Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

Impact of pharmacist intervention in reducing vancomycin-associated acute kidney injury: A systematic review and meta-analysis.

AIMS: The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS: Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS: The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION: Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.

Neutralization of Omicron BA.4/BA.5 and BA.2.75 by Booster Vaccination or BA.2 Breakthrough Infection Sera

Many new Omicron sub-lineages have been reported to evade neutralizing antibody response, including BA.2, BA.2.12.1, BA.4 and BA.5. Most recently, another emerging sub-lineage BA.2.75 has been reported in multiple countries. In this study, we constructed a comprehensive panel of pseudoviruses (PsVs), including wild-type, Delta, BA.1, BA.1.1, BA.2, BA.3, BA.2.3.1, BA.2.10.1, BA.2.12.1, BA.2.13, BA.2.75 and BA.4/BA.5, with accumulate coverage reached 91% according to the proportion of sequences deposited in GISAID database since Jan 1st, 2022. We collected serum samples from healthy adults at day14 post homologous booster with BBIBP-CorV, or heterologous booster with ZF2001, primed with two doses of BBIBP-CorV, or from convalescents immunized with three-dose inactivated vaccines prior to infection with Omicron BA.2, and tested their neutralization activity on this panel of PsVs. Our results demonstrated that all Omicron sub-lineages showed substantial evasion of neutralizing antibodies induced by vaccination and infection, although BA.2.75 accumulated the largest number of mutations in its spike, BA.4 and BA.5 showed the strongest serum escape. However, BA.2 breakthrough infection could remarkably elevated neutralization titers against all different variants, especially titers against BA.2 and its derivative sub-lineages.

Culture and identification of parietal epithelial cells of Bowman′s capsule / 中华肾脏病杂志

Objective:To explore the isolation and culture methods of mouse parietal epithelial cells (PECs) of Bowman′s capsule, so as to provide a cell tool for further study.Methods:Mouse renal corpuscles were isolated by cell sieving combined with magnetic separation. After primary culture, identified parietal epithelial cells were induced to differentiate into podocytes. Immunofluorescence staining, real-time quantitative PCR and Western blotting were used to detect specific markers of parietal epithelial cells and podocytes.Results:Primary cultured PECs grew like paving stone and expressed Claudin-1 (PECs specific marker), CD133 (stem cell marker) and CD24 (stem cell marker), without the expression of tubular epithelial cell proteins, mesangial cell and podocyte specific proteins. Cultured to 6 generations in vitro, the PECs still expressed Claudin-1, CD133 and CD24. After incubated with differentiation medium, PECs were able to express podocyte markers WT-1 and Synaptopodin. Conclusion:The renal corpuscles are extracted by cell sieving combined with magnetic separation, and the mouse PECs successfully cultured in vitro can be induced to express podocytes′ markers.

Ceftazidime Is a Potential Drug to Inhibit SARS-CoV-2 Infection In Vitro by Blocking Spike Protein-ACE2 Interaction

Coronavirus Disease 2019 (COVID-19) spreads globally as a sever pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cell entry of SARS-CoV-2 mainly depends on binding of the viral spike (S) proteins to angiotensin converting enzyme 2 (ACE2) on host cells. Therefore, repurposing of known drugs to inhibit S protein-ACE2 interaction could be a quick way to develop effective therapy for COVID-19. Using a high-throughput screening system to investigate the interaction between spike receptor binding domain (S-RBD) and ACE2 extracellular domain, we screened 3581 FDA-approved drugs and natural small molecules and identified ceftazidime as a potent compound to inhibit S-RBD-ACE2 interaction by binding to S-RBD. In addition to significantly inhibit S-RBD binding to HPAEpiC cells, ceftazidime efficiently prevented SARS-CoV-2 pseudovirus to infect ACE2-expressing 293T cells. The inhibitory concentration (IC50) was 113.2 M, which is far below the blood concentration (over 300 M) of ceftazidime in patients when clinically treated with recommended dose. Notably, ceftazidime is a drug clinically used for the treatment of pneumonia with minimal side effects compared with other antiviral drugs. Thus, ceftazidime has both anti-bacterial and anti-SARS-CoV-2 effects, which should be the first-line antibiotics used for the clinical treatment of COVID-19.

Incidence of cognitive impairment and risk factors associated with prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective@#To investigate the incidence and prognosis of cognitive impairment and to find out the risk factors associated with the outcome for better understanding and preventing cognitive impairment in maintenance hemodialysis (MHD) patients.@*Methods@#The patients who met the criteria as below: MHD patients (≥3 months) in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2000 to July 2014, ≥18 years old were enrolled and could carry on the montreal cognitive assessment (MoCA) of voluntary cooperation. According to the score of MoCA, all enrolled patients were divided into two groups: cognitive impairment (MoCA<26) group and non-cognitive impairment (MoCA≥26) group. The follow-up period was 3 years. There were 130 males, and the incidence, demography data, medical history, hemodialysis data, laboratory examination and prognosis of cognitive impairment in hemodialysis patients were prospectively compared and analyzed. Logistic regression analysis was used to investigate the risk factors of cognitive impairment. Kaplan-Meier survival curve and Cox regression model were used for prognostic analysis.@*Results@#A total of 219 MHD patients were enrolled. The incidence of cognitive impairment in MHD patients was 51.6%. There were 130 males, and the ratio of male to female was 1.46∶1. Age was (60.07±12.44) years old and dialysis vintage was (100.79±70.23) months. Compared with non-cognitive impairment group (n=106), patients in cognitive impairment group (n=113) were older, and had higher proportion of education status<12 years, history of diabetes and anuria (all P<0.05); however, the post-dialysis systolic pressure, pre-dialysis diastolic pressure, post-dialysis diastolic pressure, platelet and spKt/V were lower (all P<0.05). Multivariate logistic regression analysis showed that education status<12 years (OR=3.428, 95%CI 1.919-6.125, P<0.001), post-dialysis diastolic pressure<73 mmHg (OR=2.234, 95%CI 1.253-3.984, P=0.006) and spKt/V<1.72(OR=1.982, 95%CI 1.102-3.564, P=0.022) were the independent risk factors for cognitive impairment in MHD patients. The Kaplan-Meier survival curve analysis showed that the survival rate of patients with cognitive impairment was lower than that of non-cognitive impairment group in MHD patients during 3 years follow-up (χ2=3.977, P=0.046). Multivariate Cox regression analysis showed that cognitive impairment was an independent risk factor for death in MHD patients (RR=2.661, 95%CI 0.967-7.321, P=0.058).@*Conclusions@#Cognitive impairment is one of the common complications and an independent risk factor for death in MHD patients. The mortality is high in patients who suffer cognitive impairment. Education status<12 years, post-dialysis diastolic pressure<73 mmHg and spKt/V<1.72 are the independent risk factors for cognitive impairment in MHD patients.

Incidence of cognitive impairment and risk factors associated with prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the incidence and prognosis of cognitive impairment and to find out the risk factors associated with the outcome for better understanding and preventing cognitive impairment in maintenance hemodialysis (MHD) patients. Methods The patients who met the criteria as below: MHD patients (≥3 months) in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2000 to July 2014, ≥18 years old were enrolled and could carry on the montreal cognitive assessment (MoCA) of voluntary cooperation. According to the score of MoCA, all enrolled patients were divided into two groups: cognitive impairment (MoCA<26) group and non-cognitive impairment (MoCA≥26) group. The follow-up period was 3 years. There were 130 males, and the incidence, demography data, medical history, hemodialysis data, laboratory examination and prognosis of cognitive impairment in hemodialysis patients were prospectively compared and analyzed. Logistic regression analysis was used to investigate the risk factors of cognitive impairment. Kaplan-Meier survival curve and Cox regression model were used for prognostic analysis. Results A total of 219 MHD patients were enrolled. The incidence of cognitive impairment in MHD patients was 51.6％. There were 130 males, and the ratio of male to female was 1.46:1. Age was (60.07 ± 12.44) years old and dialysis vintage was (100.79 ± 70.23) months. Compared with non-cognitive impairment group (n=106), patients in cognitive impairment group (n=113) were older, and had higher proportion of education status<12 years, history of diabetes and anuria (all P<0.05); however, the post-dialysis systolic pressure, pre-dialysis diastolic pressure, post-dialysis diastolic pressure, platelet and spKt/V were lower (all P<0.05). Multivariate logistic regression analysis showed that education status<12 years (OR=3.428, 95％CI 1.919-6.125, P<0.001), post-dialysis diastolic pressure<73 mmHg (OR=2.234, 95％CI 1.253-3.984, P=0.006) and spKt/V<1.72(OR=1.982, 95％CI 1.102-3.564, P=0.022) were the independent risk factors for cognitive impairment in MHD patients. The Kaplan-Meier survival curve analysis showed that the survival rate of patients with cognitive impairment was lower than that of non-cognitive impairment group in MHD patients during 3 years follow-up (χ2=3.977, P=0.046). Multivariate Cox regression analysis showed that cognitive impairment was an independent risk factor for death in MHD patients (RR=2.661, 95％CI 0.967-7.321, P=0.058). Conclusions Cognitive impairment is one of the common complications and an independent risk factor for death in MHD patients. The mortality is high in patients who suffer cognitive impairment. Education status<12 years, post-dialysis diastolic pressure<73 mmHg and spKt/V<1.72 are the independent risk factors for cognitive impairment in MHD patients.