# ent

id: cord-006414-60lpjg09
type: DNA
entity:
  anti inflammatory drug HLA DR Expression auf Monozyten bei Peritonitis und Sepsis Möglichkeiten eines


id: cord-001293-dfaxj3bv
type: GGP
entity:
  Transforming growth factor beta Th T helper TLR Toll like receptor TNF Tumor necrosis factor T reg Regulatory T lymphocyte


id: cord-006426-baf2d47y
type: DNA
entity:
  IPAF infl ammasome 38 39 40 Table 1 Gram positive bacteria such as L monocytogenes S aureus and Gramnegative Aeromonas hydrophila activate


id: cord-006426-baf2d47y
type: PROTEIN
entity:
  P1 receptors HMGB1 high mobility group box 1 HSPs heat shock proteins IRAK IL 1 receptor associated kinase TRAF6 tumor necrosis factor receptor associated factor 6 NF κB nuclear factor κB Rip2 receptor interacting protein 2


id: cord-006426-baf2d47y
type: PROTEIN
entity:
  protein CARD caspase recruitment domain IPAF interleukin 1 converting enzyme ICE proteaseactivating factor LRR leucine rich repeat NACHT domain


id: cord-015946-biu5zxd1
type: PROTEIN
entity:
  plasma C reactive protein procalcitonin neutrophils macrophage migration inhibitory factor soluble urokinase type plasminogen activator receptor


id: cord-017470-sjk7a34u
type: CELL_LINE
entity:
  anti inflammatory Th 2 cell type profile 3 Immune system dysregulation 4 Mitochondrial dysfunction Although the above mechanisms can interact in a variety of ways and combinations immune system dysregulation and mitochondrial dysfunction seem to play a prevalent role As detailed above the immune system dysregulation is the imbalance between pro inflammatory


id: cord-005569-9d51l6bn
type: WORK_OF_ART
entity:
  The Neuro Intensive Care and Emergency Medicine NICEM Section of the European Society of Intensive Care Medicine ESICM


id: cord-005872-w1x1i0im
type: PROTEIN
entity:
  vascular endothelial cadherin complex platelet endothelial cell adhesion molecule 1 occludin zona occludens 1


id: cord-005872-w1x1i0im
type: PROTEIN
entity:
  Neisseria meningitidis and Neisseria gonorrhoeae Human microvascular endothelial tissue culture cell model


id: cord-005872-w1x1i0im
type: CL
entity:
  vascular endothelium Endothelial barrier resistance in multiple organs after septic and nonseptic challenges in the rat N acetylcysteine


id: cord-018840-ts2g1ux7
type: ORG
entity:
  The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group


id: cord-312197-d5d8amk7
type: DISEASE
entity:
  Treponema pallidum rubella virus herpes simplex virus cytomegalovirus toxoplasmosis Clostridium tetani HIV hepatitis B


id: cord-015082-l629n8is
type: DNA
entity:
  J 1 1 PICU Great Ormond Street Hospital London United Kingdom 2 PICU Royal Children s Hospital Melbourne Australia There


id: cord-015082-l629n8is
type: PRODUCT
entity:
  Iasonidou C 1 Pertsas E 1 Koletsos K 1 Kapravelos N 1 Tsagalof S 1 Riggos D 1 1 ICU G Papanikolaou Thessaloniki Greece Optimizing


id: cord-015082-l629n8is
type: WORK_OF_ART
entity:
  De Waele J J H C 1 Hoste E 1 Blot S 1 Colardyn F 1 1 ICU Ghent University Hospital Gent Belgium INTRODUCTION


id: cord-103081-k7ev5qkn
type: GGP
entity:
  Macrophage A and Macrophage B Mϕ A Mϕ B Both of 98 these clusters expressed classical macrophage markers


id: cord-103081-k7ev5qkn
type: WORK_OF_ART
entity:
  RNA Sequencing of Adult Kidney Rare Cell Types and Novel Cell States Revealed in Fibrosis Representation


id: cord-103081-k7ev5qkn
type: LAW
entity:
  Comprehensive Integration of Single Cell Data A Transcriptional Map of the Renal Tubule Linking Structure to Function Single Cell Transcriptomics


id: cord-252859-zir02q69
type: DNA
entity:
  genes 1 2 3 4 5 6 7 8 9 10 20 30 40 50 60 70 80 90 100 150 200 250 300 350 400 450 500 600 700 800 900 1000 2000 5000 and 10000


id: cord-302295-nblmshni
type: TAXON
entity:
  virus encephalomyocarditis virus poliovirus coxsackievirus murine cytomegalovirus herpes simplex virus


id: cord-302295-nblmshni
type: WORK_OF_ART
entity:
  Targeting Toll Like Receptors Promising Therapeutic Strategies for the Management of Sepsis Associated Pathology and Infectious Diseases


id: cord-302295-nblmshni
type: DISEASE
entity:
  HBV HIV influenza virus Herpes simplex virus Epstein Barr virus vesicular stomatitis virus papilloma virus respiratory syncytial virus and Sendai virus


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Reaktionen zu Nahrungsmittelintoleranzen und Bakterientoxinerkrankungen schwierig Nahrungsmittelallergien bestehen bei etwa 1 6


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Studie mit einer Inzidenz von 1 4500 1 6000 Allgemeinanästhesien auf In ca 6 der Fälle kam es trotz adäquater Therapie zum Tod


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  eine adäquate Gewebeperfusion ein normales Herzzeitvolumen und ein normaler Blutdruck sind dafür noch nicht ausreichend Die regionale Durchblutung auf Mikrozirkulationsebene wird durch lokale


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  zur Bildung freier Sauerstoffradikale Wasserstoffperoxid Superoxidradikal Hydroxylradikal die durch Lipidperoxidation


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Patienten mit unklarer Schockätiologie oder mit einer sich nach Volumensubstitution nicht rasch stabilisierenden


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  einer Dosis von 1 0 1 5 mg kgKG i v kann Lidocain bei Kammerfl immern pulsloser Kammertachykardie nach erfolgloser Defi


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Hypothermie mit Temperaturen zwischen 32 und 34 C eine Verbesserung des Überlebens und der neurologischen Funktion erreicht werden kann Bernard et al 2002 Group ThaCaS 2003 aufgrund der guten Ergebnisse ist


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Evidenzbasierte Empfehlungen zur Beatmung des Schockpatienten speziell des Patienten mit kardiogenem


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  einem Hämatokritwert von 30 liegt eine maximale O 2 Transportkapazität ohne Gefahr einer Gewebehypoxie vor Während


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  ist eine multifaktorielle MODS Genese unter Beteiligung der aufgeführten Mechanismen Die Komplexität des MODS macht


id: cord-020643-0yzkqykg
type: DNA
entity:
  humanes Serumalbumin bindet während eines Hämoadsorptionzyklus Endotoxin und bewirkt auf diese Weise einen deutlichen Abfall der Serumendotoxinkonzentration In einer Phase II Studie mit 145 Patienten mit vermuteter gramnegativer Sepsis davon 104 mit Peritonitis führte


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  ist durch eine Schwäche der Extremitäten Hyporefl exie verzögerte Respiratorentwöhnung und durch eine komplikationsreiche verlängerte motorische Rehabilitiation mit erhöhter Letalität gekennzeichnet Muskelrelaxanzien und Kortikosteroide können zusätzliche schädigende Effekte


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Sepsispatienten mit mindestens 2 Organversagen ausgerichtet Der gestörte Stoffwechsel bei Patienten mit MODS Schock und Sepsis


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  einer Komplexbildung mit aktiviertem Glukokortikoid Rezeptorelementen führt Da die Glukokortikoid Rezeptorzahl


id: cord-020643-0yzkqykg
type: PROTEIN
entity:
  Abb 6 22 7 Abschn 6 1 5 zur Pathophysiologie 7 Abschn 6 2 3 zur Basisdiagnostik 7 Abschn 6 3 2 und Basistherapie 7 Abschn 6 4 und zum MODS 7 Abschn 6 5 Die


id: cord-020643-0yzkqykg
type: GGP
entity:
  NOS II wurde zuerst in Makrophagen gefunden sie kommt jedoch in vielen Zelltypen vor Ihre Induktion durch zahlreiche Triggersubstanzen Tabelle 6 8 dauert einige Stunden das Enzymmolekül ist relativ


id: cord-020643-0yzkqykg
type: GGP
entity:
  Schmerz 3 Beugemechanismen 2 Streckmechanismen 1 keine verbale Antwort 5 orientiert 4 verwirrt 3 inadäquat 2 unverständlich 1 keine rameter


id: cord-020643-0yzkqykg
type: GGP
entity:
  Patienten im protrahierten kardiogenen Schock aufgezeigt werden Thiele et al 2001 ebenso wie für das Impella System Ferrari u Figulla 2005 Komplexere ventrikuläre Unterstützungssysteme wie z B das linksventrikuläre System Novacor oder biventrikuläre künstliche Herzen dienen für terminal herzinsuffi ziente Patienten zur Überbrückung


id: cord-020643-0yzkqykg
type: WORK_OF_ART
entity:
  the Outcome of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure OPTIME CHF Investigators Short


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  6 4 9 Neue Therapieansätze zur Schockbehandlung 383 6 4 10 Gerinnungsaktive Substanzen 383 6 4 11 Hypothermie Cooling 384 6 4 12


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  sind IgE unabhängige Unverträglichkeitsreaktionen ohne vorausgehende Sensibilisierung mit einem sehr


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Defekt des Immunsystems 1 500 700 im Rahmen von Bluttransfusionen auf präformierte Antikörper gegen IgA


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  etwa 1 6 der Kinder und sind im Erwachsenenalter seltener anzutreffen Schwere anaphylaktische Reaktionen auf Nahrungsmittel sind


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Rv Abnahme bis zu einem gewissen Grad eine meist vorhandene mäßige Myokarddepression maskieren kann Erst bei einer ausgeprägten Kontraktilitätsminderung wird diese als Einschränkung des


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  nicht erbracht werden konnte Superoxiddismutase Katalase Glutathionperoxidase Ascorbinsäure Glutathion


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Patienten mit unklarer Schockätiologie oder mit einer sich nach Volumensubstitution nicht rasch stabilisierenden Kreislaufl abilität sollten baldmöglichst einem


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Studien konnte gezeigt werden dass nach kardiopulmonaler Reanimation durch die Induktion einer milden therapeutischen Hypothermie mit Temperaturen zwischen 32 und 34 C eine


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  ungezielt nach Schmerz 3 Beugemechanismen 2 Streckmechanismen 1 keine verbale Antwort 5 orientiert 4 verwirrt


id: cord-020643-0yzkqykg
type: DISEASE
entity:
  Diuretika bei Intensivpatienten mit akutem Nierenversagen konnte bisher nicht gezeigt werden Eine retrospektive


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Muskelrelaxanzien sowie zur sehr seltenen septisch metastatischen Pyomyositis bereiten Das klinische Bild


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  des Auftretens des prognosebestimmenden Multiorgandysfunktionssyndroms 7 Abschn 6 5 Die Behandlung des kardiogenen Schocks


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  eine Strategie mit früher systemischer Thrombolyse und gleichzeitiger intraaortaler Gegenpulsation eine frühestmögliche Vorbehandlung darstellt bei nachfolgendem


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  Patienten mit einem Zeitintervall 6 h von Schmerzbeginn bis Randomisierung und die mit einem Zweitinfarkt


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  1 aller Infarktpatienten 0 4 5 aller Infarkttodesfälle 2 7 Tage im Mittel 4 Tage nach Hinterwandinfarkt kann


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  gsten zwischen dem 2 und 8 Tag nach Infarkt auf aber jede 3 Ruptur fi ndet bereits innerhalb der ersten 24 h statt Sie betrifft häufi ger Frauen den Erstinfarkt den Vorderwandinfarkt


id: cord-020643-0yzkqykg
type: CHEMICAL
entity:
  eine Tamponade Eine Thoraxröntgenaufnahme kann hier diagnostisch weiterführen Bei gastrointestinalen Blutungen sollten weiterführende


id: cord-023935-o2ffxgnn
type: PROTEIN
entity:
  Antithrombin III AT III B Plasminogen activator inhibitor type 1 PAI 1 C Protein C D Protein S E Tissue factor


id: cord-023935-o2ffxgnn
type: CL
entity:
  vascular blood into the left atrium the opposite pooling of blood occurs with negative pressure inspiration leading to a rise in systolic pressure In addition positive intrathoracic pressure reduces the afterload on the left ventricle by virtue of the pressure gradient from the thorax outward further augmenting this early rise in arterial pressure These two effects produce an upward movement of the systolic blood pressure coincident with the positive pressure breath referred to as the D up component of SPV Following this D up a fall in systolic pressure occurs a few beats later as the decreased venous return preload to the right ventricle that occurred during positive pressure inspiration is now evident as decreased preload to the left ventricle after a few cardiac cycles The transient reduction in right ventricular volume and output leads to a smaller left ventricular stroke volume and a brief reduction in arterial pressure that occurs later in the ventilator cycle D down An exaggerated SPV 10 mm Hg has been seen early in the setting of hypovolemia This is due to a greater D down component Several studies have shown that an increase in the SPV occurs prior to a fall in arterial pressure and may a better predictor of hypovolemia than a low pulmonary capillary wedge pressure PCWP 10 mm Hg An increase in the SPV due to a greater D down component can also occur due to high airway pressures causing decreased venous return Recently pulse pressure variation PPV has also been found to be a sensitive indicator of preload and more importantly fl uid responsiveness PPV is defi ned as the maximal pulse pressure systolic minus diastolic blood pressure less the minimum pulse pressure divided by the average of these two pressures The use of systolic pressure variation and pulse pressure variation is limited to those patients on mechanical ventilation These measurements should occur when there is no spontaneous breathing In the presence of a consistent delivered tidal volume systolic pressure variation can be used to track the adequacy of intravascular volume over time Fig 27 3 The decision to use a pulmonary catheter PAC with the goals of optimizing left ventricular preload monitoring cardiac index and measuring oxygen


id: cord-002956-e5ihpe4i
type: ORG
entity:
  the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis Septic Shock with Respiratory Failure


id: cord-022592-g7rmzsv5
type: PROTEIN
entity:
  Toll like receptors TLRs NOD like receptors NLRs retinoic acid inducible protein I like receptors RLRs peptidoglycan recognition proteins


id: cord-022592-g7rmzsv5
type: PROTEIN
entity:
  adhesion molecules e g vascular cell adhesion molecule intercellular cell adhesion molecule L selectin P selectin


id: cord-349076-x3rjasg0
type: GGP
entity:
  HLA DR human leukocyte antigen D related IgM G immunoglobulin M G IL interleukin IFN γ Interferon gamma PAMPs


id: cord-349076-x3rjasg0
type: PERSON
entity:
  An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation


id: cord-014996-p6q0f37c
type: DNA
entity:
  colloids 4 gelatin 6 HES 130 0 4 or 5 albumin 250 ml in 20 min Hemodynamic and extravascular lung water index EVLWI GEDVI


id: cord-014996-p6q0f37c
type: DNA
entity:
  S pneumoniae positive bacteriological sample pulmonary quantitative culture pleural fluid blood culture


id: cord-014996-p6q0f37c
type: DNA
entity:
  APACHE II scores 12 1 4 1 and 11 4 4 4 vs 15 0 4 5 p 0 02 and MODS scores 3 58 1 73 and 3 25 2 12 vs 4 75 3 06 p 0 027


id: cord-014996-p6q0f37c
type: GGP
entity:
  V t ScaW p 0 002 CONCLUSIONS Our data show that there is no gold standard method for estimate or calculate body weight


id: cord-014996-p6q0f37c
type: GGP
entity:
  SCS 3 15 for the GCS and 5 16 for the FOUR Beyond this threshold only the SCS provides a highly significant correlation with the risk of death Spearman 0 907 p 0 0001 A


id: cord-014996-p6q0f37c
type: WORK_OF_ART
entity:
  Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis Procalcitonin


id: cord-014996-p6q0f37c
type: DISEASE
entity:
  type 1 diabetes mellitus A Shono 1 T Mihara 1 Y Murakami 1 J Ota 1 F Kono 1 Y Saito 1 1 Shimane Universiy


id: cord-015024-2xzc0uc5
type: GGP
entity:
  2 7 1 2 L min m 2 and 80 15 mmHg Nine patients responded to fluid infusion CI C 15 About the microcirculation there was no significant difference between responders R


id: cord-015024-2xzc0uc5
type: GGP
entity:
  MAP 12 and 80 respectively CONCLUSIONS In our hands PLR was not useful identifying fluid responders in this heterogenous population of severely ill medical ICU patients the starting semirecumbent position being


id: cord-015024-2xzc0uc5
type: GGP
entity:
  7 5 1 7 and 6 1 1 7 mean SD on subjective 1 to 10 scale during day and night shifts respectively p 0 02 and the chance of making errors to increase from 3 3 1 7 to 6 2 1 3


id: cord-015024-2xzc0uc5
type: GGP
entity:
  Lactate 5 IV fluids 6 Strict fluid management It is triggered by patients satisfying two or more of the systemic inflammatory response syndrome criteria All management steps should be implemented within 1 h of the trigger time stated on the form The forms are collected and analysed every month and the results are displayed for staff working on the medical admissions unit and accident and emergency A total of 239 forms have been collected 30 diagnosed with severe sepsis The progress on all six parameters is shown below Over the initial seven month period we have demonstrated a sustained improvement in the rapid delivery of all six of the management parameters INTRODUCTION The early goal directed resuscitation has been shown to improve survival in patients presenting with septic shock A recent systematic review demonstrated the inability of central venous pressure CVP to predict the hemodynamic response to fluids infusion and it should not be used to make clinical decisions regarding fluid management in critical patients The clinical implication of this fact in septic shock is not well known OBJECTIVES The aim of this study is to determine if the resuscitation with fluids guided by CVP has clinical implications in patients with septic shock Post hoc analysis of a patients cohort with septic shock admitted in the Medical Intensive Care Unit since June 2007 to June 2009 All of them were treated on basis of a bundle


id: cord-015024-2xzc0uc5
type: ORG
entity:
  Korea 3 Peking Union Medical College Hospital Department of Critical Care Medicine Mai Hospital Intensive Care Department


id: cord-015024-2xzc0uc5
type: DISEASE
entity:
  impairment of oxygenation Decreased functional residual capacity ventilation perfusion imbalance and sympathetic stimulation


id: cord-005497-w81ysjf9
type: DNA
entity:
  1st group 1st stage 15 2 10 19 4 mmol L 2nd stage 5 2 3 9 7 6 mmol L 3rd stage 6 6 5 8 7 μmol L stage 4 9 7 8 6 12 1 μmol L stage 5 9 4 7 8 11 9 μmol L


id: cord-005497-w81ysjf9
type: DNA
entity:
  2nd group 1st stage 11 9 10 15 mmol L 2nd stage 3 7 1 7 4 1 mmol L 3rd stage 3 6 2 4 4 5 μmol L stage 4 6 5 4 4 8 2 μmol L stage 5 7 6 6 5 9 4 μmol L


id: cord-005497-w81ysjf9
type: PROTEIN
entity:
  I Boussaid D Chtourou S Sfaxi W Bahria D Hamdi M Boussen M Ben Cheikh Mongi Slim Academic Hospital Emergency Department Tunis Tunisia Critical Care 2020 24 Suppl 1 P182


id: cord-005497-w81ysjf9
type: CELL_LINE
entity:
  Greek ICU population E Nanou 1 P Vasiliou 1 E Tsigou 2 V Psallida 1 E Boutzouka 2 V Zidianakis 1 G Fildissis 1 1 Agioi Anargiroi Hospital Attiki Greece 2 Agioi Anargiroi Hospital ICU


id: cord-005497-w81ysjf9
type: DNA
entity:
  groups 11 44 and 6 35 p 0 81 6 24 and 7 41 р 0 40 1 4 and 1 6 р 1 00 6 24 and 5 29 р 0 97 respectively Rate


id: cord-005497-w81ysjf9
type: CELL_LINE
entity:
  35bed Greek university ICU C Vrettou E Douka I Papachatzakis K Sarri E Gavrielatou E Mizi S Zakynthinos 1st ICU Department University


id: cord-005497-w81ysjf9
type: GGP
entity:
  MAP R 0 03 p 0 003 R 0 03 p 0 004 Figure 1 and heart rate R 0 12 p 0 001 since systemic pressure starts to drop UFRV and UFR demonstrated good clinical response to fluid administration despite the fact that systemic blood pressure


id: cord-005497-w81ysjf9
type: ORG
entity:
  Conrick Martin Mater Misericordiae University Hospital Department of Critical Care Medicine Dublin Ireland Critical Care 2020


id: cord-005497-w81ysjf9
type: ORG
entity:
  Clinical Research Investigation and Systems Modeling of Acute Illness CRISMA Center Department of Biostatistics


id: cord-005497-w81ysjf9
type: PRODUCT
entity:
  S Erel O Ermis Ö Nadastepe L Karabıyık Gazi University School of Medicine Anesthesiology and Intensive Care


id: cord-005497-w81ysjf9
type: DISEASE
entity:
  brain injury A Semenenko 1 S Semenenko 2 A Solomonchuk 3 N Semenenko 3 Depending on the nature of the brain injury


id: cord-005497-w81ysjf9
type: DISEASE
entity:
  critically ill T Chandler R Sarkar A Bowman P Hayden Medway Maritime Hospital Critical Care Gillingham United Kingdom Critical Care 2020 24 Suppl 1 P366 Frailty


id: cord-015021-pol2qm74
type: PROTEIN
entity:
  endotoxln endorphins complement interleukins tumor necrosis factor eieosanoids platelet activating factor


id: cord-015021-pol2qm74
type: DNA
entity:
  BIRGIT NENTWIG MARION HOCKENSCHNtEDER DIRK RAUTHMANN SALIM BALIKCIOGLU ROLF COLDEWEy HELMUTH DEICHER MD Endotoxin


id: cord-015021-pol2qm74
type: PROTEIN
entity:
  rhlL lra Phase I Sepsis Syndrome Study Group The Cleveland Clinic Foundation A murine anti human TNF monoclonal antibody


id: cord-015021-pol2qm74
type: ORG
entity:
  Division of Cell Biology and Immunology Department of Pathology University of Utah School of Medicine


id: cord-015021-pol2qm74
type: WORK_OF_ART
entity:
  Dept of Surgery Klinikum Grosshadern Ludwig Maximilians University Munich Germany Dept of Surgery University of Cincinnati


id: cord-015021-pol2qm74
type: PRODUCT
entity:
  William G Cheadle M D Department of Surgery University of Louisville School of Medicine Louisville KY 40292


id: cord-015021-pol2qm74
type: DISEASE
entity:
  chronic disease sepsis OSFsi e cardiovascular CF pulmonary PF renal RF neurological NF haematological HF hepatic LF


# bib

id: cord-000522-d498qj2b
title: Reducing mortality in sepsis: new directions
author: Vincent, Jean-Louis
date: 2002-12-05
txt: ./txt/cord-000522-d498qj2b.txt
cache: ./cache/cord-000522-d498qj2b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239386/
doi: 10.1186/cc1860
summary:
  Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced. The interventions discussed encompassed low tidal volume in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) (Edward Abraham), early goal-directed therapy (EGDT) (Emanuel Rivers), drotrecogin alfa (activated) (Gordon Bernard), moderate-dose corticosteroids (Djillali Annane), and tight control of blood sugar (Greet Van den Berghe).

abstract:
  Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of new studies into practice is not always simple. A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU). Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. One of the principal investigators for each study was invited to participate in the roundtable. The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used. Each new intervention has a place in the management of patients with sepsis. Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches – an 'ICU package'. The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.


id: cord-001293-dfaxj3bv
title: Is boosting the immune system in sepsis appropriate?
author: Cavaillon, Jean-Marc
date: 2014-03-24
txt: ./txt/cord-001293-dfaxj3bv.txt
cache: ./cache/cord-001293-dfaxj3bv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035855/
doi: 10.1186/cc13787
summary:
  In response to the failure of therapies aiming to target either the up-stream microbial activators or the effector molecules of the inflammatory cascade, a new concept has emerged of boosting the immune system to counter immunosuppression that develops in patients who survive the initial, hyperinflammatory period of sepsis [1] . One can conjecture that systemic treatment with IL-7 may act in undesired places, as illustrated by the following: IL-7 worsens graft-versus-host-induced tissue inflammation [81] ; favors inflammation in colitis [82] , contributes to arthritis severity [83] ; upregulates chemokines, IFNγ, macrophage recruitment, and lung inflammation [84] ; and, finally, increases production of inflammatory cytokines by monocytes and T cells [85] . Not only are PD-1-deficient mice markedly protected from the lethality of sepsis, accompanied by a decreased bacterial burden and suppressed inflammatory cytokine response [98] , but also blockade of PD-1 or PD-L1 improves survival in a murine model of sepsis, reverses immune dysfunction, inhibits lymphocyte apoptosis, and attenuates organ dysfunction [99] [100] [101] .

abstract:
  A relative immunosuppression is observed in patients after sepsis, trauma, burns, or any severe insults. It is currently proposed that selected patients will benefit from treatment aimed at boosting their immune systems. However, the host immune response needs to be considered in context with pathogen-type, timing, and mainly tissue specificity. Indeed, the immune status of leukocytes is not universally decreased and their activated status in tissues contributes to organ failure. Accordingly, any new immune-stimulatory therapeutic intervention should take into consideration potentially deleterious effects in some situations.


id: cord-001319-mlkaowqr
title: Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome
author: Giamarellos-Bourboulis, Evangelos J
date: 2013-10-21
txt: ./txt/cord-001319-mlkaowqr.txt
cache: ./cache/cord-001319-mlkaowqr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056013/
doi: 10.1186/cc13073
summary:
  RESULTS: Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. The current study was designed in order to embed into the changes of circulating IgM levels of patients upon progression to the more severe stages of sepsis in relation with the production of IgM from circulating lymphocytes and with the final outcome. The primary endpoint was the over-time changes of IgM serum levels of patients upon progression to septic shock in relation with the final outcome that is survival or 28-day mortality. The study end point was the kinetics of serum IgM upon progression from severe sepsis to septic shock in relation with final outcome. The time curves of IgM were designed for 30 patients with severe sepsis who progressed into septic shock.

abstract:
  INTRODUCTION: The aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis. METHODS: In this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages. Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days. Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production. RESULTS: Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock. Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors. Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls. CONCLUSIONS: Specific changes of circulating IgM occur when patients with severe sepsis progress into septic shock. The distribution of IgM is lower among non-survivors.


id: cord-002956-e5ihpe4i
author: Chang, Ya-Chun
date: 2018-04-04
txt: ./txt/cord-002956-e5ihpe4i.txt
cache: ./cache/cord-002956-e5ihpe4i.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884833/
doi: 10.1038/s41598-018-24028-4
summary:
  title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure A total of 379 patients with sepsis or septic shock and acute respiratory failure requiring mechanical ventilation were admitted to the medical intensive care unit in the Kaohsiung Chang Gung Memorial Hospital from August 2013 to October 2015. We also tested and found that SOFA PaO 2 /FiO 2 subscore and GCS subscore on admission day 7 could help predict ventilator dependence on sepsis and septic shock patients with significant difference in univariate analysis ( Table 5 ). Ventilator dependence risk score, including a history of stroke and data from day 7 (thrombocytopenia, acidosis, and the higher fraction of inspired oxygen), can be applied to predict prolonged mechanical ventilation in patients who survive sepsis and septic shock.

title:
  Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure

abstract:
  We intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure. This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment. The risk factors for ventilator dependence were determined. We then constructed a ventilator dependence (VD) risk score using the identified risk factors. The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient. We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points. The area under the curve in the derivation group was 0.725 (p < 0.001). We then applied the VD risk score for validation on 175 patients. The area under the curve in the validation group was 0.658 (p = 0.001). VD risk score could be applied to predict prolonged mechanical ventilation in patients who survive sepsis/septic shock.


id: cord-005497-w81ysjf9
author: nan
date: 2020-03-24
txt: ./txt/cord-005497-w81ysjf9.txt
cache: ./cache/cord-005497-w81ysjf9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092506/
doi: 10.1186/s13054-020-2772-3
abstract: nan
summary:
  The positive NC group had more plasma transfusion (p-value 0.03) and a lower median hematocrit at 24 hrs (p-value 0.013), but similar hospital length of stay (p=0.17) and mortality rate (p=0.80) Conclusions: NC at ICU admission identifies subclinical AKI in TBI patients and it maight be used to predictclinical AKI. In patients with pneumonia requiring intensive care (ICU) admission, we hypothesise that abnormal right ventricular (RV) function is associated with an increased 90-day mortality. The objective of this study was to describe the incidence of each AKI stages as defined by KDIGO definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (RRT)), in a mixed medical and surgical population of patients hospitalized in ICU and PCU over a 10-year period (2008-2018). This study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(ICU) and hospital length of stay (LOS), and length of mechanical ventilation (LOMV).

title:
  40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium. 24-27 March 2020


id: cord-005569-9d51l6bn
author: Antonelli, Massimo
date: 2008-12-09
txt: ./txt/cord-005569-9d51l6bn.txt
cache: ./cache/cord-005569-9d51l6bn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094904/
doi: 10.1007/s00134-008-1371-6
abstract: nan
summary:
  Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 h of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filling pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure [ or =65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients).

title:
  Year in review in Intensive Care Medicine, 2008: I. Brain injury and neurology, renal failure and endocrinology, metabolism and nutrition, sepsis, infections and pneumonia


id: cord-005603-kjcbbgse
title: The epidemiology of the systemic inflammatory response
author: Brun-Buisson, C.
date: 2000
txt: ./txt/cord-005603-kjcbbgse.txt
cache: ./cache/cord-005603-kjcbbgse.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094973/
doi: 10.1007/s001340051121
summary:
  Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and > 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in > 80 % patients. In the French Bacteraemia/Sepsis study, including 24 hospitals on the one hand [5] and 170 ICUs on the other [13] both surveyed during a 2-month period, the overall incidence of severe sepsis and shock (including clinically and microbiologically documented infection) was of 6/1000 of all hospital admissions, but only of 2.9/ 1000 in medical/surgical wards and 119/1000 in ICUs ( Table 2 ).

abstract:
  Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and > 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in > 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in > 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.


id: cord-005697-l1zmrq4p
title: Is this critically ill patient immunocompromised?
author: Pène, Frédéric
date: 2015-12-02
txt: ./txt/cord-005697-l1zmrq4p.txt
cache: ./cache/cord-005697-l1zmrq4p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095223/
doi: 10.1007/s00134-015-4161-y
abstract: nan
summary:
  A subset of septic patients infected with highly virulent pathogens may die rapidly from refractory shock, disseminated intravascular coagulation, and intractable multiple organ failure as a result of hyper-cytokinemia and uncontrolled inflammatory response. However, with improvements in acute care and resuscitation therapies, this classical exuberant presentation is relatively rare nowadays, and the physician is more often challenged by a blunted clinical response to infection, with subtle findings including lethargy or depressed mental status, glucose intolerance and hyperglycemia, hypothermia, and/or a change in the white blood cell count or cell differential. In addition to overt immunosuppressive conditions (e.g., cancer and hematological malignancies, solid organ transplant, autoimmune and systemic diseases, HIV, use of immunosuppressive drugs), many septic patients commonly exhibit additional risk factors affecting immune status [3] . Regardless of underlying comorbidities and primary injuries responsible for ICU admission, a significant proportion of critically ill patients can reasonably be considered to be immunocompromised and at risk for ICU-acquired infections, especially if they develop overt signs of immunosuppression.


id: cord-005872-w1x1i0im
title: Endothelium function in sepsis
author: Volk, T.
date: 2000
txt: ./txt/cord-005872-w1x1i0im.txt
cache: ./cache/cord-005872-w1x1i0im.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095878/
doi: 10.1007/s000110050579
summary:
  Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation

abstract:
  Endothelial cells can be the prime target for an infection and infected endothelial cells may serve as an initiating system for a systemic response as these cells are able to secrete many mediators known to be of paramount importance. Endothelial cell functions in turn are regulated by these circulating mediators. Cellular interactions with leukocytes revealed protective and destructive functions. Single cell and animal studies indicate that endothelial permeability is increased and apart from clinical obvious edema formation in septic patients, the endothelial component remains unknown. Endothelial coagulation activation has been shown in vitro, however human data supporting an endothelial procoagulatory state are lacking. Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies.


id: cord-006414-60lpjg09
title: Die Diagnose der Sepsis
author: Engelmann, L.
date: 2006
txt: ./txt/cord-006414-60lpjg09.txt
cache: ./cache/cord-006414-60lpjg09.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101768/
doi: 10.1007/s00390-006-0741-y
summary:
  Patients have to be considered as septic with a serum PCT level higher than 1 ng/ml particularly when clinical signs do not exclude sepsis and in cases of positive blood cultures. Ärzten von Notaufnahmen und klinisch tätigen Ärzten steht neben dem Wissen um die variable Klinik des septischen Patienten vor allem der Laborparameter Procalcitonin zur Verfügung. CRP ist das Produkt der durch Zytokine stimulierten Hepatozyten und somit das Endergebnis der Inflammationsreaktion, damit ein Akut-Phase-Protein [48] . Patienten mit Inflammationreaktion septischer und nicht-septischer Genese unterscheiden sich nicht im CRP-Verlauf (Abb. 4), während bei gesicherter Sepsis dem CRP-Verhalten eine prognostische Bedeutung zukommt (Abb. 5; [41, 50] ) Die Inflammationsreaktion ist eine weitestgehend uniforme Reaktion des Organismus auf Schädigung. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytikines

abstract:
  The early diagnosis of sepsis is mandatory for the further reduction of mortality due to sepsis. Current findings exist that accentuate the role of the time factor, comparable with acute myocardial infarction or with ischemic stroke. On the other hand, there are no generally accepted diagnostics for sepsis, realizing the demands of early diagnosis and based on the physician’s experience. The diagnostics start with the recognition of the inflammatory reaction caused by infection (at least 2 of 4 criteria of inflammatory reaction have to be fulfilled). This definition has high sensitivity, but remarkably lower specificity and it leads either to too frequent admissions or only to hospitalization in case of a complicating organ failure. Making a careful history and knowledge about sepsis are essential for the out-patient department physicians. In addition to the varying pictures of sepsis, the clinicians have laboratory findings available, most of all procalcitonin. Patients have to be considered as septic with a serum PCT level higher than 1 ng/ml particularly when clinical signs do not exclude sepsis and in cases of positive blood cultures. Initially PCT is a product of macrophages if the defense reaction starts, but it becomes an infection marker, when the serum PCT level declines less than the half life falls.


id: cord-006426-baf2d47y
title: Immunosuppression following surgical and traumatic injury
author: Kimura, Fumio
date: 2010-08-26
txt: ./txt/cord-006426-baf2d47y.txt
cache: ./cache/cord-006426-baf2d47y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101797/
doi: 10.1007/s00595-010-4323-z
summary:
  Suppression of cell-mediated immunity may be caused by multifaceted cytokine/inhibitor profiles in the circulation and other compartments of the host, excessive activation and dysregulated recruitment of polymorphonuclear neutrophils, induction of alternatively activated or regulatory macrophages that have anti-inflammatory properties, a shift in the T-helper (Th)1/Th2 balance toward Th2, appearance of regulatory T cells, which are potent suppressors of the innate and adaptive immune system, and lymphocyte apoptosis in patients with sepsis. 13, 14 In response to major tissue injury and/or bacterial infection, endothelial and epithelial cells, as well as neutrophils, macrophages, and lymphocytes, produce powerful proinfl ammatory cytokines, especially tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6.

abstract:
  Severe sepsis and organ failure are still the major causes of postoperative morbidity and mortality after major hepatobiliary pancreatic surgery. Despite recent progress in understanding the immune conditions of abdominal sepsis, the postoperative incidence of septic complications after major visceral surgery remains high. This review focuses on the clinical and immunological parameters that determine the risk of the development and lethal outcome of postoperative septic complication following major surgery and trauma. A review of the literature indicates that surgical and traumatic injury profoundly affects the innate and adaptive immune responses, and that a marked suppression in cell-mediated immunity following an excessive inflammatory response appears to be responsible for the increased susceptibility to subsequent sepsis. The innate and adaptive immune responses are initiated and modulated by pathogen-associated molecular-pattern molecules and by damage-associated molecular-pattern molecules through the pattern-recognition receptors. Suppression of cell-mediated immunity may be caused by multifaceted cytokine/inhibitor profiles in the circulation and other compartments of the host, excessive activation and dysregulated recruitment of polymorphonuclear neutrophils, induction of alternatively activated or regulatory macrophages that have anti-inflammatory properties, a shift in the T-helper (Th)1/Th2 balance toward Th2, appearance of regulatory T cells, which are potent suppressors of the innate and adaptive immune system, and lymphocyte apoptosis in patients with sepsis. Recent basic and clinical studies have elucidated the functional effects of surgical and traumatic injury on the immune system. The research studies of interest may in future aid in the selection of appropriate therapeutic protocols.


id: cord-006460-3ayc0hne
author: Baue, Arthur E.
date: 2000-10-19
txt: ./txt/cord-006460-3ayc0hne.txt
cache: ./cache/cord-006460-3ayc0hne.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101854/
doi: 10.1007/s004230000162
summary:
  Here, then, is an example of a Nobel Prize being awarded for the study of endothelial A.E. Baue ( ✉ ) cell-produced NO on the one hand, and the concept of excess vasodilatation in septic shock, the hypothesis that this was due to NO and a clinical trial blocking NO that increased mortality on the other. 3. We have tried to lump together and treat human abnormalities according to symptoms and signs rather than to the basic causes of their diseases -we have tried to treat inflammation, sepsis, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndrome (MODS) rather than what caused them; perforated diverticulitis is not acute pancreatitis and neither are ventilator-associated pneumonia and appendicitis. There has been significant improvement in survival of patients with persistent severe organ system failure." Thus, this report confirms again (1) that better intensive care is helping, and (2) my insistence that the secret to MOF is prevention.

title:
  Multiple organ failure – the discrepancy between our scientific knowledge and understanding and the management of our patients

abstract:
  The excitement of molecular biology and of genetic knowledge and their possibilities must be balanced against our limitations in using this information for the care of our patients. There is a great discrepancy between what we know and what we can do. There are many reasons for this. A major one is that science must simplify/reduce the variables in experimentation and then generalize in terms of a specific factor or effect, whereas patients are complex with variables that we do not yet understand completely. This powerful science is now teaching us about the genetic diversity in both susceptibility and outcome of disease, and the diversity in life experiences and antigen exposures. Clinicians have tried to lump together and treat in a similar way many diverse human diseases. This has not worked well. Pancreatitis and perforated diverticulitis both produce inflammation and sepsis, but they are different processes and may both lead to multiple organ failure. This lumping together has contributed to the failure of so-called magic bullets. There are new contributors to organ damage. Gender, lifestyle and prior disease differences also complicate the care of patients. Despite this, we are slowly and gradually improving the care of our surgical patients by careful pre-, intra- and postoperative support and better, simpler and safer operations.


id: cord-014658-oeuvelb1
title: Optimal fluid management in sepsis
author: Martin, Greg S.
date: 2019-11-07
txt: ./txt/cord-014658-oeuvelb1.txt
cache: ./cache/cord-014658-oeuvelb1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851923/
doi: 10.5339/qmj.2019.qccc.40
summary:
  Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.(3) Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer''s or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.(4) The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.(5) Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death.

abstract:
  Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection.(1) Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level >2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure ≥ 65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States.(2) Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.(3) Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.(4) The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.(5) Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis. Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias.


id: cord-014996-p6q0f37c
title: Posters_Monday_12 October 2009
author: nan
date: 2009-08-06
txt: ./txt/cord-014996-p6q0f37c.txt
cache: ./cache/cord-014996-p6q0f37c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094934/
doi: 10.1007/s00134-009-1593-2
abstract: nan
summary:
  Data recorded on admission were the patient demographics with, acute physiology and chronic health evaluation II score (APACHE II), and type of admission; during intensive care stay, sepsis-related organ failure assessment score (SOFA) and clinical concomitant factors and conditions. For each severe septic patient the following data was registered: time delay, APACHE II and SOFA scores at ICU admission, diagnosis, the rate of compliance with the resucitation and management bundles, microbiological data, evolution of levels of serum lactate, empiric antibiotic therapy, length of stay and mortality in ICU. Sepsis and septic shock remain the most important causes of acute kidney injury (AKI) in critically ill patients and account for more than 50% of cases of acute renal failure (ARF) in intensive care units (ICU). There were no significant differences between the demographic data (sex, age) or the data on admission to intensive care (APACHE II score, ratio of medical to surgical patients) and duration of mechanical ventilation between the two groups.


id: cord-015021-pol2qm74
author: nan
date: 1994
txt: ./txt/cord-015021-pol2qm74.txt
cache: ./cache/cord-015021-pol2qm74.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095072/
doi: 10.1007/bf02258437
abstract: nan
summary:
  It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events.

title:
  Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches


id: cord-015024-2xzc0uc5
title: ESICM 2010 WEDNESDAY SESSIONS 13 October 2010
author: nan
date: 2010-08-31
txt: ./txt/cord-015024-2xzc0uc5.txt
cache: ./cache/cord-015024-2xzc0uc5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095088/
doi: 10.1007/s00134-010-2001-7
abstract: nan
summary:
  We performed a prospective clinical study in a 17-bed multidisciplinary intensive care unit, including 21 patients with controlled mechanical ventilation and monitored with the Vigileo Ò monitor, for whom the decision to give fluids was taken due to the presence of circulatory, including arterial hypotension (MAP B 65 mmHg or systolic arterial pressure \90 mmHg), and preserved preload-responsiveness condition, defined as SVV C10%. The aim of this study was to compare and evaluate four severity scoring systems in intensive care unit (ICU), including APACHE II, APACHE III, SASP II and MODS in severe septic patient. A prospective observational study was performed in 16 mechanically ventilated critically ill patients (12 M, age 49 ± 17 yr, BMI 25 ± 5 kg/m 2 , ICU admission day 5 ± 3, APACHE II on study 20 ± 7; mean ± SD) and 6 healthy subjects (3 M, age 24 ± 9 year, BMI 24 ± 45 kg/m 2 ).


id: cord-015082-l629n8is
title: Poster Sessions 323-461
author: nan
date: 2002-08-29
txt: ./txt/cord-015082-l629n8is.txt
cache: ./cache/cord-015082-l629n8is.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095316/
doi: 10.1007/s00134-002-1455-7
abstract: nan
summary:
  14 patients awaiting urgent cardiac surgical re-vascularisation were studied with measurement of: spirometry; percentage increase in transfer factor from sitting to lying position (TF) as an indicator of micro-vascular lung disease; overnight oximetry on air; and 24hour holter monitoring Patients, who were reintubated on decreased indices of arterial oxygenation under MOSF progressing died in 100% cases ( NIMV is effective method in complex therapy of ARF, developing in postoperative period after cardiac surgery, that leads to significant improvement of lungs biomechanics and gases change function. In a prospective observational study we performed bedside ptO2 measurements in 8 patients with sepsis/septic shock to gain insight in ptO2 values and their dynamic changes related to the course of the illness, as well as investigating the practical applicability of tissue oxygen measurement in the ICU setting.


id: cord-015946-biu5zxd1
title: Research Advances in Biomarker for Sepsis
author: Peng, Daizhi
date: 2016-11-16
txt: ./txt/cord-015946-biu5zxd1.txt
cache: ./cache/cord-015946-biu5zxd1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120075/
doi: 10.1007/978-981-10-2425-2_15
summary:
  Most commonly proposed sepsis and infection biomarkers including C-reactive protein (CRP), procalcitonin (PCT) [5, 6] , cytokines (TNF-α, IL-1, IL-6, IL-10, osteopontin) [7, 8] , chemokines [macrophage migration inhibitory factor (MIF), high-mobility-group box 1 (HMGB1)] [9, 10] , soluble receptor [soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), soluble urokinase-type plasminogen activator receptor (suPAR)] [11, 12] etc. When it comes to sepsis, by using genome-wide miRNA profiling with microarray in peripheral blood leukocytes and quantitative RT-PCR, Vasilescu [71] found that miR-150 levels were significantly reduced in both leukocytes and plasma of sepsis patients and had a negative correlation with the level of disease severity measured by the Sequential Organ Failure Assessment (SOFA) score, which made it a biomarker of early sepsis. As they were significantly correlated with disease severity, classical markers of inflammation and bacterial infection, as well as organ failure, high miR-133a levels were considered as independent biomarkers for unfavorable prognosis of critically ill patients.

abstract:
  Sepsis is one of the most common causes of death in severely injured patients worldwide. The early detection of sepsis still has to be solved in clinical practice. The delayed diagnosis often contributes to inappropriate antimicrobial treatment and subsequent high mortality. Sepsis biomarkers are produced during the host response to infection. Traditional biomarkers are polypeptides and/or proteins derived from this response. Omics-based biomarkers are screening out from all kinds of molecules of host response while high-throughout omics technologies are emerging. This review describes traditional and potential omics-based sepsis biomarkers from currently available literatures. The combination of these biomarkers would refine the identification of sepsis for further clinical and experimental sepsis studies.


id: cord-016127-tbot0fc9
title: Sepsis: Clinical Approach, Evidence-Based at the Bedside
author: Hurtado, F. J.
date: 2009-11-19
txt: ./txt/cord-016127-tbot0fc9.txt
cache: ./cache/cord-016127-tbot0fc9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120313/
doi: 10.1007/978-88-470-1436-7_25
summary:
  Since 2002 the Surviving Sepsis Campaign was introduced with the initial goal of increasing clinicians'' awareness about severe sepsis mortality and to improve outcome in this patient population. Despite the fact that most of these recommendations were not supported by high levels of evidence, they represented the international consensus on the best available standards of care for the management of sepsis. Mortality increases according to the presence of shock, and metabolic markers like arterial lactate are useful to characterize disease severity and the response to treatment [8] . The current management of severe sepsis and septic shock aims to control infection, achieve hemodynamic stabilization, modulate the immune response, and provide metabolic and organ support. The SSC is a global initiative that involves several international organizations with the common objective of elaborating evidence-based guidelines and recommendations for the management of severe sepsis and septic shock. Early goal-directed therapy in the treatment of severe sepsis and septic shock

abstract:
  Sepsis is a common disease in intensive care medicine representing almost one third of patient admissions. Its incidence has substantially increased over the past decades and overall mortality has declined during this period of time. It was reported that sepsis incidence increased from 82.7 to 240.4 per 100,000 population between 1979–2000. At the same time, sepsis global mortality decreased from 27.8 to 17.9% [1–3]. However, the absolute number of deaths significantly increased from 21.9 to 43.9 per 100,000 population. Male gender, some chronic diseases like diabetes, immunosuppressive states, human immunodeficiency virus infections, and malignancies are factors that increase the risk for sepsis. Some particular conditions like progressive number of organ dysfunctions, in-hospital-acquired infections and increasing age are associated with higher risk of death [1,4]. On the other hand, septic shock mortality only diminished from 61.6 to 53.1% [5]. This slight decline in mortality observed during recent decades could be attributable to improvements in supportive care and/or avoidance of iatrogenic complications. For example, the instrumentation of early goal resuscitation protocols not aiming at supranormal targets for cardiac output and oxygen delivery, and the use of lung protective strategies could explain at least in part this favorable change. Other strategies directed to treat the pathophysiological mechanisms involved in the septic process like recombinant human-activated protein-C (rhAPC), have also contributed to improve survival. However, mortality remains unacceptably high and further improvement in sepsis management is needed.


id: cord-017337-vq3edhxn
title: PIRO: The Key to Success?
author: Vincent, Jean-Louis
date: 2009
txt: ./txt/cord-017337-vq3edhxn.txt
cache: ./cache/cord-017337-vq3edhxn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121867/
doi: 10.1007/978-3-642-00479-7_1
summary:
  Building on a system that had emerged at the Fifth Toronto Sepsis Roundtable held in Toronto, Canada, in 2000 [6] , the sepsis defi nitions conference participants, therefore, proposed the PIRO system [5] , which can classify patients on the basis of their predisposing conditions, the nature and extent of the infection, the nature and magnitude of the host response, and the degree of concomitant organ dysfunction. The PIRO system for the grading of sepsis uses clinical and laboratory parameters to aid diagnosis and patient classifi cation, with each element being divided according to the degree of involvement (e.g., infection can be classifi ed as localized, extended, or generalized; immune response can be classifi ed as limited, extensive, or excessive; organ dysfunction can be classifi ed as mild, moderate, severe). Improved classifi cation of septic patients using the PIRO system may, thus, facilitate the development and evaluation of clinical trials of sepsis therapies and will also encourage further study into the pathophysiology and epidemiology of sepsis.

abstract:
  Sepsis continues to represent a major problem in intensive care units worldwide. Diagnosis and management are often complex due in part to the remarkably diverse nature of the septic patient. Indeed, sepsis can range in severity from mild systemic inflammation of little clinical importance through to a widespread severe inflammatory response with multiple organ failure and a mortality rate in excess of 50%. Sepsis can affect individuals of any age group, with no or multiple co-morbidities, and with many different ongoing diagnoses. It can occur as the result of infection by one or more of a multitude of microbial pathogens impacting on any of numerous different sites within the body. Given the huge complexity of sepsis and the diverse populations of patients it affects, simple definitions are of relatively little use and a more detailed framework which can be used to better characterize patients with sepsis has been proposed, much as the TNM classification (tumor size, nodal spread, metastases) has been successfully used in clinical oncology. In this chapter, we discuss the development of this PIRO system, and suggest how it may be used in the future to aid diagnosis, guide therapy, and improve prognostication.


id: cord-017376-wrhkfcff
title: Pro-resolution of Inflammation: New Hints to Manage Sepsis?
author: Liu, Yongjian
date: 2019-05-28
txt: ./txt/cord-017376-wrhkfcff.txt
cache: ./cache/cord-017376-wrhkfcff.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121927/
doi: 10.1007/978-981-13-3353-8_8
summary:
  Carbon monoxide, synthesized by HO-1, performs multiple stances of anti-inflammation and pro-resolution along with the SPMs. If the potentially beneficial effects of these mediators would be well evaluated in clinical trials, they present encouraging new hints in managing infectious maladies especially sepsis. Previous studies have shown that IV administration of RvD2 on a CLP sepsis model exhibits the following protective pro-resolution effects and increases survival rate: (1) reduce viable aerobic bacterial load in peritoneal exudates and blood; (2) reduce PMN migration into the peritoneum; (3) reduce plasma levels of IL-10 and IL-17; (4) reduce pro-inflammatory cytokine (IL-6, IL-1β, IL-23 and TNF-α) levels in plasma and peritoneum; (5) reduce concentrations of the pro-inflammatory lipids PGE2 and LTB4; while (6) increase clearance of bacteria by phagocytes in inguinal lymph nodes and in vitro; (7) enhance phagocytosis of E.

abstract:
  Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiological mechanism of sepsis is highly complex, and the mortality of in-patients suffering from sepsis is more than 10%. Severe unmanaged inflammation and inappropriate immune response characterize sepsis. Anti-inflammation therapies alone are not successful for the reason that disbalance of anti-inflammatory and pro-resolving agents. In the recent researches, the host responses during the course of self-resolving infections are found to have the involvements of specialized pro-resolution mediators (SPMs), namely, lipoxins, resolvins, protectins and maresins. These endogenous lipid metabolites are core signal molecules in the resolution of inflammation, playing a key role in regulating the inflammation and promoting return to homeostasis. Besides, heme oxygenase-1 (HO-1, a sensitive marker for oxidative stress) is also known for upregulation in inflammation profiling. Carbon monoxide, synthesized by HO-1, performs multiple stances of anti-inflammation and pro-resolution along with the SPMs. If the potentially beneficial effects of these mediators would be well evaluated in clinical trials, they present encouraging new hints in managing infectious maladies especially sepsis.


id: cord-017420-tjwxec77
title: Neutropenic Fever in the Intensive Care Unit
author: Stephens, R. Scott
date: 2019-07-09
txt: ./txt/cord-017420-tjwxec77.txt
cache: ./cache/cord-017420-tjwxec77.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121977/
doi: 10.1007/978-3-319-74588-6_118
summary:
  Neutropenic patients with septic shock tend to have more frequently positive blood cultures, more fungal infections, more multidrug-resistant bacterial infections, and higher mortality rates than immunocompetent patients. Accordingly, current guidelines for the management of neutropenic fever and sepsis recommend monotherapy with an antipseudomonal beta-lactam unless otherwise dictated by circumstances such as patient allergies, the presence of resistant organisms, or refractory hemodynamic instability [28, 57, 61] . The use of surveillance rectal cultures, performed pre-transplant and then weekly after HSCT, to identify patients with MDR infections and allow immediate initiation of antibiotic therapy targeted against MDR organisms may result in better outcomes [26] . Patients with neutropenia and sepsis are at high risk of developing multi-organ failure, particularly the acute respiratory distress syndrome (ARDS) [4, 5] . Neutropenic sepsis continues to confer a poor prognosis, with recent data suggesting an approximate 46% mortality rate in patients with hematologic malignancies who develop septic shock [7, 39, 47] .

abstract:
  Neutropenic fever is a common and potentially life-threatening condition in patients treated for cancer. Rapid initiation of appropriate antimicrobial therapy is necessary to decrease the risk of mortality. Most infections are due to gram-positive organisms, but the mortality rate is higher for gram-negative infections. Multidrug-resistant organisms are an emerging threat to neutropenic patients. Increasing data suggest that the pathophysiology of neutropenic fever and neutropenic sepsis is substantially different from non-neutropenic fever and sepsis. Additional research is needed to both further elucidate the pathogenesis of neutropenic fever and to develop additional effective antimicrobials.


id: cord-017470-sjk7a34u
title: Pathophysiology of Acute Illness and Injury
author: Arlati, Sergio
date: 2018-06-14
txt: ./txt/cord-017470-sjk7a34u.txt
cache: ./cache/cord-017470-sjk7a34u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122041/
doi: 10.1007/978-3-319-95114-0_2
summary:
  The endothelium is a key factor for production of remote organ damage as it exerts potent chemo-attracting effects on inflammatory cells, allows for leukocyte trafficking into tissues and organs, and promotes further inflammation by cytokines release. Thus, pneumococcal pneumonia can transform into severe sepsis or septic shock if a generalized inflammatory reaction develops by either cellular (neutrophils, monocytes, macrophages, endothelium) or humoral effectors (complement, contact phase proteins, leukotrienes, cytokines, chemokines) resulting into increased capillary permeability (tissue edema), vasodilation (hypotension), and coagulation activation (ischemic organ damage). However, the severe decrease of innate immune function and the widespread hibernation of nonimmune cell type (cellular hibernation response) [137, 138] make apoptosis a primary mechanism for multiple organ dysfunction and ultimately death. The loss of physiologic anticoagulation in sepsis results from the action of several humoral (IL1-β, TNF-α, and IL6, C-reactive protein) and cellular (vascular endothelial cells, monocytes, macrophages, and platelet) pro-inflammatory mediators.

abstract:
  The pathophysiology of acute illness and injury recognizes three main effectors: infection, trauma, and ischemia-reperfusion injury. Each of them can act by itself or in combination with the other two in developing a systemic inflammatory reaction syndrome (SIRS) that is a generalized reaction to the morbid event. The time course of SIRS is variable and influenced by the number and severity of subsequent insults (e.g., reparative surgery, acquired hospital infections). It occurs simultaneously with a complex of counter-regulatory mechanisms (compensatory anti-inflammatory response syndrome, CARS) that limit the aggressive effects of SIRS. In adjunct, a progressive dysfunction of the acquired (lymphocytes) immune system develops with increased risk for immunoparalysis and associated infectious complications. Both humoral and cellular effectors participate to the development of SIRS and CARS. The most important humoral mediators are pro-inflammatory (IL-1β, IL-6, IL-8, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines, complement, leukotrienes, and PAF. Effector cells include neutrophils, monocytes, macrophages, lymphocytes, and endothelial cells. The endothelium is a key factor for production of remote organ damage as it exerts potent chemo-attracting effects on inflammatory cells, allows for leukocyte trafficking into tissues and organs, and promotes further inflammation by cytokines release. Moreover, the loss of vasoregulatory properties and the increased permeability contribute to the development of hypotension and tissue edema. Finally, the disseminated activation of the coagulation cascade causes the widespread deposition of microthrombi with resulting maldistribution of capillary blood flow and ultimately hypoxic cellular damage. This mechanism together with increased vascular permeability and vasodilation is responsible for the development of the multiple organ dysfunction syndrome (MODS).


id: cord-018284-grvj99eh
title: SIRS, Sepsis und Multiorganversagen
author: Fresenius, Michael
date: 2014-10-04
txt: ./txt/cord-018284-grvj99eh.txt
cache: ./cache/cord-018284-grvj99eh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123125/
doi: 10.1007/978-3-642-44933-8_24
abstract: nan
summary:
  Selenium in Intensive Care: results of a prospective randomized, placebo-controlled, multicenter study in patients with severe systemic inflammatory response syndrome, sepsis and septic shock Effect of treatment with low doses of hydrocortisone and fludrocortisones on mortality in patients with septic shock Effect of treatment with low doses of hydrocortisone and fludrocortisones on mortality in patients with septic shock A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock Effects of high dosis of selenium, as sodium selenit, in septic shock: a placebo-controlled, randomized, double-blind, phase II study Early antimicrobial therapy in severe sepsis and septic shock Early goal-directed therapy in the treatment of severe sepsis and septic shock Hydrocortisone therapy for patients with septic shock Guidelines for the management of severe sepsis and septic shock


id: cord-018840-ts2g1ux7
title: Role of Immunoglobulin Therapy to Prevent and Treat Infections
author: Katragkou, Aspasia
date: 2018-06-19
txt: ./txt/cord-018840-ts2g1ux7.txt
cache: ./cache/cord-018840-ts2g1ux7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123824/
doi: 10.1007/978-3-319-77674-3_17
summary:
  While the main clinical applications of immunoglobulin therapy concern their use as replacement for patients with primary immunodeficiencies, or as treatment for autoimmune and inflammatory disorders, their role in infectious disease is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. The first clinical trial, which evaluated the effect of IgMA-enriched immunoglobulin preparation (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG), which have shown to contain superior antibody content against bacterial lipopolysaccharides, in an appreciable number of neutropenic patients with hematologic malignancies and sepsis or septic shock, showed that immunoglobulins had no beneficial effects [51] . A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery

abstract:
  Immunoglobulins have been used widely in medicine for a variety of diseases including infectious diseases. While the main clinical applications of immunoglobulin therapy concern their use as replacement for patients with primary immunodeficiencies, or as treatment for autoimmune and inflammatory disorders, their role in infectious disease is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. Many aspects of the therapeutic regimen of immunoglobulins even in the established indications remain open. Recently, due to the worldwide surge of immunosuppression caused by AIDS, organ transplantation, cancer, and autoimmune therapies, as well as the emergence of multidrug-resistant bacteria, there has been renewed interest in the use of antibody preparation to prevent infections in high-risk groups. Knowing the limitations of the current anti-infective armamentarium, approaches that target the host through manipulations to augment the host immune response provide a helpful aid to conventional treatment options. A substantial body of evidence has demonstrated that strategies aiming to support or stimulate immune response could be feasible approaches that would benefit immunocompromised patients. In the present chapter, we present contemporary indications of immunoglobulin administration for therapy and prophylaxis of infections in the immunocompromised population.


id: cord-020643-0yzkqykg
title: Schock
author: Müller-Werdan, U.
date: 2006
txt: ./txt/cord-020643-0yzkqykg.txt
cache: ./cache/cord-020643-0yzkqykg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143837/
doi: 10.1007/3-540-29425-2_6
abstract: nan
summary:
  Auch dass nichtinfektiöse Noxen (Trauma, Pankreatitis, herzchirurgische Operationen mit der Herz-Lungen-Maschine) zu einem ganz ähnlichen klinischen Bild wie bei bakteri-ell ausgelöster Sepsis und septischem Schock führen können, spricht für eine mehr oder weniger gemeinsame Zytokin-/Mediatorendstrecke als verantwortliche Schädigungskaskade sowohl bei infektiösen als auch bei nichtinfektiösen (SIRS, . Eine Ausnahme von dieser Regel stellt die Hirndurchblutung dar, die in der Sepsis weiterhin die Fähigkeit zur Autoregulation beibehält: Bei Patienten mit Sepsis ist die Hirndurchblutung bereits vor der Ausbildung des Schockzustandes um ein Drittel reduziert, wobei diese Durchblutungseinschränkung jedoch nicht als Ursache der septischen Enzephalopathie angesehen wird. Im Koronargefäßsystem fällt dagegen der Widerstand noch stärker ab als in den anderen Organen und demzufolge ist die Koronarperfusion bei Patienten mit septischem Schock sogar häufi g erhöht (Dhainaut et al. Die Messung des zentralen Venendrucks ist bei kritisch Kranken, insbesondere Schockpatienten, für das hämodynamische Monitoring normalerweise nicht genügend, eine Abschätzung der linksventrikulären Vorlast kann damit nicht ausreichend sicher durchgeführt werden, ebenso wenig wie mit der klinischen Einschätzung allein.


id: cord-022592-g7rmzsv5
title: Pathophysiology of Neonatal Sepsis
author: Wynn, James L.
date: 2016-07-06
txt: ./txt/cord-022592-g7rmzsv5.txt
cache: ./cache/cord-022592-g7rmzsv5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158364/
doi: 10.1016/b978-0-323-35214-7.00152-9
abstract: nan
summary:
  14, 15, [27] [28] [29] [30] [31] [32] [33] Prematurity, low birth weight (especially infants weighing less than 1,000 g), male sex, a maternal vaginal culture positive for group B streptococcus (GBS), prolonged rupture of membranes, maternal intrapartum fever, and chorioamnionitis are strongly associated with an increased risk for early-onset sepsis. In addition to the initial inflammatory response including complement activation, molecular detection of PAMPs promotes IL-1β and IL-6 production, which in turn increases the production of multiple other innate proteins that possess valuable immune function and serve to reduce pathogen load. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network


id: cord-023935-o2ffxgnn
title: Sepsis
author: Lorts, Angela
date: 2011-12-16
txt: ./txt/cord-023935-o2ffxgnn.txt
cache: ./cache/cord-023935-o2ffxgnn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178851/
doi: 10.1007/978-0-85729-923-9_27
summary:
  SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response.

abstract:
  The health care provider faced with the management of a child with septic shock relies on a comprehensive understanding of the numerous disciplines embodied in the practice of pediatric critical care medicine. The child with septic shock may have simultaneous derangements in the function of virtually every system of the body including: cardiovascular, respiratory, immune, renal, coagulation, hepatic, metabolic and neurologic. The degree to which physiologic alterations are manifest in a given patient is variable and influenced by multiple host and non-host factors including: the developmental stage, the presence of co-morbidities, pathogen-related factors, and genetic influences on both the host inflammatory response as well as the response to pharmacologic agents, all combining to have a profound influence on outcome. The clinician must possess a systematic and multifaceted approach to these critically ill patients. The goal of this chapter is to provide a comprehensive description of the epidemiology, biology and pathophysiology (at both the cellular and organ level) of sepsis, as well as outlining the current principles of managing septic shock. It will be apparent that optimal management requires a strong working knowledge of cardiovascular physiology, infectious diseases, multiple organ interactions, immunity, coagulation, pharmacology, and the molecular biology of inflammation.


id: cord-028164-yn53209z
author: Abe, Toshikazu
date: 2020-06-30
txt: ./txt/cord-028164-yn53209z.txt
cache: ./cache/cord-028164-yn53209z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324770/
doi: 10.1186/s40560-020-00465-0
summary:
  Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. RESULTS: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. Patients with infection in ICUs were compared according to whether they met sepsis-2 or sepsis-3 definition. Characteristics and in-hospital mortality were compared according to sepsis-2 and sepsis-3 definitions in this prospective observational cohort of ICU patients. In our cohort, 96 (16%) patients had "not available" (NA) sepsis-3 baseline SOFA, which was indicated as zero according to the sepsis-3 definition, although all data of chronic organ failures were tried to obtain. A majority of the patients who were admitted to the ICU with suspected infection met sepsis-2 and sepsis-3 definitions.

title:
  Epidemiology of sepsis and septic shock in intensive care units between sepsis-2 and sepsis-3 populations: sepsis prognostication in intensive care unit and emergency room (SPICE-ICU)

abstract:
  BACKGROUND: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. METHODS: This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient’s characteristics and outcomes were described according to whether they met each definition or not. RESULTS: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. CONCLUSIONS: Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. TRIAL REGISTRATION: UMIN000027452


id: cord-030385-btf502ju
author: Sun, Zhiheng
date: 2020-07-22
txt: ./txt/cord-030385-btf502ju.txt
cache: ./cache/cord-030385-btf502ju.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387432/
doi: 10.3389/fimmu.2020.01591
summary:
  However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively.

title:
  17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB

abstract:
  Sepsis is more common among males than females, and the unequal estrogen levels have been suspected to play a vital role in gender differences. Recently, trained immunity is reported to be a novel strategy for the innate immune system to fight infection. However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. In this study, sepsis was induced in mice by intraperitoneal injection of Escherichia coli (E. coli). The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. For in vitro studies, different macrophages were treated with LPS. The function of estradiol (E2) on macrophage cell lines was verified and the mechanism of E2 affecting trained immunity was explored. We demonstrated that β-glucan-induced trained immunity was more resistant to sepsis in female than male mice. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Moreover, ovariectomized (OVX) mice manifested serious sepsis consequences with a weaker trained immunity effect than female mice. Female bone marrow-derived macrophages (BMDMs) were also apt to be polarized to the M1 phenotype in response to trained immunity in vitro. Furthermore, E2 promoted trained immunity in macrophage cell lines J774 and RAW264.7. E2 was also verified to facilitate trained immunity in primary BMDMs from female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. This study is the first to indicate the role of E2 in the trained immunity induced by β-glucan to protect against E. coli-induced sepsis via the non-canonical NFκB pathway. These results improve our understanding of the molecular mechanisms governing trained immunity in gender differences.


id: cord-033064-3b4jv1zb
title: Sepsis und septischer Schock
author: Larsen, Reinhard
date: 2016-06-14
txt: ./txt/cord-033064-3b4jv1zb.txt
cache: ./cache/cord-033064-3b4jv1zb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531315/
doi: 10.1007/978-3-662-50444-4_66
summary:
  Die Sepsis ist eine lebensbedrohliche Organfunktionsstörung aufgrund einer fehlregulierten Reaktion des Körpers auf eine Infektion. Hinweise sind ein Abfall des systolischen Blutdrucks auf unter 100 mm Hg, Bewusstseinsatörungen und ein Anstieg der Atemfrequenz auf über 22/min (qSOFA-Score) Beim septischen Schock, einer Unterform der Sepsis, muss die Herz-Kreislauf-Funktion mit kardiovaskulären Medikamenten und Volumenersatz gestützt werden. Trotz intensiver Bemühungen ist die Letalität der Sepsis unverändert hoch. DIe Sepsis-Konsensuskonferenz von 2016 bewertet die SIRS-Kriterien als zu ungenau für die Diagnose einer Sepsis und empfiehlt daher, den Begriff nicht mehr zu verwenden. Sepsis ist eine systemische Entzündungsreaktion des Organismus auf eine Infektion durch Mikroorganismen (Bakterien, Viren, Pilze, Rickettsien, Protozoen). Die Sepsis ist Folge einer komplexen generalisierten Entzündungsreaktion durch eine Infektion. Trotz intensiver Bemühungen ist die Letalität der Sepsis weiterhin unverändert hoch. Eine frühzeitige Diagnosestellung und Therapie ist für das Überleben der Patienten von entscheidender Bedeutung. Eine frühzeitige Diagnosestellung und Therapie ist für das Überleben der Patienten von entscheidender Bedeutung.

abstract:
  Die Sepsis ist eine lebensbedrohliche Organfunktionsstörung aufgrund einer fehlregulierten Reaktion des Körpers auf eine Infektion. Hinweise sind ein Abfall des systolischen Blutdrucks auf unter 100 mm Hg, Bewusstseinsatörungen und ein Anstieg der Atemfrequenz auf über 22/min (qSOFA-Score) Beim septischen Schock, einer Unterform der Sepsis, muss die Herz-Kreislauf-Funktion mit kardiovaskulären Medikamenten und Volumenersatz gestützt werden. Das Serumlaktat ist auf mehr als 2 mmol/l erhöht. Trotz intensiver Bemühungen ist die Letalität der Sepsis unverändert hoch. Eine frühzeitige Diagnosestellung und Therapie ist für das Überleben der Patienten von entscheidender Bedeutung.


id: cord-103081-k7ev5qkn
author: Janosevic, Danielle
date: 2020-05-30
txt: ./txt/cord-103081-k7ev5qkn.txt
cache: ./cache/cord-103081-k7ev5qkn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.27.118620
doi: 10.1101/2020.05.27.118620
summary:
  Note that the expression of cluster-defining markers varied significantly during the injury and 63 recovery phases of sepsis ( Fig. S1b; Supplementary Table 1 ). One of the subclusters showed 112 increased expression of alternatively activated macrophages (M2) markers such as Arg1 113 (Arginase 1) and Mrc1 (Cd206) 27 at later time points (36 hours, Supplementary Fig. 4b) . Such 181 communication patterns among these four cell types may also explain macrophage clustering 182 around S1 tubules at later time points in sepsis as we previously reported 13 . To this end, we selected the differentially expressed genes from all cells combined (pseudo 203 bulk) for each time point across the mouse sepsis timeline (Supplementary Table 4) . Our data 215 cover nearly all renal cell types and are time-anchored, thus providing a detailed and precise 216 view of the evolution of sepsis in the kidney at the cellular and molecular level.

title:
  The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline

abstract:
  Clinical sepsis is a highly dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single cell RNA sequencing revealed the involvement of various cell populations in injury and repair to be temporally organized and highly orchestrated. We identified key changes in gene expression that altered cellular functions and can explain features of clinical sepsis. These changes converged towards a remarkable global cell-cell communication failure and organ shutdown at a well-defined point in the sepsis timeline. Importantly, this time point was also a transition towards the emergence of recovery pathways. This rigorous spatial and temporal definition of murine sepsis will uncover precise biomarkers and targets that can help stage and treat human sepsis.


id: cord-104180-f3hoz9bu
title: Recently published papers: inflammation, elucidation, manipulation?
author: Kirk-Bayley, Justin
date: 2003-07-03
txt: ./txt/cord-104180-f3hoz9bu.txt
cache: ./cache/cord-104180-f3hoz9bu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC270703/
doi: nan
abstract: nan
summary:
  They looked at end-organ epithelial cell apoptosis in a rabbit model of ARDS and at the effects of plasma on epithelial cells from recipients of the injurious ventilatory strategy, and analyzed samples from a previous trial into lung protective ventilation [8] . Choosing the right ventilation strategy for ARDS patients has more benefits than just lung protection, and therapeutic targeting of these factors that induce end organ apoptosis may be the next step. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study


id: cord-252859-zir02q69
title: Molecular Diagnostics in Sepsis: From Bedside to Bench
author: Chung, T. Philip
date: 2006-09-11
txt: ./txt/cord-252859-zir02q69.txt
cache: ./cache/cord-252859-zir02q69.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17084318/
doi: 10.1016/j.jamcollsurg.2006.06.028
summary:
  BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. 17, 18 We hypothesized that leukocyte gene expression profiles obtained using DNA microarrays could be used to predict septic states; in particular, distinguishing between sterile and infectious sources of systemic inflammation, a common conundrum in caring for the critically ill or injured. 30 PCA analysis of these 25 probe sets revealed that the seven experimental groups were clustered into three apparent phenotypes (Fig. 4) : control animals, LPS-treated animals (sterile source of systemic inflammation), and those that had any CLP treatment (Sepsis).

abstract:
  BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. STUDY DESIGN: Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice. RESULTS: Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. CONCLUSIONS: Sepsis induces changes in mouse leukocyte gene expression that can be used to diagnose sepsis apart from systemic inflammation.


id: cord-261633-r4qlbnc5
title: Defensins and Sepsis
author: Xie, Guo-Hao
date: 2014-08-19
txt: ./txt/cord-261633-r4qlbnc5.txt
cache: ./cache/cord-261633-r4qlbnc5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25210703/
doi: 10.1155/2014/180109
summary:
  The impact of -defensin-2 on the inflammatory response (e.g., the level of ICAM-1 expression), the severity of lung injury, and the sepsis outcome (7-day survival rate) were observed and evaluated. Previous studies showed that single nucleotide polymorphism (SNP) of -defensin-1 gene (DEFB1) correlates with chronic obstructive pulmonary disease, asthma, genetic allergy, HIV infection, and pseudomonas species infection in oral mucosa [38] [39] [40] [41] [42] . Distribution of alleles, gene types, and haplotypes associating with these loci were studied and compared between septic patients and controls, as well as between survivals and victims of severe sepsis. The authors found that patients with high copy number of DEFA1/DEFA3 were predisposed to severe sepsis and tended to have lower level of plasma HNP1-3 as well as cytokines such as TNF-, IL-6, and IL-10.

abstract:
  Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.


id: cord-270213-ygb64yxc
author: Williams, Alexander T.
date: 2020-10-02
txt: ./txt/cord-270213-ygb64yxc.txt
cache: ./cache/cord-270213-ygb64yxc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33011274/
doi: 10.1016/j.freeradbiomed.2020.09.025
summary:
  Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19. A well-described hallmark of sepsis is endothelial dysfunction in response to a cytokine 81 ''storm'', which is associated with an increase in a series of negative consequences arising from 82 overproduction of reactive oxygen species (ROS), disruption of the glycocalyx, and endothelial 83 nitric oxide synthase (eNOS) uncoupling, all contributing to increased adhesion of red blood 84 cells (RBCs), white blood cells (WBCs), and platelets to the endothelium lining, enhanced 85 platelet activation, blood stagnation, decreased tissue perfusion and increased vascular 86 permeability. Mice treated with Control-np in our study 382 experienced significantly increased vascular permeability, as shown in Figure 4 , suggesting 383 endothelial cell and glycocalyx disruption in these animals.

title:
  Control of systemic inflammation throughearly nitric oxide supplementation with nitric oxide releasing nanoparticles

abstract:
  Amelioration of immune overactivity during sepsis is key to restoring hemodynamics, microvascular blood flow, and tissue oxygenation, and in preventing multi-organ dysfunction syndrome. The systemic inflammatory response syndrome that results from sepsis ultimately leads to degradation of the endothelial glycocalyx and subsequently increased vascular leakage. Current fluid resuscitation techniques only transiently improve outcomes in sepsis, and can cause edema. Nitric oxide (NO) treatment for sepsis has shown promise in the past, but implementation is difficult due to the challenges associated with delivery and the transient nature of NO. To address this, we tested the anti-inflammatory efficacy of sustained delivery of exogenous NO using IV infused NO releasing nanoparticles (NO-np). The impact of NO-np on microhemodynamics and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model was evaluated. NO-np treatment significantly attenuated the pro-inflammatory response by promoting M2 macrophage repolarization, which reduced the presence of pro-inflammatory cytokines in the serum and slowed vascular extravasation. Combined, this resulted in significantly improved microvascular blood flow and 72-hour survival of animals treated with NO-np. The results from this study suggest that sustained supplementation of endogenous NO ameliorates and may prevent the morbidities of acute systemic inflammatory conditions. Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19.


id: cord-297039-vfuem6bk
title: Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance
author: Beltrán-García, Jesús
date: 2020-06-25
txt: ./txt/cord-297039-vfuem6bk.txt
cache: ./cache/cord-297039-vfuem6bk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/cells9061544
doi: 10.3390/cells9061544
summary:
  Recent findings propose that circular RNAs (circRNAs) may play a prominent role in regulating the patients'' immune system against different pathogens, including bacteria and viruses. Due to the role that circRNAs play in the modulation of different cytokines and immune proteins [62, 63] , altered states of alternative splicing in sepsis may alter the expression of circRNAs, which could partially explain the changes in the immune response of septic patients. However, circRNAs may play a key role in sepsis because of their ability to modulate different molecular mechanisms [10] , including inflammation [83] and immune response [62] , and to control multiple biological processes in metabolic organs (i.e., liver, pancreas [84] ) ( Figure 3 and Table 1 ). Interestingly, circRNAs may function as "molecular sponges", by controlling the expression of different types of non-coding RNAs, such as miRNAS, involved in regulating different processes in sepsis [105] [106] [107] [108] .

abstract:
  Sepsis is a life-threatening condition that occurs when the body responds to an infection that damages it is own tissues. The major problem in sepsis is rapid, vital status deterioration in patients, which can progress to septic shock with multiple organ failure if not properly treated. As there are no specific treatments, early diagnosis is mandatory to reduce high mortality. Despite more than 170 different biomarkers being postulated, early sepsis diagnosis and prognosis remain a challenge for clinicians. Recent findings propose that circular RNAs (circRNAs) may play a prominent role in regulating the patients’ immune system against different pathogens, including bacteria and viruses. Mounting evidence also suggests that the misregulation of circRNAs is an early event in a wide range of diseases, including sepsis. Despite circRNA levels being altered in sepsis, the specific mechanisms controlling the dysregulation of these noncoding RNAs are not completely elucidated, although many factors are known to affect circRNA biogenesis. Therefore, there is a need to explore the molecular pathways that lead to this disorder. This review describes the role of this new class of regulatory RNAs in sepsis and the feasibility of using circRNAs as diagnostic biomarkers for sepsis, opening up new avenues for circRNA-based medicine.


id: cord-298505-r7ihqb96
title: Sepsis, Phages, and COVID-19
author: Górski, Andrzej
date: 2020-10-15
txt: ./txt/cord-298505-r7ihqb96.txt
cache: ./cache/cord-298505-r7ihqb96.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33076482/
doi: 10.3390/pathogens9100844
summary:
  In fact, in addition to data obtained in experimental animals, there are already reports of successful phage therapy in patients with sepsis [2] . Phage therapy efficacy has also been studied in a mouse model of neonatal sepsis caused by Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Citrobacter freundii and Moraxella catarrhalis. High effectiveness of phage therapy in the treatment of experimental sepsis induced by multidrug resistant P. Further progress in phage therapy of sepsis has recently been achieved by introducing engineered phages used to treat a patient with a disseminated drug resistant mycobacterial infection. In recent years, a number of reports derived from experimental studies in animals and human clinics have suggested the potential value of phage therapy in the treatment of sepsis. The anti-inflammatory and the immunomodulating properties of phages could also be useful in the treatment of severe COVID-19 syndrome including viral sepsis (Table 2) .

abstract:
  Phage therapy has emerged as a potential novel treatment of sepsis for which no decisive progress has been achieved thus far. Obviously, phages can help eradicate local bacterial infection and bacteremia that may occur in a syndrome. For example, phages may be helpful in correcting excessive inflammatory responses and aberrant immunity that occur in sepsis. Data from animal studies strongly suggest that phages may indeed be an efficient means of therapy for experimentally induced sepsis. In recent years, a number of reports have appeared describing the successful treatment of patients with sepsis. Moreover, novel data on the anti-viral potential of phages may be interpreted as suggesting that phages could be used as an adjunct therapy in severe COVID-19. Thus, clinical trials assessing the value of phage therapy in sepsis, including viral sepsis, are urgently needed.


id: cord-302295-nblmshni
author: Savva, Athina
date: 2013-11-18
txt: ./txt/cord-302295-nblmshni.txt
cache: ./cache/cord-302295-nblmshni.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24302927/
doi: 10.3389/fimmu.2013.00387
summary:
  TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Recombinant human activated protein C (rhAPC, Xigris®, Eli Lilly), the only drug specifically registered for sepsis, has recently been withdrawn from the market following the negative results from the PROWESS-SHOCK study that did not show reduction in mortality at 28 or 90 days in patients with septic shock (4) . The discovery of TLRs and their involvement in innate immune responses has attracted much interest into the development of drugs for controlling infections and improving sepsis management. Moreover, upon infection, innate immune cells will likely sense several MAMPs via several TLRs and non-TLR PRRs. For example, Gram-negative bacteria express MAMPs that may trigger redundant inflammatory pathways through TLR2 (lipopeptides), TLR4 (LPS), TLR5 (flagellin), TLR7 (ssRNA), and TLR9 (bacterial DNA).

title:
  Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases

abstract:
  Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.


id: cord-302379-jh6jxwyn
title: Management of odontogenic infections and sepsis: an update
author: Jevon, Phil
date: 2020-09-25
txt: ./txt/cord-302379-jh6jxwyn.txt
cache: ./cache/cord-302379-jh6jxwyn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32978579/
doi: 10.1038/s41415-020-2114-5
summary:
  A patient with non-odontogenic-related infection could also present with sepsis at a dental practice. Age-specific sepsis decision support tools have been developed by the UK Sepsis Trust to help dental staff recognise and manage patients with suspected sepsis. The aim of this article is to provide an update on the management of odontogenic infections and sepsis in the dental practice. A careful history, thorough clinical examinations and a high index of suspicion will enable the GDP to diagnose and appropriately manage patients presenting with odontogenic sepsis. The ''GDP sepsis decision support tool for primary dental care'' (Fig. 3) should be applied to all adults and young people aged 12 years and over with fever (or recent fever), symptoms presenting with a source of orofacial/dental infection (including post-operative infection) or have clinical observations outside normal limits. This stresses the importance for dental teams to be familiar with sepsis and the decision tools described here for safe management of such patients.

abstract:
  The management of odontogenic infections has improved over recent decades, but further improvements are still required. The ongoing education of GDPs and their dental teams on this issue continues to be important, especially during the current COVID-19 pandemic, where remote triage poses additional difficulties and challenges. Odontogenic infections can lead to sepsis, a potentially life-threatening condition caused by the body's immune system responding in an abnormal way. This can lead to tissue damage, organ failure and death. A patient with non-odontogenic-related infection could also present with sepsis at a dental practice. Early recognition and prompt management of sepsis improves outcomes. GDPs and their dental teams should be trained in the recognition and management of sepsis. Age-specific sepsis decision support tools have been developed by the UK Sepsis Trust to help dental staff recognise and manage patients with suspected sepsis. The aim of this article is to provide an update on the management of odontogenic infections and sepsis.


id: cord-312197-d5d8amk7
title: New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis
author: Edmond, Karen
date: 2010-03-09
txt: ./txt/cord-312197-d5d8amk7.txt
cache: ./cache/cord-312197-d5d8amk7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20231868/
doi: 10.1371/journal.pmed.1000213
summary:
  Health facility infections are also a major problem in lowincome countries, but the more pressing issues are the high proportion of home deliveries in unclean environments predisposing to sepsis and ensuring that all neonates have access to effective interventions from health care providers in the first days of life 2 . Randomised controlled trials (RCTs) of maternal protein-calorie and multiple micronutrient and supplementation have demonstrated significant improvements in rates of prematurity and birth weight and variable impact on mortality; but no studies have examined their impact on rates of neonatal sepsis [20, 21] . New studies from Malawi and Nepal indicate that maternal antisepsis interventions such as vaginal chlorhexidine during labour may have a significant impact on rates of neonatal mortality and sepsis in developing countries [33] . Intrapartum antibiotic prophylaxis has been highly effective in reducing both early-onset neonatal bacterial and maternal sepsis in developed countries [35] .

abstract:
  Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.


id: cord-347833-b3yrxkt0
author: Ahlström, Björn
date: 2020-09-04
txt: ./txt/cord-347833-b3yrxkt0.txt
cache: ./cache/cord-347833-b3yrxkt0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32887659/
doi: 10.1186/s13054-020-03203-y
summary:
  We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients. CONCLUSION: Although dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort. The following covariates were chosen from available variables through directed acyclic graph analysis and a literature review: sepsis; age [1] and sex, all of which have been previously described as independent risk factors for dementia [33] ; CCI; SAPS3 box 2+3; hospital length of stay (H-LoS); ICU-LoS; invasive ventilator therapy; and RRT. However, after adjusting for age, sex, CCI score, SAPS3 box 2+3, H-LoS, ICU-LoS, invasive ventilator therapy, and RRT, sepsis was no longer an independent risk factor for dementia (HR 1.01, 95% CI 0.91-1.11) (Fig. 4) 

title:
  A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort

abstract:
  BACKGROUND: Developing dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients. METHODS: We identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1 year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity. RESULTS: One year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61 years (interquartile range, IQR 43–72). The patients were followed for up to 11 years (median 3.9 years, IQR 1.7–6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p < 0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91–1.11, p = 0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model. CONCLUSION: Although dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort. TRIAL REGISTRATION: This study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).


id: cord-348785-f67amppy
author: Kapicibaşi, Hasan Oğuz
date: 2020-07-13
txt: ./txt/cord-348785-f67amppy.txt
cache: ./cache/cord-348785-f67amppy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32667585/
doi: 10.1590/s0102-865020200060000004
summary:
  PURPOSE: This experimental sepsis model created with Escherichia coli aimed to investigate the histopathological effects of two different doses of ozone combined with antibiotherapy on lung tissue. Based on the known positive and negative effects of ozone, in our study we aimed to assess the effect of two different doses of ozone therapy added to antibiotic treatment in an experimental sepsis model induced with Escherichia coli on the histopathologic findings observed in the inflammatory process in the lungs. In an experimental necrotizing pancreatitis model, ozone therapy was seen to be more effective to reduce oxidative stress levels, tissue injury and bacterial translocation rates compared to hyperbaric oxygen treatment 30 . Data obtained as a result of our study lead to the consideration that ozone therapy administered in addition to antibiotherapy may cause negative effects on lung tissue damaged due to sepsis.

title:
  Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model

abstract:
  PURPOSE: This experimental sepsis model created with Escherichia coli aimed to investigate the histopathological effects of two different doses of ozone combined with antibiotherapy on lung tissue. METHODS: Rats were divided into 5 groups. Then sepsis was induced intraperitoneally in the first 4 groups. The 1(st) group was treated with cefepime, the 2(nd) and 3(rd) groups were treated with cefepime combined with ozone at a dose of 0.6 mg/kg and 1.1 mg/kg. Lung tissue sections were stained with hematoxylin-eosin and assessed under light microscope and scored between 0-4 in terms of histopathological findings. RESULTS: In the comparisons between Group 1 and Group 4 in terms of cellular damage (p=0.030), inflammation (p=0.000) and overall score (p=0.007), statistically significant positive effects were observed in favor of Group 1. In the comparisons of Groups 2 and 3 with Group 4, only positive effects were observed in terms of inflammation (p=0.020, p=0.012, respectively). CONCLUSION: Although negative histopathological effects of ozone on tissue injury were detected, it was noteworthy that the increase in the ozone dose reduced the number of damaged parameters.


id: cord-349076-x3rjasg0
title: Use of Intravenous Immunoglobulins in Sepsis Therapy—A Clinical View
author: Jarczak, Dominik
date: 2020-08-03
txt: ./txt/cord-349076-x3rjasg0.txt
cache: ./cache/cord-349076-x3rjasg0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32756325/
doi: 10.3390/ijms21155543
summary:
  With this review, we aim to provide an overview of the role of immunoglobulins, with emphasis on IgM-enriched formulations, in the therapy of adult patients with sepsis and septic shock. The clinical rationale for IVIg therapy in sepsis can be categorized as follows: the role of immunoglobulins in (i) recognition and clearance of pathogens and toxins, (ii) scavenging and inhibition of up-and downstream mediator gene transcription, and (iii) anti-apoptotic effects on immune cells. The clinical rationale for IVIg therapy in sepsis can be categorized as follows: the role of immunoglobulins in (i) recognition and clearance of pathogens and toxins, (ii) scavenging and inhibition of up-and downstream mediator gene transcription, and (iii) anti-apoptotic effects on immune cells. Relationship between the timing of administration of IgM and IgA enriched immunoglobulins in patients with severe sepsis and septic shock and the outcome: A retrospective analysis Effects of the timing of administration of IgM-and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients

abstract:
  Sepsis is a life-threatening organ dysfunction, defined by a dysregulated host immune response to infection. During sepsis, the finely tuned system of immunity, inflammation and anti-inflammation is disturbed in a variety of ways. Both pro-inflammatory and anti-inflammatory pathways are upregulated, activation of the coagulation cascade and complement and sepsis-induced lymphopenia occur. Due to the manifold interactions in this network, the use of IgM-enriched intravenous immunoglobulins seems to be a promising therapeutic approach. Unfortunately, there is still a lack of evidence-based data to answer the important questions of appropriate patient populations, optimal timing and dosage of intravenous immunoglobulins. With this review, we aim to provide an overview of the role of immunoglobulins, with emphasis on IgM-enriched formulations, in the therapy of adult patients with sepsis and septic shock.


id: cord-354384-bshj0w3o
author: Tanak, Ambalika S.
date: 2020-10-19
txt: ./txt/cord-354384-bshj0w3o.txt
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url: https://doi.org/10.1016/j.bios.2020.112726
doi: 10.1016/j.bios.2020.112726
summary:
  As a point-of-care treatment option, to date, no molecular host biomarker panel is available which makes an informed decision on the specific intervention based on the diagnosis of the immune response or the ability to detect improvements in the status of patients with sepsis (Albert-Vega et al., 2018; Gunsolus et al., 2019) . To address this technological gap this work demonstrates first-of-a-kind near-patient testing ''DETecT Sepsis'' (Direct Electrochemical Technique Targeting Sepsis) sensor, which directly measures a panel of five host immune biomarkers in <5 minutes to guide the physician with active feedback on patient immune status for better therapeutic administration. The advantages of the DETecT Sepsis sensor over existing point-of-care tests are: (i) direct hassle-free measurement from a single drop of undiluted blood plasma; (ii) allows sepsis stratification based on the body''s hyper and hypo immune response; (iii) specifically surface engineered sensor design facilitates high sensitivity and specificity; (iv) portable handheld format enables multi-measure capabilities at near-patient testing.

title:
  Multiplexed cytokine detection using electrochemical point-of-care sensing device towards rapid sepsis endotyping

abstract:
  The implementation of endotype-driven effective intervention strategies is now considered as an important component for sepsis management. Rapid screening and frequent monitoring of immune responses are critical for evidence-based informed decisions in the early hours of patient arrival. Current technologies focus on pathogen identification that lacks rapid testing of the patient's immune response, impeding clinicians from providing appropriate sepsis treatment. Herein, we demonstrate a first-of-its-kind novel point-of-care device that uses a unique approach by directly monitoring a panel of five cytokine biomarkers (IL-6, IL-8, IL-10, TRAIL & IP-10), that is attributed as a sign of the body's host immune response to sepsis. The developed point-of-care device encompasses a disposable sensor cartridge attached to an electrochemical reader. High sensitivity is achieved owing to the unique sensor design with an array of nanofilm semiconducting/metal electrode interface that is functionalized with specific capture probes to measure target biomarkers simultaneously using non-faradaic electrochemical impedance spectroscopy. The sensor has a detection limit of ∼1 pg/mL and provides results in less than 5 min from a single drop of an undiluted plasma sample. Furthermore, the sensor demonstrates an excellent correlation (Pearson's r > 0.90) with the reference method for a total n = 40 clinical samples and the sensor's performance is ∼30 times faster compared to the standard reference technique. We have demonstrated the sensor's effectiveness to enhance diagnosis with a mechanistic biomarker-guided approach which can be helpful towards disease endotypying for effective clinical management of sepsis at the patient bedside.


