Transplantation最新文献

Background: Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting.

Methods: This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up.

Results: There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P  < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P  = 0.08).

Conclusions: In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.

Background: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients.

Methods: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases.

Results: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died.

Conclusions: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.

Cellular senescence has been identified as a potential driver of age-associated loss of organ function and as a mediator of age-related disease. Novel strategies in targeting senescent cells have shown promise in several organ systems to counteract functional decline, chronic inflammation, and age-dependent loss of repair capacity. Transgenic models have provided proof of principle that senolysis, the elimination of senescent cells, is an attractive strategy to overcome many age-related pathologies. The translation into clinical application is now possible with the emergence of drug-based senotherapies. In this review, we will discuss different senotherapeutic approaches and their modes of action. Senolytics eliminate senescent cells preferentially through the induction of apoptosis in senescent but not in normal cells, whereas senomorphics rather interact with the proinflammatory profile present in senescent cells. In the context of transplantation, the natural clearance of senescent cells might be reduced because of dysfunctional immune surveillance under immunosuppression. The transplantation setting allows for different applications of senotherapies. Conditioning donor organs before and during the ex situ phase offers the opportunity to interfere with accumulating senescence, ultimately reducing the burden of life-limiting comorbidities in chronically ill recipients.

Background: It remains unclear whether physicians should accept transplantation offers for candidates with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test due to the potential risk of severe infection after initiating immunosuppressive therapy.

Methods: A multicenter observational study was conducted in 19 French solid organ transplantation units. Patients on the waiting list for liver or kidney transplants who had a positive SARS-CoV-2 reverse transcription polymerase chain reaction nasopharyngeal swab at the time of transplantation were recorded.

Results: Sixty-five patients were included. The recipients were predominantly men (n = 40; 62%) with a mean age of 55.4 y (SD = 16.5). On the day of transplantation, 2 patients exhibited symptoms compatible with COVID-19. The majority of patients (n = 55; 85%) underwent thoracic imaging, with only 3 patients showing imaging results compatible with COVID-19. Ten patients (28%) had a cycle threshold value <30. Anti-SARS-CoV-2 spike protein serology within 3 mo before transplantation was available for 36 patients; only 2 patients were seronegative. Due to COVID-19, physicians adapted the immunosuppressive therapy for 16 patients (25%). Specific antiviral therapy was used for 15 patients (23%), primarily remdesivir (n = 12). Overall, the majority of patients did not receive any adjustment of immunosuppressive therapy or antiviral treatment (n = 36; 55%). The outcomes were generally favorable even for patients with the lowest cycle threshold values, indicating a high viral load. Four patients died during follow-up, although none of these deaths were attributable to COVID-19.

Conclusions: Transplantation appears to be safe for patients who are asymptomatic or have mild symptoms, reassuring thoracic imaging, and a history of anti-SARS-CoV-2 infection and/or immunization.