Associations of MRI-derived kidney volume, kidney function, body composition and physical performance in ≈38 000 UK Biobank participants: a population-based observational study.

Background: Kidney volume is used as a predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition and physical performance. Methods: In this observational study, MRI-derived kidney volume measurements from 38 526 UK Biobank participants were analysed. Major kidney volume-related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference in bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume-related measures and clinicodemographic factors. Cox or logistic regression was used to identify the risks of death, non-kidney cancer, myocardial infarction, ischaemic stroke and chronic kidney disease (CKD). Results: The median of BSA-adjusted TKV and the difference in kidney volume were 141.9 ml/m2 [interquartile range (IQR) 128.1-156.9] and 1.08-fold (IQR 1.04-1.15), respectively. Higher BSA-adjusted TKV was significantly associated with higher estimated glomerular filtration rate {eGFR; ß = 0.43 [95% confidence interval (CI) 0.42-0.44]; P < .001}, greater muscle volume [ß = 0.50 (95% CI 0.48-0.51); P < .001] and greater mean handgrip strength [ß = 0.15 (95% CI 0.13-0.16); P < .001] but lower visceral adipose tissue volume [VAT; ß = -0.09 (95% CI -0.11 to -0.07); P < .001] in adjusted models. A greater difference in bilateral kidney volumes was associated with lower eGFR, muscle volume and physical performance but with higher proteinuria and VAT. Higher BSA-adjusted TKV was significantly associated with a reduced risk of CKD [odds ratio (OR) 0.7 (95% CI 0.63-0.77); P < .001], while a greater difference in kidney volume was significantly associated with an increased risk of CKD [OR 1.13 (95% CI 1.07-1.20); P < .001]. Conclusion: Higher BSA-adjusted TKV and lower differences in bilateral kidney volumes are associated with higher kidney function, muscle volume and physical performance and a reduced risk of CKD.

Differences of nutritional intake habits and Dietary Inflammatory Index score between occupational classifications in the Korean working population.

Background: Human nutrient intake is closely related to the conditions of their workplace. Methods: This study used data from the Korean National Health and Nutritional Examination Survey (KNHANES) conducted between 2016 and 2020. The study population comprised individuals aged 19 to 65 years who were engaged in paid work, excluding soldiers (total = 12,201, male = 5,872, female = 6,329). The primary outcome of interest was the Dietary Inflammatory Index (DII) score, which was calculated using dietary intake data. Generalized linear models were used for statistical analyses. Results: Pink-collar workers had higher DII scores, indicating a potentially higher inflammatory diet than white-collar workers (mean: 2.18 vs. 1.89, p < 0.001). Green and blue-collar workers displayed lower levels of dietary inflammation (green: 1.64 vs. 1.89, p = 0.019, blue: 1.79 vs. 1.89, p = 0.022). After adjusting for sex, age, income, education, and energy intake, the sole trend that persisted was the comparison between white-collar and pink-collar workers. Conclusions: DII scores and dietary patterns differed among occupational groups and genders.

Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea.

BACKGROUND: Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. METHODS: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. RESULTS: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. CONCLUSION: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease.

We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer's disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer's and Parkinson's disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide - a proxy for traffic-related air pollution - and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.

Thrombocytopenia after Aortic Valve Replacement Using Sutureless Valves.

Background: Sutureless valves are widely used in aortic valve replacement surgery, with Perceval valves and Intuity valves being particularly prominent. However, concerns have been raised about postoperative thrombocytopenia with Perceval valves (Corcym, UK). We conducted a comparative analysis with the Intuity valve (Edwards Lifesciences, USA), and assessed how thrombocytopenia affected patient and transfusion outcomes. Methods: Among 595 patients who underwent aortic valve replacement from June 2016 to March 2023, sutureless valves were used in 53 (Perceval: n=23; Intuity: n=30). Platelet counts were monitored during hospitalization and outpatient visits. Daily platelet count changes were compared between groups, and the results from patients who underwent procedures using Carpentier Edwards Perimount Magna valves were used as a reference group. Results: Compared to the Intuity group, the Perceval group showed a significantly higher amount of platelet transfusion (5.48±1.64 packs vs. 0.60±0.44 packs, p=0.008). During the postoperative period, severe thrombocytopenia (<50,000/µL) was significantly more prevalent in the Perceval group (56.5%, n=13) than in the Intuity group (6.7%, n=2). After initial postoperative depletion, daily platelet counts increased, with significant differences observed in the extent of improvement between the Perceval and Intuity groups (p<0.001). However, there was no significant difference in early mortality or the incidence of neurological complications between the 2 groups. Conclusion: The severity of postoperative thrombocytopenia differed significantly between the Perceval and Intuity valves. The Perceval group showed a significantly higher prevalence of severe thrombocytopenia and higher platelet transfusion volumes. However, thrombocytopenia gradually recovered during the postoperative period in both groups, and the early outcomes were similar in both groups.

Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target.

BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.

Evaluation of risk stratification for acute kidney injury: a comparative analysis of EKFC, 2009 and 2021 CKD-EPI glomerular filtration estimating equations.

BACKGROUND: The adoption of the 2021 CKD-EPIcr equation for glomerular filtration rate (GFR) estimation provided a race-free eGFR calculation. However, the discriminative performance for AKI risk has been rarely validated. We aimed to evaluate the differences in acute kidney injury (AKI) prediction or reclassification power according to the three eGFR equations. METHODS: We performed a retrospective observational study within a tertiary hospital from 2011 to 2021. Acute kidney injury was defined according to KDIGO serum creatinine criteria. Glomerular filtration rate estimates were calculated by three GFR estimating equations: 2009 and 2021 CKD-EPIcr, and EKFC. In three equations, AKI prediction performance was evaluated with area under receiver operator curves (AUROC) and reclassification power was evaluated with net reclassification improvement analysis. RESULTS: A total of 187,139 individuals, including 27,447 (14.7%) AKI and 159,692 (85.3%) controls, were enrolled. In the multivariable regression prediction model, the 2009 CKD-EPIcr model (continuous eGFR model 2, 0.7583 [0.755-0.7617]) showed superior performance in AKI prediction to the 2021 CKD-EPIcr (0.7564 [0.7531-0.7597], < 0.001) or EKFC model in AUROC (0.7577 [0.7543-0.761], < 0.001). Moreover, in reclassification of AKI, the 2021 CKD-EPIcr and EKFC models showed a worse classification performance than the 2009 CKD-EPIcr model. (- 7.24 [- 8.21-- 6.21], - 2.38 [- 2.72-- 1.97]). CONCLUSION: Regarding AKI risk stratification, the 2009 CKD-EPIcr equation showed better discriminative performance compared to the 2021 CKD-EPIcr equation in the study population.

Apathy scores in Parkinson's disease relate to EEG components in an incentivized motor task.

Apathy is one of the most prevalent non-motor symptoms of Parkinson's disease and is characterized by decreased goal-directed behaviour due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson's disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson's disease using EEG data recorded during an incentivized motor task. Thirteen Parkinson's disease patients with apathy and 13 Parkinson's disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analysed using multiset canonical correlation analysis to detect different orthogonal components of temporally consistent event-related spectral perturbations across trials and participants. The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12-20 Hz) power (i.e. beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson's disease patients with apathy compared with healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in healthy controls but not Parkinson's disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4-8 Hz) power in Parkinson's disease patients with apathy during the reward cue and squeezing compared with healthy controls (HCs), and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power. Our results emphasize that altered low-beta and low-theta oscillations are critical for reward processing and motor planning in Parkinson's disease patients with apathy and these may provide a target for non-invasive neuromodulation.

HDAC11 Regulates Palmitate-induced NLRP3 Inflammasome Activation by Inducing YAP Expression in THP-1 Cells and PBMCs.

Histone deacetylase 11 (HDAC11) has been implicated in the pathogenesis of metabolic diseases characterized by chronic low-grade inflammation, such as obesity. However, the influence of HDAC11 on inflammation and the specific effect of HDAC11 on the palmitic acid (PA)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation are poorly understood. The effect of PA treatment on HDAC11 activity and the NLRP3 inflammasome was investigated in human peripheral blood mononuclear cells and THP-1 cells. The PA-induced responses of key markers of NLRP3 inflammasome activation, including NLRP3 gene expression, caspase-1 p10 activation, cleaved IL-1ß production, and extracellular IL-1ß release, were assessed as well. The role of HDAC11 was explored using a specific inhibitor of HDAC11 and by knockdown using small interfering (si)HDAC11 RNA. The relationship between HDAC11 and yes-associated protein (YAP) in the PA-induced NLRP3 inflammasome was investigated in THP-1 cells with HDAC11 or YAP knockdown. Following PA treatment, HDAC11 activity and protein levels increased significantly, concomitant with activation of the NLRP3 inflammasome. Notably, PA-induced the upregulation of NLRP3, caspase-1 p10 activation, the production of cleaved IL-1ß, and the release of IL-1ß into the extracellular space, all of which were attenuated by FT895 treatment and by HDAC11 knockdown. In THP-1 cells, PA induced the expression of YAP and its interaction with NLRP3, resulting in NLRP3 inflammasome activation, whereas both were inhibited by FT895 and siHDAC11 RNA. These findings demonstrate a pivotal role for HDAC11 in the PA-induced activation of the NLRP3 inflammasome. HDAC11 inhibition thus represents a promising therapeutic strategy for mitigating NLRP3 inflammasome-related inflammation in the context of obesity.

Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study.

OBJECTIVE: Evidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with 'underlying' chronic kidney disease (CKD) remains scarce, although PPI use is generally associated with acute interstitial nephritis or incident CKD. We aimed to investigate the association between PPI initiation and the risk of adverse outcomes in patients with CKD in the absence of any deterministic indications for PPI usage. DESIGN: Retrospective observational study. SETTING: Korea National Health Insurance Service database from 2009 to 2017. PARTICIPANTS: A retrospective cohort of new PPI and histamine H2-receptor antagonists (H2RA) users among people with CKD. Patients with a history of gastrointestinal bleeding or those who had an endoscopic or image-based upper gastrointestinal tract evaluation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The study subjects were followed to ascertain clinical outcomes including mortality, end-stage kidney disease (ESKD), myocardial infarction and stroke. The HRs of outcomes were measured using a Cox regression model after adjusting for multiple variables. We applied an inverse probability of treatment weighting (IPTW) model to control for residual confounders. RESULTS: We included a total of 1038 PPI and 3090 H2RA users without deterministic indications for treatment. IPTW-weighted Cox regression analysis showed that PPI initiation was more significantly associated with a higher ESKD risk compared with that of H2RA initiation (adjusted HR 1.72 (95% CI 1.19 to 2.48)), whereas the risks of mortality or cardiovascular outcomes were similar between the two groups. In the subgroup analysis, multivariable Cox regression analysis showed that the association between PPI use and the progression to ESKD remained significant in non-diabetic and low estimated glomerular filtration rate (<60 mL/min/1.73 m2) groups (adjusted HR 1.72 (95% CI 1.19 to 2.48) and 1.63 (95% CI 1.09 to 2.43), respectively). CONCLUSIONS: Initiation of PPI administration may not be recommended in patients with CKD without deterministic indication, as their usage was associated with a higher risk of ESKD.

Associations of metabolic variabilities and cardiovascular outcomes according to estimated glomerular filtration rate in chronic kidney disease: a nationwide observational cohort study.

Background: The impact of baseline estimated glomerular filtration rate (eGFR) on the risk of adverse outcomes according to metabolic parameter variabilities in chronic kidney disease has rarely been investigated. Methods: We conducted a retrospective nationwide cohort study using the National Health Insurance System data in Korea from 2007 to 2013 to identify individuals with three or more health screenings. The metabolic components variability was defined as intraindividual variability between measurements using the variability independent of the mean. The metabolic variability score was defined as the total number of high-variability metabolic components. Multivariable-adjusted Cox regression analysis was conducted to evaluate the risks of all-cause mortality, myocardial infarction, and ischemic stroke. Results: During a mean follow-up of 6.0 ± 0.7 years, 223,531 deaths, 107,140 myocardial infarctions, and 116,182 ischemic strokes were identified in 9,971,562 patients. Low eGFR categories and higher metabolic variability scores were associated with a higher risk of adverse outcomes. The degree of association between metabolic variability and adverse outcomes was significantly larger in those with low eGFR categories than in those with preserved eGFR (p for interaction < 0.001). Representatively, those with high metabolic variability in the eGFR of <15 mL/min/1.73 m2 group showed a prominently higher risk for all-cause mortality (adjusted hazard ratio [aHR], 5.28; 95% confidence interval [CI], 4.02-6.94) when the degree was compared to the findings in those with preserved (eGFR of ≥60 mL/min/1.73 m2) kidney function (aHR, 2.55; 95% CI, 2.41-2.69). Conclusion: The degree of adverse association between metabolic variability and poor prognosis is accentuated in patients with impaired kidney function.

Primary sclerosing cholangitis causally affects kidney function decline: A Mendelian randomization study.

BACKGROUND AND AIM: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long-term detrimental effects on kidney function. METHODS: Two-sample summary-level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC-specific multi-trait analyzed genome-wide association study (GWAS) of European ancestry. Summary-level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random-effects inverse-variance weighted (MR-IVW), and a series of pleiotropy-robust analyses were performed to investigate the causal effects and ascertain their robustness. RESULTS: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log-transformed eGFR (MR-IVW; beta = -0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR-IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR-IVW; odds ratio = 1.07; 95% confidence interval = 1.06-1.08; P < 0.001). The main findings were supported by pleiotropy-robust analysis, including MR-Egger with bootstrapped error and weighted median. CONCLUSIONS: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms.

Role of extracorporeal life support for traumatic hemopericardium: A single level I trauma center review.

BACKGROUND: Traumatic hemopericardium may lead to cardiac tamponade, arrhythmia, arrest, or death and requires emergency surgery. We reviewed cases of traumatic hemopericardium in our center and the role of extracorporeal life support in these cases. METHODS: From November 2011 to January 2022, 28 patients with significant hemopericardium and suspected cardiac injury were enrolled. In our center, surgery is the primary treatment of choice; however, if the patient is in an unstable condition, extracorporeal life support is administered in the emergency room prior to surgery. RESULTS: Preoperative extracorporeal life support was applied to 10 patients (36 %). Two patients (20 %) were converted from extracorporeal life support to cardiopulmonary bypass during operation. After surgery, 2 patients (20 %) needed postoperative extracorporeal membrane oxygenation support. Overall, 21 patients (75 %) survived; of these, 6 (29 %) received extracorporeal life support. Meanwhile, 7 patients (25 %) died; of these, 4 patients (57 %) received extracorporeal life support. CONCLUSION: Resuscitation method is the most crucial survival strategy in patients with severe chest trauma. Extracorporeal life support in cases of traumatic hemopericardium may be beneficial and efficient in stabilizing patients prior to surgery.

Menopausal hormone therapy and risk for dementia in women with CKD: A nationwide observational cohort study.

AIM: The risk for dementia is increased in postmenopausal women. The incidences of premature menopause and dementia have increased in patients with chronic kidney disease (CKD). The potential benefits of hormone replacement therapy (HRT) on cognitive function may be a more critical issue for patients with CKD. METHODS: Women aged >40 years with or without HRT were identified using the 2009 National Health Screening Questionnaire. Women who were newly diagnosed with CKD between 2009 and 2013 were enrolled. HRT was used as an exposure variable, and participants were followed from the day CKD was diagnosed to December 2019. The hazard ratio (HR) for dementia was evaluated using Cox proportional hazards regression analysis. RESULTS: We included 755 426 postmenopausal women with CKD. The median follow-up period was 7.3 (IQR, 5.8-8.7) years. All-cause dementia, Alzheimer's disease, and vascular dementia occurred in 107 848 (14.3%), 87 833 (11.6%), and 10 245 (1.4%) women, respectively. HRT was significantly associated with a lower risk for dementia in the adjusted Cox regression model (all-cause dementia: HR 0.80; 95% confidence interval [CI] 0.78-0.82; p < 0.001; Alzheimer's disease: HR 0.80; 95% CI 0.77-0.82; p < 0.001; vascular dementia: HR 0.80; 95% CI 0.74-0.87; p < 0.001). CONCLUSIONS: HRT was significantly associated with a lower risk for CKD-related cognitive dysfunction in postmenopausal women. Prospective studies are needed to determine whether HRT lowers the risk for dementia in menopausal women with CKD.

Predicting Development of Chronic Obstructive Pulmonary Disease and its Risk Factor Analysis.

Chronic Obstructive Pulmonary Disease (COPD) is an irreversible airway obstruction with a high societal burden. Although smoking is known to be the biggest risk factor, additional components need to be considered. In this study, we aim to identify COPD risk factors by applying machine learning models that integrate sociodemographic, clinical, and genetic data to predict COPD development.Clinical relevance- This study assessed the risk factors of COPD in sociodemographic, clinical, and genetic data. We have determined that sociodemographic factors are highly associate to the development of COPD.

Cardiovascular and Mortality Risks in Young Health Screening Examinees With Marginal Estimated GFR.

Introduction: Additional evidence is necessary to interpret kidney function parameters in young adults, particularly in those with marginal estimated glomerular filtration rate (eGFR) values. Therefore, we aimed to investigate the association between eGFR and adverse outcomes in general young adults. Methods: We performed a nationwide retrospective cohort study using the health-screening database of South Korea. We included young adults aged 20-39 years without a history of major adverse cardiovascular events (MACE) or kidney failure, who underwent nationwide health screening in 2012. The study exposure was eGFR categorized into 15 ml/min per 1.73 m2 intervals. The risks of all-cause mortality and MACE were calculated using Cox regression analysis, adjusted for various clinicodemographic characteristics. Results: In total, 3,132,409 young adults were included in this study. During a median follow-up of 7.3 years, marginal eGFR (60-75 ml/min per 1.73 m2) was not significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 0.80 [0.74-0.87]). The results were similar for MACE outcomes (aHR, 0.94 [0.87-1.01]). Although the presence of dipstick albuminuria had a significant interaction with the association between eGFR categories and all-cause mortality (interaction term P = 0.028), the risks of all-cause mortality were not significantly higher (aHR, 0.98 [0.62, 1.55]) in those with albuminuria and eGFR 60-75 ml/min per 1.73 m2. Conclusion: Marginal eGFR was not associated with higher risks of all-cause mortality and MACE in general young adults. Additional clinical investigations for incidentally found marginal eGFR values may be discouraged in general young adults.

Impact of albuminuria on early-onset type 2 diabetes mellitus: a nationwide population-based study.

Background: Early-onset diabetes mellitus has a significant lifetime burden and is associated with higher morbidity and mortality. Since insulin resistance is one of the mechanisms of podocyte injury, we aimed to evaluate the effect of albuminuria on newly developed early-onset type 2 diabetes mellitus (T2DM). Methods: We screened 6,891,399 subjects aged ≥20 and <40 years without a history of prediabetes or diabetes from the Korean National Health Insurance Service database between 2009 and 2012. A multivariate Cox proportional hazard model was used to identify the impact of albuminuria on early-onset T2DM. Results: Among a total of 5,383,779 subjects, 62,148 subjects (1.2%) developed early-onset diabetes over 7.3 ± 1.2 years. Albuminuria was significantly associated with early-onset T2DM (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.55-1.70) after adjustment for age, sex, anthropometric data, physical exercise status, serum glucose, and total cholesterol. The risk of early-onset T2DM increased more in subjects with more components of metabolic syndrome (MetS). Among each component of MetS, hypertriglyceridemia was prominently associated with early-onset T2DM (aHR, 2.02; 95% CI, 1.81-2.25) in subjects with albuminuria. Conclusion: Dipstick albuminuria was significantly associated with early-onset T2DM in young adult populations. Close monitoring of albuminuria is warranted for disease risk modification, especially in subjects with MetS.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

Automatic segmentation of white matter hyperintensities in T2-FLAIR with AQUA: A comparative validation study against conventional methods.

White matter hyperintensities (WMHs) are lesions in the white matter of the brain that are associated with cognitive decline and an increased risk of dementia. The manual segmentation of WMHs is highly time-consuming and prone to intra- and inter-variability. Therefore, automatic segmentation approaches are gaining attention as a more efficient and objective means to detect and monitor WMHs. In this study, we propose AQUA, a deep learning model designed for fully automatic segmentation of WMHs from T2-FLAIR scans, which improves upon our previous study for small lesion detection and incorporating a multicenter approach. AQUA implements a two-dimensional U-Net architecture and uses patch-based training. Additionally, the network was modified to include Bottleneck Attention Module on each convolutional block of both the encoder and decoder to enhance performance for small-sized WMH. We evaluated the performance and robustness of AQUA by comparing it with five well-known supervised and unsupervised methods for automatic segmentation of WMHs (LGA, LPA, SLS, UBO, and BIANCA). To accomplish this, we tested these six methods on the MICCAI 2017 WMH Segmentation Challenge dataset, which contains MRI images from 170 elderly participants with WMHs of presumed vascular origin, and assessed their robustness across multiple sites and scanner types. The results showed that AQUA achieved superior performance in terms of spatial (Dice = 0.72) and volumetric (logAVD = 0.10) agreement with the manual segmentation compared to the other methods. While the recall and F1-score were moderate at 0.49 and 0.59, respectively, they improved to 0.75 and 0.82 when excluding small lesions (≤ 6 voxels). Remarkably, despite being trained on a different dataset with different ethnic backgrounds, lesion loads, and scanners, AQUA's results were comparable to the top 10 ranked methods of the MICCAI challenge. The findings suggest that AQUA is effective and practical for automatic segmentation of WMHs from T2-FLAIR scans, which could help identify individuals at risk of cognitive decline and dementia and allow for early intervention and management.

Pulsed-dye laser as an effective treatment for recalcitrant granulomatous rosacea and a potential regulator of CXCL9 expression.

Granulomatous rosacea (GR) is a rare and distinct variant of rosacea. We report three cases of recalcitrant GR successfully treated with pulsed-dye laser (PDL) and provide experimental evidence supporting its potential as a treatment option. PDL treatment demonstrated remarkable efficacy in the three clinical cases, despite their resistance to conventional therapies. Chemokine ligand 9 (CXCL9), a key chemokine involved in inflammation and granuloma formation, was found to be increased in skin sections from all three patients. In vitro experiments using human monocytes and dermal fibroblasts demonstrated that PDL treatment significantly reduced CXCL9 expression in fibroblasts. These findings suggest that PDL may modulate CXCL9 secretion in fibroblasts, potentially limiting the recruitment of immune cells to the lesion. Although further research is needed to fully understand the precise mechanisms underlying the role of CXCL9 in GR, PDL may be a promising therapeutic approach for refractory GR.