The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies.

BACKGROUND: Early-onset pneumonia (EOP) after out-of-hospital cardiac arrest is frequently observed. Causative factors are loss of airway protection during cardiac arrest, pulmonary contusion, and emergency airway management. We assessed the incidence, risk factors, and clinical course of EOP, and evaluated the impact of an early exchange of the prehospitally inserted endotracheal tube (ETT). METHODS: In our retrospective analysis we included 104 consecutive subjects admitted to our ICU after out-of-hospital cardiac arrest between 2007 and 2012. All subjects underwent therapeutic hypothermia. We analyzed clinical course, inflammation indicators, Clinical Pulmonary Infection Score, occurrence of EOP, duration of ventilatory support, microbiological findings, and short-term outcome. RESULTS: Of the 104 subjects, 46.2% received an exchange of ETT directly after hospital admission. Neither ETT exchange nor observed aspiration were associated with elevated CPIS or EOP, nor with proof of microorganisms in respiratory secretions. We found no differences in duration of ventilatory support, P aO 2 /F IO 2 , ICU days, or outcome. C-reactive protein was significantly higher in subjects with aspiration (P ‫؍‬ .046). Sex, age, smoking status, aspiration, cause of cardiac arrest, first detected heart rhythm, and use of supraglottic airways devices were not associated with EOP. Subjects with EOP had a longer need for ventilatory support (P ‫؍‬ .005), higher tracheotomy rate (P ‫؍‬ .03), longer ICU stay (P ‫؍‬ .005), higher C-reactive protein (P < .001), higher body temperature (P ‫؍‬ .003), higher Clinical Pulmonary Infection Score (P < .001), and lower P aO 2 /F IO 2 (P ‫؍‬ .008). CONCLUSIONS: The rate of EOP was not significantly influenced by the exchange of the preclinically inserted ETT, but was associated with longer need for mechanical ventilation and ICU stay.

Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.

In this single-center study, several important covariates were associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock who were supported by venoarterial extracorporeal membrane oxygenation and the ENCOURAGE score was found to be externally valid for predicting survival to hospital discharge.

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