To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

https://link.springer.com/content/pdf/10.1007%2Fs00134-017-4683-6.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

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The pathogenesis of rheumatoid arthritis.

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

Eukaryotic cells can initiate several distinct programmes of self-destruction, and the nature of the cell death process (non-inflammatory or proinflammatory) instructs responses of neighbouring cells, which in turn dictates important systemic physiological outcomes Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, heart attack or cancer, and is crucial for controlling microbial infections Pathogens have evolved mechanisms to inhibit pyroptosis, enhancing their ability to persist and cause disease Ultimately, there is a competition between host and pathogen to regulate pyroptosis, and the outcome dictates life or death of the host

/pdf/pyroptosis-host-cell-death-and-inflammation-4f2vauj8tx.pdf

Pyroptosis: host cell death and inflammation

Inactivation of unused alleles of human immunoglobulin light chain genes as a mechanism of self-preservation.

A receptor ligand system that can facilitate the unconditional killing of epithelial tumour cells by a subset of tumour infiltrating lymphocytes has been reported by a group at the Fred Hutchinson Cancer Research Centre, Seattle.1 

We have known for many years that a subset of γ/δ T cells is specifically associated with immune responses at epithelial surfaces. Whereas γ/δ T cells in the blood predominantly use the Vδ2 delta chain, recognising soluble non-peptide antigens, the intraepithelial γ/δ T cells use the alternative Vδ1. Until quite recently there was no known ligand for these cells. Earlier work by this group, which has previously been highlighted in Gut ,2 3 demonstrated that these Vδ1 bearing cells recognise the ligands MICA and the closely related MICB, molecules which are distantly related to MHC class I but do not present intracellular peptide antigens. MICA is expressed patchily in normal gut epithelium, possibly induced in response to cellular distress, but not by other normal epithelia. It was therefore hypothesised that γ/δ T cells using Vδ1 patrol the gut, lysing those epithelial cells expressing MICA/B as a consequence of antigenic or chemical …

/pdf/innate-immunity-to-carcinomas-2nkb4i7ss3.pdf

Innate immunity to carcinomas

In sepsis, impaired function and loss of antigen-presenting cells are observed in secondary lymphoid organs [1], the site where antigen-dependent B cell differentiation occurs in health. How these changes in sepsis affect B cell differentiation into memory B cells is at present undefined.

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Activation-associated death of memory b cells in peripheral circulation in adults with sepsis

Introduction This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling—a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. Methods and analysis In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. Ethics and dissemination This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions—and ultimately to assist with keeping congregate settings open that are essential for our social fabric. Trial registration number ClinicalTrials.gov (#NCT05145803).

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Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting

Jo Spencer

Papers

Inactivation of unused alleles of human immunoglobulin light chain genes as a mechanism of self-preservation.

Innate immunity to carcinomas

Activation-associated death of memory b cells in peripheral circulation in adults with sepsis

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting

Quantitative assessment of NFκB transcription factor activity.