Continuously infused amphotericin B deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia.

Continuous administration of amphotericin B deoxycholate over 24 hours (24 h-D-AmB) is better tolerated than rapid infusions. However, toxicity and outcome have not been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h-D-AmB to a patient group without exposure to 24 h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h-D-AmB, and 48 (26.5%) did not. Reasons for 24 h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for febrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. Amphotericin B deoxycholate over 24 hours was given for a median 7 days (interquartile range 3-13). Peak creatinine concentration was higher in the 24 h-D-AmB-group (104.5 vs. 76 µmol/L, P < .001) but normalized within 1 month after therapy (65.5 vs. 65 µmol/L, P = .979). In neither of the 2 groups, end-stage renal disease occurred. There was no difference in 60-day survival (90% vs. 90%) and 2-year survival (58% vs. 58%). Invasive fungal disease partial response or better was observed in 68% of the patients. We conclude that antifungal therapy with continuously infused amphotericin B deoxycholate is safe in patients with AML. An antiinfective strategy based on 24 h-D-AmB in first line followed by an oral triazole compound represents an economically attractive treatment option.

Total Muscle Area and Visceral Adipose Tissue Measurements for Frailty Assessment in TAVR Patients.

Background: Transcatheter aortic valve replacement (TAVR) is a treatment option for severe aortic valve stenosis. Pre-TAVR assessments, extending beyond anatomy, include evaluating frailty. Potential frailty parameters in pre-TAVR computed tomography (CT) scans are not fully explored but could contribute to a comprehensive frailty assessment. The primary objective was to investigate the impact of total muscle area (TMA) and visceral adipose tissue (VAT) as frailty parameters on 5-year all-cause mortality in patients undergoing TAVR. Methods: Between 01/2017 and 12/2018, consecutive TAVR patients undergoing CT scans enabling TMA and VAT measurements were included. Results: A total of 500 patients qualified for combined TMA and VAT analysis. Age was not associated with a higher risk of 5-year mortality (HR 1.02, 95% CI: 0.998-1.049; p = 0.069). Body surface area normalized TMA (nTMA) was significantly associated with 5-year, all-cause mortality (HR 0.927, 95% CI: 0.927-0.997; p = 0.033), while VAT had no effect (HR 1.002, 95% CI: 0.99-1.015; p = 0.7). The effect of nTMA on 5-year, all-cause mortality was gender dependent: the protective effect of higher nTMA was found in male patients (pinteraction: sex × nTMA = 0.007). Conclusions: Normalized total muscle area derived from a routine CT scan before transcatheter aortic valve replacement complements frailty assessment in patients undergoing TAVR.