OBJECTIVES:

To determine whether spontaneous reporting rates of myocarditis and pericarditis differed in immunocompromised patients compared with the whole population overall, and in terms of demographics, vaccine dose and time-to-onset.

DESIGN:

Systematic review of spontaneously reported data from the European Union/European Economic Area (EU/EEA), the USA and the UK.

DATA SOURCES:

EudraVigilance (EU/EEA), Vaccine Adverse Event Reporting System (VAERS; USA) and the Medicines and Healthcare products Regulatory Agency (UK) spontaneous reporting databases were searched from date of vaccine launch to 1 December 2021.

ELIGIBILITY CRITERIA:

Publicly available spontaneous reporting data for 'myocarditis' and 'pericarditis' from EU/EEA and USA following COVID-19 messenger RNA vaccines. Reports with comorbidities or concurrent medication indicative of transplantation, HIV infection or cancer ('immunocompromised' population) were compared with each overall database population.

DATA EXTRACTION AND SYNTHESIS:

Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for immunocompromised populations for each data source, stratified by age, sex, dose and time-to-onset (where available). Seriousness of each event was determined according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline E2A definition. Proportional reporting ratio (PRR) was calculated.

RESULTS:

There were 178 reports of myocarditis and pericarditis among immunocompromised individuals overall. Seriousness was comparable between the immunocompromised and overall populations in both databases. No trends in age or sex were observed among immunocompromised individuals. Most reports followed a second vaccine dose and occurred within 14 days. The frequency of reporting was similar to the wider population (PRR=1.36 (95% CI=0.89 to 1.82) for VAERS population).

CONCLUSIONS:

Myocarditis and pericarditis following COVID-19 vaccination are very rare, and benefits of COVID-19 vaccination continue to outweigh any perceived risks. Reporting rates of myocarditis and pericarditis were similar in immunocompromised individuals, however defining characteristics differed compared with the whole population; therefore, continued monitoring of adverse events following vaccination remains vital to understand differences between population subgroups.

INTRODUCTION:

Great advancements in solid organ transplantation (SOT) have allowed patients to have better chances to survive longer and enjoy a quality life after surgery. This increasing number of SOTs and improved long-term survival rates lead to an increasing demand for plastic, esthetic and reconstructive breast procedures.

MATERIAL AND METHODS:

A literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using searching terms related to esthetic and reconstructive breast surgery was conducted across three databases: PubMed, Scopus and Google Scholar. Included articles were analyzed to extract data points of interest including patient age, type of surgery, organ transplanted, underlying conditions associated with organ transplantation, follow-up, immunosuppressive drugs and their side effects, perioperative management and complications related to the breast plastic procedures in SOT recipients.

RESULTS:

A total of 1,298 articles were retrieved from the mentioned electronic databases. Eight full articles were finally included in this systematic review. In these articles, a total of 41 cases of breast plastic surgery after solid organ transplantation were reported. Procedures were esthetic in nature in 26.83% of cases (11 of 41 cases) and reconstructive in 73.17% of them (30 of 41 cases). No deaths were reported.

CONCLUSIONS:

Although esthetic and reconstructive breast surgery could be performed safely in SOT recipients, the dosage of immunosuppression and patient's overall health status with regard to the length and extent of the planned procedure should always be taken into account. From the literature data analysis, it is not possible to draw a statistical conclusion that the complication rate of surgery in immunosuppressed post-transplant patients is the same as in normal, not immunosuppressed population. Further and more valid clinical studies are warranted.

BACKGROUND:

Mycophenolic acid (MPA) is among the most commonly prescribed medications for immunosuppression following organ transplantation. Highly variable MPA exposure and drug response are observed among individuals receiving the same dosage of the drug. Identification of candidate genes whose polymorphisms could be used to predict MPA exposure and clinical outcome is of clinical value.

OBJECTIVES:

This study aimed to determine the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of MPA in humans by means of a systematic review and meta-analysis.

METHODS:

A systematic search was conducted on PubMed, EMBASE, Web of Sciences, Scopus, and the Cochrane Library databases. A meta-analysis was conducted to determine any associations between genetic polymorphisms and pharmacokinetic or pharmacodynamic parameters of MPA. Pooled-effect estimates were calculated by means of the random-effects model.

RESULTS:

A total of 37 studies involving 3844 individuals were included in the meta-analysis. Heterozygous carriers of the UGT1A9 -275T>A polymorphism were observed to have a significantly lower MPA exposure than wild-type individuals. Four single nucleotide polymorphisms (SNPs), namely UGT1A9 -2152C>T, UGT1A8 518C>G, UGT2B7 211G>T, and SLCO1B1 521T>C, were also significantly associated with altered MPA pharmacokinetics. However, none of the investigated SNPs, including SNPs in the IMPDH gene, were found to be associated with the clinical efficacy of MPA. The only SNP that was associated with adverse outcomes was SLCO1B3 344T>G.

CONCLUSIONS:

The present systematic review and meta-analysis identified six SNPs that were significantly associated with pharmacokinetic variability or adverse effects of MPA. Our findings represent the basis for future research and clinical implications with regard to the role of pharmacogenetics in MPA pharmacokinetics and drug response.

The use of direct-acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin K antagonists (VKAs) in the general population. However, insufficient data regarding DOAC use in solid organ transplant (SOT) recipients and numerous pharmacokinetic and pharmacodynamic considerations limit their use in this highly selected patient population. A systematic review of recent clinical evidence on the safety and efficacy of DOACs compared to VKAs in SOT recipients was conducted. Additional considerations including transplant-specific strategies for DOAC reversal and common pharmacokinetic/pharmacodynamic concerns were also reviewed. Although current evidence is limited to single-center retrospective analyses, DOACs, especially apixaban, appear to be a safe and effective alternative to VKAs for SOT recipients with stable graft function and without drug-drug interactions. Reliable data on DOAC reversal at the time of transplant surgery are lacking, and clinicians should consider idarucizumab, andexanet alfa, and other non-specific reversal agents on an individual patient basis. There is no evidence supporting deviations from the Food and Drug Administration labeling recommendations for DOAC dosing in the setting of drug-drug interactions, obesity, and renal function, especially in patients on hemodialysis.

OBJECTIVES:

Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients. We aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients.

DESIGN:

Systematic review.

DATA SOURCES:

We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019.

ELIGIBILITY CRITERIA:

We included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients.

DATA EXTRACTION AND SYNTHESIS:

Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework.

RESULTS:

Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI -0.84 to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low.

CONCLUSIONS:

Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice.

PROSPERO REGISTRATION NUMBER:

CRD42017063962.

Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta-analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high-risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high-risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.