Causal effects of gut microbiota on sepsis and sepsis-related death: insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology.

BACKGROUND: Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. METHODS: We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. RESULTS: Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. CONCLUSION: Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Diffusion Tensor and Kurtosis MRI-Based Radiomics Analysis of Kidney Injury in Type 2 Diabetes.

BACKGROUND: Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) can provide quantitative parameters that show promise for evaluation of diabetic kidney disease (DKD). The combination of radiomics with DTI and DKI may hold potential clinical value in detecting DKD. PURPOSE: To investigate radiomics models of DKI and DTI for predicting DKD in type 2 diabetes mellitus (T2DM) and evaluate their performance in automated renal parenchyma segmentation. STUDY TYPE: Prospective. POPULATION: One hundred and sixty-three T2DM patients (87 DKD; 63 females; 27-80 years), randomly divided into training cohort (N = 114) and validation cohort (N = 49). FIELD STRENGTH/SEQUENCE: 1.5-T, diffusion spectrum imaging (DSI) with 9 different b-values. ASSESSMENT: The images of DSI were processed to generate DKI and DTI parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The Swin UNETR model was trained with 5-fold cross-validation using 100 samples for renal parenchyma segmentation. Subsequently, radiomics features were automatically extracted from each parameter map. The performance of the radiomics models on the validation cohort was evaluated by utilizing the receiver operating characteristic (ROC) curve. STATISTICAL TESTS: Mann-Whitney U test, Chi-squared test, Pearson correlation coefficient, least absolute shrinkage and selection operator (LASSO), dice similarity coefficient (DSC), decision curve analysis (DCA), area under the curve (AUC), and DeLong's test. The threshold for statistical significance was set at P < 0.05. RESULTS: The DKI_MD achieved the best segmentation performance (DSC, 0.925 ± 0.011). A combined radiomics model (DTI_FA, DTI_MD, DKI_FA, DKI_MD, and DKI_RD) showed the best performance (AUC, 0.918; 95% confidence interval [CI]: 0.820-0.991). When the threshold probability was greater than 20%, the combined model provided the greatest net benefit. Among the single parameter maps, the DTI_FA exhibited superior diagnostic performance (AUC, 887; 95% CI: 0.779-0.972). DATA CONCLUSION: The radiomics signature constructed based on DKI and DTI may be used as an accurate and non-invasive tool to identify T2DM and DKD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Update on kidney injury caused by multiple myeloma.

Multiple myeloma (MM) is a form of clonal plasma cell malignancy that associates with clinical manifestations such as anemia, hypercalcemia, bone pain, and renal impairment. Approximately 20-50% of MM patients at initial diagnosis experience renal injury, a vital complication that significantly influences prognosis and quality of life. This review seeks to clarify the multifaceted mechanisms of renal injury in MM, scrutinizing the pathogenic role of monoclonal proteins, the impact of hypercalcemia, and direct renal infiltration by plasma cells. Furthermore, it evaluates current diagnostic approaches, reviews management strategies, and highlights potential avenues for future research. By incorporating the latest scientific evidence and insights, this article aims to provide a comprehensive understanding of MM-associated renal impairment, offering a valuable resource for researchers and clinicians in handling this complex complication.

Incidence, risk factors and outcome of postoperative acute kidney injury in China.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

Detecting Neonatal AKI by Serum Cystatin C.

SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.

Novel risk factors for craniofacial microsomia and assessment of their utility in clinic diagnosis.

Craniofacial microsomia (CFM, OMIM%164 210) is one of the most common congenital facial abnormalities worldwide, but it's genetic risk factors and environmental threats are poorly investigated, as well as their interaction, making the diagnosis and prenatal screening of CFM impossible. We perform a comprehensive association study on the largest CFM cohort of 6074 samples. We identify 15 significant (P < 5 × 10-8) associated genomic loci (including eight previously reported) and decipher 107 candidates based on multi-omics data. Gene Ontology term enrichment found that these candidates are mainly enriched in neural crest cell (NCC) development and hypoxic environment. Single-cell RNA-seq data of mouse embryo demonstrate that nine of them show dramatic expression change during early cranial NCC development whose dysplasia is involved in pathogeny of CFM. Furthermore, we construct a well-performed CFM risk-predicting model based on polygenic risk score (PRS) method and estimate seven environmental risk factors that interacting with PRS. Single-nucleotide polymorphism-based PRS is significantly associated with CFM [P = 7.22 × 10-58, odds ratio = 3.15, 95% confidence interval (CI) 2.74-3.63], and the top fifth percentile has a 6.8-fold CFM risk comparing with the 10th percentile. Father's smoking increases CFM risk as evidenced by interaction parameter of -0.324 (95% CI -0.578 to -0.070, P = 0.011) with PRS. In conclusion, the newly identified risk loci will significantly improve our understandings of genetics contribution to CFM. The risk prediction model is promising for CFM prediction, and father's smoking is a key environmental risk factor for CFM through interacting with genetic factors.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

The association of cognition with protein energy wasting and synaptic transmission in chronic kidney disease.

INTRODUCTION: In recent years, consciousness impairment in patients with end-stage renal disease (ESRD) has been paid more and more attention, but the cause and mechanism of consciousness state change is not clear. METHODS: As the hippocampus played a crucial role in consciousness, we explored the pathological and electrophysiological changes in chronic kidney disease (CKD) mouse hippocampus. RESULTS: Whole-cell recordings in hippocampal neurons showed that miniature excitatory postsynaptic current (mEPSC) frequency decreased, but the amplitude was unaltered in CKD_8w mice. In addition, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor-mediated EPSCs (AMPAR-EPSCs) and N-methyl-D-aspartic acid receptor-mediated EPSCs (NMDAR-EPSCs) in hippocampal Schaffer collateral-CA1 synapses displayed a significant decline in CKD_8w mice. Although the ratio of AMPAR-/NMDAR-EPSCs did not change, the paired-pulse ratio (PPR) in CKD_8w mice increased. Intriguingly, the mEPSC frequency and AMPAR-/NMDAR-EPSCs amplitudes were positively associated with body weight, and the mEPSC frequency was negatively correlated with serum creatinine in CKD_8w mice, indicating a potential correlation between cognition and nutritional status in patients with CKD. To confirm the above hypothesis, we collected the clinical data from multiple hemodialysis centers to analyze the correlation between cognition and nutritional status. CONCLUSION: Our analysis indicated that protein energy wasting (PEW) was a possible independent risk factor for consciousness dysfunction in maintenance hemodialysis (MHD) patients. Our results provided a more detailed mechanism underlying the cognitive impairment (CI) in ESRD patients at the synaptic level. Last but not least, our results showed that PEW was a probable new independent risk factor for CI in cases with ESRD.

Low intracellular water and incident cognitive impairment in chronic hemodialysis patients.

OBJECTIVE: To explore the effect of intracellular water (ICW) evaluated by the bioelectrical Impedance Spectroscopy (BIS) on the risk of incident cognitive impairment (CI) in chronic hemodialysis (HD) patients. METHODS: Three thousand three hundred eighty-five patients were recruited and monitored prospectively for up to 3 years (the median follow-up time, 2 years) in this observational cohort study. Mini-Mental State Examination score (MMSE) was used to assess the global cognitive function. ICW was measured by body composition monitor based on BIS. Multiple Cox regression models, stratified analyses, and interactive analyses were conducted. RESULTS: During the follow-up period, 1256 patients (37.1%) experienced incident CI. The incidence of CI was increased with decreasing quartiles of ICW (27.4%, 32.2%, 38.9%, and 50.1% for the fourth, third, second, and first quartiles, respectively). Decreased ICW was significantly associated with incident CI. The association remained statistically significant even after adjusting for age, sex, education, albumin, C-reactive protein, residual renal function and various medical histories. The hazard ratios were 1.38 (1.17-1.64) and 1.28 (1.08-1.52) for ICW quartile 1 and quartile 2, respectively (reference, quartile 4). The association stably existed across subgroups, and the residual renal function had an interactive role in the association between ICW and incident CI (p = 0.014). CONCLUSION: Low baseline ICW was an independent risk factor for CI in chronic HD patients. Our finding highlights the necessity of using BIS to measure body composition when assessing the risk of CI in HD patients.

A radiomics based approach using adrenal gland and periadrenal fat CT images to allocate COVID-19 health care resources fairly.

BACKGROUND: The value of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied extensively. We assess the value of radiomics features from the adrenal gland and periadrenal fat CT images in predicting COVID-19 disease exacerbation. METHODS: A total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed a 3D V-net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted. RESULTS: The auto-segmentation framework yielded a dice value 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833 in the validation set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was between 0.4 and 0.8 in the validation set or between 0.3 and 0.7 in the test set, it could gain more net benefits using RN than FM and CM. CONCLUSIONS: Radiomics features extracted from the adrenal gland and periadrenal fat CT images are related to disease exacerbation in patients with COVID-19.

Decreased intracellular water is associated with sarcopenic obesity in chronic haemodialysis patients.

OBJECTIVE: To explore the association between intracellular water (ICW) and sarcopenic obesity in patients undergoing chronic haemodialysis (HD). METHODS: A multicentre, cross-sectional study of 3354 adult chronic HD patients was conducted in 20 haemodialysis centres from June 1, 2021, to August 30, 2021. The diagnosis of sarcopenic obesity was made according to the revised Asian Working Group's definition of sarcopenia combined with obesity per the body fat percentage definition. Body composition was evaluated by a body composition monitor using bioimpedance spectroscopy. Multiple logistic regression models, stratified analyses, interactive analyses, and receiver-operating characteristic analyses were conducted. RESULTS: A total of 752 patients were diagnosed with sarcopenic obesity among 3354 participants. The patients were grouped by sex-specific ICW median levels, and the prevalence of sarcopenic obesity was significantly higher in the low ICW group than in the high ICW group (41.3%vs 3.0%). Decreased ICW was significantly associated with sarcopenic obesity. The association remained statistically significant even after adjusting for dialysis vintage, age, body mass index, biochemical indicators, and various medical histories. The odds ratios of the low ICW group were much higher than those of the high ICW group in both males and females (P for trend < 0.001). The association was stable across subgroups, and the interaction analysis showed that age, body mass index and history of diabetes had interactive roles in the association between ICW and sarcopenic obesity (P for interaction < 0.05). Furthermore, the ICW cut-off values for identifying sarcopenic obesity were 19.1 kg and 14.5 kg for males and females, respectively. CONCLUSION: Decreased ICW was an independent risk factor for sarcopenic obesity in chronic HD patients. The measurement of ICW by bioimpedance spectroscopy might be a non-invasive and valid means for identifying the risk of future sarcopenic obesity in HD patients.

Increased Predialysis Extracellular to Intracellular Water Ratio Is Associated With Sarcopenia in Hemodialysis Patients.

OBJECTIVE: To explore the association between fluid overload, evaluated by a new fluid overload indicator, the bioelectrical impedance analysis-derived whole-body extracellular to intracellular water ratio (ECW/ICW), and sarcopenia in maintenance hemodialysis (MHD) patients. METHODS: A multicenter, cross-sectional study that included 3320 adult MHD patients was conducted in 20 hemodialysis centers of Guizhou Province, Southwest China from June 1, 2020, to September 30, 2020. The diagnosis of sarcopenia was based on the Asian Working Group's definition of sarcopenia. Multiple logistic regression models, stratified analyses, and interactive analyses were conducted. RESULTS: A total of 3196 participants were included in the final analysis. The prevalence of sarcopenia was 36.2% in the total population. The prevalence of sarcopenia was increased with increasing quartiles of ECW/ICW (18.1%, 33.3%, 37.8%, and 55.4% for the first, second, third, and fourth quartiles, respectively). Increased ECW/ICW was significantly associated with sarcopenia. The association remained statistically significant even after adjusting for age, sex, body mass index (BMI), dialysis vintage, C-reactive protein, and various medical histories. The odds ratios were 2.11 (1.41, 3.14), 1.83 (1.22, 2.76), and 3.45 (2.21, 5.39) for ECW/ICW quartiles 2-4, respectively (P for trend <.001). The interaction analysis showed that history of diabetes had an interactive role in the association between ECW/ICW and sarcopenia (P for interaction = .034). The association stably existed across subgroups and was more prominent in older patients and those with higher BMI and a history of diabetes. CONCLUSIONS: Elevated ECW/ICW was associated with increased sarcopenia risk independent of BMI, prealbumin, C-reactive protein, and other potential confounders in MHD patients. The association was more prominent in older patients and those with higher BMI and a history of diabetes, suggesting that controlling volume balance may help to reduce the occurrence of sarcopenia in these populations.

Multiplex lateral flow test strip for detection of carbapenemase genes using barcoded tetrahedral DNA capture probe-based biosensing interface.

Carbapenem-resistant Enterobacterales pose significant global health challenges due to their rapid spread and ability to hydrolyse various beta-lactam antibiotics. Rapid tests for these carbapenemase genes are crucial to ensure appropriate prescription administration and infection control. In this study, we developed a rapid visual nanodiagnostic platform for multiplexed detection of carbapenemase genes using a lateral flow strip. The nanodiagnostic strip was designed with separate barcoded DNA tetrahedrons for the blaKPC and blaNDM genes. These tetrahedrons were distributed on a nitrocellulose membrane at two different test lines as capture probes. When tested against a panel of carbapenemase genes, the tetrahedral probes captured single-stranded amplicons of asymmetric PCR via strand hybridisation. The amplicons acted as bridging elements, binding the DNA-modified gold nanoparticles to the test line of the strip, resulting in clear visual readouts specific to the blaKPC and blaNDM genes. By employing barcoded tetrahedrons and asymmetric PCR in conjunction with the lateral flow strip, a single diagnostic test enabled the detection of multiple carbapenemase genes. The test yielded results as low as 0.12 fM for blaKPC and 0.05 fM for blaNDM within 75 min. Furthermore, the strip effectively identified specific carbapenemase genes in clinical isolates using real-time PCR, antibody-based lateral flow systems for carbapenemase detection, and carbapenemase phenotype experiments. Thus, the strip develop has a high potential for testing blaKPC and blaNDM genes in practice.

U-shaped association of serum magnesium with mild cognitive impairment among hemodialysis patients: a multicenter study.

BACKGROUND: The optimal serum magnesium level of patients undergoing hemodialysis (HD) with cognitive impairment is still unclear. This study aimed to evaluate the association between serum magnesium levels and mild cognitive impairment among HD patients. METHODS: This was a multicenter observational study. Patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China were recruited into the study. HD patients were divided into five groups according to serum magnesium quintile. Cognitive function was measured with Mini Mental State Examination. The outcome was an incident mild cognitive impairment (MCI). Multivariate logistic regression analysis, restricted cubic spline and subgroup analysis were applied to explore the association of serum magnesium level with MCI. RESULTS: Among 3562 HD patients (mean age 54.3 years, 60.1% male), the prevalence of MCI was 27.2%. After adjusting for confounders, serum magnesium 0.41-0.83 mmol/L [odds ratios (OR) 1.55, 95% confidence interval (CI): 1.10-2.18] had a higher risk of MCI compared with serum magnesium of 1.19-1.45 mmol/L. A U-shaped association was identified between the serum magnesium and incident MCI (P for non-linearity = 0.004). The optimal range of magnesium level with the lowest risk of MCI was 1.12-1.24 mmol/L. As the serum magnesium level was lower than 1.12 mmol/L, the risk of MCI decreased by 24% per standard deviation (SD) increase in serum magnesium (OR 0.76, 95%CI: 0.62-0.93); when the serum magnesium level exceeds 1.24 mmol/L, a rise per SD increased the risk of MCI by 21% (OR = 1.20, 95%CI: 1.02-1.43). Subgroup analyses demonstrated that the associations were robust among individuals with low educational level, smoking, living alone, no working, and without hypertension or diabetes. CONCLUSIONS: Serum magnesium has a U-shaped association with MCI among HD patients. Both lower and higher serum magnesium can increase the risk of MCI for this population specifically. The optimal serum magnesium range with the lowest risk of MCI was 1.12-1.24 mmol/L.

Increased extracellular water/body mass is associated with functional impairment in hemodialysis patients.

BACKGROUND: Functional impairment, malnutrition and fluid overload are prevalent in patients undergoing maintenance hemodialysis (MHD). The extracellular water/body cell mass ratio (ECW/BCM) is a new indicator reflecting fluid overload and malnutrition. A previous study has suggested that it performs better than other indices in assessing fluid status. This study investigates the relationship between pre-dialysis whole-body ECW/BCM and physical function in MHD patients. METHODS: We conducted a multicenter, cross-sectional study in Guizhou Province in Southwest China. The Karnofsky Performance Status (KPS) was used to evaluate patients' functional status. Patients with KPS scores of ≤ 80 were considered to have a functional impairment. The body composition was measured using the body composition monitor (BCM), and the value of the ECW/BCM ratio was calculated. The subjects were classified into three groups according to ECW/BCM tertiles. Multiple logistic regression models and interactive analyses were conducted. RESULTS: The final analysis included 2818 subjects. Multivariate logistic regression analyses showed that compared with the lowest tertile (tertile 1), the adjusted odds ratio of functional impairment were 1.95 (95% CI: 1.21-3.13, p < 0.001) and 2.10 (95% CI: 1.31-3.37, p < 0.001) in the second and the third tertiles of ECW/BCM, respectively after adjusting for age, sex, current smoking status, history of stroke, heart failure, diabetes, and myocardial infarction. Subgroup analysis showed that the association existed stably across all subgroups stratified by age, gender, cognitive impairment (CI), history of stroke, heart failure, and diabetes (all p values for interaction >0.05). CONCLUSIONS: Elevated ECW/BCM is independently linked to an increased risk of functional impairment in patients with MHD.

The association of left ventricular fraction shortening with cardiovascular events in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) patients have a high incidence of cardiovascular events (CVEs). Left ventricular fraction shortening (LVFS), one of the echocardiographic parameters, is an independent risk factor for mortality in previous studies. The aim of this study was to evaluate associations between LVFS and CVEs in PD patients. METHODS: This was a single-center observational cohort study. Seven hundred and eighty-four PD patients were enrolled from 1 January 2012 to 1 June 2021 and followed until 1 June 2022. The primary outcome was the incidence of CVEs. PD patients were categorized into three groups according to the tertiles of LVFS levels (tertile 1-tertile 3). Kaplan-Meier method, Cox proportional hazard models and competing risk regression models were used for survival analysis. The areas under the curve (AUC) of receiver-operating characteristic analysis was used to determine the predictive values of LVFS for CVEs. A preplanned subgroup analysis was assessed according to age, gender, and the presence of hypertension and dyslipidemia, etc. RESULTS: During a median follow-up period of 42.3 months (interquartile range 24.0-79.0 months), 259 CVEs occurred. Compared to the other two groups respectively, patients in tertile 3 group had the lowest incidence of CVEs (24.5% vs 31.6% vs 43.0%, respectively, p < 0.05). After multiple adjustments, the tertile 3 group was associated with the 45.1% decrease in the CVEs hazard compared to that of the tertile1 group (SHR = 0.549, 95%CI: 0.395-0.762, p < 0.001). Subgroup analysis demonstrated that tertile 1 group as the reference, the association between LVFS and CVEs in tertile 3 group was robust among female patients (HR = 0.506, 95%CI: 0.309-0.829, p = 0.007), aged < 45 years (HR = 0.496, 95%CI: 0.331-0.744, p = 0.001), history of hypertension (HR = 0.586, 95%CI: 0.349-0.872, p = 0.008) and combined with dyslipidemia (HR = 0.464, 95%CI: 0.269-0.799, p = 0.006). CONCLUSIONS: This study suggests that LVFS is independently associated with the increased risk of CVEs in PD patients, especially those with aged < 45 years, female, with hypertension and dyslipidemia.

Traceability in food processing: problems, methods, and performance evaluations-a review.

Processed food has become an indispensable part of the human food chain. It provides rich nutrition for human health and satisfies various other requirements for food consumption. However, establishing traceability systems for processed food faces a different set of challenges compared to primary agro-food, because of the variety of raw materials, batch mixing, and resource transformation. In this paper, progress in the traceability of processed food is reviewed. Based on an analysis of the food supply chain and processing stage, the problem of traceability in food processing results from the transformations that the resources go through. Methods to implement traceability in food processing, including physical separation in different lots, defining and associating batches, isotope analysis and DNA tracking, statistical data models, internal traceability system development, artificial intelligence (AI), and blockchain-based approaches are summarized. Traceability is evaluated based on recall effects, TRUs (traceable resource units), and comprehensive granularity. Different methods have different advantages and disadvantages. The combined application of different methods should consider the specific application scenarios in food processing to improve granularity. On the other hand, novel technologies, including batch mixing optimization with AI, quality forecasting with big data, and credible traceability with blockchain, are presented in the context of improving traceability performance in food processing.

The Impact of Malnutrition, Inflammation on Cognitive Impairment in Hemodialysis Patients: A Multicenter Study.

INTRODUCTION: Cognitive impairment is prevalent in patients undergoing hemodialysis (HD), which is related to the nutritional and inflammatory status of this population. Malnutrition-inflammation score (MIS) has been identified as a useful tool to evaluate nutrition and inflammation status. The aim of this study is to investigate the association between MIS and cognitive impairment in HD patients. METHODS: This was a multicenter observational cohort study with 1,591 patients undergoing HD. Nutritional and inflammatory status was evaluated with MIS, anthropometric measurements, and body composition assessments. Cognitive function was evaluated with the Mini Mental State Examination (MMSE). The associations between MIS and cognitive impairment were analyzed by multivariable logistic regression models. RESULTS: Among 1,591 HD patients, the mean MIS was 6.0 ± 2.6. Patients with higher MIS had significantly lower MMSE scores. 311 patients had cognitive impairment. After adjusting clinical confounders, higher MIS was independently associated with increased rate of cognitive impairment both as a categorized variable (OR, 1.358; 95% CI, 1.010-1.825; p = 0.045) and as a continuous variable (OR, 1.113; 95% CI, 1.053-1.178; p < 0.001). Subgroup analysis showed a stronger association between MIS and cognitive impairment in males, the population with age 41-60 years, and 61-80 years, no smoker, living by oneself, HD combined with or without hemoperfusion as dialysis modality. ROC curve analysis of MIS showed 60.1% sensitivity and 52.0% specificity in predicting cognitive impairment (AUC 0.604; 95% CI 0.567-0.640, p < 0.001). CONCLUSIONS: MIS was independently associated with cognitive impairment in HD patients.

Roxadustat (FG-4592) protects against ischaemia/reperfusion-induced acute kidney injury through inhibiting the mitochondrial damage pathway in mice.

Ischaemia-reperfusion (I/R) is one of the main factors of acute kidney injury (AKI). mitochondrial damage pathway are important features of I/R induced-acute kidney injury (IRI-AKI). Hypoxia-inducible factor (HIF) expression in renal tubule segments is up-regulated during AKI. Herein, we investigated the role of FG-4592 in a mouse model of IRI-AKI to confirm whether FG-4592 is beneficial in AKI. We found that pretreatment with FG-4592 significantly ameliorated renal function and renal histological damage in mice after IRI. Furthermore, these results suggest that pretreatment with FG-4592 significantly reduced the tubular cells apoptosis (decreased TUNEL-positive cells, Bax, caspase12 levels), attenuated mitochondrial damage (increased ATPß, PPARγ, mitochondrial DNA copy number, and decreased cytoplasmic cytochrome C), and alleviated DNA damage after IRI. In conclusion, pretreatment with FG-4592 may effectively prevent kidney from IRI possibly by via diminishing tubular cells injuries and protection of mitochondrial damage pathway. These results further validate that FG-4592 may be an effective drug in the clinical treatment of IRI-AKI.

Muscle strength performed better than muscle mass in identifying cognitive impairment risk in maintenance hemodialysis patients.

OBJECTIVES: The association between muscle mass and cognitive impairment (CI) is conflicting. We aimed to evaluate and compare the associations of muscle strength, muscle mass and CI risk in maintenance hemodialysis (MHD) patients. METHODS: We conducted a multicenter, cross-sectional study. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) score. Muscle strength was assessed by hand grip strength (HGS), muscle mass was assessed by lean tissue mass (LTM). Education status was divided into two groups: lower education status (senior middle school and below) and higher education status (high school and above). Multivariable logistic regression models and subgroup analyses were performed. Receiver-operating characteristic (ROC) analyses were conducted to compare their predictive power in discriminating CI. RESULTS: 2827 adult MHD patients were included in our final analysis. Patients in the lowest quartile of HGS was 2.82-fold as likely to have CI as compared to those in the highest quartile, while participants in the lowest quartile of LTM group were 1.52-fold as likely to have CI, when compared with the highest quartile group of LTM after adjusting for age, gender and education level. The association persisted in all subgroups except for women and well-educated participants. There was a significant interaction between HGS and education status on CI and age played an interactive role in the association between LTM and incident CI (P for interaction < 0.05). The AUC value of the HGS was significantly higher than that of LTM (0.69 VS 0.63, P < 0.001). CONCLUSIONS: Muscle strength performed better than muscle mass in identifying individuals at high risk of CI, particularly in male and less educated Chinese MHD patients. LEVEL OF EVIDENCE: Level V, cross-sectional study.