Effectiveness of Combined Hemodialysis-Hemadsorption Therapy in Improving Uremic Toxin Clearance, Inflammatory Markers, and Symptoms in Maintenance Hemodialysis Patients.

INTRODUCTION: Combined hemodialysis (HD) and hemadsorption (HA) therapy has shown the highest clearance rates for middle and large-sized uremic toxin molecules and reduced mortality rates among maintenance HD (MHD) patients. This study aims to investigate the effectiveness of combined HD and HA therapy in patients undergoing MHD. METHODS: Forty patients with end-stage renal disease (ESRD) were divided into three groups: HD only (14), HD+biweekly HA (14), and HD+weekly HA (12). The duration of the study was 8 weeks. Uremic toxins (ß2-microglobulin, leptin, parathyroid hormone), inflammatory markers (interleukin-6, C-reactive protein), and symptoms (appetite, pruritus, sleep quality) were assessed before the start and at the completion of therapy. Changes in the parameters were compared between the three groups. Mean differences of parameters in each group were also compared between before and after therapy. RESULTS: Decrease in BUN level (-61.34 mg/dL [95% CI:-71.33 to -51.34], p <0.0001) and pruritus score (-3.93 [95% CI:-6.89 to -0.97], p=0.013) was significantly larger in HD+biweekly HA group compared to the others. Only HD + biweekly HA group showed significant reductions in CRP level (-0.10 mg/L [95%: -0.18 to -0.01], p=0.034), VAS appetite score (10.43 [95% CI: 4.99 to 15.87], p = 0.001), and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p =0.013) after therapy. Both HD+biweekly HA (-2.79 [95% CI: -4.97 to -0.60], p=0.016) and HD+weekly HA group (-2.33 [95% CI: -4.59 to -0.08], p=0.044) exhibited a significant improvement in sleep quality score after therapy. CONCLUSIONS: HD combined with a biweekly HA is associated with a greater reduction in BUN level and better improvement of pruritus in ESRD patients compared to HD alone. HD+biweekly HA can significantly reduce CRP levels, alleviate pruritus, improve appetite, and enhance sleep quality.

Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study.

BACKGROUND: A significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients. METHODS: Patients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs). RESULTS: The geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89-9,571.94) U/mL (p = < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63-27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported. CONCLUSIONS: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.

Eribulin in breast cancer: Current insights and therapeutic perspectives.

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.

Five-year survival analysis and predictors of mortality of adult hemodialysis patients in Indonesia: a nationwide database analysis.

BACKGROUND: Hemodialysis (HD) is the modality of renal replacement therapy (RRT) with the highest mortality rate. The identification of prognostic factors will help achieve better outcomes among HD patients. In this study, we sought to conduct a survival analysis and determine the predictors of mortality among adult Indonesian HD patients using data obtained from Indonesian Renal Registry (IRR). METHODS: This is a retrospective cohort study which reviewed all adult hemodialysis patients in Indonesia based on the records of IRR during 2007-2022. Variables analyzed in this study include age, sex, etiology of CKD, cause of death, HD frequency, and initial vascular access. A 5-year follow-up was performed until the outcome of death or drop out was found. RESULTS: Among 99,552 eligible patients, the mean survival length was 1536.21 ± 2.50 days. The 5-year survival rate was 77%. Cox proportional hazard regression model revealed demographic and clinical characteristics that are significantly associated with mortality: male sex (HR: 1.038, 95% CI 1.002-1.075), age of 60 years or older (HR: 1.329, 95% CI 1.281-1.379), diabetic nephropathy (HR: 1.347, 95% CI 1.249-1.452), twice-weekly hemodialysis frequency (HR: 1.080, 95% CI 1.011-1.155), initial vascular accesses with femoral vein puncture (HR: 2.710, 95% CI 2.568-2.860), and CVC (HR: 2.992, 95% CI 2.848-3.144). CONCLUSIONS: The 5-year survival rate of Indonesian HD patients is 77. Male sex, age of HD onset at 60 years or older, diabetic nephropathy, twice-weekly HD frequency, and the initial vascular accesses with femoral vein puncture and CVC are associated with increased risk of mortality.

Antibiotic use reduces the efficacy of immune checkpoint inhibitors in patients with urothelial carcinoma: A systematic review and meta-analysis.

CONTEXT: Antibiotics have been suggested to diminish the efficacy of immune checkpoint inhibitors (ICIs) by alterations of the gut microbiota. OBJECTIVE: To perform a meta-analysis summarizing the effect of antibiotics on the overall survival (OS) and progression-free survival (PFS) of urothelial cancer (UC) patients receiving ICI. EVIDENCE ACQUISITION: PubMed, EMBASE (Ovid), and the Cochrane Library were searched to identify studies published up to July 14, 2023. Studies reporting the associations between antibiotics use and OS and PFS in UC patients treated with ICI were included in this systematic review and meta-analysis. The random-effect model was used to pool the Hazard Ratios (HRs) for OS and PFS with 95% confidence interval (95%CI). The ROBINS-I was used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform the quality of evidence. EVIDENCE SYNTHESIS: Thirteen nonrandomized studies involving a total of 5,095 ICI-treated UC patients were included in this review, of which 1434 (28%) received antibiotics. Overall, compared to patients who did not receive antibiotics, the pooled HRs for OS and PFS in those who received antibiotics were 1.45 [95% CI 1.25-1.68] and 1.40 [95% CI 1.05-1.87], respectively. Subgroup analysis revealed that the types of ICI and timing of antibiotic initiation did not influence the effect of antibiotics on OS and PFS in UC patients (P > 0.05). CONCLUSIONS: Antibiotic use significantly reduced OS and PFS in UC patients receiving ICI. While antibiotics remain crucial for the treatment of infections in UC patients, antibiotics should be prescribed cautiously in UC patients receiving ICI. PATIENT SUMMARY: Antibiotic use is associated with worsened survival in UC patients receiving immune checkpoint inhibitors.

Outcomes of vaccinations against respiratory diseases in patients with end-stage renal disease undergoing hemodialysis: A systematic review and meta-analysis.

Due to the nature of the disease, end-stage renal disease (ESRD) patients suffer from dysfunction of the adaptive immune system, which leads to a poorer response to vaccination. Accordingly, it is crucial to evaluate the efficacy and safety of management strategies, including vaccinations, which could potentially reduce the risk of respiratory diseases, such as pneumonia, influenza, or COVID-19, and its associated outcomes. We searched PubMed, CENTRAL, ScienceDirect, Scopus, ProQuest, and Google Scholar databases using designated MeSH keywords. The risk of bias was assessed using ROBINS-I. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Relative risk (RR) and 95% confidence interval (CI) were calculated. Heterogeneity was investigated using forest plots and I2 statistics. This systematic review included a total of 48 studies, with 13 studies of influenza (H1N1 and H3N2) vaccination and 35 studies of COVID-19 vaccination. H1N1 vaccination in ESRD patients undergoing hemodialysis induced lower seroconversion rates (RR 0.62, 95% CI: 0.56-0.68, p <0.00001) and lower seroprotection rates (RR 0.76, 95% CI: 0.70-0.83, p <0.00001) compared to controls. H3N2 vaccination in ESRD patients undergoing hemodialysis yielded lower seroconversion rates (RR 0.76, 95% CI: 0.68-0.85, p <0.00001) and lower seroprotection rates (RR 0.84, 95% CI: 0.77-0.90, p <0.00001) compared to controls. Twenty-nine studies demonstrate significantly lower antibody levels in ESRD patients undergoing hemodialysis compared to the controls following COVID-19 vaccination. This review presents evidence of lower seroconversion and seroprotection rates after vaccination against viral respiratory diseases in patients with ESRD undergoing hemodialysis. Since hemodialysis patients are more susceptible to infection and severe disease progression, a weakened yet substantial serological response can be considered adequate to recommend vaccination against respiratory diseases in this population. Vaccination dose, schedule, or strategy adjustments should be considered in stable ESRD patients on maintenance hemodialysis. Trial registration: Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255983, identifier: CRD42021255983.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccine in haemodialysis patients: a prospective cohort study.

End-stage renal disease patients on haemodialysis (HD) have been largely excluded from SARS-CoV-2 vaccine trials due to safety reasons and shown to mount lower responses to vaccination. This study aims to evaluate the immunogenicity and safety of inactivated COVID-19 vaccine among HD patients compared to healthy controls. All subjects who received the primary inactivated COVID-19 vaccination had their blood samples tested 21 days after the second dose. We report the immunogenicity based on anti-RBD IgG titre (IU/mL), the inhibition rate of neutralizing antibodies (NAbs) (%) to RBD, and seroconversion rates. Adverse events were assessed within 30 min and on the 7th day after each dose. Among 75 HD patients and 71 healthy controls, we observed no significant difference in all immunogenicity measures: anti-RBD IgG GMT (277.91 ± 7.13 IU/mL vs. 315.50 ± 3.50 IU/mL, p = 0.645), NAbs inhibition rate (82% [53-96] vs. 84% [39-98], p = 0.654), and seroconversion rates (anti-RBD IgG: 86.7% vs. 85.9%, p = 0.895; NAbs: 45.3% vs. 60.6%, p = 0.065). The number of adverse events is not significantly different between the two groups. The primary inactivated SARS-CoV-2 vaccination elicits an adequate antibody response and can be safely administered in haemodialysis patients.