Objectives: Describe pediatric palliative care consult in children with heart disease; retrospectively apply Center to Advance Palliative Care criteria for pediatric palliative care consults; determine the impact of pediatric palliative care on end of life. Design: A retrospective single-center study. Setting: A 16-bed cardiac ICU in a university-affiliated tertiary care children’s hospital. Patients: Children (0–21 yr old) with heart disease admitted to the cardiac ICU from January 2014 to June 2017. Measurements and Main Results: Over 1,000 patients (n = 1, 389) were admitted to the cardiac ICU with 112 (8%) receiving a pediatric palliative care consultation. Patients who received a consult were different from those who did not. Patients who received pediatric palliative care were younger at first hospital admission (median 63 vs 239 d; p = 0.003), had a higher median number of complex chronic conditions at the end of first hospitalization (3 vs 1; p < 0.001), longer cumulative length of stay in the cardiac ICU (11 vs 2 d; p < 0.001) and hospital (60 vs 7 d; p < 0.001), and higher mortality rates (38% vs 3%; p < 0.001). When comparing location and modes of death, patients who received pediatric palliative care were more likely to die at home (24% vs 2%; p = 0.02) and had more comfort care at the end of life (36% vs 2%; p = 0.002) compared to those who did not. The Center to Advance Palliative Care guidelines identified 158 patients who were eligible for pediatric palliative care consultation; however, only 30 patients (19%) in our sample received a consult. Conclusions: Pediatric palliative care consult rarely occurred in the cardiac ICU. Patients who received a consult were medically complex and experienced high mortality. Comfort care at the end of life and death at home was more common when pediatric palliative care was consulted. Missed referrals were apparent when Center to Advance Palliative Care criteria were retrospectively applied.

Recent work reveals that the innate immune system is able to recognize self targets and initiate an inflammatory response similar to that of pathogens. One novel example of this innate autoimmunity is ischemia/reperfusion (I/R) injury, in which reperfusion of the ischemic tissues elicits an acute inflammatory response activated by natural IgM (nIgM) binding to ischemia-specific self antigens, which are non-muscle myosin heavy chains type II (NMHC-II) subtype A and C. Subsequently, the complement lectin pathway is activated and eventually tissue injury occurs. Although earlier studies in the intestinal model showed that the classical complement pathway did not initiate I/R injury, C1q deposition was still observed in the local injured tissues by imaging analysis. Moreover, the involvement of the alternative complement pathway became unclear due to conflicting reports using different knockout mice. To explore the immediate downstream pathway following nIgM-ischemic antigen interaction, we isolated the nIgM-ischemic antigen immunocomplexes from the local tissue of animals treated in the intestinal I/R injury model, and examined the presence of initial molecules of three complement pathways. Our results showed that mannan-binding lectin (MBL), the early molecule of the lectin pathway, was present in the nIgM-ischemic Ag immunocomplex. In addition, C1q, the initial molecule of the classical pathway was also detected on the immunocomplex. However, Factor B, the early molecule in the alternative pathway, was not detected in the immunocomplex. To further examine the role of the alternative pathway in I/R injury, we utilized Factor B knockout mice in the intestinal model. Our results showed that Factor B knockout mice were not protected from local tissue injury, and their complement system was activated in the local tissues by nIgM during I/R. These results indicated that the lectin complement pathway operates immediately downstream of the nIgM-ischemic antigen interaction during intestinal I/R. Furthermore, the classical complement pathway also appears to interact with the of nIgM-ischemic antigen immunocomplex. Finally, the alternative complement pathway is not involved in I/R injury induction in the current intestinal model.

Objective: Retrospectively apply criteria from Center to Advance Palliative Care to a cohort of children treated in a cardiac ICU and compare children who received a palliative care consultation to those who were eligible for but did not receive one. Methods: Medical records of children admitted to a cardiac ICU between January 2014 and June 2017 were reviewed. Selected criteria include cardiac ICU length of stay >14 days and/or ≥ 3 hospitalisations within a 6-month period. Measurements and Results: A consultation occurred in 17% (n = 48) of 288 eligible children. Children who received a consult had longer cardiac ICU (27 days versus 17 days; p < 0.001) and hospital (91 days versus 35 days; p < 0.001) lengths of stay, more complex chronic conditions at the end of first hospitalisation (3 versus1; p < 0.001) and the end of the study (4 vs.2; p < 0.001), and higher mortality (42% versus 7%; p < 0.001) when compared with the non-consulted group. Of the 142 pre-natally diagnosed children, only one received a pre-natal consult and 23 received it post-natally. Children who received a consultation (n = 48) were almost 2 months of age at the time of the consult. Conclusions: Less than a quarter of eligible children received a consultation. The consultation usually occurred in the context of medical complexity, high risk of mortality, and at an older age, suggesting potential opportunities for more and earlier paediatric palliative care involvement in the cardiac ICU. Screening criteria to identify patients for a consultation may increase the use of palliative care services in the cardiac ICU.

BackgroundMost clinical and natural microbial communities live and evolve in spatially structured environments. When changes in environmental conditions trigger evolutionary responses, spatial structure can impact the types of adaptive response and the extent to which they spread. In particular, localized competition in a spatial landscape can lead to the emergence of a larger number of different adaptive trajectories than would be found in well-mixed populations. Our goal was to determine how two levels of spatial structure affect genomic diversity in a population and how this diversity is manifested spatially.Methodology/Principal FindingsWe serially transferred bacteriophage populations growing at high temperatures (40°C) on agar plates for 550 generations at two levels of spatial structure. The level of spatial structure was determined by whether the physical locations of the phage subsamples were preserved or disrupted at each passage to fresh bacterial host populations. When spatial structure of the phage populations was preserved, there was significantly greater diversity on a global scale with restricted and patchy distribution. When spatial structure was disrupted with passaging to fresh hosts, beneficial mutants were spread across the entire plate. This resulted in reduced diversity, possibly due to clonal interference as the most fit mutants entered into competition on a global scale. Almost all substitutions present at the end of the adaptation in the populations with disrupted spatial structure were also present in the populations with structure preserved.Conclusions/SignificanceOur results are consistent with the patchy nature of the spread of adaptive mutants in a spatial landscape. Spatial structure enhances diversity and slows fixation of beneficial mutants. This added diversity could be beneficial in fluctuating environments. We also connect observed substitutions and their effects on fitness to aspects of phage biology, and we provide evidence that some substitutions exclude each other.

Patients with severe, COVID-related multi-organ failure often require extracorporeal life support (ECLS) such as extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT). An ECLS can alter drug exposure via multiple mechanisms. Remdesivir (RDV) and its active metabolite GS-441524 are likely to interact with ECLS circuits, resulting in lower than expected exposures. We evaluated circuit-drug interactions in closed loop, ex vivo ECMO and CRRT circuits. We found that mean (standard deviation) recovery of RDV at 6 hours after dosing was low in both the ECMO (33.3% [2.0]) and CRRT (3.5% [0.4]) circuits. This drug loss appears to be due primarily to drug adsorption by the circuit materials and potentially due to metabolism in the blood. GS-441524 recovery at 6 hours was high in the ECMO circuit 75.8% (16.5); however, was not detectable at 6 hours in the CRRT circuit. Loss in the CRRT circuit appears to be due primarily to efficient hemodiafiltration. The extent of loss for both molecules, especially in CRRT, suggests that in patients supported with ECMO and CRRT, RDV dosing adjustments are needed.