CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

Efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus: A meta-analysis and systematic review.

BACKGROUND: The incidence of pruritus associated with hemodialysis (HD) patients can be as high as 70%, and ~ 40% of patients suffer from moderate to severe systemic pruritus. Difelikefalin (CR845), a peripheral restrictor κ-opioid receptor agonist, activates opioid receptors on peripheral neurons and immune cells to relieve pruritus in patients. However, the clinical effect of difelikefalin on HD-related pruritus is unclear. Therefore, the purpose of this meta-analysis and systematic review was to investigate the safety and efficacy of difelikefalin in the treatment of HD-associated pruritus. OBJECTIVE: This study explored the efficacy and safety of difelikefalin in the treatment of pruritus in HD patients by systematic review and meta-analysis. MATERIALS AND METHODS: Randomized controlled trials on difelikefalin in the treatment of pruritus in HD patients were retrieved from PubMed, Embase, Cochrane Library, and Web of Science electronic databases. The retrieval deadline was January 1, 2023. Stata 15.0 software was used for data analysis of the included studies. RESULTS: A total of 4 randomized controlled trials were included, totaling 1,268 patients (736 patients in the experimental group and 532 patients in the control group). Results of the meta-analysis showed that, compared with the control group, difelikefalin could significantly improve the Worst Itch Numeric Rating Scale score (improvement > 3; risk ratio (RR) = 1.28, 95% confidence interval (CI) (1.07, 1.53)), decrease the 5-D itch score (standardized mean difference = -0.43, 95% CI (-0.55, -0.30)), and significantly improve adverse events (RR = 1.33, 95% CI (1.13, 1.56)). CONCLUSION: Although difelikefalin can improve itching symptoms in HD patients, it can also increase adverse reactions based on the current literature. Therefore, more studies are needed to further explore the safety and efficacy of difelikefalin treatment.

COVID-19 and outcomes in Chinese peritoneal dialysis patients.

BACKGROUND: Reports on COVID-19 in peritoneal dialysis (PD) patients are scarce in China. This study aimed to describe the characteristics and outcomes of PD patients with COVID-19 after China abandoned the 'zero-COVID' policy. METHODS: This single-centre retrospective study included patients receiving PD who underwent testing for COVID-19 infections between 7 December 2022 and 7 January 2023. Outcomes of interest included factors associated with positive COVID-19 testing result and clinical outcomes including COVID-19-related hospitalisation and severe COVID-19, which were analysed using logistic regression analyses. RESULTS: A total of 349 PD patients (male 53.6%, age 49 ± 13 years old) were included, and 235 patients (67.3%) were infected. There were no significant differences between COVID-19 and non-COVID-19 patients other than higher proportion of vaccinated patients and slow transporters in the patients who tested positive for COVID-19 (44.7% vs. 28.1%, p = 0.003; 8.7% vs. 1.8%, p = 0.03, respectively). Multivariate analysis showed COVID-19 was associated with vaccination (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.02-2.86) and slow transport type (compared with average transport type, OR: 4.52, 95% CI: 1.01-20.21). Among the patients with infection, 38 (16.2%) patients were hospitalised, 18 (7.7%) patients had severe disease and 9 (3.8%) patients died. In multivariate logistic analysis, both age (OR: 1.04, 95% CI: 1.01-1.07; OR: 1.06, 95% CI: 1.02-1.11) and hyponatremia (OR: 5.44, 95% CI: 1.63-18.13; OR: 6.50, 95% CI: 1.77-23.85) were independent risk factors for COVID-19-related hospitalisation and severe disease. CONCLUSIONS: Although vaccinated patients were more likely to have tested positive for COVID-19 infection, they appeared to have less severe infection and less need for hospitalisation. Patients who were older with a history of hyponatremia were more likely to experience adverse outcomes from COVID-19.

Association of intradialysis blood sodium level, blood pressure variability, and hydration status with hemodialysis-related headache: a prospective cohort study.

OBJECTIVE: To identify primary factors contributing to hemodialysis-related headache (HRH) in maintenance hemodialysis (MHD) patients. METHODS: Adult outpatients receiving MHD were prospectively enrolled from a hemodialysis (HD) center of a tertiary hospital in China. Twelve dialysis sessions were successively monitored for each patient. HRH is defined as having at least three headache episodes that begin during HD and resolve within 72 h of HD session completion. Blood gas analysis during headache episodes and body composition analysis after dialysis were conducted. Hour-to-hour vital sign variability during dialysis was assessed using the metric of average real variability (ARV). Multivariable logistic regression analysis was conducted to explore the factors triggering HRH. RESULTS: A total of 95 Chinese MHD patients were enrolled, with 92 patients (60.9% were males) included in the final analysis. The mean age of the 92 patients was 59.3 ± 17.5 years, and the median dialysis vintage was 27.1 (12-46.2) months. Among them, 12 patients (13%) complained of 42 headache attacks, and eight (8.7%) were diagnosed with HRH. For eight patients with HRH, headache occurred 100.3 ± 69.5 min after the start of dialysis, with a mean VAS score of 4.3 ± 1 points. The quality of headaches was dull (six patients), pulsating (one patient), or stabbing pain (one patient); all the headaches were bilateral, with one having concomitant vomiting. The intradialysis headache duration and the whole headache duration were 98.8 ± 68.1 and 120 (65-217.5) minutes, respectively. Younger age (OR = 0.844, 95% CI 0.719-0.991, p = 0.039), decreased blood sodium level (OR = 0.309 in the range of 133-142 mmol/L, 95% CI 0.111-0.856, p = 0.024), increased ARV of intradialysis systolic blood pressure (OR = 3.067, 95% CI 1.006-9.348, p = 0.049) and ratio of overhydration to dry weight (OR = 1.990, 95% CI 1.033-3.832, p = 0.040) were found to be independent risk factors for HRH. CONCLUSIONS: This study suggested a significant attribution of blood sodium, hydration status and blood pressure variability to HRH.

Prognostic Value of the Baseline and Early Changes in Monocyte-to-Lymphocyte Ratio for Short-Term Mortality among Critically Ill Patients with Acute Kidney Injury.

(1) Background: Inflammation plays an important role in the onset and progression of acute kidney injury (AKI). Despite this, evidence regarding the prognostic effect of the monocyte-to-lymphocyte ratio (MLR), a novel systemic inflammation marker, among patients with AKI is scarce. This study sets out to investigate the prognostic potential of both baseline and early changes in MLR for short-term mortality among critically ill patients with AKI. (2) Method: Eligible patients with AKI from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. MLR cutoff values were determined using maximally selected rank statistics and tertiles. The clinical outcomes were 30-day and 90-day mortality in the intensive care unit. A restricted cubic splines model and Cox proportional hazards models were utilized to evaluate the association between the baseline MLR and short-term mortality. Then, the trends in MLR over time were compared between the 30-day survivors and non-survivors using a generalized additive mixed model (GAMM). (3) Result: A total of 15,986 patients were enrolled. Multivariable Cox regression analysis identified baseline MLR ≥ 0.48 as an independent risk factor predicting 30-day mortality (HR 1.33, 95%CI 1.24, 1.45, p < 0.001) and 90-day mortality (HR 1.34, 95%CI 1.23, 1.52, p < 0.001) after adjusting for potential confounders. Similar trends were observed for 30-day and 90-day mortality when tertiles were used to group patients. The restricted cubic splines model revealed a non-linear association between MLR and 30-day and 90-day mortality (both p for non-linear < 0.001, both p for overall < 0.001). The area under the curve of 0.64 for MLR was higher than that of monocytes (0.55) and lymphocytes (0.61). In the subgroup analyses, despite the noted significant interactions, the direction of the observed association between MLR and 30-day mortality was consistent across most prespecified subgroups, except for shock and black ethnicity. The GAMM results highlighted that, as time went on, MLR in the 30-day survival group consistently declined, whereas MLR in the non-survival group rose within 15 days post-ICU admission. The difference between the two groups persisted significantly even after adjusting for confounders (p = 0.006). (4) Conclusion: A higher baseline MLR was identified as an independent risk factor predicting 30-day and 90-day mortality. The early increase in MLR was associated with high 30-day mortality, suggesting that dynamic monitoring of MLR could potentially better predict survival in critically ill patients with AKI.

Utilization of Hydrogels in Mesenchymal Stem Cell-Based Therapy for Kidney Diseases.

Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven their safety and effectiveness in treating acute kidney injury (AKI) and chronic kidney disease (CKD), but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional (3D) networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and the factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study.

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients. PURPOSE: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients. METHODS: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated. RESULTS: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength. CONCLUSION: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.

Additional antibiotic lock in peritoneal dialysis-associated refractory peritonitis: A case series study and literature survey.

BACKGROUND: Refractory peritonitis is one of the leading causes of catheter failure in peritoneal dialysis (PD) patients. However, there are no established curative therapies available, and only catheter removal should be performed. Here we present a case series study to illustrate the efficacy of antibiotic lock for PD-associated refractory peritonitis. MATERIALS AND METHODS: Patients with refractory peritonitis treated with intraperitoneal antibiotics plus antibiotic lock from September 2020 to March 2022 were retrospectively analyzed. Medical cure was identified as a success of treatment. RESULTS: We identified 11 patients, of which 7 (63.64%) had a history of PD-associated peritonitis, with the episode of continuous ambulatory peritoneal dialysis (CAPD) ranging from 1 to 158 months at a median of 36 (9.5, 50.5) months. The dialysis effluent culture showed Gram-positive, Gram-negative bacteria, and was culture-negative in 5, 2, and 4 cases, respectively. The cure rates were 85.71% for culture-positive cases and 25% for culture-negative cases, and the total cure rate was 63.64%. No relevant adverse events occurred, including sepsis. CONCLUSIONS: Treatment with the additional antibiotic lock was successful in most cases, especially in those that were culture-positive. Additional antibiotic lock deserves great attention and further investigation in treating PD-associated refractory peritonitis.

Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients.

BACKGROUND: There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF. METHODS: This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association Class II-IV HF. The concentrations of valsartan, sacubitril and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF). RESULTS: Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50 mg twice daily (BID), 100 mg once daily and 100 mg BID. The plasma maximum drug concentrations in the 100 mg BID group were 1995 ± 1499 ng/mL for valsartan, 171 ± 148 ng/mL for sacubitril and 13 686 ± 7418 ng/mL for LBQ657. The 24-h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25 ± 10.32 mmHg and 10.10 ± 8.00 mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00-18 198.00) from baseline, while LVEF increased by 5.00 (-0.25 to 9.25) from baseline after SV treatment. CONCLUSIONS: PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100 mg BID SV is safe and effective in patients with PD with complications of hypertension or HF.

Vascular Calcification Exacerbates Abnormal Blood Pressure Variability in Chronic Kidney Disease: A "Two-Step" Study in Rats.

INTRODUCTION: Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) with poor cardiovascular prognosis. The aim of this study was to explore the impact of VC on blood pressure variability (BPV) in animal models of CKD. METHODS: Two optimal modelling methods, adenine high-phosphorus (HP) diet + calcitriol and 5/6 nephrectomy (Nx) + HP diet + calcitriol, for CKD-VC were chosen from the first-step experiment for the next step. A total of 36 male Wistar rats were randomly assigned to the standard-chow, sham-operated, adenine, 5/6Nx, adenine-VC, and 5/6Nx-VC groups. Continuous blood pressure (BP) measurement using the BP-2000 animal noninvasive BP analyser was started at the 9th week for the standard-chow, adenine, and adenine-VC groups and at the 7th week for the sham-operated, 5/6Nx, and 5/6Nx-VC groups. BPV metrics (BPVs), including the difference between maximum and minimum values, standard deviation, coefficient of variation, average real variability, and residuals derived from the generalized linear model of BP, were calculated. RESULTS: The first experiment showed that the use of calcitriol accelerated the progression of VC in CKD rats (the modelling period was shortened from 16 weeks to 4-8 weeks) and confirmed the occurrence of VC at weeks 8 and 6 in the adenine-VC and 5/6Nx-VC groups, respectively. In the second experiment, 13 of 20 hour-to-hour BPVs increased significantly with the development of CKD and VC. BPV differences among the standard-chow, adenine, and adenine-VC groups were mainly due to the differences between the standard-chow and adenine-VC groups (7 of 10 BPVs were significantly different), followed by the differences between the standard-chow and adenine groups (3 of 10). BPV differences among the sham-operated, 5/6Nx, and 5/6Nx-VC groups were caused by the differences between the 5/6Nx-VC and 5/6Nx groups (4 of 10) or the 5/6Nx-VC and sham-operated groups (3 of 10). CONCLUSION: An increased BPV is observed in CKD rats, and VC further aggravates the abnormality of BPVs independent of CKD.

[Catheter Replacement Methods in Hemodialysis Patients With Dysfunctional Tunneled-Cuffed Catheters With Fibrin Sheaths]. / 对形成纤维蛋白鞘的带涤纶套和隧道透析导管的更换方式探索.

Objective: Tunneled-cuffed catheters (TCCs) are frequently used for establishing hemodialysis access for maintenance hemodialysis in older patients with exhausted resources of peripheral vessels. Fibrin sheath formation around the catheter is one of the most common complications of long-term use of indwelling catheter, which may cause the malfunction of the catheter. In this study, we intend to compare the prognosis of two catheter replacement methods, in situ replacement and replacement through a fibrin sheath crevice, with both being assisted by balloon dilation, and to explore the optimal catheter replacement process. Methods: A retrospective study was conducted with 52 patients who underwent a replacement of their TCCs. Among them, 27 cases had their TCC replaced by the modified method of replacement through a fibrin sheath crevice and were referred to as the sheath crevice group, while 25 cases underwent in situ catheter replacement and were referred to as the in situ group. The primary outcome indicators included maximum blood flow in hemodialysis catheter and the urea clearance rate calculated by Kt/V values at the 1, 3, and 6-month follow-ups. The secondary outcomes included dialyzer alarms being set off and catheter-related infections during follow-up. Results: There was no significant difference between the general data of the two groups. There was no massive blood loss during the replacement procedure. Neither were there cardiac tamponade, catheter-associated infections, or other complications. Follow-ups were made 1, 3, and 6 months after the replacement procedure. The sheath crevice group had higher catheter blood flow and Kt/V values at the 6-month follow-up than the in situ group did ([241.85±9.62] mL/min vs. [234.40±11.21] mL/min, P=0.014 and 1.31±0.55 vs. 1.27±0.49, P=0.005, respectively). During the follow-up process, access alarms were reported in 5 patients (three in the in situ group and two in the sheath crevice group) during dialysis. No catheter-associated infection occurred in either group. Conclusion: The catheter replacement method of balloon dilation-assisted catheter insertion through a fibrin sheath crevice is safe and effective, resulting in better long-term catheter blood flow compared with that of in situ catheter replacement.

Resolvin D1 attenuates sepsis induced acute kidney injury targeting mitochondria and NF-κB signaling pathway.

Background: Acute kidney injury is a highly common and multifactorial renal disease resulting in significant morbidity and mortality, especially sepsis-induced acute kidney injury. There is no effective therapy available to treat or prevent sepsis-induced acute kidney injury. One of the specialized pro-resolving mediators, Resolvin D1 exhibits special anti-inflammatory effects in several inflammatory disease models, but there is little evidence about the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. Methods: We conducted experiments to explore the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. In vitro, human proximal tubular epithelial cells were used to test the apoptosis ratio, cell viability and reactive oxygen species level. In vivo, C57BL/6 mice were injected with lipopolysaccharide to establish a sepsis-induced acute kidney injury model. Renal function and structure, apoptosis ratio of kidney cells, mitochondrial structure and function and related protein and gene levels were assessed. Results: In vitro, the resolvin D1-treated group showed higher cell viability and lower reactive oxygen species levels and apoptosis ratios than the LPS group. In vivo, Resolvin D1 can not only improve renal function and mitochondrial function but also reduce the apoptosis ratio, while mediating mitochondrial dynamics and inhibiting NF-κB pathway. Conclusions: Resolvin D1 has a good renoprotective effect by maintaining mitochondrial dynamics and inhibiting the NF-κB pathway.

The association between weight-adjusted-waist index and abdominal aortic calcification in adults aged ≥ 40 years: results from NHANES 2013-2014.

The negative effects of obesity on the cardiovascular health have drawn much attention. Weight-adjusted-waist index (WWI) has been proved to reflect weight-independent centripetal obesity. However, the association between WWI and abdominal aortic calcification (AAC) has not been reported before. Using data from National Health and Nutrition Examination Survey 2013-2014, we aimed to determine the relationship of WWI and AAC in adults aged ≥ 40 years. WWI was determined by dividing waist circumference by the square root of weight. AAC was measured by dual-energy X-ray absorptiometry and quantified by Kauppila scores. Severe AAC (SAAC) was defined as an AAC score > 6. We utilized weighed multivariable logistic regression and generalized additive model to explore the independent association between WWI and AAC. Threshold effects were further calculated by two-piecewise linear regression model. 3082 participants were enrolled in our analysis, of which 48.2% were male. WWI was positively associated with AAC scores (ß = 0.34, 95% CI 0.05-0.63) and exhibited a nonlinear relationship with SAAC. On the left of the breakpoint (WWI = 11.11), WWI and SAAC were positively associated (OR = 2.86, 95% CI 1.40-5.84), while no such relationship was found on the right (OR = 1.07, 95% CI 0.77-1.48). Our findings indicated that WWI may serve as a simple biomarker of AAC in US adults aged ≥ 40 years.

Exosomal STAT1 derived from high phosphorus­stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/ß­catenin signaling pathway.

Vascular calcification is commonly observed in chronic kidney disease. The mechanism of how the calcification signal from endothelial cells is transmitted to vascular smooth muscle cells (VSMCs) remains unknown. The aim of the present study was to investigate whether exosomes from HUVECs (HUVEC­Exos) could regulate VSMC calcification and its potential signaling pathway. HUVEC­Exos were isolated from HUVECs under no phosphorus (NP) and high phosphorus (HP) conditions. Alizarin Red S staining and calcium (Ca) content analysis were carried out to detect calcification in VSMCs. Proteomics analysis was carried out to detect the differential expression of exosomal proteins. Protein and mRNA levels were measured by western blot analysis and reverse transcription­quantitative PCR (RT­qPCR). Exosomes derived from HP­HUVECs promoted the calcification of VSMCs, as assessed by Alizarin Red S staining, alkaline phosphatase activity assays, Ca content measurements and the increased expression of runt­related transcription factor 2 and osteopontin. Proteomic analysis detected the upregulation of STAT1 in HP­exosomes from HUVECs (HUVEC­Exos) compared with NP­HUVEC­Exos, which was also confirmed by western blot analysis and RT­qPCR. Inhibition of STAT1 expression in VSMCs using fludarabine or knockdown of STAT1 expression using small interfering RNA alleviated the calcification of VSMCs. Furthermore, lithium chloride (Wnt activator) reversed the protective effect of STAT1 inhibition on VSMC calcification, while Dickkopf­1 (Wnt inhibitor) exerted the opposite effect, suggesting that activation of the Wnt/ß­catenin signaling pathway was involved in STAT1­mediated VSMC calcification. In conclusion, the present results indicated that exosomal STAT1 derived from HP­treated HUVECs could promote VSMC calcification, and activation of the Wnt/ß­catenin pathway may be a potential mechanism of the VSMC calcification promoted by exosomes.

The value of urinary interleukin-18 in predicting acute kidney injury: a systematic review and meta-analysis.

AIMS: The aim of this study was to systematically review relevant studies to evaluate the value of urinary interleukin-18 (uIL-18) in predicting acute kidney injury (AKI). METHODS: A comprehensive search of PubMed, Medline, Embase, and Cochrane Library was conducted for literature published up to 1 August 2022. Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was applied to assess the literature quality. Then, relevant data were extracted from each eligible study and a random-effects regression model was utilized to pool sensitivity, specificity, and construct summary receiver operating characteristic (SROC) and area under curve (AUC). RESULTS: Twenty-six studies with 7183 patients were enrolled and relevant information was extracted. The estimated sensitivity and specificity of uIL-18 in the diagnosis of AKI were 0.64 (95% confidence interval (CI): 0.54-0.73) and 0.77 (95%CI: 0.71-0.83), respectively. The pooled diagnostic odds ratio (DOR) was 6.08 (95%CI: 3.63-10.18), and the AUC of uIL-18 in predicting AKI was 0.78 (95%CI: 0.74-0.81). Subgroup analysis showed that uIL-18 in pediatric patients was more effective in predicting AKI than in adults (DOR: 7.33 versus 5.75; AUC: 0.81 versus 0.77). CONCLUSIONS: Urinary IL-18 could be a relatively good biomarker with moderate predictive value for AKI, especially in pediatric patients. However, further research and clinical settings are still needed to validate our findings.

The association between caffeine intake and risk of kidney stones: A population-based study.

Background: Although many studies have proven the beneficial effects of caffeine on human health, the association between caffeine intake and the risk of kidney stones is limited in large epidemiologic studies. Objectives: We aimed to investigate the association between caffeine intake and the risk of kidney stones. Methods: A total of 30,716 participants (with weight numbers of 204, 189, and 886) with a history of kidney stone were included in this analysis. All data were survey-weighted, and corresponding logistic regression models were performed to examine the associations between caffeine intake and the risk of kidney stones. Results: In a fully adjusted model, a per-quartile increase in caffeine intake was associated with a 5.32% decreased risk of kidney stones. In the subgroup analysis, the multivariate-adjusted odds ratios (95% confidence intervals) of the risk of kidney stones for per-quartile increments in caffeine intake were 0.9650 (0.9643, 0.9656) for men, 0.9320 (0.9313, 0.9327) for women, 0.9384 (0.9378, 0.9389) for white race individuals, 1.0281 (1.0270, 1.0292) for nonwhite race individuals, 0.9460 (0.9455, 0.9465) for overweight/obese individuals, and 0.9314 (0.9303, 0.9324) for non-overweight individuals, 0.9100 (0.9094, 0.9105) for caffeine from coffee, and 1.0021 (1.0013, 1.0029) for caffeine from non-coffee sources. Conclusion: Caffeine intake was negatively associated with the risk of kidney stones. In subgroup analyses, the negative association of caffeine with kidney stone risk was only found in white individuals. In addition, the decreased risk was found higher in women and non-overweight individuals. Especially for women, white individuals and non-overweight individuals. The protective effect of caffeine intake from coffee on stone formation was more significant than that of caffeine from non-coffee sources.

Revascularization of chronic total occlusion coronary artery and cardiac regeneration.

Coronary chronic total occlusion (CTO) contributes to the progression of heart failure in patients with ischemic cardiomyopathy. Randomized controlled trials demonstrated that percutaneous coronary intervention (PCI) for CTO significantly improves angina symptoms and quality of life but fails to reduce clinical events compared with optimal medical therapy. Even so, intervening physicians strongly support CTO-PCI. Cardiac regeneration therapy after CTO-PCI should be a promising approach to improving the prognosis of ischemic cardiomyopathy. However, the relationship between CTO revascularization and cardiac regeneration has rarely been studied, and experimental studies on cardiac regeneration usually employ rodent models with permanent ligation of the coronary artery rather than reopening of the occlusive artery. Limited early-stage clinical trials demonstrated that cell therapy for cardiac regeneration in ischemic cardiomyopathy reduces scar size, reverses cardiac remodeling, and promotes angiogenesis. This review focuses on the status quo of CTO-PCI in ischemic cardiomyopathy and the clinical prospect of cardiac regeneration in this setting.

Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification.

BACKGROUND: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. METHODS: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. RESULTS: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (ß = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (ß = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. CONCLUSION: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.

The association between weight-adjusted-waist index and increased urinary albumin excretion in adults: A population-based study.

Aims: The negative effect of obesity on kidney health has been reported. The association between weight-adjusted-waist index (WWI, a newly developed adiposity index) and albuminuria has not been reported earlier. Methods: This cross-sectional study was conducted among adults with complete data about WWI and urinary albumin-to-creatinine ratio (ACR) in 2005-2018 National Health and Nutrition Examination Survey (NHANES). WWI was calculated as waist circumference (WC) divided by the square root of weight. Weighted multivariable logistic regression and generalized additive model were employed to explore the independent relationship between WWI with albuminuria and its non-linearity. A two-piecewise linear regression model was used to calculate the threshold effect. Subgroup analysis and interaction tests were also performed. Results: A total of 36,921 participants were enrolled with a prevalence of albuminuria of 9.32%. The prevalence of albuminuria increased with the higher WWI tertiles (Tertile 1: 5.31%, Tertile 2: 8.23%, Tertile 3: 15.65%). WWI was positively associated with a higher likelihood of albuminuria (OR = 1.28, 95% CI: 1.15-1.43), and this relationship remains stable in subgroups (all P for trend > 0.05). Non-linear positive relationships were detected in females with a breakpoint of 10.93. A positive association between WWI and albuminuria (OR = 1.39, 95% CI: 1.20-1.61) was observed on the right of the breakpoint, while the association on the left was of no statistical significance. WWI showed a stronger correlation with albuminuria (OR = 1.28) than other markers of obesity including body mass index (BMI, OR = 1.02) and WC (OR = 1.01). Conclusion: Weight-adjusted-waist index levels were positively related to an increased likelihood of albuminuria in United States adults and showed a stronger relationship than BMI and WC. Our findings indicated that WWI may serve as a simple anthropometric index to predict albuminuria.