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Vaccines (Basel). 2023 Jun 21;11(7) doi: 10.3390/vaccines11071130.
The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully elucidated. We conducted a systematic review and meta-analysis to assess the efficacy and safety associated with this additional dose of the COVID-19 vaccine in the SOT recipients. A comprehensive search was conducted to identify studies on SOT patients without prior natural SARS-CoV-2 infection who received the fourth dose of the COVID-19 vaccine. Serological antibody responses following vaccination were synthesized by a meta-analysis of proportions. The proportions for each outcome were integrated by using a random-effects model. Approximately 56-92% of the SOT patients developed a humoral immune response, and the pooled seroprevalence rate was 75% (95% confidence interval [CI], 62-82%) after administering the third vaccine dose. Following the fourth dose of vaccination, approximately 76-95% of the patients developed a humoral immune response. The pooled seroprevalence rate after the fourth dose was 85% (95% CI, 79-91%). Of the patients who initially tested seronegative after the second dose, approximately 22-76% of patients subsequently became seropositive after the third dose. The pooled seroconversion rate for the third dose was 47% (95% CI, 31-64%). Among the patients who were seronegative after the third dose, approximately 25-76% turned seropositive after the fourth dose. The pooled seroconversion rate after the fourth dose was 51% (95% CI, 40-63%). Safety data were reported in three studies, demonstrating that adverse effects following the fourth dose were generally mild, and patients with these adverse effects did not require hospitalization. No transplant rejection or serious adverse events were observed. A fourth dose of the COVID-19 vaccine in SOT recipients was associated with an improved humoral immune response, and the vaccine was considered relatively safe. |
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BMJ Open. 2022 Dec 1;12(12):e062747 doi: 10.1136/bmjopen-2022-062747.
CET Conclusion
INTRODUCTION:
Kidney transplant recipients (KTRs) are at an increased risk of hospitalisation and death from COVID-19. Vaccination against SARS-CoV-2 is our primary risk mitigation strategy, yet vaccine effectiveness in KTRs is suboptimal. Strategies to enhance vaccine efficacy are therefore required. Current evidence supports the role of the gut microbiota in shaping the immune response to vaccination. Gut dysbiosis is common in KTRs and is a potential contributor to impaired COVID-19 vaccine responses. We hypothesise that dietary fibre supplementation will attenuate gut dysbiosis and promote vaccine responsiveness in KTRs. METHODS AND ANALYSIS:Rapamycin and inulin for third-dose vaccine response stimulation-inulin is a multicentre, randomised, prospective, double-blinded, placebo-controlled pilot trial examining the effect of dietary inulin supplementation prior to a third dose of COVID-19 vaccine in KTRs who have failed to develop protective immunity following a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to inulin (active) or maltodextrin (placebo control), administered as 20 g/day of powdered supplement dissolved in water, for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm that achieve in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third dose of COVID-19 vaccine. Secondary outcomes include the safety and tolerability of dietary inulin, the diversity and differential abundance of gut microbiota, and vaccine-specific immune cell populations and responses. ETHICS AND DISSEMINATION:Ethics approval was obtained from the Central Adelaide Local Health Network (CALHN) Human Research Ethics Committee (HREC) (approval number: 2021/HRE00354) and the Sydney Local Health District (SHLD) HREC (approval numbers: X21-0411 and 2021/STE04280). Results of this trial will be published following peer-review and presented at scientific meetings and congresses. TRIAL REGISTRATION NUMBER:ACTRN12621001465842. |
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Front Pharmacol. 2022 Oct 6;13:982472 doi: 10.3389/fphar.2022.982472.
Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer's solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer's solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear. Objective: To compare the effects of sodium bicarbonate Ringer's solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation. Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively. Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38-0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006). Conclusion: Sodium bicarbonate Ringer's solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation. |
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Transplant Direct. 2021 Sep 7;7(10):e753 doi: 10.1097/TXD.0000000000001202.
CET Conclusion
UNLABELLED:
Poor patient knowledge about transplantation is a significant problem following kidney transplant. A video-based educational intervention was developed to supplement standard education provided by transplant teams. METHODS:A multicenter randomized controlled trial tested the intervention delivered to patients undergoing assessment or waitlisted for kidney transplant. Adult participants were randomized to the control (standard education) or the intervention group, consisting of electronic access to the videos (or digital video disks if no internet) plus standard education. Differences between groups in changes in transplant knowledge (measured by the Kidney Transplant Understanding Tool), education satisfaction, self-efficacy, and quality of life (secondary outcomes) were evaluated by a preintervention and postintervention survey. Video viewing habits were tracked and described for patients in the intervention group. RESULTS:One hundred sixty-two patients were enrolled, with 132 completing both questionnaires (n = 64 intervention and n = 68 control), with similar enrollment from 3 Canadian sites. Video viewing statistics in the complete cases indicated that 78% (50/64) watched the videos, with 70% (45/64) viewing them electronically, while 8% (5/64) received digital video disks and self-reported participation. Baseline knowledge scores in the intent-to-treat population were 55.4 ± 6.5 and 55.7 ± 7.1 in the intervention and control, respectively. The mean knowledge change in the intervention (2.1 ± 3.6) was significantly higher than in the control group (0.8 ± 3.4, P < 0.02). In the per-protocol analysis (patients with objective evidence of watching at least 80% of the videos), the knowledge improvements were 3.4 ± 3.8. Video group participants reported higher satisfaction with education (P < 0.02) and expressed positive comments in open-ended feedback. CONCLUSIONS:Electronic video education in the pretransplant setting improved knowledge and satisfaction. |
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Transpl Infect Dis. 2021 Aug;23(4):e13696 doi: 10.1111/tid.13696.
BACKGROUND:
Since phase III trials for the most prominent vaccines excluded immunocompromised or immunosuppressed patients, data on safety and efficacy of SARS-CoV-2 vaccines for recipients of solid organ transplantations are scarce. AIMS:Our study offers a synthesis of expert opinions aligned with available data addressing key questions of the clinical management of SARS-CoV-2 vaccinations for transplant patients. METHOD:An online research was performed retrieving available recommendations by national and international transplantation organizations and state institutions on SARS-CoV2 vaccination management for transplant recipients. RESULTS:Eleven key statements were identified from recommendations by 18 national and international societies, and consensus for the individual statements was evaluated by means of the Society Recommendation Consensus score. The highest consensus level (SRC A) was found for prioritized access to vaccination for transplant patients despite anticipation of a weakened immune response. All currently authorized vaccines can be considered safe for transplant patients (SRC A). The handling of immunosuppressive medication, the timely management of vaccines, and other aspects were aligned with available expert opinions. CONCLUSION:Expert consensus can be determined for crucial aspects of the implementation of SARS-CoV-2 vaccination programs. We hereby offer a tool for immediate decision-making until empirical data becomes available. |
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Cell Res. 2020 Aug;30(8):708-710 doi: 10.1038/s41422-020-0369-7.
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Clin Transplant. 2018 Mar;32(3):e13193 doi: 10.1111/ctr.13193.
OBJECTIVE:
The aim of this study was to conduct a meta-analysis of published reports to compare long-term outcomes after liver transplantation (LT) and liver resection (LR), respectively, in patients with HBV-related hepatocellular carcinoma (HCC) beyond the Milan criterion. METHODS:A systematic search of the Embase, Medline, PubMed databases, and the Cochrane Library was performed using both medical subject headings (MeSH) and truncated word searches to identify all comparative studies published on this topic. The primary outcomes were postoperative overall survival (OS) and disease-free survival (DFS). We calculated the pooled hazard ratios (HR) with 95% confidence intervals (95% CI) of OS and DFS. RESULTS:Pooled analysis of six studies, with a total of 1697 patients with HCC beyond Milan criteria, did not reveal a statistically significant improvement in OS in patients undergoing LT vs LR (LT vs LR, HR: 0.83, 95% CI: 0.68-1.01, P = .06), without significant heterogeneity (χ2 = 8.38, I2 = 40.3%, P = .137). Five studies with a total of 1511 patients were included in pooled analysis of DFS between LT and LR group. In the fixed-effects model, patients in the LT group gained significantly better DFS (LT vs LR, HR: 0.45, 95% CI: 0.37-0.56, P < .001) than patients in the LR group, with no significant heterogeneity (χ2 = 6.80, I2 = 41.6%, P = .144). Four studies provided the data of adjusted HRs (LT vs LR). In the fixed-effects model, patients in the LT group had significantly better OS (HR: 0.58, 95% CI: 0.44-0.77, P < .001, I2 = 0%) and DFS (HR: 0.14, 95% CI: 0.08-0.23, P < .001, I2 = 0%) than those of patients in the LR group. The sensitivity analyses revealed that the results were robust. CONCLUSION:Our meta-analysis demonstrated that HBV-related patients with HCC beyond Milan criterion who underwent LT gained better OS and DFS compared with patients who underwent LR after adjusting confounding factors. |
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Ther Drug Monit. 2017 Feb;39(1):13-20 doi: 10.1097/FTD.0000000000000364.
BACKGROUND:
Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS:We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus. In this analysis, we considered TI ≤2 as a criterion to define a drug as having an NTI. RESULTS:Published literature indicates that cyclosporine has a TI of 2-3, which falls just short of our criteria to be classified as having an NTI. We found sirolimus and tacrolimus to have a therapeutic range of 5-12 ng/mL and of 5-20 ng/mL, respectively, but were unable to calculate the TI. CONCLUSIONS:Although the current literature does not provide a clear indication that these drugs have an NTI, the routine use of therapeutic drug monitoring in clinical practice suggests that more stringent testing of their pharmacokinetic and pharmacodynamic properties should be performed before the approval of generic formulations. |