Effect of a Management Algorithm for Wet Contamination of Peritoneal Dialysis System on the Prevention of Peritonitis: A Prospective Observational Study

Introduction: Wet contamination was a common problem of peritoneal dialysis (PD) system. We developed a management algorithm for wet contamination of PD system (wet contamination) on the basis of the related research literature and clinical practice experience. The purpose of this study was to observe clinical effect of the management algorithm on the prevention of peritonitis. Methods: Patients treated wet contamination in a single PD center between October 2017 and September 2022 were included. A management algorithm was established to treat wet contamination. It comprised identification of the contamination type, addressing contaminated or aging catheters, prophylactic antibiotics, and retraining. Demographic data and clinical data about wet contamination were collected and compared. Results: One hundred and forty-one cases of wet contamination were included in this study. The mean age was 51.7 ± 14.1 years, and 49.6% were female. The proportion of diabetic nephropathy was 9.9%. The median PD duration was 27.0 (1.7–79.7) months. Eighteen episodes (12.8%) of wet contamination-associated peritonitis developed after wet contamination. The main pathogenic bacteria of peritonitis were Gram-positive bacteria (33.3%) and Gram-negative bacteria (27.8%). The incidence of wet contamination-associated peritonitis in the compliance with the management algorithm group was significantly lower than that in the non-compliance with the management algorithm group (0.9 vs. 48.6%; p < 0.001). Non-compliance with management algorithm (OR = 185.861, p < 0.001) together with advance age (OR = 1.116, p < 0.001) and longer distance from home to hospital (OR = 1.007, p < 0.001) were independent risk factors for wet contamination-associated peritonitis. Conclusion: The management algorithm for wet contamination of PD system could reduce the risk of peritonitis

Association of Lean Body Mass Index and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

Background/Aims: The relationship between peritoneal protein clearance (PPCl) and nutritional status in peritoneal dialysis (PD) population have not been clarified. This study aims to investigate the relationship between PPCl and nutritional status in PD population. Methods: Prevalent PD patients were enrolled in the cross-sectional survey in a single center from April to November 2013. The total amount of protein loss in the dialysate was calculated. PPCl reflects the individual differences of peritoneal protein loss, and is calculated by the formula, that PPCl (ml/day)=24-h dialysate protein loss / (albumin/0.4783). Nutritional status measured by lean body mass index (LBMI) was assessed by multi-frequency bioelectrical impedance analysis (BIA). Results: Totally 351 PD patients (55% male, 17.1% with diabetes, mean age 47.7±14.3 years) were included. The median PPC l was 58 ml/day. Patients were divided into four groups for comparison according to the PPC quartiles. Compared with lower PPCl quartiles, patients with higher PPCl had higher body mass index (BMI) (P< 0.001), body surface area (BSA) (P < 0 .001), LBMI (P<0.001), 4-hour D/P creatinine ratio (P< 0.001), and lower residual renal CCl (P<0.001). Compared with conventional body index (BMI and BSA) in ROC analysis, LBMI (area under curve: 0.71, 95% confidence interval [CI]: 0.66-0.77) had better performance in predicting higher PPCl. After adjustment in logistic regression models, each 1 kg/m2 increase of LBMI (odd ratio[OR] =1.37; 95% CI: 1.17-1.60), each 0.1 increase of 4-hour D/P creatinine ratio (OR =1.47; 95% CI: 1.11-1.93), and every 1 L/week/1.73m2 decrease of residual renal CCl (OR =0.98; 95% CI: 0.96-0.99) were independently associated with higher PPCl (> 58 ml/day). Conclusion: Higher LBMI was independently associated with higher , indicating that better nutritional status dominates peritoneal protein metabolism in PD patients

Establishment of the 1st Chinese national standard for CA6 neutralizing antibody

Coxsackievirus A6 (CA6) is one of the major causative agents of herpangina and hand-foot-mouth disease (HFMD). Since 2008, CA6 has circulated widely around the world. Especially in Asia-Pacific region CA6 had even replaced enterovirus A71 (EV71) and coxsackievirus A16 (CA16) as the main prevalent strain of HFMD. In the recent 10 years, monovalent and multivalent vaccines against CA6 have been researched and developed by manufacturers from China, Korea, and the USA. The neutralizing antibody titer is a key indicator for accurately evaluating immunogenicity of vaccine. However, so far, the World Health Organization international standard for CA6 neutralizing antibody has not been available. In order to meet the needs of evaluating the immunogenicity of vaccines against CA6, the first Chinese national standard for CA6 neutralizing antibody was established, which was conducted to ensure that methods used to measure the neutralizing antibody titers against CA6 are accurate, reliable, and comparable. Three lyophilized candidate standards (29#, 39# and 44#) were produced with 0.40 ml/vial from plasma samples donated by healthy individuals. The collaborative study showed that the 29# candidate standard could effectively minimize the variability in neutralization titers between labs and across challenging viruses of different genotypes (A, D1, and D3). Therefore, the 29# candidate sample was established as the first Chinese national standard for CA6 neutralizing antibody test. This standard has good long-term stability and was assigned a potency of 150 units per milliliter (U/ml) of CA6 neutralizing antibody. It will contribute to ensure uniformity of potency or activity of vaccines and potentially therapeutic antibody preparations

A Cocktail of Lipid Nanoparticle-mRNA Vaccines Broaden Immune Responses against β-Coronaviruses in a Murine Model

Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging β-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. Thus, pan-β-coronavirus vaccine strategies to combat the upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, and M, targeting the spike protein of SARS-CoV-2 Omicron, Delta, SARS-CoV, and MERS-CoV, respectively, were synthesized and characterized for purity and integrity. All four LNP-mRNAs induced effective cellular and humoral immune responses against the corresponding spike protein antigens in mice. Furthermore, LNP-mRNA S and D induced neutralizing antibodies against SARS-CoV and SARS-CoV-2, which failed to cross-react with MERS-CoV. Subsequent evaluation of sequential and cocktail immunizations with LNP-mRNA O, D, S, and M effectively elicited broad immunity against SARS-CoV-2 variants, SARS-CoV, and MERS-CoV. A direct comparison of the sequential with cocktail regimens indicated that the cocktail vaccination strategy induced more potent neutralizing antibodies and T-cell responses against heterotypic viruses as well as broader antibody activity against pan-β-coronaviruses. Overall, these results present a potential pan-β-coronavirus vaccine strategy for improved preparedness prior to future coronavirus threats

Research progress on substitution of in vivo method(s) by in vitro method(s) for human vaccine potency assays

Introduction Potency is a critical quality attribute for controlling quality consistency and relevant biological properties of vaccines. Owing to the high demand for animals, lengthy operations and high variability of in vivo methods, in vitro alternatives for human vaccine potency assays are extensively developed. Areas covered Herein, in vivo and in vitro methods for potency assays of previously licensed human vaccines were sorted, followed by a brief description of the background for substituting in vivo methods with in vitro alternatives. Based on the analysis of current research on the substitution of vaccine potency assays, barriers and suggestions for substituting were proposed. Expert opinion Owing to the variability of in vivo methods, the correlation between in vivo and in vitro methods may be low. One or more in vitro method(s) that determine the vaccine antigen content and functions, should be established. Since the substitution involves with the change of critical quality attributes and specifications, the specifications of in vitro methods should be appropriately set to maintain the efficacy of vaccines. For novel vaccines in research and development, in vitro methods for monitoring the consistency and relevant biological properties, should be established based on reflecting the immunogenicity of vaccines

The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients

Abstract Background Results concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up. Methods This retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality. Results A total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21–48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46–2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28–2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47–9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years. Conclusions Peritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration

Research progress on vaccine efficacy against SARS-CoV-2 variants of concern

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate worldwide and a variety of variants have emerged. Variants of concern (VOC) designated by the World Health Organization (WHO) have triggered epidemic waves due to their strong infectivity or pathogenicity and potential immune escape, among other reasons. Although large-scale vaccination campaigns undertaken globally have contributed to the improved control of SARS-CoV-2, the efficacies of current vaccines against VOCs have declined to various degrees. In particular, the highly infectious Delta and Omicron variants have caused recent epidemics and prompted concerns about control measures. This review summarizes current VOCs, the protective efficacy of vaccines against VOCs, and the shortcomings in methods for evaluating vaccine efficacy. In addition, strategies for responding to variants are proposed for future epidemic prevention and control as well as for vaccine research and development