Adaptive evolution of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the urinary tract of a single patient.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR-hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR-hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR-hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of rmpADC, the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence ISKpn26. Postswitching, the hypomucoid variant showed a 9.0-fold decrease in mice sepsis mortality, a >170.0-fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9-fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4-fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of rmpADC or capsule synthesis gene wcaJ, mediated by ISKpn26 insertion/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the ISKpn26-associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.

VEGF-B is involved in diabetic peripheral neuropathy in patients with type 2 diabetes.

Aims: This study aims to explore the potential role of vascular endothelial growth factor-B (VEGF-B) in the pathogenesis of diabetic peripheral neuropathy (DPN). The expression of VEGFRs were reanalysed by using gene arrays of peripheral nerve samples from mouse models of DPN retrieved from the GEO database. 213 T2D patients as well as 31 healthy individuals were recruited. The serum VEGF-B was detected and its relationship with DPN was analysed. The elevated VEGFR1 was the only change of VEGFR gene expression in the peripheral nerve from mouse models of DPN. The level of serum VEGF-B in T2D patients with DPN was higher than that in T2D patients without DPN and healthy people. Analysis of correlation and binary logistic regression confirmed that the increased serum VEGF-B level was an independent risk factor of DPN in T2D patients. VEGF-B-VEGFR1 signaling pathway may be involved in the development of DPN.

Myeloid-derived growth factor in diseases: structure, function and mechanisms.

Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).

Dual-Mode Separation and SERS Detection of Carbaryl with PA-6/AuNRs@ZIF-8 Films.

Appropriate separation and enrichment steps can enhance the performance of SERS assays. For rapid, in-situ detection of carbaryl, a novel PA-6/AuNRs@ZIF-8 film that can be applied to dual-mode separation and SERS detection, has been developed. In the film, PA-6 was used as a TLC substrate for the initial separation of the substance to be measured. ZIF-8 provides chemical enhancement in SERS as well as enrichment and secondary separation of the analytes. Utilizing this film, we have successfully implemented a TLC-SERS rapid detection scheme, resulting in a detection limit for carbaryl as low as 1 × 10-9 M in lake water in 15 min, which is significantly lower than existing standards. Additionally, the manufacturing cost of one PA-6/AuNRs@ZIF-8 film can be kept within the range of $0.20-$0.40 economically, presenting substantial financial advantages. The method is highly promising for pesticide detection as well as forensic in-situ testing.

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy.

Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. Exosomes can be derived from cancer cells as well as cellular components in tumor microenvironment. After secretion, the exosomes carrying a wide range of bioactive cargos can be ingested by local or distant recipient cells. The released cargos act through a variety of mechanisms to elicit multiple biological effects and impact most if not all hallmarks of cancer. Moreover, owing to their excellent biocompatibility and capability of being easily engineered or modified, exosomes are currently exploited as a promising platform for cancer targeted therapy. In this review, we first summarize the current knowledge of roles of exosomes in risk and etiology, initiation and progression of cancer, as well as their underlying molecular mechanisms. The aptamer-modified exosome as a promising platform for cancer targeted therapy is then briefly introduced. We also discuss the future directions for emerging roles of exosome in tumor biology and perspective of aptamer-modified exosomes in cancer therapy.

X-ray-induced piezoresponse during X-ray photon correlation spectroscopy of PbMg1/3Nb2/3O3.

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg1/3Nb2/3O3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination.

Optical wireless communication using a flexible and waterproof perovskite color converter.

In this Letter, the CH3NH3PbBr3 nanocrystals (NCs) are embedded into the interstices of the fluorine (polyvinyl fluoride/polyvinylidene fluoride, PVF/PVDF) matrix on polyethylene terephthalate (PET) substrate to introduce new advantages, such as being flexible and waterproof, while maintaining the high optical performance of perovskites. The sample's photoluminescence (PL) spectra under 325 nm laser is a green emission peaked at 537 nm with full width at half maximum (FWHM) of about 21.2 nm and a fast PL decay time. As a color converter, it shows high optical absorption and can transform light from solar-blind ultraviolet to a blue region into a green region in air, water, and bending conditions. While excited by a 270 nm ultraviolet light-emitting diode (LED), the system's observed -3 dB bandwidth with the color converter is near 4.4 MHz in air and water conditions with well-eye diagrams at a data rate of 30 Mbps. Finally, we demonstrate an audio transmission application with an ultraviolet light source, a color conversion layer, and a low-cost silicon-based photodetector.

Pyroptosis and its role in autoimmune skin disease.

Autoimmune skin disease is a kind of heterogeneous disease with complicated pathogenesis. Many factors such as genetic, infectious, environmental and even psychological factors may interact together to trigger a synergistic effect for the development of abnormal innate and adaptive immune responses. Although the exact mechanisms remain unclear, recent evidence suggests that pyroptosis plays a pivotal role in the development of autoimmune skin disease. The feature of pyroptosis is the first formation of pores in cellular membranes, then cell rupture and the release of intracellular substances and pro-inflammatory cytokines, such as interleukin-1 beta (IL-1ß) and IL-18. This hyperactive inflammatory programmed cell death damages the homeostasis of the immune system and advances autoimmunity. This review briefly summarises the molecular regulatory mechanisms of pyrin domain-containing protein 3 (NLRP3) inflammasome and gasdermin family, as well as the molecular mechanisms of pyroptosis, highlights the latest progress of pyroptosis in autoimmune skin disease, including systemic lupus erythematosus, psoriasis, atopic dermatitis and systemic scleroderma and attempts to identify its potential advantages as a therapeutic target or prognostic biomarker for these diseases.

The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Anisotropic growth of gold anchors on CdSe semiconductor quantum platelets for self-assembled architectures with well-connected electronic circuits for the electrochemical detection of enrofloxacin.

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

Immobilising an acid-cleavable dimeric phthalocyanine on gold nanobipyramids for intracellular pH detection and photodynamic elimination of cancer cells.

An acetal-linked dimeric phthalocyanine has been synthesised and immobilised on the surface of gold nanobipyramids. The resulting nanocomposite serves as a highly sensitive probe for intracellular pH through its acid-responsive fluorescence and surface-enhanced Raman scattering signals. The phthalocyanine units released in the acidic intracellular environment can also effectively eliminate the cancer cells upon light irradiation, rendering this simple fabricated nanosystem a bimodal and bifunctional theranostic agent.

Extracellular ATP- and adenosine-mediated purinergic signaling modulates inducible nitric oxide synthase (iNOS) gene expression, enzyme activity and nitric oxide production in common carp (Cyprinus carpio) head kidney macrophages.

Inducible nitric oxide (NO) synthase (iNOS) is a key immune mediator for production of inflammatory mediator NO from l-arginine. Tight regulation of iNOS expression and enzyme activity is critical for proper NO productions under inflammation and infection conditions. However, the regulatory mechanism for iNOS expression and enzyme activity in fish remains largely unknown. Here, we show that extracellular ATP treatment significantly up-regulates iNOS gene expression and enzyme activity, and consequently leads to enhanced NO production in Cyprinus carpio head kidney macrophages (HKMs). We further show that the extracellular ATP-induced iNOS enzyme activity and NO production can be attenuated by pharmacological inhibition of the ATP-gated P2X4 and P2X7 receptors with their respective specific antagonists, but enhanced by overexpression of P2X4 and P2X7 receptors in grass carp ovary cells. In contrast, adenosine administration significantly reduces iNOS gene expression, enzyme activity and NO production in carp HKMs, and these inhibitory effects can be reversed by pharmacological inhibition of adenosine receptors with the antagonist XAC. Furthermore, LPS- and poly(I:C)-induced iNOS gene expression, enzyme activity, and NO production are significantly attenuated by blockade of P2X4 and P2X7 receptors with their respective specific antagonists in carp HKMs, while overexpression of P2X and P2X7 receptors results in enhanced iNOS gene expression, enzyme activity and NO production in LPS- and poly(I:C)-treated grass carp ovary cells. Taken together, we firstly report an opposite role of extracellular ATP/adenosine-mediated purinergic signaling in modulating iNOS-NO system activity in fish.

Arsenic-Hyperaccumulator Pteris vittata Effectively Uses Sparingly-Soluble Phosphate Rock: Rhizosphere Solubilization, Nutrient Improvement, and Arsenic Accumulation.

Sparingly-soluble phosphate rock (PR), a raw material for P-fertilizer production, can be effectively utilized by the As-hyperaccumulator Pteris vittata but not most plants. In this study, we investigated the associated mechanisms by measuring dissolved organic carbon (DOC) and acid phosphatase in the rhizosphere, and nutrient uptake and gene expression related to the As metabolism in P. vittata. The plants were grown in a soil containing 200 mg kg-1 As and/or 1.5% PR for 30 days. Compared to the As treatment, the P. vittata biomass was increased by 33% to 4.6 g plant-1 in the As+PR treatment, corresponding to 27% decrease in its frond oxidative stress as measured by malondialdehyde. Due to PR-enhanced DOC production in the rhizosphere, the Ca, P, and As contents in P. vittata fronds were increased by 17% to 9.7 g kg-1, 29% to 5.0 g kg-1, and 57% to 1045 mg kg-1 in the As+PR treatment, thereby supporting its better growth. Besides, PR-induced rhizosphere pH increase from 5.0 to 6.9 promoted greater P uptake by P. vittata probably via upregulating low-affinity P transporters PvPTB1;1/1;2 by 3.7-4.1 folds. Consequently, 29% lower available-P induced the 3.3-fold upregulation of high-affinity P transporter PvPht1;3 in the As+PR treatment, which was probably responsible for the 58% decrease in available-As content in the rhizosphere. Consistent with the enhanced As translocation and sequestration, arsenite antiporters PvACR3/3;3 were upregulated by 1.8-4.4 folds in the As+PR than As treatment. In short, sparingly-soluble PR enhanced the Ca, P, and As availability in P. vittata rhizosphere and improved their uptake via upregulating genes related to As metabolism, suggesting its potential application for improving phytoremediation in As-contaminated soils.

Novel Phosphate Transporter-B PvPTB1;1/1;2 Contribute to Efficient Phosphate Uptake and Arsenic Accumulation in As-Hyperaccumulator Pteris vittata.

Arsenic (As) contamination in soil poses a potential threat to human health via crop uptake. As-hyperaccumulator Pteris vittata serves as a model plant to study As uptake and associated mechanisms. This study focuses on a novel P/AsV transport system mediated by low-affinity phosphate transporter-B 1 family (PTB1) in P. vittata. Here, we identified two plasma-membrane-localized PTB1 genes, PvPTB1;1/1;2, in vascular plants for the first time, which were 4.4-40-fold greater in expression in P. vittata than in other Pteris ferns. Functional complementation of a yeast P-uptake mutant and enhanced P accumulation in transgenic Arabidopsis thaliana confirmed their role in P uptake. Moreover, the expression of PvPTB1;1/1;2 facilitated the transport and accumulation of As in both yeast and A. thaliana shoots, demonstrating a comparable AsV uptake capacity. Microdissection-qPCR analysis and single-cell transcriptome analysis collectively suggest that PvPTB1;1/1;2 are specifically expressed in the epidermal cells of P. vittata roots. PTB1 may play a pivotal role in efficient P recycling during phytate secretion and hydrolysis in P. vittata roots. In summary, the dual P transport mechanisms consisting of high-affinity Pht1 and low-affinity PTB1 may have contributed to the efficient P/As uptake in P. vittata, thereby contributing to efficient phytoremediation for As-contaminated soils.

Understanding Variations in Ferrate Detection through the ABTS Method in the Presence of Electron-Rich Organic Compounds.

The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from ∼88 to 100%. Reducing substances consumed ABTS•+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Ph•), promoting the transformation of Fe(VI) → Fe(V) → Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTS•+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.

Assessing nicotine pharmacokinetics of new generation tobacco products and conventional cigarettes: a systematic review and meta-analysis.

INTRODUCTION: New generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis. METHODS: A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to the peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences (SMD), facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted. RESULTS: The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs. CONCLUSIONS: NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation. IMPLICATION: This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternative to CCs in helping smokers to manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction.

Evaluation and systematic review of guidance documents for status epilepticus.

Guidance documents play a pivotal role in shaping the management of status epilepticus (SE). However, the methodological quality of these documents remains uncertain. In this systematic review, we comprehensively searched 12 literature and guideline databases to assess the quality of clinical practice guidelines and consensus statements related to SE management using the AGREE II methodology. Additionally, we summarized the associated recommendations. We identified a total of 14 clinical practice guidelines and 11 consensus statements spanning the period from 1993 to 2022. The median score for clarity of presentation was 71.8% (ranging from 15.3% to 91.7%), indicating generally good clarity. However, the aspect of editorial independence received poor ratings, with a median score of 32.1% (ranging from 0% to 83.3%). Notably, the 2016 guideline published by the American Epilepsy Society in Epilepsy (AES) received the highest overall scores. Across these guidance documents, there was consistency in the definition and diagnosis of SE. However, significant variability was observed in therapeutic recommendations, particularly in terms of the timing for adding or changing medications. The methodological approaches used in most SE guidance documents require improvement, and the disparities in recommendations highlight existing gaps in evidence. Enhanced methodological rigor results in increased standardization of the guideline, consequently augmenting its reference value. Given the urgency of SE as an emergency condition, it is imperative that these documents also address relevant management strategies before admission.

Association between brominated flame retardants (PBDEs and PBB153) exposure and hypertension in U.S. adults: results from NHANES 2005-2016.

BACKGROUND: Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. RESULTS: 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (ß:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. CONCLUSION: Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

Coffee consumption and risk of kidney function decline in a Dutch population-based cohort.

BACKGROUND AND AIMS: Whether coffee consumption is associated with changes in estimated glomerular filtration rate (eGFR) is unknown. We investigated the relationship between coffee consumption and annual eGFR change in a large Dutch population-based study. METHODS AND RESULTS: This study was performed in 78,346 participants without chronic kidney disease (CKD) in the population-based Lifelines Cohort Study. Coffee consumption was assessed at baseline using food frequency questionnaires. Outcomes were annual eGFR change and a composite kidney outcome (defined as eGFR <60 mL/min per 1.73 m2 or >20 % eGFR decline). Multivariable linear and logistic regression analyses were used to evaluate the associations of coffee consumption (categories and cups/day) with kidney outcomes. Overall, 90 % of the participants drank coffee daily and 36 % drank >2-4 cups/day. Unadjusted mean ± SD annual eGFR change ranged from -2.86 ± 2.96 (for non-coffee drinkers) to -2.35 ± 2.62 (for participants consuming >6 cups/day) mL/min per 1.73 m2. During 3.6 ± 0.9 years follow-up, 11.1 % of participants reached the composite kidney outcome. As compared to non-coffee drinkers, higher coffee consumption was associated with less annual eGFR decline in multivariable models (ß [95 % CIs] ranged from 0.15 [0.07, 0.22] for >0-2 cups/day to 0.29 [0.20, 0.38] for >6 cups/day, P-trend <0.001). Consumption of one more cup of coffee per day was associated with a 3 % lower risk of the composite kidney outcome (OR [95%CI], 0.97 [0.96, 0.99]). The inverse association was more pronounced in a subgroup of individuals with diabetes. CONCLUSION: Coffee consumption was inversely associated with annual eGFR change and CKD risk in a large Dutch population-based cohort.

Clinical characteristics and risk factors of cardiac involvement in pediatric immunoglobulin A vasculitis: A 7-year retrospective study from a single tertiary medical center.

Immunoglobulin A vasculitis(IgAV) is the most common form of systemic vasculitis affecting children. To date, cardiac involvement in pediatric IgAV has not been fully investigated and its prevalence may be underestimated. This study aims to reveal the clinical and laboratory characteristics of cardiac involvement in pediatric IgAV and further determine its risk factors. A total of 1451 children with IgAV were recruited between January 2016 and December 2022. According to the severity of cardiac involvement, the patients were divided into the myocarditis/suspected myocarditis group, cardiac abnormalities group, and non-cardiac involvement group. Demographic, clinical, and laboratory characteristics were retrospectively extracted from the individual data collected in the medical records. Among the 1451 pediatric IgAV patients, 179 (12.3%) were identified with cardiac involvement, including 154 (10.6%) with cardiac abnormalities and 25 (1.7%) with myocarditis/suspected myocarditis. Cardiac involvement in pediatric IgAV mainly manifested as elevated cardiac biomarker levels (n = 162), electrocardiogram abnormalities (n = 46), and echocardiogram/chest X-ray abnormalities (n = 15); however, cardiac-related symptoms were only observed in 15.1% of patients with cardiac involvement. Multivariate analysis demonstrated that interval from disease onset to diagnosis > 7 days (OR, 2.157; 95% CI, 1.523-3.057; p < 0.001), IgAV with multi-organ involvement (OR, 1.806; 95% CI, 1.242-2.627; p = 0.002), and elevated D-dimer levels (OR, 1.939; 95% CI, 1.259-2.985; p < 0.001) were independent risk factors for cardiac involvement in pediatric IgAV. The length of hospital stay was significantly longer in the myocarditis/suspected myocarditis group compared with the other two groups (p < 0.05).     Conclusion: This study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. What is Known: • Immunoglobulin A vasculitis (IgAV) is the most common form of systemic vasculitis affecting children and adolescents, which exhibits diverse clinical manifestations. Cases of severe IgAV complicated by cardiac involvement have been anecdotally reported. What is New: • The present study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV.