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Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety.Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19.Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients.Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232).Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Since deterministic prediction errors of wind power cannot be avoided, probabilistic prediction can adequately describe the uncertainty of wind power and, thus, provide further guidance to dispatching authorities for decision making. Current probabilistic prediction methods for wind power are still incomplete in mining its physical variation process. Therefore, this study constructs a new framework for short-term wind power probabilistic forecasting considering the spatio-temporal dependence of errors by mining the spatio-temporal characteristics of historical wind power data and numerical weather forecasts at numerical weather prediction (NWP). First, the deterministic prediction results are obtained by an improved deep belief network (DBN); then, a multi-location NWP is introduced to propose a multi-level error scenario partitioning method considering the spatio-temporal dependence property. Finally, a new error sample set is formed by reconstructing the kernel density estimation method to adapt the model, and the short-term wind power probability prediction at different confidence levels is carried out. It is, thus, concluded that the effectiveness of the overall framework under the probabilistic prediction considering spatio-temporal dependence is verified in a wind farm in Jilin, China, and the prediction accuracy is effectively and significantly improved compared with the same confidence level, and the coverage of the evaluation index prediction interval is improved by 1.23, 0.72, and 0.80%, and the average bandwidth of the prediction interval is reduced by 2.14, 1.40, and 0.63%, which confirms the proposed effectiveness and feasibility of the method.

IntroductionUF insufficiency is a major limitation in PD efficiency and sustainability. Our study object to investigate the efficacy of intraperitoneal inflammation marker, IL-6 level as a predictor of UF insufficiency in continuous ambulatory peritoneal dialysis (CAPD) patients.MethodsStable prevalent CAPD patients were enrolled in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6 AR). Patients were divided into two groups according to the median of IL-6 AR and prospectively followed up until death, transfer to permanent HD, recovery of renal function, kidney transplantation, transfer to other centers, lost to follow-up or to the end of study (January 31, 2021). Factors associated with UF capacity as well as dialysate IL-6 AR were assessed by multivariable linear regression. Cox proportional hazards model was used to examine the association between dialysate IL-6 AR and UF insufficiency.ResultsA total of 291 PD patients were enrolled, including 148 males (51%) with a mean age of 56.6 ± 14.1 years and a median PD duration of 33.4 (12.7–57.5) months. No correlation was found between dialysate IL-6 AR and UF capacity at baseline. PD duration was found positively correlated with baseline dialysate IL-6 AR, while 24h urine volume was negatively correlated with baseline dialysate IL-6 AR (P < 0.05). By the end of study, UF insufficiency was observed in 56 (19.2%) patients. Patients in the high IL-6 AR group showed a significantly inferior UF insufficiency-free survival when compared with their counterparts in the low IL-6 AR group (P = 0.001). In the multivariate Cox regression analysis, after adjusting for DM, previous peritonitis episode and 24h urine volume, higher baseline dialysate IL-6 AR (HR 3.639, 95% CI 1.776–7.456, P = 0.002) were associated with an increased risk of UF insufficiency. The area under the ROC curve (AUC) for baseline IL-6 AR to predict UF insufficiency was 0.663 (95% CI, 0.580–0.746; P < 0.001).ConclusionOur study suggested that the dialysate IL-6 AR could be a potential predictor of UF insufficiency in patients undergoing PD.

IntroductionAssociation of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl.MethodsPrevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018).ResultsA total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1–57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2–50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000–1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl.ConclusionHigh Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.

Background: Cerebrovascular and cardiovascular diseases contribute substantially to the mortality of end-stage renal disease patients. We sought to combine pulse wave velocity (PWV) with galectin-3 to predict the mortality and cerebrovascular and cardiovascular events in hemodialysis patients.Methods and Results: End-stage renal disease patients who underwent stable hemodialysis were screened for inclusion. Patients with preexisting cardiovascular and cerebrovascular diseases were excluded. The primary endpoint was a composite of all-cause mortality and major adverse cerebrovascular and cardiovascular events. Receiver operating characteristic curve analysis was used to determine the optimal cutoffs to dichotomize PWV and galectin-3. The study population was then stratified into four groups based on these cutoffs. Both univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio and 95% confidence interval (CI) for clinical factors. Model performance was compared among models with or without PWV and galectin-3. A total of 284 patients were enrolled. During a median follow-up of 31 months, 57 patients (20.1%) reached the primary endpoint. The optimal cutoffs for PWV and galectin-3 were 7.9 m/s and 30.5 ng/ml, respectively. In the multivariable regression analysis, the high PWV–high galectin-3 group was associated with a 3-fold increased risk of all-cause mortality and major adverse cerebrovascular and cardiovascular events (hazard ratio = 3.19, 95% CI: 1.05–9.66, p = 0.04) compared with the low PWV–low galectin-3 group. The combination of PWV and galectin-3 was associated with improved model discrimination, calibration, and reclassification.Conclusions: The combination of PWV and galectin-3 can be used to predict mortality and cerebral and cardiovascular complications in hemodialysis patients.

Compared with a single energy harvester, this tuning fork double-armed cone-shaped flexure transducer can fundamentally solve the problems of high resonance frequency, low output efficiency, and narrow bandwidth of the flexure transducer. Since the transducer limits the clamping losses of the cantilever beam, it provides sufficient stiffness-mass balance to lower the resonance frequency of the system and extend the bandwidth. The tapered structure provides sufficient strain gradient for the flexoelectric effect, improving the output efficiency of the whole system. The vibration frequency of the tuning fork structure and the derivation of the bandwidth formula are analyzed theoretically, and then the electrode width and thickness of the cone structure are studied through simulation to analyze the transducer output response, resonant frequency, bandwidth, and output impedance.