No abstract

Background. A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients. Methods. Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed. Results. Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02). Conclusions. For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%.

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations () were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively ( = 0.001* [asterisk means that statistical test is significant]), and the PSZ exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively ( < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL /dose ratio (/) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution ( = 0.034*). The ERL / was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.

| INTRODUC TI ONCalcineurin inhibitors (CNI) are the backbone of immunosuppression in solid organ transplantation, but long-term exposure is often associated with nephrotoxicity. 1 Belatacept (BTC) (Nulojix ® ) is a highaffinity CTLA4Ig indicated for the prophylaxis of graft rejection in adults receiving a renal transplant in combination with mycophenolic acid (MPA) and corticosteroids. 2,3 The BENEFIT study demonstrated that BTC-based regimens were associated with a similar incidence of acute rejection but improved renal function compared to a cyclosporine-based regimen in renal transplant recipients. 4 The BENEFIT and BENEFIT-EXT studies showed that the risk of posttransplant

&lt;p&gt;&lt;strong&gt;Abstract.&lt;/strong&gt; Two three-year-long time series of hourly measurements of the fugacity of CO&lt;sub&gt;2&lt;/sub&gt; (fCO&lt;sub&gt;2&lt;/sub&gt;) in the upper 10&amp;#8201;m of the surface layer of the northwestern Mediterranean Sea have been recorded by CARIOCA sensors almost two decades apart, in 1995&amp;#8211;1997 and 2013&amp;#8211;2015. By combining them with alkalinity derived from measured temperature and salinity, we calculated changes of pH and dissolved inorganic carbon (DIC). DIC increased in surface seawater by ~&amp;#8201;25&amp;#8201;&amp;#956;mol&amp;#8201;kg&lt;sup&gt;&amp;#8722;1&lt;/sup&gt; and fCO&lt;sub&gt;2&lt;/sub&gt; by 40&amp;#8201;&amp;#956;atm, whereas seawater pH decreased by ~&amp;#8201;0.04 (0.0021&amp;#8201;yr&lt;sup&gt;&amp;#8722;1&lt;/sup&gt;). The DIC increase is larger than expected from equilibrium with atmospheric CO&lt;sub&gt;2&lt;/sub&gt;. This supports the hypothesis of a ~&amp;#8201;15&amp;#8201;% contribution of the Atlantic Ocean as a source of anthropogenic carbon to the Mediterranean Sea through the strait of Gibraltar. We estimate that the part of DIC accumulated over the last 18 years represents ~&amp;#8201;30&amp;#8201;% of the total change since the beginning of the industrial period.&lt;/p&gt;