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Lancet Infect Dis. 2023 Mar;23(3):307-319 doi: 10.1016/S1473-3099(22)00650-8.
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Surgery. 2023 Apr;173(4):1072-1078 doi: 10.1016/j.surg.2022.11.011.
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J Nephrol. 2023 Mar;36(2):537-550 doi: 10.1007/s40620-022-01458-y.
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Lancet Infect Dis. 2023 Mar;23(3):307-319 doi: 10.1016/S1473-3099(22)00650-8.
CET Conclusion
Expert Review
Study Details
BACKGROUND:
An urgent need exists to improve the suboptimal COVID-19 vaccine response in kidney transplant recipients (KTRs). We aimed to compare three alternative strategies with a control single dose mRNA-1273 vaccination: a double vaccine dose, heterologous vaccination, and temporary discontinuation of mycophenolate mofetil or mycophenolic acid. METHODS:This open-label randomised trial, done in four university medical centres in the Netherlands, enrolled KTRs without seroconversion after two or three doses of an mRNA vaccine. Between Oct 20, 2021, and Feb 2, 2022, 230 KTRs were randomly assigned block-wise per centre by a web-based system in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination, assessed in all participants who had a baseline measurement and who completed day 28 after vaccination without SARS-CoV-2 infection. Safety was assessed as a secondary outcome in all vaccinated patients by incidence of solicited adverse events, acute rejection or other serious adverse events. This trial is registered with ClinicalTrials.gov, NCT05030974 and is closed. FINDINGS:Between April 23, 2021, and July 2, 2021, of 12 158 invited Dutch KTRs, 3828 with a functioning kidney transplant participated in a national survey for antibody measurement after COVID-19 vaccination. Of these patients, 1311 did not seroconvert after their second vaccination and another 761 not even after a third. From these seronegative patients, 345 agreed to participate in our repeated vaccination study. Vaccination with 2 × mRNA-1273 or Ad26.COV2-S was not superior to single mRNA-1273, with seroresponse rates of 49 (68%) of 72 (95% CI 56-79), 46 (63%) of 73 (51-74), and 50 (68%) of 73 (57-79), respectively. The difference with single mRNA-1273 was -0·4% (-16 to 15; p=0·96) for 2 × mRNA-1273 and -6% (-21 to 10; p=0·49) for Ad26.COV2-S. Mycophenolate mofetil- was also not superior to mycophenolate mofetil+, with seroresponse rates of 37 (80%) of 46 (66-91) and 31 (67%) of 46 (52-80), and a difference of 13% (-5 to 31; p=0·15). Local adverse events were more frequent after a single and double dose of mRNA-1273 than after Ad26.COV2-S (65 [92%] of 71, 67 [92%] of 73, and 38 [50%] of 76, respectively; p<0·0001). No acute rejection occurred. There were no serious adverse events related to vaccination. INTERPRETATION:Repeated vaccination increases SARS-CoV-2-specific antibodies in KTRs, without further enhancement by use of a higher dose, a heterologous vaccine, or 2 weeks discontinuation of mycophenolate mofetil or mycophenolic acid. To achieve a stronger response, possibly required to neutralise new virus variants, repeated booster vaccination is needed. FUNDING:The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation. |
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Surgery. 2023 Apr;173(4):1072-1078 doi: 10.1016/j.surg.2022.11.011.
CET Conclusion
Study Details
BACKGROUND:
Postoperative complications of surgical incisions are frequent in liver transplantation. However, evidence justifying the use of incisional negative pressure wound therapy to improve surgical wound outcomes remains limited. METHODS:Participating patients were randomly assigned to receive incisional negative pressure wound therapy or standard surgical dressing on the closed surgical incision of the liver transplantation. The primary endpoint was surgical site infection incidence 30 days postoperatively. The secondary endpoints included surgical site events (ie, surgical site infection, dehiscence, hematoma, and seroma) and wound quality of life. RESULTS:Between December 2018 and September 2021, 108 patients (54 in the incisional negative pressure wound therapy group and 54 in the control group) were enrolled in this study. The incidence of surgical site infection at 30 days postoperatively was 7.4% in the treatment group and 13% in the control group (P = .34). The rate of surgical site events was similar in the treatment in the and control group (27.8% vs 29.6%, P = .83). In relation to wound quality of life, the mean score was 75.20 ± 7.27 in the incisional negative pressure wound therapy group and 72.82 ± 10.57 in the control group (P = .23). CONCLUSION:The prophylactic use of negative pressure wound therapy on primarily closed incisions did not significantly reduce incisional surgical site infection and surgical site event rates after liver transplantation compared with standard surgical dressings. |
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Clin Transplant. 2023 Mar;37(3):e14867 doi: 10.1111/ctr.14867.
INTRODUCTION:
Liver transplantation (LT) is the choice of therapeutic option for end-stage hepatic GSD patients; however, reports about the long-term outcome of LT in these patients have remained controversial. METHODS:We performed a systematic review and meta-analysis of observational studies published until Dec 31, 2021, that investigated the long-term outcome of LT in hepatic GSD patients. A literature search in the MEDLINE/PubMed, EMBASE,Cochrane Library, Scopus and Web of Science Core Collection databases was performed. RESULTS:14 studies with 210 patients were included in our analysis. As the results showed, the pooled proportion of GSD patients with complications after liver transplant (e.g., hemorrhagic shock, biliary complications, tacrolimus encephalopathy, chronic hepatitis, hepatic artery thrombosis, hepatic adenoma, sepsis, liver dysfunction, chronic rejection, acute cellular rejection, and CMV infection) was 27.7% (95% CI: 20.42-35.67) without heterogeneity (I2 = 24.04%), as calculated by the random-effect model. The pooled proportion of GSD patients with complications related to GSD after LT, including HCC (Hepatocellular carcinoma), renal complication, muscle problems, delayed menarche, persistent neutropenia, pneumonitis, renal failure, and hepatic adenoma was 22.2% (95% CI: 7.97-40.01) with high heterogeneity (I2 = 82.47%). Subgroup analysis including the age of patients (adult/pediatric), duration of follow-up, and type of donor was conducted to investigate the resources of heterogeneity. CONCLUSION:According to our investigation and review analysis, most GSD patients showed significant outcome improvement after liver transplantation. Overall, our findings showed an excellent outcome of liver transplantation in GSD patients; however, it needs further investigations to be confirmed. |
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Eur J Intern Med. 2023 Mar;109:58-67 doi: 10.1016/j.ejim.2022.12.009.
BACKGROUND:
Sex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT). METHODS:A systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615. RESULTS:After retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83-0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86-0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76-0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males. CONCLUSIONS:Females represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management. |
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Surgery. 2023 Apr;173(4):1052-1059 doi: 10.1016/j.surg.2022.11.033.
BACKGROUND:
Surgical site occurrences pose a threat to patient health, potentially resulting in significant increases in health care spending caused by using additional resources. The objective of this study was to reach a consensus among a group of experts in incisional negative pressure wound therapy to determine the indications for using this type of treatment prophylactically and to analyze the associated risk factors of surgical site occurrences in abdominal surgery. METHODS:A group of experts in incisional negative pressure wound therapy from Spain and Portugal was formed among general surgery specialists who frequently perform colorectal, esophagogastric, or abdominal wall surgery. The Coordinating Committee performed a bibliographic search to identify the most relevant publications and to create a summary table to serve as a decision-making protocol regarding the use of prophylactic incisional negative pressure wound therapy based on factors related to the patient and type of procedure. RESULTS:The patient risk factors associated with surgical site occurrence development such as age, immunosuppression, anticoagulation, hypoalbuminemia, smoking, American Society of Anesthesiologists classification, diabetes, obesity, and malnutrition were analyzed. For surgical procedure factors, surgical time, repeated surgeries, organ transplantation, need for blood transfusion, complex abdominal wall reconstruction, surgery at a contaminated site, open abdomen closure, emergency surgery, and hyperthermic intraperitoneal chemotherapy were analyzed. CONCLUSION:In our experience, this consensus has been achieved on a tailored set of recommendations on patient and surgical aspects that should be considered to reduce the risk of surgical site occurrences with the use of prophylactic incisional negative pressure wound therapy, particularly in areas where the evidence base is controversial or lacking. |
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Transplant Proc. 2023 Feb 27; doi: 10.1016/j.transproceed.2022.11.005.
BACKGROUND:
Takotsubo syndrome (TTS) has been reported in solid-organ transplant recipients. However, the pooled data regarding TTS after liver transplant remain limited. METHODS:A systematic review was performed through February 2022 using PubMed, Embase, Scopus, and Google Scholar to review case reports/series and original studies on liver transplant-associated TTS. Descriptive analysis was performed for case reports and pooled analysis for the prevalence using random effects models. RESULTS:A total of 56 case reports were included from 30 articles (51.8 % male; mean age, 53 years; India 56%, US 27%, and Europe 8.93%) and 10 original studies (US 88.65%, India 10.92%) revealing liver transplant-associated TTS. The pooled prevalence of TTS was 1.1% (95% Cl, 0.6%-1.7%) of all liver transplants with comparable rates in studies from India and the US (P = .92). Indications for liver transplant included end-stage liver disease due to alcohol-related cirrhosis (25%), hepatitis C virus infection (17.9%), hepatocellular carcinoma (10.7%), and non-alcohol-related steatohepatitis (8.9%); the average Model for End-Stage Liver Disease score was 24.75. TTS commonly presented as hypotension (30%), dyspnea (14%), and oliguria, occurring mostly post-transplant (82%), whereas 14% were intraoperative. Common electrocardiogram findings were ST changes, ventricular tachycardia, and atrial fibrillation. Common echocardiogram findings showed left ventricular apical ballooning in 46.5% of cases and reduced ejection fraction < 20% in 41.9% of cases. Common complications were cardiogenic shock (32.1 %), acute kidney injury (12.5%), arrhythmia, stroke, cardiac arrest, and hepatic artery thrombosis. Mechanical circulatory support was required in 30.3%. Recurrence was reported in 15, and mortality in 30.4% of patients. CONCLUSIONS:Takotsubo syndrome prevalence after liver transplant is significantly higher than TTS prevalence in general US hospitalizations with potentially worse outcomes. Prospective registries reporting TTS in liver transplant recipients are warranted. |
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Adv Ther. 2023 Mar;40(3):1267-1281 doi: 10.1007/s12325-022-02383-z.
INTRODUCTION:
Following hematopoietic stem cell transplantation or solid organ transplantation, patients are at risk of developing Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD), which is an ultra-rare and potentially lethal hematologic malignancy. Common treatments for EBV+ PTLD include rituximab alone or combined with chemotherapy. Given specific considerations for this population, including severity of the underlying condition requiring transplant, the rigors of the transplant procedure, as well as risks to the transplanted organ, there is a group of patients with EBV+ PTLD for whom chemotherapy may be inappropriate; however, there is limited information characterizing these patients. This study aimed to reach expert consensus on the key characteristics of patients for whom chemotherapy may be inappropriate in a real-world setting. METHODS:A two-round modified Delphi study was conducted to reach consensus among clinicians with expertise treating EBV+ PTLD. Articles identified in a targeted literature review guided the development of round 1 and 2 topics and related statements. The consensus threshold for round 1 statements was 75.0%. If consensus was achieved in round 1, the statement was not discussed further in round 2. The consensus thresholds for round 2 were moderate (62.5-75.0%), strong (87.5%), or complete (100.0%). RESULTS:The panel was composed of a total of eight clinicians (seven hematologists/hemato-oncologists) from six European countries. The panel generated a final list of 43 consensus recommendations on the following topics: terminology used to describe patients for whom chemotherapy may be inappropriate; demographic characteristics; organ transplant characteristics; comorbidities that preclude the use of chemotherapy; EBV+ PTLD characteristics; and factors related to treatment-related mortality and morbidity. CONCLUSIONS:This modified Delphi panel successfully achieved consensus on key topics and statements that characterized patients with EBV+ PTLD for whom chemotherapy may be inappropriate. These recommendations will inform clinicians and aid in the treatment of EBV+ PTLD. |
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Transplant Proc. 2023 Feb 21; doi: 10.1016/j.transproceed.2023.01.013.
BACKGROUND:
Mycophenolate mofetil exhibits pharmacologic mechanisms different from calcineurin inhibitors. Therefore, the dose of calcineurin inhibitors can be reduced along with side effects for effective immunosuppression. We aimed to evaluate the efficacy and safety of tacrolimus and corticosteroid in combination with or without mycophenolate mofetil in living donor liver transplantation (LDLT) recipients infected with hepatitis B virus (HBV). METHODS:A randomized, open-label, comparative, multicenter, phase IV study was conducted with 119 patients from January 2014 to September 2017. In the full analysis set population, 58 and 59 patients were included in the study group (triple-drug regimen: TacroBell + My-rept + corticosteroid) and the control group (dual-drug regimen: TacroBell + corticosteroid), respectively. In the per protocol set population, 49 and 42 patients were included in the study and control groups, respectively. RESULTS:In the full analysis set population, the incidence of biopsy-proven acute cellular rejection (rejection activity index score ≥4) was 3.4% in the study group; however, this finding was not observed in the control group (P = .468). Hepatitis B virus recurrence was observed in one patient in the control group. No cases of biopsy-proven acute cellular rejection and HBV recurrence were observed in the per protocol set population. The incidences of serious adverse events were 25.9% and 18.0% in the study and control groups, respectively; however, the difference between the groups was not statistically significant (P = .376). CONCLUSION:Although the study involved a small number of patients, the triple-drug regimen can be considered safe and effective for immunosuppression after living donor liver transplantation in patients infected with HBV. |
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J Nephrol. 2023 Mar;36(2):537-550 doi: 10.1007/s40620-022-01458-y.
CET Conclusion
Study Details
INTRODUCTION:
Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast, immunosuppression is considered to increase the risk of mortality, infection, and malignancy. We aimed to assess the evidence regarding superiority of early or late withdrawal of maintenance immunosuppression post renal transplant failure. METHODS:A literature search of the PubMed, WOS, Ovid, and Scopus databases was conducted. Combined relative risks, (RRs), mean differences, and 95% confidence intervals (CIs) were calculated by using a random-effect model. RESULTS:Ten studies involving 1187 patients with kidney transplant failure were included. No difference could be detected between patients with early withdrawal of immunosuppressive drugs (≤ 3 months) or prolonged immunosuppressive treatment (> 3 months) regarding mortality (95% CI 0.91-2.28), panel reactive antibodies (PRAs) (95% CI - 0.75-30.10), re-transplantation rate (95% CI 0.55-1.35), infectious episodes (95% CI 0.67, 1.17), cancer (95% CI 0.26-1.54), and graft nephrectomy (95% CI 0.82-1.63). Similarly, no difference was found between immunosuppressive drug withdrawal over < 6 or ≥ 6 months regarding mortality (95% CI 0.16, 2.89), re-transplantation rate (95% CI 0.85-1.55), cancer (95% CI 0.37-1.63), and allograft nephrectomy (95% CI 0.87-4.33). CONCLUSION:Prolonged maintenance immunosuppression post kidney transplant failure is not associated with increased risk of mortality, infection, or malignancy, or reduced risk of sensitization or allograft nephrectomy compared with early withdrawal. |
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Ren Fail. 2023 Dec;45(1):2169618 doi: 10.1080/0886022X.2023.2169618.
BACKGROUND:
Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS:This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS:Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS:The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease. |