Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Update on the Application of Ultrasonography in Understanding Autosomal Dominant Polycystic Kidney Disease.

With an estimated prevalence of 1 in 1000 individuals globally, autosomal dominant polycystic kidney disease (ADPKD) stands as the most prevalent inherited renal disorder. Ultrasonography (US) is the most widely used imaging modality in the diagnosis and monitoring of ADPKD. This review discusses the role of US in the evaluation of ADPKD, including its diagnostic accuracy, limitations, and recent advances. An overview of the pathophysiology and clinical manifestations of ADPKD has also been provided. Furthermore, the potential of US as a noninvasive tool for the assessment of disease progression and treatment response is examined. Overall, US remains an essential tool for the management of ADPKD, and ongoing research efforts are aimed at improving its diagnostic and prognostic capabilities.

Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study.

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013-2014 National Health and Nutrition Examination Survey.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants (p value for trend = 0.028), and quartile increases in the levels of DPhP (p value for trend = 0.01), BDCPP (p value for trend = 0.001), and BCEP (p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism.

Prevalence and varieties of complementary and alternative medicine usage among individuals with pre-dialysis chronic kidney disease in Taiwan: an investigative cross-sectional analysis.

BACKGROUND: Complementary and alternative medicine (CAM) is frequently used in the general population, yet only limited data are available regarding the prevalence of these medications in patients with chronic kidney disease (CKD). Hence, our study aimed to explore the prevalence and types of CAM in Taiwanese patients with CKD. METHODS: A cross-sectional questionnaire survey was conducted by face-to-face interview of 275 pre-dialysis patients without dialysis treatment or kidney transplant at an outpatient nephrology clinic in Taiwan from March 2021 to June 2023. The study outcomes were the prevalence of CAM, CAM types, reasons for using CAM, and sources of information about CAM. RESULTS: Overall, 128 patients (46.5%) were using CAM, but no significant differences from non-CAM users in the various CKD stages (p = 0.156) were found. CAM usage was high in the age range of 20-60 years and duration of CKD ≤ 5 years (p < 0.05). The most commonly used type of CAM was nutritional approaches (79.7%), followed by other complementary health approaches (26.6%). The most commonly utilized modalities of CAM were vitamins and minerals (38.3%), and only 27.1% of patients disclosed their CAM use to their physicians. The most common sources of information about CAM were family and friends, cited by 66% of the participants. Health promotion and a proactive attitude were reported by 40% of users as the reasons for using CAM. CONCLUSIONS: The present study provides data on the CAM usage among CKD patients and adds to the increasing evidence on CAM use. Because some of these practices have safety concerns, better education from healthcare providers on the risks and benefits of CAM therapy is needed by CKD patients.

Human Poisoning with Chlorpyrifos and Cypermethrin Pesticide Mixture: Assessment of Clinical Outcome of Cases Admitted in a Tertiary Care Hospital in Taiwan.

Background and Purpose: There is an overall paucity of data regarding the human toxicity of chlorpyrifos and cypermethrin pesticide mixture. Both organophosphate and pyrethroid insecticides are metabolized by carboxylesterases. Thus, its pesticide combination, organophosphates may boost the toxicity of pyrethroids via inhibited its detoxification by carboxylesterases. This study examined the clinical course, laboratory tests, and outcomes of patients with chlorpyrifos, cypermethrin or their pesticide mixture poisoning, and to determine what association, if any, might exist between these findings. Patients and Methods: Between 2000 and 2021, 121 patients poisoned with chlorpyrifos, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. Patients were categorized as chlorpyrifos (n=82), cypermethrin (n=27) or chlorpyrifos and cypermethrin (n=12) groups. Demographic, clinical, laboratory and mortality data were collected for analysis. Results: The patients experienced a broad range of clinical symptoms, including aspiration pneumonia (44.6%), salivation (42.5%), acute respiratory failure (41.3%), acute kidney injury (13.9%), seizures (7.5%), hypotension (2.6%), etc. Leukocytosis (12,700±6600 /uL) and elevated serum C-reactive protein level (36.8±50.4 mg/L) were common. The acute respiratory failure rate was 41.3%, comprising 48.8% in chlorpyrifos, 11.1% in cypermethrin as well as 58.3% in chlorpyrifos and cypermethrin poisoning. Patients with chlorpyrifos and cypermethrin pesticide mixture poisoning suffered higher rates of acute respiratory failure (P=0.001) and salivation (P=0.001), but lower Glasgow Coma Scale score (P=0.011) and serum cholinesterase level (P<0.001) than other groups. A total of 17 (14.0%) patients expired. The mortality rate was 14.0%, including 17.1% in chlorpyrifos, 3.7% in cypermethrin as well as 16.7% in chlorpyrifos and cypermethrin poisoning. No significant differences in mortality rate were noted (P=0.214). Conclusion: Chlorpyrifos pesticide accounted for the major toxicity of the pesticide mixture. While the data show a higher rate of respiratory failure in the chlorpyrifos and cypermethrin pesticide mixture group than others, other measures of toxicity such as mortality and length of stay were not increased.

Juan Bi Tang, a traditional Chinese medicine, for alleviating pain related to arteriovenous fistula in maintenance hemodialysis patients: An interventional pilot study with brief review.

Myofascial pain around an arteriovenous fistula (AVF) during hemodialysis (HD) can affect a patient compliance with HD and quality of life. Prolonged use of analgesics is often associated with increased adverse events. Juan Bi Tang (JBT) is an ancient decoction of Chinese traditional medicinal plants commonly used to treat spasms and pain in the shoulder and upper arm, and it is popularly believed to have favorable outcomes in Asian populations. This interventional prospective pilot study was worked to demonstrate the potential of JBT for fistula-associated myofascial pain in HD patients and to prepare for future randomized controlled trials. Eligible patients were enrolled in this study and took JBT to treat fistula-associated myofascial pain for 4 weeks. Pain scores on a visual analogue scale (VAS) were reported at baseline, after a 4-week intervention, and 2 weeks after completion of treatment. The Kidney Disease Quality of Life 36-Item Short Form and a safety laboratory monitor were statistically compared between different time points. A total of 20 patients were selected as eligible participants and completed the intervention and questionnaires. The mean VAS score was significantly reduced after JBT treatment (P < .01). Participants reported improved physical (P < .01) and mental health (P < .05) after treatment. However, only improvements in mental health were preserved 2 weeks after the end of treatment (P < .05). In this study, complementary JBT for HD patients with fistula-related myofascial pain was viable and well tolerated, and it demonstrated the expected effects on pain control.

Levels of organophosphate flame retardants and their metabolites among 391 volunteers in Taiwan: difference between adults and children.

Background: Organophosphate flame retardants (OPFRs) are ubiquitous in the environment. The compositions and concentrations of different OPFRs metabolites vary in different environments depending on different human activities. The objective of the present study was to evaluate the exposure of different age groups to OPFRs in Taiwan. Methods: Volunteers provided urine samples and responded to questionnaires including demographic factors, underlying disease, lifestyle information, and occupation from October 2021 to January 2022. OPFR measurements were performed using a Waters Acquity Ultra-Performance Liquid Chromatography system coupled with a Waters Xevo TQ-XS mass spectrometer. Results: A total of 391 volunteers (74 children and 317 adults) were enrolled in this study. The concentrations (presented as µg/g creatinine) of bis(1,3-dichloro-2-propyl) phosphate (BDCPP, p = 0.029) and tri-n-butyl phosphate (TNBP, p = 0.008) were higher in the adult group, while the concentrations of bis-2-chloroethyl phosphate (BCEP, p = 0.024), diphenyl phosphate (DPHP, p < 0.001), tris(1,3-dichloro-2-propyl) phosphate (TDCPP, p = 0.009), and Tris(2-butoxyethyl) phosphate (TBEP, p = 0.007) were higher in the child group. Compared with school age children (>6 years), the concentration of di(2-n-butoxyethyl) phthalate (DBEP, 1.14 vs. 0.20 µg/g creatinine, p = 0.001), DPHP (1.23 vs. 0.54 µg/g creatinine, p = 0.036), TBEP (1.63 vs. 0.29 µg/g creatinine, p < 0.001), and the sum of OPFR metabolites (ΣOPFRs, 6.58 vs. 2.04 µg/g creatinine, p < 0.001) were statistically higher in preschool-aged children. After adjusting for confounding factors, pre-school age [odds ratio (OR): 4.579, 95% confidence interval (CI): 1.389-13.115] and current smoker (OR: 5.328, 95%CI: 1.858-14.955) were independently associated with the risk of ΣOPFRs higher than 90 percentile. Conclusion: This study revealed the distribution of different OPFRs metabolites in children and adults. DBEP, DPHP, TBEP, and ΣOPFR were higher in preschool-aged children. Pre-school age and current smoking status were independent risk factors for ΣOPFRs higher than 90 percentile.

Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects.

Background: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years. Objectives: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population. Methods: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined. Results: The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 µg/L (standard deviation (SD) of 1.91 µg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 µg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns. Conclusion: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.

Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women.

Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This study aimed to compare mortality rate and cardiovascular events between denosumab and raloxifene in osteoporotic women. Risks of CVD development and all-cause mortality were estimated using Cox proportional hazard regression. A total of 7972 (3986 in each group) women were recruited between January 2003 and December 2018. No significant difference between denosumab and raloxifene was observed in composite CVDs, myocardial infarction, or congestive heart failure. However, comparison of the propensity score matched cohorts revealed that patients with proportion of days covered (PDC) ≥60% had lower incidence of ischemic stroke in the denosumab group than that in the raloxifene group (aHR 0.68; 95% CI 0.47-0.98; p = 0.0399). In addition, all-cause mortality was lower in the denosumab group than in the raloxifene group (aHR 0.59; 95% CI 0.48-0.72; p = 0.001), except in patients aged <65 y/o in this cohort study. We concluded that denosumab is superior to raloxifene in lowering risks of all-cause mortality and certain ischemic strokes in osteoporotic women.

Clinical effectiveness of molnupiravir in patients with COVID-19 undergoing haemodialysis.

BACKGROUND: Molnupiravir is an essential oral antiviral agent against coronavirus disease 2019 (COVID-19); however, its real-world effectiveness has not been evaluated in patients undergoing haemodialysis (HD). METHODS: This multi-centre retrospective study, involving 225 patients undergoing HD with initially mild or asymptomatic COVID-19, was conducted to compare the risks of 30-day COVID-19-related acute care visits between patients receiving and not receiving molnupiravir. Patients who received molnupiravir were stratified by rapid antigen detection (RAD) test results on day 7 after disease onset to assess whether rapid molnupiravir introduction accelerated viral clearance. RESULTS: Thirty-day COVID-19-related acute care visits were reported in 9.41% and 21.74% of the molnupiravir and control groups, respectively, and use of molnupiravir markedly reduced the risk of acute care visits after adjusting for baseline characteristics via propensity score weighting [hazard ratio 0.218, 95% confidence interval (CI) 0.074-0.642; P=0.006]. The tolerability of molnupiravir in the enrolled patients was generally acceptable, with only 11.88% of molnupiravir users reporting mild adverse events. Moreover, rapid initiation of molnupiravir within 1 day of COVID-19 onset was an independent predictor of conversion to a negative RAD test result on day 7 after disease onset (odds ratio 6.207, 95% CI 2.509-15.358; P<0.001). CONCLUSIONS: Molnupiravir is well tolerated and decreases the medical needs in patients with COVID-19 undergoing HD. Furthermore, the rapid initiation of molnupiravir accelerates viral clearance in patients with COVID-19 undergoing HD. These findings highlight the therapeutic role of molnupiravir for this vulnerable population.

Human Poisoning with Methomyl and Cypermethrin Pesticide Mixture.

There is limited literature analyzing the outcome of human poisoning with methomyl and cypermethrin pesticide mixture. Between 2002 and 2018, a total of 63 patients intoxicated with methomyl, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. The patients were categorized into three groups based on the type of pesticide, as methomyl (n = 10), cypermethrin (n = 31), or methomyl and cypermethrin (n = 22). Demographic, clinical, laboratory, and mortality data were obtained for analysis. The patients were aged 54.9 ± 18.9 years. Following ingestion, the patients experienced a wide range of clinical symptoms, including aspiration pneumonia (50.8%), acute respiratory failure (41.3%), acute kidney injury (33.3%), multiple organ failure (19.0%), emesis (19.0%), acute hepatitis (12.7%), diarrhea (7.9%), seizures (4.8%), lacrimation (4.8%), etc. After analysis, it was found that patients with methomyl and cypermethrin poisoning suffered higher incidences of acute respiratory failure (p < 0.001), aspiration pneumonia (p = 0.004), acute kidney injury (p = 0.011), and multiple organ failure (p < 0.001) than the other groups. Laboratory analyses revealed that patients with methomyl and cypermethrin poisoning had a higher creatinine level (p = 0.011), white blood cell count (p < 0.001), and neutrophil count (p = 0.019) than the other groups. A total of seven (11.1%) patients died. The average duration of hospitalization was 9.8 ± 10.0 days. In a multivariate logistic regression model, it was revealed that methomyl pesticide (p = 0.045) or methomyl and cypermethrin pesticide mixture (p = 0.013) were significant risk factors for acute respiratory failure. Nevertheless, no mortality risk factor could be identified. Therefore, the analytical results suggest that methomyl pesticide is the major contributor to the toxicity of methomyl and cypermethrin pesticide mixture poisoning. More research is needed.

Slow skeletal muscle troponin T acts as a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma.

Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.

Interleukin-18 and Gelsolin Are Associated with Acute Kidney Disease after Cardiac Catheterization.

Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12-24 h), and late post-procedure (7-10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523-14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027-3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization.

Real-World Effectiveness of SARS-CoV-2 Vaccine Booster in Hemodialysis Patients with COVID-19 Receiving Molnupiravir.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster is one of the most essential strategies against coronavirus disease 2019 (COVID-19) in the era of emerging variants. However, the effectiveness of SARS-CoV-2 vaccine boosters has not much been investigated in hemodialysis (HD) patients receiving oral antiviral agents. In this retrospective study involving 258 HD patients with COVID-19 receiving molnupiravir, we stratified the study cohort according to vaccination status and compared the baseline characteristics and risks of 30-day composite events (COVID-19-related acute care visits, hospitalization, or mortality) among groups. Our analysis demonstrated that the SARS-CoV-2 vaccine boosters markedly decreased the risk of composite events in HD patients (hazard ratio (95% confidence interval), 0.163 (0.063-0.423) for three vs. ≤ two doses of vaccination, p < 0.001; 0.309 (0.115-0.830) for four vs. ≤ two doses of vaccination, p = 0.020). The benefits of vaccine boosters were similar between patients receiving mRNA-based and protein-based boosters and between those with post-booster intervals of ≤ 120 and > 120 days. In conclusion, for HD patients with initially mild or asymptomatic COVID-19 receiving molnupiravir, the benefits of SARS-CoV-2 vaccine boosters are prominent, irrespective of booster vaccine types.

The associations between renal disease severity and exposure to organophosphate flame retardants in patients with chronic kidney disease.

Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032-3.005) per log µg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065-3.086) per log µg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228-0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937-0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants.

Updates on the Pivotal Roles of Mitochondria in Urothelial Carcinoma.

Mitochondria are important organelles responsible for energy production, redox homeostasis, oncogenic signaling, cell death, and apoptosis. Deregulated mitochondrial metabolism and biogenesis are often observed during cancer development and progression. Reports have described the crucial roles of mitochondria in urothelial carcinoma (UC), which is a major global health challenge. This review focuses on research advances in the role of mitochondria in UC. Here, we discuss the pathogenic roles of mitochondria in UC and update the mitochondria-targeted therapies. We aim to offer a better understanding of the mitochondria-modulated pathogenesis of UC and hope that this review will allow the development of novel mitochondria-targeted therapies.

Exogenous BMP7 administration attenuated vascular calcification and improved bone disorders in chronic uremic rats.

Vascular calcification is commonly observed in chronic kidney disease (CKD) and is associated with increased morbidity and mortality. This study examined whether exogenous BMP7 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats. After an adenine diet for 4 weeks, the animals were injected with BMP7 for 2 weeks. Biochemical data, kidney tissue, bony structure, and vascular calcification of the thoracic aorta were examined and compared. Reduced renal function, hyperphosphatemia, and hyperparathyroidism with low 1,25(OH)2 vitamin D levels were observed in the adenine group. MicroCT revealed reduced bone mineral density (BMD), decreased bone and tissue volume ratio (BV/TV), and decreased trabecular number with increased separation. Marked vascular calcification was observed in adenine-fed animals, and immunohistochemical analysis showed increased expression of BMP2, RUNX2, vitamin D receptor (VDR), and Pit1 in aortic tissue. Treatment with BMP7 was associated with reduced serum phosphate, intact parathyroid hormone, FGF23, sclerostin, and DKK1 levels. BMP7 administration was accompanied with improvements in BMD and BV/TV. The increase in BMP2, RUNX2, VDR, and Pit1 was reversed by BMP7. In conclusion, exogenous BMP7 administration improved hyperphosphatemia and hyperparathyroidism in adenine-induced CKD. This treatment also attenuated vascular calcification and modulated structural abnormalities in the skeletal system.

Exposure to tris(2-butoxyethyl) phosphate induces abnormal sperm morphology and testicular histopathology in male rats.

Tris(2-butoxyethyl) phosphate (TBEP) is one of the most abundant organophosphate flame retardants in the environment. This study aimed to evaluate the effect of TBEP exposure during adolescence on male reproductive function in adult rats. Male Sprague-Dawley rats were treated with 20 and 200 mg/kg body weight of TBEP or corn oil from postnatal day (PND) 42 to PND 105. A significant increase in the proportion of sperm with abnormal morphology (flattened head and bent tail) and superoxide anion (O2-.) production in the sperm of the 200 mg/kg treated group was observed (p < 0.05). Excessive production of sperm hydrogen peroxide (H2O2) was found in both the 20 and 200 mg/kg treatment groups (p < 0.05). Disruption of testicular structure was observed in the 20 and 200 mg/kg treated groups and seminiferous tubule degeneration was observed in the 200 mg/kg treated group. Our study demonstrated the adverse effects of TBEP on male reproductive function in rats.

Predictors of Acute Kidney Disease Severity in Hospitalized Patients with Acute Kidney Injury.

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them based on the AKD stages defined by the Acute Dialysis Quality Initiative criteria. Demographic, clinical, hematologic, and biochemical profiles, as well as 30-day outcomes, were compared between subgroups. In the analysis, the use of offending drugs (odds ratio, OR (95% confidence interval, CI), AKD stage 3 vs. non-AKD, 3.132 (1.304−7.526), p = 0.011, AKD stage 2 vs. non-AKD, 2.314 (1.049−5.107), p = 0.038), high AKI severity (OR (95% CI), AKD stage 3 vs. non-AKD, 6.214 (2.658−14.526), p < 0.001), and early dialysis requirement (OR (95% CI), AKD stage 3 vs. non-AKD, 3.366 (1.008−11.242), p = 0.049) were identified as independent predictors of AKD severity. Moreover, a higher AKD severity was associated with higher 30-day mortality and lower dialysis-independent survival rates. In conclusion, our study demonstrated that offending drug use, AKI severity, and early dialysis requirement were independent predictors of AKD severity, and high AKD severity had negative impact on post-AKI outcomes.