Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / The Systemic Inflammatory Response Syndrome (SIRS) is characterized by an excessive release of inflammatory mediators as a systemic inflammatory response to a serious clinical injuries. The use of glutamine in nutraceutical doses has been studied as a strategy in tissue protection and preservative of tissue metabolic function in stressful situations, helping to improve the immune response of patients. The effects of enteral glutamine supplementation in nutraceutical doses on the inflammatory markers, of glycolytic metabolism, of immune system and of oxidative stress were studied in adult and elderly patients with SIRS in a prospective, clinical, randomized, controlled, double-blind crossover study. Thirty six moderately severe patients admitted to the Intensive Care Unit were selected according to pre-defined criteria, diagnosis of SIRS and the APACHE II score (>10<20), distributed into two groups and submitted to the supplementation with 1 litre of enteral nutrition with addition of 30g of L-glutamine or calcium caseinate or 1 litre of enteral nutrition with addition of 30g of calcium caseinate or L-glutamine for two days, pause for one day only with diet, followed by four days of supplementation. Blood samples were collected before (T0) and after (T1) each supplementation. For evaluation blood parameters (hematocrit, leukocytes, lymphocytes, monocytes, prealbumin, blood urea nitrogen, creatinine, glucose, lactate, C-peptide and insulin), IL-1, IL-6, IL-10 and TNF&#945; were also assayed. Glutathione, TBARS, and glutamine and glutamate amino acids were measured. Six patients died during the study. Thirty patients finished the study, 16 men (53%) and 14 (47%) women, median age 74.4 years (30-92 years) in moderately severe state of health (APACHE II 13.1 - range 10-19). All patients developed SIRS and were given enteral nutrition supplemented with L-glutamine or calcium caseinate, 1464kcal/day (range 792-1914kcal/day). The use of L-glutamine in nutraceutical dose of 30g/day showed no changes in blood parameters. All laboratory parameters remained within normal values except the blood urea [Calcium Caseinate T1=47.0mg/dL (range 34.0-69.0 mg/dL) versus Glutamine T1=50.0mg/dL (36.75-75.0mg/dL); p=0.030]. Creatinine concentrations were not statistically different. There was no statistically significant difference in assessment of inflammatory parameters (IL-1, IL-6, IL-10 E TNF&#945;). Leukocytes count decreased significantly in both groups [Calcium Caseinate T0=13.650 1/mm3 (10.148-18.250 1/mm3) versus T1=11.500 1/mm3 (8.050-29.100 1/mm3); p=0,019] and [Glutamine T0=12.850 1/mm3 (11.155-15.550 1/mm3) versus T1=11.000 1/mm3 (9.200-16.325 1/mm3); p=0.046]. There was increase statistically significant difference in lymphocytes count between groups [Calcium Caseinate T1=1085 1/mm3 (range 805-1363 1/mm3) versus Glutamine T1=1916 1/mm3 (1301-2517 l/mm3); p<0.0001] and Calcium Caseinate group decreases [T0=1288 1/mm3 (range 834-2209 1/mm3) versus T1=1085 1/mm3 (range 805-1363 1/mm3); p=0.0324] and Glutamine group increases [T0=954 1/mm3 (range 785-1442 1/mm3) versus T1=1916 1/mm3 (range 1301-2517 l/mm3); p<0.0001]. Blood concentration of TBARS decreased significantly in both groups [Calcium Caseinate T0=20.56&#61549;mol MDA/ml (range 13.64-20.56&#61549;mol MDA/ml); p=0.001] and [Glutamine T0=17.67 &#61549;mol MDA/ml (range 8.11-34.98 &#61549;mol MDA/ml) versus T1=16.52 &#61549;mol MDA/ml (range 5.41-21.86 &#61549;mol MDA/ml); p=0.020]. The blood concentrations of Gluthatione showed a statistically significant reduction in caseinate group (T0=486.0&#61549;mol/ml (range 486.0Â165.8&#61549;mol/ml versus T1=451.0Â167.4&#61549;mol/ml; p=0.047) and no statistically significant difference in the glutamine group, nor between groups. However, there were no differences between groups. Glutamine and glutamate were not statistically different. Enteral nutrition supplemented with glutamine in nutraceutical doses of 30g/day increase lymphocyte count, helps to reduce lipid peroxidation and maintains the antioxidant glutathione capacity, interfering beneficially modulating the inflammatory response and stress, but present no effect upon cytokines concentrations or glycolytic parameters. / A SÃndrome da Resposta InflamatÃria SistÃmica (SRIS) caracteriza-se por uma liberaÃÃo excessiva de mediadores inflamatÃrios a uma sÃrie de situaÃÃes clÃnicas graves. A utilizaÃÃo da glutamina em doses nutracÃuticas tem sido estudada como uma estratÃgia de proteÃÃo tecidual e metabÃlica em situaÃÃes de estresse, melhorando a resposta imune de pacientes. Os efeitos da nutriÃÃo enteral suplementada com 30g/dia de glutamina sobre os marcadores inflamatÃrios, do metabolismo glicolÃtico, da funÃÃo imune e do estresse oxidativo foram estudados em pacientes adultos e idosos com SRIS. Foi realizado estudo clÃnico prospectivo, randomizado, controlado, duplo-cego, cruzado. Trinta e seis pacientes internados em Unidade de Terapia Intensiva foram selecionados pelos critÃrios do estudo, diagnÃstico da SRIS e score APACHE II (>10<20), distribuÃdos em dois grupos e submetidos à suplementaÃÃo com 1 litro de dieta enteral suplementada com 30g de L-glutamina ou caseinato de cÃlcio ou 1 litro de dieta enteral suplementada com 30g de caseinato de cÃlcio ou L-glutamina por dois dias, intervalo de um dia somente com dieta, perfazendo quatro dias de dieta com suplementaÃÃo. Amostras de sangue foram coletadas antes (T0) e apÃs (T1) cada suplementaÃÃo. Foram realizadas anÃlises do hematÃcrito, leucÃcitos, linfÃcitos, monÃcitos, prÃ-albumina, urÃia, creatinina, glicose, lactato, peptÃdeo-C e insulina, das IL-1, IL-6, IL-10, TNF&#945;, glutationa, TBARS e dos aminoÃcidos glutamina e glutamato. Seis pacientes foram a Ãbito durante o estudo e trinta pacientes concluÃram o estudo, sendo 16(53%) homens e 14(47%) mulheres, mediana de idade 74,4 anos (30-92 anos), moderadamente graves, mediana de APACHE II 13,1 (10-19) e mediana de ingestÃo calÃrica de 1464kcal/dia (792-1914kcal/dia). O uso L-glutamina em dose nutracÃutica de 30g/dia nÃo mostrou alteraÃÃes nos parÃmetros hematolÃgicos. Houve aumento da urÃia [Caseinato T1=47,000mg/dL (34,000-69,000mg/dL) versus Glutamina T1=50,000mg/dL (36,750-75,000mg/dL); p=0,030] na comparaÃÃo intergrupos, mas nÃo houve diferenÃa estatisticamente significante de creatinina em nenhum dos grupos. NÃo houve alteraÃÃo estatisticamente significante nos parÃmetros inflamatÃrios (IL-1, IL-6, IL-10 e TNF&#945;). A contagem de leucÃcitos diminuiu significantemente em ambos os grupos [Caseinato T0=13.650 1/mm3 (10.148-18.250 1/mm3) versus T1=11.500 1/mm3 (8.050-29.100 1/mm3); p=0,019] e [Glutamina T0=12.850 1/mm3 (11.155-15.550 1/mm3) versus T1=11.000 1/mm3 (9.200-16.325 1/mm3); p=0,046]. Houve aumento estatisticamente significante na contagem de linfÃcitos na comparaÃÃo intergrupos [Caseinato T1=1.085 1/mm3 (805-1.363 1/mm3) versus Glutamina T1=1.916 1/mm3 (1.301-2.517 l/mm3); p<0,0001], uma diminuiÃÃo estatisticamente significante no grupo Caseinato [T0=1.288 1/mm3 (834-2.209 1/mm3) versus T1=1.085 1/mm3 (805-1.363 1/mm3); p=0,0324] e aumento no grupo Glutamina [T0=954 1/mm3 (785-1.442 1/mm3) versus T1=1.916 1/mm3 (1.301-2.517 l/mm3); p<0,0001]. Observou-se reduÃÃo estatisticamente significante na dosagem do TBARS na comparaÃÃo intragrupos [Caseinato T0=20,56&#61549;mol MDA/ml (13,64-20,56&#61549;mol MDA/ml) versus T1=15,08 &#61549;mol MDA/ml (13,64-20,56 &#61549;mol MDA/ml); p=0,001] e [Glutamina T0=17,67 &#61549;mol MDA/ml (8,11-34,98 &#61549;mol MDA/ml) versus T1=16,52 &#61549;mol MDA/ml (5,41-21,86 &#61549;mol MDA/ml); p=0,020], mas nÃo houve diferenÃas intergrupos. A concentraÃÃo sanguÃnea de glutationa apresentou uma reduÃÃo estatisticamente significante no grupo Caseinato (T0=486,00&#61549;mol/mlÂ165,80&#61549;mol/ml) versus T1=451,00Â167,40&#61549;mol/ml; p=0,047) e nÃo houve diferenÃa no grupo Glutamina, tampouco entre os grupos. Glutamina e glutamato nÃo demonstraram diferenÃas estatisticamente significantes. Conclui-se que a nutriÃÃo enteral suplementada com glutamina em dose nutracÃutica de 30g/dia em pacientes moderadamente graves promove um aumento dos linfÃcitos, contribui para reduzir a peroxidaÃÃo lipÃdica e mantÃm a capacidade antioxidante da glutationa, interferindo de forma benÃfica na modulaÃÃo da resposta inflamatÃria e do estresse, mas nÃo apresenta nenhum efeito sobre a concentraÃÃo de citocinas ou parÃmetros glicolÃticos.

Bakgrund och problemformulering: Sepsis är ett akut livshotande sjukdomstillstånd som är svårt att upptäcka och har en hög mortalitet. Tid till behandling är av yttersta vikt för denna utsatta patientgrupp. På grund av diffusa symtom är sjukdomstillståndet svårt att identifiera i prehospital vård. Detta kan medföra fördröjning av behandling med vätska och antibiotika, vilket kan leda till försämrad prognos. Syfte: Syftet är att beskriva det prehospitala förloppet bland patienter med slutdiagnosen sepsis med speciellt fokus på tidig identifiering och att relatera ovanstående till utfall bedömt som död inom 30 dagar. Metod: En kvantitativ retrospektiv registerstudie genomfördes. Samtliga patienter (n=775) hade fått diagnos sepsis utifrån specifik ICD-kod någon gång under vårdprocessen på ett sjukhus i Västsverige under 2015 och 2016. I studien inkluderades de patienter (n=232) som transporterades och/eller bedömdes av ambulans före ankomst till sjukhus, samt fick huvuddiagnosen sepsis baserat på en specifik ICD-kod vid utskrivning på någon av sjukhusets vårdavdelningar. Resultat: Ambulanssjuksköterskan misstänkte diagnosen sepsis i 20 % av fallen. Majoriteten av patienterna hade en hög prioritet efter bedömning enligt RETTS. De patienter som inte överlevde hade lägre systoliskt blodtryck, lägre syremättnad och högre andningsfrekvens. Däremot var inte andelen patienter där det förelåg en prehospital identifiering av sepsis signifikant skild mellan de som överlevde och de som inte överlevde. Diskussion: Fler hjälpmedel är en möjlighet för ambulanssjuksköterskan för att bli mer pricksäker i sin bedömning av misstänkta sepsispatienter. Detta skulle kunna tidigarelägga behandlingen och förhoppningsvis därmed öka överlevnaden.

Bakgrund: Sepsis är ett vanligt förekommande sjukdomstillstånd vilket, utan korrekt och adekvat behandling, kan utvecklas till svår sepsis och septisk chock med högre mortalitet som följd. Som ambulanssjuksköterska är det viktigt att i tidigt skede diagnostisera och förmedla misstanke om detta tillstånd. Syfte: Syftet är att beskriva patientkarakteristika samt undersöka ambulanssjuksköterskans förmåga att identifiera, bedöma och prioritera de patienter som vårdats i ambulans och fått slutdiagnosen sepsis. Metod: Studien är en kvantitativ, retrospektiv observationsstudie med journalgranskning som datakälla. Den inkluderade populationen är samtliga patienter som blivit inskrivna på ett länssjukhus i sydvästra Sverige med slutdiagnos sepsis under perioden 1 januari 2016 till 31 december 2016 och som vårdats i ambulans i samband med vårdtillfället. Resultat: Totalt 580 patienter vårdades på det aktuella sjukhuset med slutdiagnos sepsis under den angivna tidsperioden. Av dessa vårdades 60,9% i ambulans till sjukhuset (n=353) och inkluderades i studien. Patientens tillstånd bedömdes som sepsis i 36.3% av fallen (n=128). Patienter där ambulanssjuksköterskan bedömt tillståndet som sepsis erhåller i större utsträckning behandling och prioriteras högre. Inga signifikanta skillnader avseende strukturerad bedömning och anamnesinhämtning kunde identifieras. Slutsats: Träffsäkerheten hos ambulanssjuksköterskan att identifiera tillståndet sepsis är relativt hög, men utrymme för förbättring föreligger. De identifierade patienterna hade högre andningsfrekvens, temperatur och de patienter som ambulanssjuksköterskan har bedömt som sepsis prioriteras högre och erhåller behandling i större utsträckning. Resultatet visar även att det inte finns några skillnader avseende ambulanssjuksköterskans första bedömning, anamnesinhämtning och strukturerad bedömning. Mer forskning, utbildning och standardiserade beslutsstöd skulle kunna öka andelen patienter där en sepsis identifieras.

Orientador: Tomomasa Yano / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-27T12:09:55Z (GMT). No. of bitstreams: 1 Tibo_LuizHenriqueSoares_M.pdf: 5939486 bytes, checksum: b93497f16ad2e0392928acc05650e417 (MD5) Previous issue date: 2015 / Resumo: O sobrenadante de cultivo de Escherichia coli isolada de pacientes com sepse (SEPEC) causou alongamento e perda de junção intercelular em células endoteliais de veia umbilical humana (HUVEC) em menos de 18 horas de incubação. O fator citotóxico envolvido foi purificado em sistema de cromatografia líquida (FPLC) a partir do sobrenadante da amostra SEPEC 15 e, através de eletroforese desnaturante (SDS-PAGE), foi observado que este fator tem massa molecular de aproximadamente 150kDa e é formado por pelo menos duas subunidades. Ensaios de transcitose em Transwell e a monitoração da permeabilidade de monocamada de células HUVEC, por meio de medições da resistência elétrica transendotelial (TEER), indicaram que este fator citotóxico auxilia a passagem de SEPEC através de monocamada de células HUVEC, cultivadas em insertos Transwell, no período de 30 minutos. Porém, quando incubadas com a citotoxina por mais de 30 minutos, as células HUVEC morrem devido à citotoxicidade do fator citotóxico. Estes resultados sugerem que esta citotoxina pode ser um importante fator de virulência de SEPEC, auxiliando o acesso deste patógeno à corrente sanguínea / Abstract: The culture supernatant of Escherichia coli isolated from patients with sepsis (SEPEC) caused elongation and loss of intercellular junction in endothelial cells of human umbilical vein (HUVEC) in less than 18 hours of incubation. The cytotoxic factor involved was purified by liquid chromatography system (FPLC) from the SEPEC 15 sample supernatant and, by denaturing electrophoresis (SDS-PAGE), it was found that this factor has a molecular mass of approximately 150kDa and is formed by the least two subunits. Transwell Transcytosis assays and monitoring the permeability of HUVEC monolayer by measurements of transendothelial electrical resistance (TEER) indicated that this cytotoxic factor helps SEPEC passing through HUVEC monolayer cells cultured in Transwell inserts, in a 30 minutes period. However, when incubated with cytotoxin for more than 30 minutes, the HUVEC cells die due to the cytotoxicity of the cytotoxic factor. These results suggest that this cytotoxin can be an important virulence factor of SEPEC, assisting this pathogen access to the bloodstream / Mestrado / Microbiologia / Mestre em Genética e Biologia Molecular

Bakgrund: Sepsis är ett akut sjukdomstillstånd med varierande symtom och är därför svårt att upptäcka. Tillståndet innebär lidande för patienten och mortaliteten bland drabbade är hög. Snabb identifiering och behandling är av betydelse för patientens hälsa och överlevnad. Sjuksköterskan har ansvar för omvårdnaden, såväl för beroende som oberoende omvårdnadsåtgärder. För att möjliggöra god och säker vård ska sjuksköterskan arbeta förebyggande med patientsäkerhetsarbete. Syfte: Syftet var att undersöka faktorer i sjuksköterskans arbete som är viktiga för att tidigt upptäcka och behandla patienter med sepsis. Metod: Artiklar med kvantitativ design har sammanställts till en litteraturöversikt och analyserats med deduktiv ansats. I urval och datainsamling har Polit och Becks niostegsmodell används och totalt gick 11 artiklar vidare från kvalitetsgranskning till resultat. Resultat: Tre faktorer hittades; Utbildning, screeningverktyg samt riktlinjer för behandling vid sepsis. Utbildning ledde till ökad kunskap och ökade sjuksköterskans förmåga att identifiera sepsis. Vid användning av riktlinjer ökade följsamheten till behandlingsåtgärder och tiden till behandling minskade. Screeningverktyg och riktlinjer för behandling minskade mortaliteten. Slutsats: Sjuksköterskans är central i arbetet för tidig upptäckt och behandling, då sjuksköterskan screenade patienter för sepsis, initierade till och utförde behandlingsåtgärder. För att säker vård ska möjliggöras vid sepsis krävs såväl kunskap, screeningverktyg samt riktlinjer för behandling. / Background: Sepsis is a critical condition with varying symptoms that makes it difficult to detect. The mortality is high and the condition causes the patient suffering. Early identification and rapid treatment is important for the patient's health and survival. The nurse is responsible for nursing care, both independent interventions and ordered by physicians.  The nurse needs to work preventing regards patients and providers safety to provide good care. Aim: To survey factors for early detection and treatment in the nurse's work with patients having sepsis. Method:  A literature overview with quantitative articles and a deductive approach. For selection and collection of data Polit and Becks nine-way model was used. A total of 11 articles was quality reviewed and included to the result.  Results: Three factors were found; Education, screening tools and guidelines for treatment of sepsis. Education led to increased knowledge and increased the nurse's ability to identify sepsis. When using guidelines, adherence to treatment measures increased and time to treatment decreased. Furthermore, screening tools and treatment guidelines were found to reduce mortality. Conclusion: The nurse is central in the work of early detection and treatment. The nurse screened patients for sepsis, initiated and fulfilled treatment measures. Knowledge, screening tools and guidelines for treatment are required to enable safe care in the case of sepsis.

Sepsis is among the most prevalent diagnosed critical illnesses in the United States today. Although advances have reduced the overall morbidity and mortality associated with this illness, the enormous number of deaths associated with it shows a need for improved diagnostic and therapeutic optionsgent. Our laboratory has utilized RNA based technologies to aid in the treatment of histone induced multiple organ dysfunction syndrome seen in sepsis. Histones are proteins found in the nucleus of every cell in our body and have been shown to be released during sepsis. Such release induces damage to other cells, causing a feed forward cycle that results in organ failure and death. Several therapeutics have been utilized to neutralize histones but have shown considerable toxicity. This thesis describes the generation of single stranded RNA aptamers to bind and neutralize histone mediate damage without unwanted toxicity. We demonstrate that our aptamers selectively bind to histones but not serum proteins. In addition, we establish that our aptamers can neutralize all histone mediated cellular response in vitro and in vivo. Finally, we determined that our aptamers are able inhibit the histone feed forward cycle in a temporal fashion in our murine model of multiple organ dysfunction. This novel therapeutic demonstrates the selectivity and effectiveness needed to inhibit histones in several critical illnesses.

Sepsis, a life-threatening organ dysfunction caused by dysregulated host immune response to infection, is one of the leading causes of death within intensive care units (ICUs) in the United States. Developing specific therapies to treat sepsis is a current challenge for translational research, where over 100 drugs developed to target pro- and anti-inflammatory pathways in sepsis have failed to pass clinical trials. The recent challenge in translating effective sepsis pharmaceuticals from animals to humans has led some researchers to question the overall viability of using specific pathogen free (SPF) mice as an animal model for sepsis in human beings. SFP mice are raised in a barrier facility designed to prevent exposure to specific pathogens, while humans are exposed to a wide range of pathogens on a daily basis. Acknowledging the influence that prior environmental pathogen exposure has on the immune system’s response to future infections, researchers have developed the cohoused (CoH) mouse model as a potential alternative to SPF mice for use in research on immunological diseases such as sepsis. CoH mice are SPF mice cohoused with “dirty” pet store mice for 60 days, which increases their pathogen exposure and results in mice with immune experience more comparable to humans. Although the CoH model shows promise, a recent study conducted by Huggins et al shows increased sepsis-induced morbidity and mortality of CoH mice compared to SPF mice when using the lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) models of sepsis. The experiments described in this thesis aim to further compare the inflammatory response of SPF, CoH, and pet store mice after intra-peritoneal injections of either LPS or cecal slurry (CS) to identify potential differences among these mouse groups and better understand why CoH mice experience increased mortality during sepsis. A baseline experiment was performed on each of these mice groups for comparison. Our baseline experiments demonstrate significant elevations in peritoneal immune cells within CoH mice compared to SPF mice. CS experiments demonstrate a significantly higher infiltration of immune cells in CoH mice following cecal slurry injection compared to SPF mice, suggesting that environmental pathogen exposure influences host inflammatory response within the peritoneum. However, LPS experiments were largely inconclusive. No significant differences were observed between SPF and CoH mice in regard to immune cell infiltration within the peritoneum, while blood analysis showed significant elevations in Tumor Necrosis Factor alpha (TNFa) and Interleukin 6 (IL-6) with increasing environmental pathogen exposure. Since the inflammatory response within the peritoneum to LPS was not significantly different between SPF and CoH mice, future studies could expand upon these results by investigating other tissue compartments in SPF and CoH mice following LPS injection into the peritoneum to provide a more complete comparison between these mice during LPS induced sepsis.

Background: Magnetic resonance imaging (MRI) techniques are rarely used in the context of abdominal sepsis and in sepsis research. This study investigates the impact of MRI for monitoring septic peritonitis in an animal model (colon ascendens stent-induced peritonitis, CASP). The CASP model closely mimics that of human disease and is highly standardized. The most frequently employed readout parameter in mouse CASP studies is prolonged or decreased rate of survival. Monitoring the progression of peritonitis via MRI could provide a helpful tool in the evaluation of severity. The use of alternative readout systems could very well reduce the number of research animals. Perspectively, clinical improvement after certain treatment could be classified. Methods: This study describes for the first time MRI findings following the induction of septic peritonitis in mice using the CASP model. Two sublethal groups of mice with septic peritonitis were investigated. Each had received one of two differing stent diameters in order to control the leakage of feces into the abdominal cavity. Each mouse served as its own control. Imaging and analyses were performed blinded. Gut diameters, stomach volume, abdominal organ wall diameters, and volume of the adrenal glands were measured. Serum corticosterone levels were detected using ELISA. Serum IL-6, TNF-α, IL-1β, and IL-10 levels were screened by cytometric bead array. Statistical analysis was performed using the Mann-Whitney U test for nonparametric probes and the Kruskal-Wallis and t tests. Results: Using a 7-tesla MRI scanner 24 and 48 h after induction of septic peritonitis, interenteric fluid, organ swelling of spleen and adrenal glands, as well as dilatation of the stomach were compared to nonseptic conditions. Swelling of adrenal glands resulted in an increased serum corticosterone level. In addition, the wall of the intestine bowel was thickened. Based upon these findings, an MRI score (MRI sepsis score, MSS) for abdominal sepsis in mice was established. Reduced stent sizes led to reduced severity of the abdominal sepsis, which could be reproduced in the MSS, which is described here for the first time. Conclusions: Intraabdominal variations during septic peritonitis are detectable by MRI techniques. MRI methods should become a more important tool for the evaluation of abdominal peritonitis. MSS could provide an interesting tool for the evaluation of therapeutic strategies.

Introduktion: Sepsis är ett globalt hälsoproblem som förekommer inom alla instanser i vården. Sepsis är initialt svårt att identifiera, vilket medför en omfattande underdiagnostisering och hög mortalitet. Trots att den svenska sjukvården är välutvecklad avlider omkring 20 % av de som insjuknar i sepsis. Tidig identifiering är av stor vikt, då detta ökar chansen för överlevnad och minimerar risken för komplikationer. Tidig identifiering är avgörande för utfallet och sjuksköterskan innehar i sitt patientnära arbete ett viktigt ansvar. Syfte: Syftet med litteraturstudien var att beskriva sjuksköterskans erfarenheter av tidig identifiering av sepsis. Metod: Litteraturstudien utformades enligt Polit och Beck (2020) nio steg. Databassökning genomfördes i databaserna Cinahl och Pubmed. Litteraturstudiens resultat baserades på 11 kvalitetsgranskade artiklar. Åtta utav dessa tillämpade kvantitativ metod, två tillämpade kvalitativ metod och en använde sig utav mixad metod. Resultat: Databearbetningen och analysen resulterade i fyra teman; betydelse av kunskap, betydelse av yrkeserfarenhet, betydelse av teamarbete och betydelse av en fungerande organisation. Slutsats: Sjuksköterskans erfarenheter av tidig identifiering av sepsis kantas av stor kunskapsbrist kring tillståndet, behovet av yrkeserfarenhet och teamarbete, samt ett flertal brister inom organisationen. Resultatet antyder att det finns ett omfattande behov av utbildning och organisatoriska förändringar i den kliniska verksamheten.

Endothelial cell dysfunction contributes to sepsis induced initiate immune response and the infiltration of immune cells into organs, resulting in organ injury. Heat shock protein A12B (HSPA12B) is predominantly expressed in endothelial cells. The present study investigated whether endothelial HSPA12B could regulate macrophage pro-inflammatory response during sepsis. Wild type (WT) and endothelial cell-specific HSPA12B deficient (HSPA12B–/–) mice were subjected to CLP sepsis. Mortality and cardiac function were monitored. Higher mortality, worsened cardiac dysfunction, and greater infiltrated macrophages in the myocardium and spleen were observed in HSPA12B–/– septic mice compared with the WT septic mice. The serum levels of TNF-α and IL-1β were higher and the levels of IL-10 were lower in HSPA12B–/– septic mice than in WT septic mice. Importantly, endothelial exosomes contain HSPA12B which can be uptaken by macrophages. Interestingly, endothelial exosomal HSPA12B significantly increases IL-10 levels and decreases TNF-α and IL-1β production in LPS-stimulated macrophages. Mechanistic studies show that endothelial exosomal HSPA12B downregulates NF-κB activation and nuclear translocation in LPS stimulated macrophages. These data suggest that endothelial HSPA12B plays a novel role in the regulation of macrophage pro-inflammatory response via exosomes during sepsis and that sepsis induced cardiomyopathy and mortality are associated with endothelial cell deficiency of HSPA12B.