The interplay between drugs and the kidney in premature neonates

The kidney plays a central role in the clearance of drugs. However, renal drug handling entails more than glomerular filtration and includes tubular excretion and reabsorption, and intracellular metabolization by cellular enzyme systems, such as the Cytochrome P450 isoenzymes. All these processes show maturation from birth onwards, which is one of the reasons why drug dosing in children is not simply similar to dosing in small adults. As kidney development normally finishes around the 36th week of gestation, being born prematurely will result in even more immature renal drug handling. Environmental effects, such as extra-uterine growth restriction, sepsis, asphyxia, or drug treatments like caffeine, aminoglycosides, or non-steroidal anti-inflammatory drugs, may further hamper drug handling in the kidney. Dosing in preterm neonates is therefore dependent on many factors that need to be taken into account. Drug treatment may significantly hamper postnatal kidney development in preterm neonates, just like renal immaturity has an impact on drug handling. The restricted kidney development results in a lower number of nephrons that may have several long-term sequelae, such as hypertension, albuminuria, and renal failure. This review focuses on the interplay between drugs and the kidney in premature neonates.     

Bone regeneration performance of surface-treated porous titanium

The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid–alkali (AcAl), alkali–acid–heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.     

Left ventricular assist device implants in patients on extracorporeal membrane oxygenation: do we need cardiopulmonary bypass?

Open in a separate window OBJECTIVESImplanting a durable left ventricular assist device (LVAD) in a patient on extracorporeal life support (ECLS) is challenging. The goal of this study was to compare the results of patients from a European registry who had a durable LVAD implanted with or without transition from ECLS to cardiopulmonary bypass (CPB).METHODSA total of 531 patients on ECLS support who had an LVAD implant between January 2010 and August 2018 were analysed; after 1:1 propensity score matching, we identified and compared 175 patients in each group.RESULTSThe duration of preoperative ECLS was 7 [standard deviation (SD) 6] vs 7 (SD 6) days in patients with or without CPB (P = 0.984). The surgical time was longer in the CPB group [285 (SD 72) vs 209 [SD 75] min; P ≤ 0.001). The postoperative chest tube output was comparable [1513 (SD 1311) vs 1390 (SD 1121) ml; P = 0.3]. However, re-exploration for bleeding was necessary in 41% vs 29% of patients with or without CPB (P = 0.01) and a significantly higher number of packed red blood cells and fresh frozen plasma [8 (SD 8) vs 6 (SD 4) units; P = 0.001 and 6 (SD 7) vs 5 (SD 5) units; P = 0.03] were administered to patients operated on with CPB. A postoperative mechanical right ventricular support device was necessary in 50% vs 41% of patients (P = 0.08). The stroke rate was not significantly different (P 0.99). No difference in survival was observed.CONCLUSIONSOmitting CPB for an LVAD implant in patients on ECLS is safe and results in shorter operating time, less re-exploration for bleeding and fewer blood products. However, no survival benefit is observed.