Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms.

OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits.

OBJECTIVES: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. METHODS: Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. RESULTS: Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. CONCLUSIONS: Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.

Room-temperature epitaxial welding of 3D and 2D perovskites.

Formation of epitaxial heterostructures via post-growth self-assembly is important in the design and preparation of functional hybrid systems combining unique properties of the constituents. This is particularly attractive for the construction of metal halide perovskite heterostructures, since their conventional solution synthesis usually leads to non-uniformity in composition, crystal phase and dimensionality. Herein, we demonstrate that a series of two-dimensional and three-dimensional perovskites of different composition and crystal phase can form epitaxial heterostructures through a ligand-assisted welding process at room temperature. Using the CsPbBr3/PEA2PbBr4 heterostructure as a demonstration, in addition to the effective charge and energy transfer across the epitaxial interface, localized lattice strain was observed at the interface, which was extended to the top layer of the two-dimensional perovskite, leading to multiple new sub-bandgap emissions at low temperature. Given the versatility of our strategy, unlimited hybrid systems are anticipated, yielding composition-, interface- and/or orientation-dependent properties.

Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes.

OBJECTIVE: To investigate the therapeutic effect and mechanism of metformin on knee OA in normal diet (ND) mice or high-fat diet (HFD)-induced obese mice. METHODS: Destabilization of the medial meniscus surgery was performed in ND mice or HFD mice, and metformin was administrated in drinking water or not. The changes of OA joint structure, infiltration and polarization of synovial macrophages and circulating and local levels of leptin and adiponectin were evaluated. In vitro, the effects of metformin on chondrocytes and macrophages, and of conditioned mediums derived from mouse abdominal fat on murine chondrogenic cell line ATDC5 and murine macrophage cell line RAW264.7, were detected. RESULTS: Metformin showed protective effects on OA, characterized by reductions on OARSI score [2.00, 95% CI (1.15, 2.86) for ND mice and 3.17, 95% CI (2.37, 3.96) for HFD mice] and synovitis score [1.17, 95% CI (0.27, 2.06) for ND mice and 2.50, 95% CI (1.49, 3.51) for HFD mice] after 10 weeks of treatment, and the effects were more significant in HFD mice than in ND mice. Mechanistically, in addition to decreasing apoptosis and matrix-degrading enzymes expression in chondrocytes as well as infiltration and pro-inflammatory differentiation of synovial macrophages, metformin reduced leptin secretion by adipose tissue in HFD mice. CONCLUSIONS: Metformin protects against knee OA which could be through reducing apoptosis and catabolism of chondrocytes, and suppressing infiltration and pro-inflammatory polarization of synovial macrophages. For obese mice, metformin has a greater protective effect in knee OA additionally through reducing leptin secretion from adipose tissue.

Epidemiological study of capillary malformation among 7299 infants under 1 year of age in China.

BACKGROUND: Capillary malformation (CM) is the most common vascular malformation. Large scale studies on its incidence and risk factors are limited in China. OBJECTIVE: Our study aimed to investigate the incidence of CM in Chinese infants and to evaluate its potential risk factors. METHODS: A cross-sectional study, including 7299 infants (aged < 1 year) were collected by a self-administered questionnaire. Independent-samples T tests or χ2 tests and multivariable logistic models were used to examine the potential risk factors for CM. RESULTS: The incidences of salmon patches and port-wine stains (PWSs) were 9.10% and 0.80%, respectively. In analyses, male sex (OR: 1.32, 95% CI: 1.12-1.55) and birth hypoxia (OR: 5.61, 95% CI: 4.39-7.16) were risk factors for salmon patches. Birth hypoxia (OR: 12.58, 95% CI: 7.26-21.79) and pregnancy-induced hypertension syndrome (PIH; OR: 3.66, 95% CI: 1.49-8.99) were associated with a higher risk of PWSs. CONCLUSION: This epidemiological study had the largest sample size of infants with CM in the world thus far, which updated its incidence in Chinese infants and found the potential risk factors for CM.

Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.

OBJECTIVE: This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). METHODS: BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. RESULTS: A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The "has-miR-424-5p/lncRNA PVT1" was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. CONCLUSION: IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

MRI-based Texture Analysis of Infrapatellar Fat Pad to Predict Knee Osteoarthritis Incidence.

Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort. All knees had a Kellgren-Lawrence grade of 1 or less at baseline. During the 4-year follow-up, case participants were matched 1:1 to control participants, with incident radiographic KOA as the outcome. MRI scans were segmented at the incident time point of KOA (hereafter, P0), 1 year before P0 (hereafter, P-1), and baseline. MRI-based three-dimensional texture analysis was performed to extract IPFP texture features. Least absolute shrinkage and selection operator and multivariable logistic regressions were applied in the development cohort and evaluated in the test cohort. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative value of the clinical score, IPFP texture score, and MRI Osteoarthritis Knee Score. Results Participants were allocated to development (n = 500, 340 women; mean age, 60 years) and test (n = 190, 120 women; mean age, 61 years) cohorts. In both cohorts, IPFP texture scores (AUC ≥0.75 for all) showed greater discrimination than clinical scores (AUC ≤0.69 for all) at baseline, P-1, and P0, with significant differences in pairwise comparisons (P ≤ .002 for all). Greater predictive and concurrent validities of IPFP texture scores (AUC ≥0.75 for all) compared with MRI Osteoarthritis Knee Scores (AUC ≤0.66 for all) were also demonstrated (P < .001 for all). Conclusion MRI-based three-dimensional texture of the infrapatellar fat pad was associated with future development of knee osteoarthritis. ClinicalTrials.gov registration no.: NCT00080171 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Fischer in this issue.

Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis.

OBJECTIVE: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. METHODS: Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. RESULTS: Five components explained 78% of the total variance. IL-1ß, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. CONCLUSION: Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.

Signal intensity alteration and maximal area of pericruciate fat pad are associated with incident radiographic osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. METHODS: Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. RESULTS: The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10-1.50], 1.52 [1.30-1.78], 1.50 [1.27-1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03-1.42], 1.27 [1.07-1.52], 1.37 [1.15-1.62], respectively) were significantly associated with incident ROA. CONCLUSIONS: PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. KEY POINTS: • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA.

Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study.

BACKGROUND: It is uncertain whether metformin use is associated with reduced risk of joint replacement in patients with type 2 diabetes mellitus. We aimed to establish whether metformin use was associated with a reduced risk of total knee replacement (TKR) or total hip replacement (THR) among these patients. METHODS: We selected patients with type 2 diabetes mellitus that was diagnosed between 2000 and 2012 from the Taiwan National Health Insurance Research Database. We used prescription time-distribution matching and propensity-score matching to balance potential confounders between metformin users and nonusers. We assessed the risks of TKR or THR using Cox proportional hazards regression. RESULTS: We included 20 347 participants who were not treated with metformin and 20 347 who were treated with metformin, for a total of 40 694 participants (mean age 63 yr, standard deviation 11 yr; 49.8% were women) after prescription time-distribution matching. Compared with participants who did not use metformin, those who used metformin had lower risks of TKR or THR (adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.60-0.81 for TKR or THR; adjusted HR 0.71, 95% CI 0.61-0.84 for TKR; adjusted HR 0.61, 95% CI 0.41-0.92 for THR) after adjustment for covariates. Propensity-score matching analyses (10 163 participants not treated with metformin v. 10 163 treated with metformin) and sensitivity analyses using inverse probability of treatment weighting and competing risk regression showed similar results. INTERPRETATION: Metformin use in patients with type 2 diabetes mellitus was associated with a significantly reduced risk of total joint replacement. Randomized controlled clinical trials in patients with osteoarthritis are warranted to determine whether metformin is effective in decreasing the need for joint replacement.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). METHODS: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. RESULTS: One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. CONCLUSIONS: Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

Aqueous MnV2 O6 -Zn Battery with High Operating Voltage and Energy Density.

Aqueous Zn ion batteries (AZIBs), featuring low cost, long-term cycling stability, and superior safety are promising for applications in advanced energy storage devices. However, they still suffer from unsatisfactory energy density and operating voltage, which are closely related to cathode materials used. Herein, the use of monoclinic MnV2 O6 (MVO) is reported, which can be activated for high-capacity Zn ions storage by electrochemically oxidizing part of the Mn2+ to Mn3+ or Mn4+ while the remaining Mn2+ ions act as binders/pillars to hold the layer structure of MVO and maintain its integrity during charging/discharging process. Moreover, after introducing carbon nanotubes (CNT), the MVO:CNT composite not only provides robust 3D Zn-ion diffusion channels but also shows enhanced structural integrity. As a result, a MVO:CNT cathode delivers a high midpoint voltage (1.38 V after 3000 cycles at 2 A g-1 ) and a high energy density of 597.9 W h kg-1 . Moreover, DFT analyses clearly illustrate stepwise Zn ion insertion into the MnV2 O6 lattice, and ex-situ analyses results further verify the highly structural reversibility of the MnV2 O6 cathode upon extended cycling, demonstrating the good potential of MnV2 O6 for the establishment of viable aqueous Zn ion battery systems.

Osteoarthritic infrapatellar fat pad aggravates cartilage degradation via activation of p38MAPK and ERK1/2 pathways.

OBJECTIVE: This study aimed to investigate the biochemical effects of osteoarthritic infrapatellar fat pad (IPFP) on cartilage and the underlying mechanisms. METHODS: Human IPFP and articular cartilage were collected from end-stage osteoarthritis (OA) patients during total knee arthroplasty. IPFP-derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. Functional effect of osteoarthritic IPFP was explored in human primary chondrocytes and articular cartilage in vitro and ex vivo. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. RESULTS: Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling, were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes, while inhibition of other signaling pathways had no similar results. In addition, IL-1ß and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played key roles in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway. CONCLUSION: Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1ß and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.

Depression in patients with knee osteoarthritis: risk factors and associations with joint symptoms.

BACKGROUND: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). METHODS: Three hundred ninety-seven participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. RESULTS: The presence and incidence of depression was 25.4 and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. CONCLUSION: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01176344 . Anzctr.org.au identifier: ACTRN12610000495022 .

Fibrinogen/Albumin ratio: A more powerful prognostic index for patients with end-stage renal disease.

BACKGROUND: Microinflammation is linked to an increased risk of death due to cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). Although the fibrinogen/albumin ratio (FAR), a novel inflammatory marker, has been shown to predict mortality in various diseases, limited evidence is available for its role in ESRD. The purpose of this study is to explore the prognostic value of the FAR in ESRD patients on peritoneal dialysis (PD). METHODS: In this retrospective observational study, we enrolled patients with ESRD who underwent PD therapy in our hospital between 1 January 2011 and 31 December 2017. The Kaplan-Meier method and Cox proportional hazards models were used to determine the contact between the FAR level and mortality. RESULTS: A total of 562 patients were enrolled in our research. The median FAR was 0.12, and patients were divided into two groups (low FAR group: FAR < 0.12, n = 250, and high FAR group: FAR ≥ 0.12, n = 312) according to the median FAR. Kaplan-Meier curves showed that the cumulative incidences of both all-cause mortality and CVD mortality were significantly higher in patients with FAR ≥ 0.12 (both P < .001). In multivariable analysis, the high FAR group had an important increased risk of all-cause and CVD mortality (HR: 1.80; 95% CI: 1.03-3.14, P = .038 and HR: 2.31; 95% CI: 1.17-4.59, P = .016, respectively). CONCLUSIONS: Our results suggest that a high baseline FAR value is an independent prognostic factor in ESRD patients on PD.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.