Transpl Infect Dis. 2022 Dec 12;e14000 doi: 10.1111/tid.14000.
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BACKGROUND:
Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT. METHODS:We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs. RESULTS:Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N. CONCLUSION:Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT. |
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BMJ Open. 2022 Dec 1;12(12):e062747 doi: 10.1136/bmjopen-2022-062747.
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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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BMC Nephrol. 2022 Nov 7;23(1):357 doi: 10.1186/s12882-022-02989-z.
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BACKGROUND:
Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS:The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION:This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION:clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR:Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org . |
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Transplant Proc. 2022 Nov;54(9):2434-2438 doi: 10.1016/j.transproceed.2022.10.001.
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BACKGROUND:
During the 1900s, tacrolimus became the mainstay immunosuppressive agent to prevent rejection after kidney transplant. Subsequently, an extended-release tacrolimus (ER-Tac) formulation was developed to improve adherence, and its generic version has been marketed over the last years. This study examines the differences in efficacy and safety between the generic ER-Tac (Conferoport) and the reference brand-name drug (Advagraf). METHODS:Prospective, randomized and parallel single-center study (May 2020 to June 2021) with 52 kidney transplant recipients who were randomly assigned to 1 of the following groups: study group (Conferoport, n = 31) and control group (Advagraf, n = 21). The variables of interest were collected and analyzed to compare tacrolimus efficacy and safety between them. Demographic characteristics of the patients and clinical donor data were homogeneous in both groups (P > .05). RESULTS:No statistically significant differences were found among treatments regarding dosage used, levels, creatinine, and proteinuria (P > .05), with these variables presenting a downward trend during follow-up and, consequently, the improvement of graft function. Analyses also revealed the absence of differences concerning the incidence of acute rejection and intrapatient variability (coefficient of variation) throughout the first year of evolution between both formulations (P > .05). A total of 5 graft losses occurred, 2 resulting from patient death. CONCLUSIONS:In our experience, we found no significant differences between the measured parameters in relation to the efficacy and safety profile of both drugs, with generic ER-Tac being an alternative comparable with the reference brand-name ER-Tac. |
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Transplant Proc. 2022 Oct;54(8):2117-2124 doi: 10.1016/j.transproceed.2022.08.008.
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BACKGROUND:
We evaluated the efficacy and safety of eculizumab in comparison with plasmapheresis and intravenous immunoglobulin therapy in renal transplant recipients diagnosed with antibody-mediated rejection (AMR). METHODS:This was a multicenter, open-label, prospective, randomized analysis. The patients were randomized by therapy type (eg, eculizumab infusions or standard of care [SOC]: plasmapheresis/intravenous immunoglobulin). The patients (ie, eculizumab arm: 7 patients, SOC arm: 4 patients) were evaluated for the continued presence of donor-specific antibodies (DSAs) and C4d (staining on biopsy), as well as histologic evidence, using repeat renal biopsy after treatment. RESULTS:The allograft biopsies revealed that eculizumab did not prevent the progression to transplant glomerulopathy. Only 2 patients in the SOC arm experienced rejection reversal, and no graft losses occurred in either group. After AMR treatment, the DSA titers generally decreased compared to titers taken at the time of AMR diagnosis. There were no serious adverse effects in the eculizumab arm. CONCLUSIONS:Eculizumab alone cannot treat AMR effectively and does not prevent acute AMR from progressing to chronic AMR or transplant glomerulopathy. However, it should be considered as a potential alternative therapy because it may be associated with decreased DSA levels. |
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Anesth Essays Res. 2022 Apr-Jun;16(2):231-237 doi: 10.4103/aer.aer_92_22.
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BACKGROUND AND AIMS:
Transversus abdominis plane (TAP) block has been used to provide analgesia in renal transplant surgery with varying results. This study was designed to assess if the addition of clonidine in TAP block would decrease 24-h postoperative morphine consumption in adult renal transplant recipients. MATERIALS AND METHODS:Forty adult patients undergoing renal transplantation under general anesthesia in a tertiary care hospital were randomized into either group RC (TAP block with 20 mL of 0.5% ropivacaine plus 2 μg.kg-1 clonidine) or group R (TAP block with 20 mL 0.5% ropivacaine) after induction of anesthesia. Postoperative analgesia was provided using patient-controlled morphine. The primary outcome was 24-h patient-controlled morphine consumption. The secondary outcomes were a) intraoperative hemodynamics, b) fentanyl and ephedrine requirement, c) postoperative pain using the Visual Analog Scale at 0, 2, 6, 12 and 24 hours, d) time to first postoperative analgesia, e) postoperative hemodynamics, and f) side effects. RESULTS:There was no significant difference in postoperative morphine consumption between the groups (25 mg in group RC vs. 28.5 mg in group R) (median interquartile range) (P = 0.439). Postoperative pain scores were comparable between the groups. Intraoperatively, fewer patients required rescue fentanyl in group RC (7 patients) as compared to group R (17 patients) (P = 0.003). Significantly more patients in group RC required ephedrine boluses as compared to group R (9 patients in group RC vs. 2 in group R, P = 0.014). CONCLUSIONS:The addition of 2 μg.kg-1 clonidine to ropivacaine in TAP block did not reduce 24-h postoperative morphine consumption after renal transplantation. It reduced the need for intraoperative analgesics but increased the need for intraoperative ephedrine administration. |
Ann Transplant. 2022 Nov 22;27:e937988 doi: 10.12659/AOT.937988.
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BACKGROUND The study objective was to evaluate the effect of everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared with a standard TAC (sTAC) regimen on hepatocellular carcinoma (HCC) recurrence in de novo living-donor liver transplantation recipients (LDLTRs) with primary HCC at liver transplantation through 5 years after transplantation. MATERIAL AND METHODS In this multicenter, non-interventional study, LDLTRs with primary HCC, who were previously randomized to either everolimus plus reduced tacrolimus (EVR+rTAC) or standard tacrolimus (sTAC), and who completed the 2-year core H2307 study, were followed up. Data were collected retrospectively (end of core to the start of follow-up study), and prospectively (during the 3-year follow-up study). RESULTS Of 117 LDLTRs with HCC at LT in the core H2307 study (EVR+rTAC, N=56; sTAC, N=61), 86 patients (EVR+rTAC, N=41; sTAC, N=45) entered the follow-up study. Overall HCC recurrence was lower but statistically non-significant in the EVR+rTAC group (3.6% vs 11.5% in sTAC; P=0.136) at 5 years after LT. There was no graft loss or chronic rejection. Acute rejection and death were comparable between treatment groups. Higher mean estimated glomerular filtration rate in the EVR+rTAC group (76.8 vs 65.8 mL/min/1.73 m² in sTAC) was maintained up to 5 years. Reported adverse events were numerically lower in the EVR+rTAC group (41.0% vs 53.5% sTAC) but not statistically significant. CONCLUSIONS Although statistically not significant, early EVR initiation reduced HCC recurrence, with comparable efficacy and safety, and better long-term renal function, than that of sTAC treatment. |
Pulm Ther. 2022 Dec 13;1-13 doi: 10.1007/s41030-022-00209-5.
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INTRODUCTION:
Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. METHODS:A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). RESULTS:Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. CONCLUSIONS:The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation. |
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J Artif Organs. 2022 Dec 8; doi: 10.1007/s10047-022-01376-7.
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Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a reliable and effective extracorporeal life support during lung transplantation (LTx). However, the clinical benefit of delayed VV-ECMO weaning remains unclear. The current study aims to investigate whether delayed weaning of VV-ECMO is more beneficial to the rehabilitation for lung transplant patients. Patients who underwent LTx with VV-ECMO between January 2017 and January 2019 were included. Enrollment of patients was suitable for weaning off ECMO immediately after surgery. Randomization was performed in the operating room. Postoperative outcomes were compared between the two groups. Besides, univariate and multivariable logistic regressions were performed to estimate risk of postoperative complications. Compared to VV-ECMO weaning immediately after LTx, delayed weaning was associated with shorter hospital length of stay (days, 31 vs. 46; P < 0.05), lower incidence of noninvasive ventilation (4.3% vs. 24.4%; P < 0.05), primary graft dysfunction (PGD) (6.4% vs. 29.3%; P < 0.05), atrial fibrillation (AF) (4.3% vs. 22%, P < 0.05), and respiratory failure (4.3% vs. 19.5%; P < 0.05). Multivariable logistic regressions revealed that VV-ECMO weaning after LTx was independently correlated with increased risk of developing PGD [odds ratio (OR), 5.97, 95% CI 1.16-30.74], AF (OR, 6.87, 95% CI 1.66-28.47) and respiratory failure (OR, 6.02, 95% CI 1.12-32.49) by comparison of delayed VV-ECMO weaning. Patients with delayed VV-ECMO weaning are associated with lower complications and short hospital length of stay, while it relates to longer mechanical ventilation. These findings suggest that delayed VV-ECMO after LTx can facilitate rehabilitation. |
J Orthop. 2022 Nov 26;35:150-154 doi: 10.1016/j.jor.2022.11.015.
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INTRODUCTION:
The purpose of this study is to report a systematic review and meta-analysis of solid organ transplant (SOT) patients undergoing shoulder arthroplasty to compare functional and radiographic outcomes, demographics, and complications with non-transplant patients. METHODS:Studies were included if they examined patients undergoing shoulder arthroplasty in the setting of prior solid organ transplantation and included post operative range of motion, patient-reported outcomes, complications, or revisions. Studies were excluded if they were national database analyses or lacked clinical data. Pubmed, MEDLine, Scopus, and Web of Science were queried using relevant search terms in July 2022. Data was pooled, weighted, and a paired t-test and chi-square analysis was performed. RESULTS:There were 71 SOT and 159 non-SOT shoulders included in the study. The most common indication for surgery was avascular necrosis (n = 26) in the solid organ transplant group and osteoarthritis (n = 60) in the non-SOT group. Forward elevation, external rotation, ASES, and VAS pain scores improved significantly in both cohorts following surgery. There was no significant difference in age at surgery (p-value = 0.20), postoperative forward elevation (p-value = 0.08), postoperative external rotation (0.84), and postoperative ASES scores (p-value = 0.11) between the two cohorts. VAS pain scores were significantly lower in the SOT cohort (p-value<0.01). The risk of death was significantly higher in the SOT group (p-value<0.01). but the rate of overall complications (p = 0.47), surgical complication (p-value = 0.79), or revision surgery (p-value = 1.00) was not significantly different between the two cohorts. CONCLUSION:Shoulder arthroplasty is a safe, effective option in patients following solid organ transplant. There is not an increased risk of adverse outcomes, and SOT patients had comparable range of motion and patient-reported outcomes when compared to their non-SOT peers. LEVEL OF EVIDENCE:III. |