoma: A single-center thirty-year experience.

Background: The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival. Methods: Medical records of patients, who were diagnosed with ACC at Taipei Veterans General Hospital between January 1992 and June 2021, were reviewed. Patient demographics, tumor characteristics, and subsequent treatment were analyzed with regard to overall survival and progression-free survival using Kaplan-Meier methods and a Cox regression model. Results: Sixty-seven patients were included. Females (65.7%) were more susceptible to ACC, with a younger onset and active hormonal secretion. One-half of the patients exhibited distant metastases at the time of diagnosis. The European Network for the Study of Adrenal Tumours (ENSAT) stage (hazard ratio [HR] 3.60 [95% confidence interval (CI) 1.25-10.38]; p=0.018), large vessel invasion (HR 5.19 [95% CI 1.75-15.37]; p=0.003), and mitotane use (HR 0.27 [95% CI 0.11-0.70]; p=0.007) were significantly associated with overall survival (OS). There was no single factor independently associated with progression-free survival. Conclusion: ENSAT stage had a substantial impact on overall survival though there was no difference in OS between patients with stage II and stage III ACC. Large vessel invasion portended poor prognosis and influenced OS significantly. Moreover, mitotane only improved clinical outcomes of patients with stage IV disease.

Macrophage inflammatory protein-1ß as a novel therapeutic target for renal protection in diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide and the prevalence of DKD has increased over recent decades. Inflammation is involved in the development and progression of DKD. In this study, we explored the potential role of macrophage inflammatory protein-1ß (MIP-1ß) in DKD. Clinical non-diabetic subjects and DKD patients with different levels of urine albumin-to-creatinine ratio (ACR) were enrolled in the study. Leprdb/db mice and MIP-1ß knockout mice were also used as mouse models for DKD. We found that serum MIP-1ß levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1ß is activated in clinical DKD. The administration of anti-MIP-1ß antibodies attenuated DKD severity in the Leprdb/db mice, which also showed reduced glomerular hypertrophy and podocyte injury, as well as decreased inflammation and fibrosis, suggesting that MIP-1ß plays a role in the development of DKD. The MIP-1ß knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1ß knockout mice showed less high glucose-induced inflammation and fibrosis compared to those from wild-type mice. In conclusion, the inhibition or deletion of MIP-1ß protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1ß strategies could potentially be used to treat DKD.

Protocol for an OpenSAFELY cohort study collecting patient-reported outcome measures using the TPP Airmid smartphone application and linked big data to quantify the health and economic costs of long COVID (OpenPROMPT).

INTRODUCTION: The impact of long COVID on health-related quality of-life (HRQoL) and productivity is not currently known. It is important to understand who is worst affected by long COVID and the cost to the National Health Service (NHS) and society, so that strategies like booster vaccines can be prioritised to the right people. OpenPROMPT aims to understand the impact of long COVID on HRQoL in adults attending English primary care. METHODS AND ANALYSIS: We will ask people to participate in this cohort study through a smartphone app (Airmid), and completing a series of questionnaires held within the app. Questionnaires will ask about HRQoL, productivity and symptoms of long COVID. Participants will be asked to fill in the questionnaires once a month, for 90 days. Questionnaire responses will be linked, where possible, to participants' existing health records from primary care, secondary care, and COVID testing and vaccination data. Analysis will take place using the OpenSAFELY data platform and will estimate the impact of long COVID on HRQoL, productivity and cost to the NHS. ETHICS AND DISSEMINATION: The Proportionate Review Sub-Committee of the South Central-Berkshire B Research Ethics Committee has reviewed and approved the study and have agreed that we can ask people to take part (22/SC/0198). Our results will provide information to support long-term care, and make recommendations for prevention of long COVID in the future. TRIAL REGISTRATION NUMBER: NCT05552612.

Fat mass as an important predictor of persistent hypertension in patients with primary aldosteronism after adrenalectomy.

Aldosterone excess is present in obesity and is associated with involvement in the pathogenesis of obesity. We evaluate the impact of body obesity as measured by body composition monitor (BCM) on clinical outcomes in patients with unilateral primary aldosteronism (uPA) after adrenalectomy. The BCM device was used to assess body composition before and after adrenalectomy. We used fat mass (FM) and body mass index (BMI) to classify obesity and divided obesity into three groups: clinical overweight (BMI (kg/m2) ≥25); normal weight obesity (NWO, FM (%) ≥ 35 for women, >25 for men & BMI < 25); and no obesity (FM < 35 for women, <25 for men & BMI < 25). A total of 130 unilateral PA (uPA) patients received adrenalectomy, and 27 EH patients were identified; uPA patients with hypertension remission were found to have lower FM (p = 0.046), BMI (p < 0.001), and lower prevalence of overweight (p = 0.001). In the logistic regression model, patients with clinical overweight (OR = 2.9, p = 0.007), NWO (OR = 3.04, p = 0.041) and longer HTN duration (years, OR = 1.065, p = 0.013) were at the risk of persistent hypertension after adrenalectomy. Obesity status was strongly associated with persistent hypertension in uPA patients after adrenalectomy. However, patients in the NWO group also carried higher risk of persistent hypertension. Therefore, assessment of pre-obesity and overweight in uPA patients are extremely important, especially in those who have normal BMI.

Association between vitamin D and incident herpes zoster: a UK Biobank study.

BACKGROUND: Vitamin D has immunomodulatory effects, but any association with herpes zoster (HZ) is unclear. AIM: To explore the association between vitamin D status and risk of incident HZ in adults in the UK. DESIGN AND SETTING: A cohort study involving participants of UK Biobank (a database containing the health information from half a million individuals) across England, Wales, and Scotland, who had at least one vitamin D testing result with linked primary care electronic health records. METHOD: The primary exposure was vitamin D status, categorised as deficient (<25 nmol/L), insufficient (25-49 nmol/L), or sufficient (≥50 nmol/L). The secondary exposures were self-reported vitamin D supplementation at baseline assessment and vitamin D prescription records. The outcome was diagnosed incident HZ, identified from linked primary care or hospital inpatient records. Weibull regression was used, adjusting for potential confounders, including demographic factors, comorbidities, and immunosuppression. RESULTS: In total, 177 572 eligible participants were included in the analysis, with a mean follow-up time of 10.1 years (standard deviation 1.9 years). No evidence showed that low vitamin D was associated with a higher incidence of HZ, compared with people with sufficient vitamin D (deficient: adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] = 0.90 to 1.10; insufficient: HR 1.03, 95% CI = 0.96 to 1.10). No evidence was found that supplementing vitamin D or receiving vitamin D prescription was associated with HZ incidence (supplementation: HR 0.88, 95% CI = 0.67 to 1.16; prescription: HR 1.11, 95% CI = 0.91 to 1.34). CONCLUSION: No association of vitamin D status, supplementation, or prescription with incident HZ was observed. No evidence supported vitamin D supplementation as a strategy to prevent HZ.

CCL4 Deletion Accelerates Wound Healing by Improving Endothelial Cell Functions in Diabetes Mellitus.

Chronic inflammation in diabetes mellitus (DM) is the leading cause of non-healing wounds. Chemokine CC motif ligand 4 (CCL4) is enhanced in the circulation and in the wounds of DM patients. This study aimed to investigate the effect of endogenous CCL4 inhibition on diabetic wound healing. Endothelial progenitor cells (EPCs) and human dermal microvascular endothelial cells (HDMECs) were used. Mice were injected with streptozotocin to generate hyperglycemia. An enhanced CCL4 level as well as decreased tube formation and migration abilities were observed in high-glucose-treated HDMECs and in EPCs from type 2 DM patients. CCL4 inhibition by siRNA restored the damaged cell function by upregulating the Akt/endothelial nitric oxide synthase/vascular endothelial growth factor/stromal cell-derived factor-1α pathways. Wild-type diabetic mice had delayed wound repair, whereas the CCL4-knockout diabetic mice showed an accelerated rate of wound closure. In a Matrigel plug assay, CCL4-knockout diabetic mice showed higher blood vessel and hemoglobin levels. Higher CD31 and Ki67 expression in the wound area and Matrigel plugs was detected in the CCL4-knockout diabetic mice. CCL4-knockout mice had upregulated angiogenic factors and downregulated inflammatory factors. This study might provide the theoretical basis for CCL4 inhibition as a therapeutic option for clinical diabetic wound treatment.

SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension.

Objective: SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension. Methods: Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR). Results: In cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158-9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529-227.005, P = 0.022) than their counterparts. Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.

The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank.

BACKGROUND: Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. OBJECTIVE: To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. METHODS: We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at <25 nmol/L, insufficiency at 25-49 nmol/L and sufficiency at ≥ 50 nmol/L. Secondary exposures were self-reported or prescribed vitamin D supplements. The primary outcome was laboratory-confirmed or clinically diagnosed SARS-CoV-2 infections. The secondary outcomes included hospitalisation and mortality due to COVID-19. We used multivariable Cox regression models stratified by summertime months and non-summertime months, adjusting for demographic factors and underlying comorbidities. RESULTS: We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77-0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01-1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. CONCLUSION: We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

Fibroblast Growth Factor 21 Levels Exhibit the Association With Renal Outcomes in Subjects With Type 2 Diabetes Mellitus.

Background: Whether microalbuminuria predicts renal outcomes in patients with type 2 diabetes mellitus (T2DM) is argued. Fibroblast growth factor 21 (FGF-21) levels were elevated by the pathogenic process of diabetic kidney disease. The purpose of the study was to evaluate the associations of FGF-21 and renal outcomes in subjects with T2DM. Methods: Chinese patients with T2DM were enrolled and then observed prospectively, and FGF-21 levels at baseline were measured. The associations of FGF-21 levels and renal composite events, defined by a drop > 30% of eGFR or worsening category of albuminuria, were evaluated using Cox analysis. The appropriate cut-off value of FGF-21 was mapped by the receiver operating characteristic (ROC) curve. Results: Among 312 subjects, higher FGF-21 levels were associated with higher risks of renal events in Cox analysis. The area under the curve of FGF-21 levels in the ROC curve was optimal (0.67, p < 0.001), and the cut-off value of 1.40 pg/dl exhibited the best sensitivity (76.2%) and specificity (53.5%). The frequency of renal composite events was higher in subjects with FGF-21 ≥ 1.40 pg/dl than in others (30% vs. 10%, p<0.001 by the log-rank test). The worse renal outcomes predicted by FGF-21 ≥ 1.40 pg/dl were confirmed using the adjustments of Cox sequential models (hazard ratio 2.28, 95% confidence interval 1.23-4.24, p=0.009) and consistent across subjects with different status of baseline characteristics and renal risks. Conclusion: FGF-21 levels were proportional to the risks of renal events in broad- spectrum Chinese T2DM subjects, making it a potential biomarker to predict the renal outcomes of T2DM.

Soluble tumor necrosis factor receptor 2 is associated with progressive diabetic kidney disease in patients with type 2 diabetes mellitus.

BACKGROUND: Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. RESULTS: Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57-0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23-4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. CONCLUSIONS: Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.