These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologic agents.

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce.Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing.Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance.Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation.Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.

Background: Most clinical trials of sepsis treatment modalities fail at their primary objective of establishing superiority over placebo when added to background standard of care. While there is no definitive explanation for the high failure rate, it might be stated that our attempts to insert a new therapeutic agent into standard of care encounters severe problems with definition of exactly what stage is ongoing, and what are the criteria for progression or resolution from that time point onwards. Clearly there is need for a means of defining steps in the septic process that would apply to individuals, and to better define the course of sepsis in each patient after they are enrolled in a trial. Methods: For core model development, 30 septic patients were studied for time-related progression in relation to biomarkers, employing a Load Model in a neural net algorithm in MatLab. Causative bacterial infections were linked to primary infection sites. In order to minimize overparameterization, the model was allowed to estimate outputs using the best three input parameters. Bacterial load was tracked from origin using clinical and microbiologic data to provide an estimate at the start of sepsis. The bacterial load as well as clinical and laboratory parameters were model inputs with the output parameter being organ failures and/ or mortality. Results: At onset of sepsis, human bacterial load estimates ranged from between 10 8 and 10 11 CFU, which is consistent with inocula in animal models of sepsis. Sepsis proceeds to organ failures and mortality in a series of steps that are initially linked to bacterial load and inflammatory response, followed by coagulopathy, ischemia, oxygen deprivation in organs and tissues, and culminating in organ failures. The later stages of sepsis are all driven by metabolic parameters, and there seems to be little benefit to blocking inflammation at later stages. Substrate and oxygen deficiencies must be addressed first. Conclusion: Neural net progression models based on biomarkers and physiological markers are able to describe the evolution of sepsis to septic shock, organ failures, and provide some evidence that mortality may be a consequence of the stages of sepsis. Overall, these models appear useful to the task of sorting out organ failure endpoints and mechanisms in individual patients with sepsis progression across sepsis to septic shock. P2Extracellular matrix turnover, angiogenesis and endothelial function in acute lung injury: relationship to pulmonary dysfunction and outcome S Sayed * , N Idriss, H Sayyed Faculty of Medicine, Assuit University, Assuit, Egypt E-mail: 1@bmc.com Critical Care 2012, 16(Suppl 3):P2 Background: Acute lung injury (ALI) is a syndrome with a diagnostic criteria based on hypoxemia and a classical radiological appearance, with acute respiratory distress syndrome at the severe end of the disease. Facts recommended the occurrence of rupture of the basement membranes and interstitial matrix remodeling during ALI. Matrix metalloproteinases (MMPs) participate in...

BackgroundThe publication of Swiss guidelines for the care of infants at the limit of viability (22-25 completed weeks) was followed by increased survival rates in the more mature infants (25 completed weeks). At the same time, considerable centre-to-centre (CTC) differences were noted. Objectives To examine the trend of survival rates of borderline viable infants over a 10-year-period and to further explore CTC differences. Design Population-based, retrospective cohort study.