Background In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). MethodsWe did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). Findings 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0•85-1•22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 μg/L to 757 μg/L), whereas the lymphocyte count increased to more than 1•0 × 10⁹ cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died.Interpretation During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown.Funding None.

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, “in our practice” statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, “in our practice” statements were provided. In addition, 49 research priorities were identified. Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

Whether regulating mutual funds or chemical manufacturers, government's policy decisions depend on information possessed by industry. But it is not in any industry's interests to share information that will lead to costly regulations. So how do government regulators secure needed information from industry? Since information disclosed by any firm cannot be retrieved and can be used to regulate the entire sector, industry faces a collective action problem in maintaining silence. While collective silence is easy to maintain if all firms' interests are aligned, their payoffs for disclosure can vary due to heterogeneous effects of regulation and heterogeneous beliefs about the regulator's expected actions with or without any given information. The regulator's strategy is therefore to resist or break down industry's collective silence, either by (1) exploiting asymmetries in firms' interests in disclosure, or (2) selectively rewarding or punishing individual firms to create incentives for disclosure. Both of these strategies work best when pursued informally, in less visible ways, since other firms can be expected to inflict retribution on any squealer. Although informal relationships have been long deplored due to the risk of regulatory bias or capture, our analysis shows how they can be beneficial to government in playing the information game. This has important implications for regulatory procedure. Since total transparency would detract from government's ability to secure valuable information, administrative law needs to balance between the competing needs of transparency to prevent abuse and opacity to facilitate information exchange. Securing Truth for Power: Informational Strategy and Regulatory Policy Making "The … power that is involved here is the power to get information from those who best can give it and who are most interested in not doing so."

Earlier, better prediction of severe AKI has the potential to improve AKI associated patient outcomes. Compared to isolated, context-free changes in SCr, renal angina risk assessment improved accuracy for prediction of severe AKI in critically ill children and young adults.

Objectives: In children, coronavirus disease 2019 is usually mild but can develop severe hypoxemic failure or a severe multisystem inflammatory syndrome, the latter considered to be a postinfectious syndrome, with cardiac involvement alone or together with a toxic shock like-presentation. Given the novelty of severe acute respiratory syndrome coronavirus 2, the causative agent of the recent coronavirus disease 2019 pandemic, little is known about the pathophysiology and phenotypic expressions of this new infectious disease nor the optimal treatment approach. Study Selection: From inception to July 10, 2020, repeated PubMed and open Web searches have been done by the scientific section collaborative group members of the European Society of Pediatric and Neonatal Intensive Care. Data Extraction: There is little in the way of clinical research in children affected by coronavirus disease 2019, apart from descriptive data and epidemiology. Data Synthesis: Even though basic treatment and organ support considerations seem not to differ much from other critical illness, such as pediatric septic shock and multiple organ failure, seen in PICUs, some specific issues must be considered when caring for children with severe coronavirus disease 2019 disease. Conclusions: In this clinical guidance article, we review the current clinical knowledge of coronavirus disease 2019 disease in critically ill children and discuss some specific treatment concepts based mainly on expert opinion based on limited experience and the lack of any completed controlled trials in children at this time.

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Definition and epidemiology of SA-AKI Definition of SA-AKI and sepsis-induced AKICurrently, no universally accepted definition of SA-AKI exists 15 . To support clinical guidelines, quality improvement initiatives, and future research, we propose that the presence of both sepsis (as currently defined in adults by the Sepsis-3 criteria) and AKI (as presently defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria) should define SA-AKI 1,16 (Box 1). SA-AKI is a heterogeneous syndrome that occurs as the consequence of either direct mechanisms related to infection or the host response to infection, or indirect mechanisms driven by unwanted sequelae of sepsis or sepsis therapies 17 . As such, the term SA-AKI operationally unifies the presence of AKI (according to clinical, biochemical and functional criteria) in the context of sepsis as a specific disease phenotype that is characterized by a specific trajectory and outcome 18,19 .Sepsis-induced AKI (SI-AKI) can be considered to be a subphenotype of SA-AKI, in which sepsis-induced mechanisms drive kidney damage directly. Thus, by definition, SI-AKI excludes injury that primarily develops as the indirect consequence of sepsis or sepsis therapies (for example, AKI caused by antimicrobial agent-induced nephrotoxicity or abdominal compartment syndrome) 20,21 . Importantly, mechanisms that underlie cellular and organ injury in ischaemic AKI or nephrotoxic AKI, such as microcirculation failure, inflammation and mitochondrial injury, might also contribute to SI-AKI. The limited availability of clinical tools such as biomarkers that can aid early identification complicate Many aspects of SA-AKI rema...

Continuous renal replacement therapy can be used successfully in critically ill children with pediatric acute liver failure to provide stability and bridge to transplantation. Inability to reduce ammonia by 48 hours confers poor prognosis. Continuous renal replacement therapy should be considered at an early stage to help prevent further deterioration and buy time for potential spontaneous recovery or bridge to liver transplantation.