Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14–16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre‐ and post‐PIRRT. Ertapenem 500 mg followed by 500 mg post‐PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134122/1/jcph727.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134122/2/jcph727_am.pd

Bariatric surgery and kidney disease outcomes in severely obese youth: Bariatric surgery and kidney disease

Bariatric surgery, an emerging treatment for severely obese youth with and without T2D, provides marked improvement in insulin resistance, beta-cell function, and central adiposity. Further, preliminary data suggest that bariatric surgery also results in significant improvement in markers of obesity-related nephropathy and DKD, beyond that which can be achieved with current medical interventions. Yet, the mechanisms whereby bariatric surgery attenuates kidney disease remain unclear. This review summarizes the data on the effects of bariatric surgery on obesity-related nephropathy and DKD in youth with and without T2D, in addition to potential mechanisms underlying the nephroprotective effects of weight loss surgery and how these may differ in Roux-en-Y gastric bypass vs. vertical sleeve gastrectomy. Finally, we discuss potential future non-surgical therapies to mitigate kidney disease

Geschichtliche Angaben zu den Kriegsschul- und Militaircasino-Gebäuden in Metz, der frühern französischen Militairhochschul-Anlage, des einstigen 1222 gegründeten Benedictinerklosters St. Arnulf daselbst

GESCHICHTLICHE ANGABEN ZU DEN KRIEGSSCHUL- UND MILITAIRCASINO-GEBÄUDEN IN METZ, DER FRÜHERN FRANZÖSISCHEN MILITAIRHOCHSCHUL-ANLAGE, DES EINSTIGEN 1222 GEGRÜNDETEN BENEDICTINERKLOSTERS ST. ARNULF DASELBST Geschichtliche Angaben zu den Kriegsschul- und Militaircasino-Gebäuden in Metz, der frühern französischen Militairhochschul-Anlage, des einstigen 1222 gegründeten Benedictinerklosters St. Arnulf daselbst ([1]) Einband ( - ) Titelseite ([1]) Text ([3]) I. a) Erläuterung zum Kloster (Tafel 10) (7) II. Erläuterung zur Hochschule des Artillerie- und Geniecorps (Tafel 10) (7) III. Erläuterung zum Casino (Tafel 12) (8) Taf. 10. Die Abtei St. Arnulf bis zum Jahre 1794. (1rgef) Taf. 11. Hochschule der Artillerie und des Geniecorps (2rgef) Taf. 12. Allgemeines Militaircasino in Metz (3rgef) Taf. 13. Grundrisse des allgemeinen Militaircasino in Metz (4rgef

Graft survival of pediatric kidney transplant recipients selected for de novo steroid avoidance-a propensity score-matched study.

BackgroundSteroid-avoidance protocols have gained popularity in pediatric kidney transplant recipients at low immunologic risk. The long-term safety of steroid avoidance in children with immunologic risk factors remains unknown.MethodsPediatric kidney transplant recipients from 2004 to 2014 in the Organ Procurement and Transplantation Network database who received tacrolimus and mycophenolate immunosuppression were investigated. Propensity score matching was used to compare graft survival in 1624 children who received steroid avoidance with 1624 children who received steroid-based immunosuppression. The effect of steroid avoidance on graft failure among immunologic risk strata was estimated using Cox proportional hazards regression in this propensity score-matched cohort.ResultsIt was observed that 5-year graft survival was mildly improved in children receiving steroid avoidance (84.8% versus 81.2%, P = 0.03). This improvement in graft survival occurred in the first 2 years following transplant, when the hazard ratio (HR) for allograft failure in children receiving steroid avoidance was 0.62 [95% confidence interval (CI) 0.45-0.86]. In contrast, steroid avoidance was not associated with improved allograft survival during Years 2-10 following transplant (HR = 0.93; 95% CI 0.75-1.15). During this time period, HRs (95% CIs) for allograft failure within immunologic risk strata were not significantly different from the null value of 1: repeat kidney transplants, 1.84 (0.84-4.05); African-Americans, 1.02 (0.67-1.56); sensitized recipients, 1.24 (0.63-2.43); recipients of deceased donor kidneys, 1.02 (0.79-1.32); recipients of completely human leukocyte antigen-mismatched kidneys, 0.80 (0.47-1.37); and recipients with pretransplant glomerular disease, 0.94 (0.71-1.23).ConclusionsIn pediatric kidney transplant recipients receiving tacrolimus- and mycophenolate-based immunosuppression, steroid avoidance can be safely practiced in children with immunologic risk factors