Efficacy of the Cytokine Adsorption Therapy in Patients with Severe COVID-19-Associated Pneumonia: Lesson Learned from a Prospective Observational Study.

INTRODUCTION: Severe COVID-19 pneumonia can activate a cytokine storm. Hemoperfusion can reduce pro-inflammatory cytokines in sepsis but is still debated in the COVID-19 setting. Thus, we sought to investigate the benefits of HA-330 cytokine adsorption through clinical and laboratory outcomes. METHODS: We conducted a single-center prospective observational study in adults with severe COVID-19 pneumonia admitted to the intensive care unit at Chiang Mai University Hospital (Chiang Mai, Thailand). Those with cytokine storms indicated by organ injury, including acute respiratory distress syndrome (ARDS), and high inflammatory markers were included. Patients treated with the HA-330 device were classified as a hemoperfusion group, while those without cytokine adsorption were classified as a control group. We compared the outcomes on day 7 after treatment and evaluated the factors associated with 60-day mortality. RESULTS: A total of 112 patients were enrolled. Thirty-eight patients received hemoperfusion, while 74 patients did not. Baseline cytokine storm parameters were comparable. In univariate analysis, there was an improvement in clinical and laboratory effects from hemoperfusion therapy. In multivariate analysis, APACHE II score, SOFA score, PaO2/FiO2, the number of hemoperfusion sessions, the amount of blood purified, high-sensitivity C-reactive protein, and IL-6 were associated with mortality. Using at least 3 sessions of hemoperfusion could mitigate, the 60-day mortality (adjusted odds ratio 0.25, 95% confidence interval: 0.03-0.33, p = 0.001). By categorizing the amount of blood treated into 3 groups of <1 L/kg, 1-2 L/kg, and ≥2 L/kg, there was a linear dose-response association with survival, which was better in the higher volume purified (mortality 60% vs. 33.3% vs. 0%, respectively, p = 0.015). CONCLUSIONS: The early initiation of HA-330 hemoperfusion could improve the severity score and laboratory outcomes of COVID-19 ARDS. The optimal dose of at least three sessions or the amount of blood purified greater than 1 L/kg was associated with a reduction in 60-day mortality.

Effect of Curcuminoids on Contrast-Induced Acute Kidney Injury after Elective Coronary Angiography or Intervention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: The role of curcuminoids, a striking antioxidant, in prevention of contrast-induced acute kidney injury (CI-AKI) remains unknown. We aimed to evaluate the efficacy and safety of curcuminoids in preventing CI-AKI in patients undergoing elective coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). METHODS: We randomized 114 patients who were undergoing elective CAG and/or PCI to receive curcuminoids, 4 g/day (1 day before and 1 day after the procedure, n = 56), or placebo (n = 58). Serum creatinine was assessed at baseline, 12, 24, and 48 h after contrast exposure. The primary endpoint was development of CI-AKI defined as serum creatinine increase ≥0.3 mg/dL within 48 h after contrast exposure. The secondary endpoint was the occurrence of kidney injury defined by >30% increase in urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: Baseline characteristics were comparable between the two groups. Seven (12.7%) in curcuminoids group and eight (14.0%) in placebo group developed CI-AKI (p = 0.84). The incidence of increased urine NGAL was comparable in the placebo and curcuminoids group (39.6% vs. 50%, respectively; p = 0.34). None in both groups had drug-related adverse events. CONCLUSION: This is a pilot study to demonstrate the safety and tolerability of curcuminoids in patients undergoing elective CAG and/or PCI. Curcuminoids have no protective effects against kidney injury after elective CAG and/or PCI.

Pharmacokinetics of intravenous piperacillin/tazobactam among patients with peritoneal dialysis-associated peritonitis.

Currently, pharmacokinetic information on intravenous (IV) piperacillin/tazobactam in patients with peritoneal dialysis-associated peritonitis (PD peritonitis) is limited. This study employed a prospective single-dose pharmacokinetic design to assess the pharmacokinetics of IV piperacillin/tazobactam in these patients. Four patients with PD peritonitis who received an IV loading dose of 4000 mg/500 mg piperacillin/tazobactam were enrolled in this study. The concentrations of piperacillin and tazobactam in plasma, peritoneal dialysis fluid (PDF) and urine were determined by high-performance liquid chromatography. Non-compartmental methods were used for pharmacokinetic analysis. During a 6-h dwell time for chronic ambulatory peritoneal dialysis (CAPD), 9.23 ± 4.01% of the piperacillin was recovered in the PDF. This result is greater than that observed in patients without peritonitis in prior research. Piperacillin's PD clearance (CLPD), steady-state volume of distribution (Vss) and terminal half-life (t 1/2) were 5.79 ± 2.55 mL/min, 24.35 ± 11.26 L and 5.74 ± 1.53 h, respectively. These values are also higher than those of patients without peritonitis in a prior study. Eight hours following the loading dosage, the plasma and PDF piperacillin concentrations of all patients (98.25 ± 26.03 and 52.70 ± 22.99 mg/L, respectively) surpassed the Pseudomonas aeruginosa and Enterobacterales Clinical and Laboratory Standards Institute susceptible breakpoints. In summary, the CLPD, Vss and t 1/2 for piperacillin were found to be greater in patients with PD peritonitis than in CAPD patients without peritonitis when compared with the results of a previous study. The IV loading dose of 4000 mg/500 mg piperacillin/tazobactam is sufficient to treat peritonitis caused by susceptible P. aeruginosa and Enterobacterales. The multiple-dose pharmacokinetics of IV piperacillin and tazobactam in this specific patient group should be further investigated.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study.

BACKGROUND: Vaccines that prevent SARS-CoV-2 infection are considered the most promising approach to modulating the pandemic. There is scarce evidence on the efficacy and safety of different vaccine prime-boost combinations in MHD patients since most clinical trials have used homologous mRNA vaccine regimens. METHODS: This prospective observational study assessed the immunogenicity and safety of homologous CoronaVac® (SV-SV), ChAdOx1 nCoV-19 (AZD1222) (AZ-AZ), and the heterologous prime-boost of SV-AZ, among MHD patients. RESULTS: A total of 130 MHD participants were recruited. On day 28, after the second dose, seroconversion results of the surrogate virus neutralization test were not different between vaccine regimens. The magnitude of the receptor-binding domain-specific IgG was highest among the SV-AZ. Different vaccine regimens had a distinct impact on seroconversion, for which the heterologous vaccine regimen demonstrated a higher probability of seroconversion (OR 10.12; p = 0.020, and OR 1.81; p = 0.437 for SV-AZ vs. SV-SV, and SV-AZ vs. AZ-AZ, respectively). There were no serious adverse events reported in any of the vaccine groups. CONCLUSIONS: Immunization with SV-SV, AZ-AZ, and SV-AZ could generate humoral immunity without any serious adverse events among MHD patients. Using the heterologous vaccine prime-boost seemed to be more efficacious in terms of inducing immunogenicity.

Correction: Narongkiatikhun et al. Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study. Vaccines 2023, 11, 175.

The authors wish to make the following correction to this paper [...].

Effectiveness of Renin-Angiotensin-Aldosterone System Blockade on Residual Kidney Function and Peritoneal Membrane Function in Peritoneal Dialysis Patients: A Network Meta-Analysis.

We performed a network meta-analysis of randomised controlled trials (RCTs) and non-randomised studies in adult peritoneal dialysis patients to evaluate the effects of specific renin-angiotensin aldosterone systems (RAAS) blockade classes on residual kidney function and peritoneal membrane function. Key outcome parameters included the following: residual glomerular filtration rate (rGFR), urine volume, anuria, dialysate-to-plasma creatinine ratio (D/P Cr), and acceptability of treatment. Indirect treatment effects were compared using random-effects model. Pooled standardised mean differences (SMDs) and odd ratios (ORs) were estimated with 95% confidence intervals (CIs). We identified 10 RCTs (n = 484) and 10 non-randomised studies (n = 3,305). Regarding changes in rGFR, RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were more efficacious than active control (SMD 0.55 [0.06-1.04] and 0.62 [0.19-1.04], respectively) with the protective effect on rGFR observed only after usage ≥12 months, and no differences among ACEIs and ARBs. Compared with active control, only ACEIs showed a significantly decreased risk of anuria (OR 0.62 [0.41-0.95]). No difference among treatments for urine volume and acceptability of treatment were observed, whereas evidence for D/P Cr is inconclusive. The small number of randomised studies and differences in outcome definitions used may limit the quality of the evidence.

A Clinical Risk Prediction Tool for Peritonitis-Associated Treatment Failure in Peritoneal Dialysis Patients.

A tool to predict peritonitis-associated treatment failure among peritoneal dialysis (PD) patients has not yet been established. We conducted a multicentre, retrospective cohort study among 1,025 PD patients between 2006 and 2016 in Thailand to develop and internally validate such a tool. Treatment failure was defined as either a requirement for catheter removal, a switch to haemodialysis, or peritonitis-associated mortality. Prediction model performances were analysed using discrimination (C-statistics) and calibration (Hosmer-Lemeshow test) tests. Predictors were weighted to calculate a risk score. In total, 435 patients with 855 episodes of peritonitis were identified; 215 (25.2%) episodes resulted in treatment failure. A total risk score of 11.5 was developed including, diabetes, systolic blood pressure <90 mmHg, and dialysate leukocyte count >1,000/mm3 and >100/mm3 on days 3-4 and day 5, respectively. The discrimination (C-statistic = 0.92; 95%CI, 0.89-0.94) and calibration (P > 0.05) indicated an excellent performance. No significant difference was observed in the internal validation cohort. The rate of treatment failure in the different groups was 3.0% (low-risk, <1.5 points), 54.4% (moderate-risk, 1.5-9 points), and 89.5% (high-risk, >9 points). A simplified risk-scoring scheme to predict treatment failure may be useful for clinical decision making regarding PD patients with peritonitis. External validation studies are needed.

Double filtration plasmapheresis in different diseases in Thailand.

Double filtration plasmapheresis (DFPP) was applied to the treatment of two different categories from 100 cases that had been collected over a 5 year period (2007-2011). These categories were allocated into groups by size of toxic substances, which were classified as two different kinds of diseases. Group I comprised diseases that were caused by alloimmunity in transplantation, autoimmune diseases, complicated nephrotic syndrome, pure red cell aplasia, and toxemia of pregnancy. This group was treated with a plasma separator (plasmaflow-05, Asahi Kasei) and plasma fractionators, EC-20W. The second group, which included hyperviscosity syndrome, was treated by the same plasma separator, but with different plasma fractionators using EC-40W. This group included diabetes nephropathy, hyperlipidemia, peripheral arterial diseases, and neurosensory hearing loss. Both groups used 1.5 plasma volumes in each treatment for three sessions in two consecutive weeks. The result of treatment in group I showed that plasma immunoglobulin G (IgG) was decreased substantially by 66% in either transplant or lupus nephritis patients after the third session. In the second group, IgM, fibrinogen, and lipid markedly responded to the treatment. Two diabetes nephropathy patients showed stable renal function for more than 12 months. Peripheral arterial disease was shown to benefit from significantly decreasing fibrinogen and IgM, which resulted in clinical tissue oxygenation. Neither bleeding diathesis nor membrane anaphylaxis were reported from the treatment. In summary, apheresis patients were shown to benefit in hypersensitized and hyperviscosity syndrome.