Prevalence of questioning regarding life-sustaining treatment and time utilisation by forgoing treatment in Francophone PICUs

International audiencePURPOSE:Our goal is to assess the prevalence of questioning about the appropriateness of initiating or maintaining life-sustaining treatments (LST) in French-speaking paediatric intensive care units (PICUs) and to evaluate time utilisation related to decision-making processes (DMP).METHODS:18-month, multicentre, prospective, descriptive, observational study in 15 French-speaking PICUs.RESULTS:Among the 5,602 children admitted, 410 died (7.3%), including 175 after forgoing LST (42.7% of deaths). LST was questioned in 308 children (5.5%) with a prevalence of 13.3 per 100 patient-days. More than 30% of children survived despite the appropriateness of LST being questioned (23% despite a decision to forgo treatment). Median caregiver time spent on making and presenting the decisions was 11 h per child.CONCLUSIONS:In this study, on any given day in each 10-bed PICU, there was more than one child for whom a DMP was underway. Of children, 23% survived despite a decision to forgo LST being made, which underlines the need to elaborate a care plan for these children. Also, DMP represented a large amount of staff time that is undervalued but necessary to ensure optimal palliative practice in PICU

Normally and abnormally functioning left-sided porcine bioprosthetic valves after long-term implantation in patients: Distinct spectra of histologic and histochemical changes

This morphologic study (X-ray examination of gross specimens, histologic study and histochemical staining) compares two groups of explanted left-sided biopros-thetic valves: group 1,6 valves with normal cusp function and group II, 10 valves with significant dysfunction. Implantation periods ranged from 26 to 79 months. A computerized descriptive statistical method (principal component analysis) is used to analyze the qualitative results. Although qualitatively identical alterations are observed in both groups, the findings in the deep layers of the cusps of severe collagen breakdown, intensive fibrin penetration and various degrees of calcification are restricted to group II. Other findings of interest in both groups include amyloid deposits (four cases) and layering of fusiform host cells on the cusp surface (three cases).The computerized study shows that individuals of one clinical group are morphologically different from those of the other. Mechanical stress may contribute to surface alterations early after implantation, while further collagen breakdown and macrophagic activity result in deep penetration of plasma components and fibrin. Subsequent calcification is likely to be dystrophic rather than metabolic. Colonization of the cuspal surface by endothelial cells after long-term implantation of bioprosthetic valves expresses a new type of relation between host and bioprosthesis

Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?

INTRODUCTION: We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success. METHOD: Conducted in a tertiary paediatric intensive care unit at a university hospital, this prospective study included 54 children receiving mechanical ventilation (≥6 hours) who underwent 57 episodes of weaning. We calculated the indices proposed by the TF (spontaneous respiratory rate, paediatric rapid shallow breathing, rapid shallow breathing occlusion pressure [ROP] and maximal inspiratory pressure during an occlusion test [Pi(max)]) and weaning endurance indices (pressure-time index, tension-time index obtained from P(0.1 )[TTI(1)] and from airway pressure [TTI(2)]) during spontaneous breathing. Performances of each TF index and combinations of them were calculated, and the best single index and combination were identified. Weaning endurance parameters (TTI(1 )and TTI(2)) were calculated and the best index was determined using a logistic regression model. Regression coefficients were estimated using the maximum likelihood ratio (LR) method. Hosmer–Lemeshow test was used to estimate goodness-of-fit of the model. An equation was constructed to predict weaning success. Finally, we calculated the performances of combinations of best TF indices and best endurance index. RESULTS: The best single TF index was ROP, the best TF combination was represented by the expression (0.66 × ROP) + (0.34 × Pi(max)), and the best endurance index was the TTI(2), although their performance was poor. The best model resulting from the combination of these indices was defined by the following expression: (0.6 × ROP) – (0.1 × Pi(max)) + (0.5 × TTI(2)). This integrated index was a good weaning predictor (P < 0.01), with a LR(+ )of 6.4 and LR(+)/LR(- )ratio of 12.5. However, at a threshold value <1.3 it was only predictive of weaning success (LR(- )= 0.5). CONCLUSION: The proposed combined index, incorporating endurance, was of modest value in predicting weaning outcome. This is the first report of the value of endurance parameters in predicting weaning success in children. Currently, clinical judgement associated with spontaneous breathing trials apparently remain superior

Refining the Pediatric Multiple Organ Dysfunction Syndrome

Since its introduction into the medical literature in the 1970s, the term multiple organ dysfunction syndrome (or some variant) has been applied broadly to any patient with >1 concurrent organ dysfunction. However, the epidemiology, mechanisms, time course, and outcomes among children with multiple organ dysfunction vary substantially. We posit that the term pediatric multiple organ dysfunction syndrome (or MODS) should be reserved for patients with a systemic pathologic state resulting from a common mechanism (or mechanisms) that affects numerous organ systems simultaneously. In contrast, children in whom organ injuries are attributable to distinct mechanisms should be considered to have additive organ system dysfunctions but not the syndrome of MODS. Although such differentiation may not always be possible with current scientific knowledge, we make the case for how attempts to differentiate multiple organ dysfunction from other states of additive organ dysfunctions can help to evolve clinical and research priorities in diagnosis, monitoring, and therapy from largely organ-specific to more holistic strategies

Synthesis of new para-aminobenzoic acid derivatives, in vitro biological evaluation and preclinical validation of DAB-2-28 as a therapeutic option for the treatment of bladder cancer

Chronic inflammation plays a crucial role in bladder cancer (BCa) development and progression. To offer a unique treatment opportunity for this type of cancer, a hydrazide derivative namely, DAB-1, was recently identified in our laboratory as a potential drug to target cancer-related inflammation. In preclinical models of murine BCa, this particular compound exhibited remarkable anticancer activities. Structurally, DAB-1 is made from para-aminobenzoic acid and bears two different components, a maleimide and a hydrazide moieties, which are critical for its anti-inflammatory activity and its anticancer properties. In order to improve its biological potential, the hydrazide moiety was further modified to provide 3 ​s-generation molecules named, DAB-2-28, DAB-2-31A, and DAB-2-31B, and two third-generation molecules named, DAB-3-27 and DAB-3-33. Data from in vitro studies revealed that, among the different DAB molecules under study, DAB-2-28 has less cytotoxic activity with greater efficiency than DAB-1 to inhibit the production of nitric oxide (NO) induced by the combination of IFNγ with TNFα, as well as the activation of pro-tumoral and pro-inflammatory signaling pathways IL6/STAT3 and TNFα/NFκB. Moreover, while DAB-2-28 exhibited similar anti-inflammatory activity in vivo to DAB-1 in a model of carrageenan-induced acute inflammation, it efficiently inhibited the expression of the enzymes iNOS and COX-2 induced by the combined activation of IFNγ with LPS in peritoneal macrophages. Notably, analysis of the growth kinetics of MB49-I tumors implanted subcutaneously in C57Bl/6 mice showed that DAB-2-28 was more efficient to inhibit tumor development. In conclusion, this study provided preclinical proof-of-principle for DAB-2-28 molecule in the treatment of BCa.Fil: Oufqir, Yassine. Université du Québec a Montreal; CanadáFil: Fortin, Laurie. Université du Québec a Montreal; CanadáFil: Girouard, Julie. Université du Québec a Montreal; CanadáFil: Cloutier, Francis. Université du Québec a Montreal; CanadáFil: Cloutier, Maude. Université du Québec a Montreal; CanadáFil: Leclerc, Marie France. Université du Québec a Montreal; CanadáFil: Belgorosky, Denise. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bérubé, Gervais. Université du Québec a Montreal; CanadáFil: Reyes-Moreno, Carlos. Université du Québec a Montreal; Canad

Scoring Systems for Organ Dysfunction and Multiple Organ Dysfunction: The PODIUM Consensus Conference

CONTEXT Multiple scores exist to characterize organ dysfunction in children. OBJECTIVE To review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020. STUDY SELECTION Studies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. DATA EXTRACTION Data were abstracted into a standard data extraction form by a task force member. RESULTS Of 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially. LIMITATIONS While scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely. CONCLUSIONS The multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children

Enhance quality care performance: Determination of the variables for establishing a common database in French paediatric critical care units

Abstract Selected variables for the French Paediatric Intensive Care registry. Rationale, aims, and objectives Providing quality care requires follow-up in regard to clinical and economic activities. Over the past decade, medical databases and patient registries have expanded considerably, particularly in paediatric critical care medicine (eg, the Paediatric Intensive Care Audit Network (PICANet) in the UK, the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry in Australia and New Zealand, and the Virtual Paediatric Intensive Care Unit Performance System (VPS) in the USA). Such a registry is not yet available in France. The aim of this study was to determine variables that ought to be included in a French paediatric critical care registry. Methods Variables, items, and subitems from 3 foreign registries and 2 French local databases were used. Items described each variable, and subitems described items. The Delphi method was used to evaluate and rate 65 variables, 90 items, and 17 subitems taking into account importance or relevance based on input from 28 French physicians affiliated with the French Paediatric Critical Care Group. Two ratings were used between January and May 2013. Results Fifteen files from 10 paediatric intensive care units were included. Out of 65 potential variables, 48 (74%) were considered to be indispensable, 16 (25%) were considered to be optional, and 1 (2%) was considered to be irrelevant. Out of 90 potential items, 62 (69%) were considered to be relevant, 23 (26%) were considered to be of little relevance, and 5 (6%) were considered to be irrelevant. Out of 17 potential subitems, 9 (53%) were considered to be relevant, 6 (35%) were considered to be of little relevance, and 2 (12%) were considered to be irrelevant. Conclusions The necessary variables that ought to be included in a French paediatric critical care registry were identified. The challenge now is to develop the French registry for paediatric intensive care units

High Cyclin E Staining Index in Blastemal, Stromal or Epithelial Cells Is Correlated with Tumor Aggressiveness in Patients with Nephroblastoma

PURPOSE: Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies. METHODOLOGY/PRINCIPAL FINDINGS: A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.5% in epithelial cells. The highest values were found for anaplastic nephroblastoma. A correlation between cyclin E and Ki-67 SI was found for the blastemal component and for the epithelial component. Univariate analysis showed prognostic significance for metastases with cyclin E SI in stromal cells, epithelial cells and blastemal cells (p = 0.03, p = 0.01 and p = 0.002, respectively) as well as with Ki-67 SI in blastema (p<10(-4)). The most striking data were that both cyclin E SI and blastemal Ki-67 SI discriminated between patients with metastases and patients without metastasis among intermediate-risk nephroblastoma. CONCLUSIONS: Our findings show that a high cyclin E SI in all components of nephroblastoma is correlated with tumor aggressiveness and metastases, and that assessment of its expression may have prognostic value in the categorization of nephroblastoma