BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.
- MeSH
- albuminy terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- noradrenalin terapeutické užití MeSH
- sepse * farmakoterapie etiologie MeSH
- septický šok * farmakoterapie komplikace MeSH
- tekutinová terapie škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: The CLASSIC trial assessed the effects of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock. This pre-planned study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE). METHODS: We analysed mortality, serious adverse events (SAEs), serious adverse reactions (SARs) and days alive without life-support within 90 days using Bayesian models with weakly informative priors. HTE on mortality was assessed according to five baseline variables: disease severity, vasopressor dose, lactate levels, creatinine values and IV fluid volumes given before randomisation. RESULTS: The absolute difference in mortality was 0.2%-points (95% credible interval: -5.0 to 5.4; 47% posterior probability of benefit [risk difference <0.0%-points]) with restrictive IV fluid. The posterior probabilities of benefits with restrictive IV fluid were 72% for SAEs, 52% for SARs and 61% for days alive without life-support. The posterior probabilities of no clinically important differences (absolute risk difference ≤2%-points) between the groups were 56% for mortality, 49% for SAEs, 90% for SARs and 38% for days alive without life-support. There was 97% probability of HTE for previous IV fluid volumes analysed continuously, that is, potentially relatively lower mortality of restrictive IV fluids with higher previous IV fluids. No substantial evidence of HTE was found in the other analyses. CONCLUSION: We could not rule out clinically important effects of restrictive IV fluid therapy on mortality, SAEs or days alive without life-support, but substantial effects on SARs were unlikely. IV fluids given before randomisation might interact with IV fluid strategy.
- MeSH
- Bayesova věta MeSH
- dospělí MeSH
- jednotky intenzivní péče MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- septický šok * terapie MeSH
- tekutinová terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. BACKGROUND: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. METHODS: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. RESULTS: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. CONCLUSIONS: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia or very early stages of cervical cancer increases the risk of preterm prelabor rupture of membranes in subsequent pregnancies. The risk increases with the length of the excised cone. The subset of cases with preterm prelabor rupture of membranes and a history of cervical excisional treatment could also be at higher risk of intraamniotic infection/inflammation. However, there is a paucity of relevant information on this subject. OBJECTIVE: This study aimed to assess the differences in the rates of intraamniotic infection/inflammation and early-onset neonatal sepsis between singleton preterm prelabor rupture of membranes pregnancies without and with a history of cervical excisional treatment, and to investigate the association between these complications of preterm prelabor rupture of membranes and the excised cone length. STUDY DESIGN: This retrospective cohort study included 770 preterm prelabor rupture of membranes pregnancies in which transabdominal amniocentesis was performed as part of standard clinical management to assess the intraamniotic environment. The maternal and perinatal medical records of all included women were reviewed to obtain information on the absence or presence of history of cervical excisional treatment and neonatal outcomes. Women whose records contained any information on history of cervical excisional treatment were contacted by phone and in writing to inform them of the study and request permission to collect relevant information from their medical records. Women were divided into 4 subgroups according to the presence of microorganisms and/or their nucleic acids (through culturing and molecular biology methods) in amniotic fluid and/or intraamniotic inflammation (through amniotic fluid interleukin-6 concentration evaluation): intraamniotic infection (presence of both), sterile intraamniotic inflammation (intraamniotic inflammation alone), microbial invasion of the amniotic cavity without inflammation (presence of microorganisms and/or their nucleic acids in amniotic fluid alone), and negative amniotic fluid for infection/inflammation (absence of both). RESULTS: A history of cervical excisional treatment was found in 10% (76/765) of the women. Of these, 82% (62/76) had a history of only 1 treatment, and information on cone length was available for 97% (60/62) of them. Women with a history of cervical excisional treatment had higher rates of intraamniotic infection (with, 25% [19/76] vs without, 12% [85/689]; adjusted odds ratio, 2.5; adjusted P=.004), microbial invasion of the amniotic cavity without inflammation (with, 25% [19/76] vs without, 11% [74/689]; adjusted odds ratio, 3.1; adjusted P<.0001), and early-onset neonatal sepsis (with, 8% [11/76] vs without, 3% [23/689]; adjusted odds ratio, 2.9; adjusted P=.02) compared with those without such history. Quartiles of cone length (range: 3-32 mm) were used to categorize the women into 4 quartile subgroups (first: 3-8 mm; second: 9-12 mm; third: 13-17 mm; and fourth: 18-32 mm). Cone length of ≥18 mm was associated with higher rates of intraamniotic infection (with, 29% [5/15] vs without, 12% [85/689]; adjusted odds ratio, 3.0; adjusted P=.05), microbial invasion of the amniotic cavity without inflammation (with, 40% [6/15] vs without, 11% [74/689]; adjusted odds ratio, 6.1; adjusted P=.003), and early-onset neonatal sepsis (with, 20% [3/15] vs without, 3% [23/689]; adjusted odds ratio, 5.7; adjusted P=.02). CONCLUSION: History of cervical excisional treatment increases risks of intraamniotic infection, microbial invasion of the amniotic cavity without inflammation, and development of early-onset neonatal sepsis in a subsequent pregnancy complicated by preterm prelabor rupture of membranes.
- MeSH
- chorioamnionitida * epidemiologie etiologie MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká sepse * MeSH
- plodová voda MeSH
- předčasný odtok plodové vody * epidemiologie MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- zánět komplikace MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
To investigate the effect of hydrogen sulfide (H2S) on myocardial injury in sepsis-induced myocardial dysfunction (SIMD), male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg, i.p.) to induce cardiac dysfunction without or with the H2S donor sodium hydrosulfide (NaHS) (50 μmol/kg, i.p.) administration 3 h after LPS injection. Six hours after the LPS injection, echocardiography, cardiac hematoxylin and eosin (HE) staining, myocardial damage and inflammatory biomarkers and Western blot results were analyzed. In mice, the administration of LPS decreased left ventricular ejection fraction (LVEF) by 30 % along with lowered H2S levels (35 % reduction). It was observed that cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) levels were all increased (by 0.22-fold, 2000-fold and 0.66-fold respectively). HE staining revealed structural damage and inflammatory cell infiltration in the myocardial tissue after LPS administration. Moreover, after 6 h of LPS treatment, toll-like receptor 4 (TLR4) and nod-like receptor protein 3 (NLRP3) expressions were up-regulated 2.7-fold and 1.6-fold respectively. When compared to the septic mice, NaHS enhanced ventricular function (by 0.19-fold), decreased cTnI, TNF-alpha, and IL-1beta levels (by 11 %, 33 %, and 16 % respectively) and downregulated TLR4 and NLRP3 expressions (by 64 % and 31 % respectively). Furthermore, NaHS did not further improve cardiac function and inflammation in TLR4-/- mice or mice in which NLRP3 activation was inhibited by MCC950, after LPS injection. In conclusion, these findings imply that decreased endogenous H2S promotes the progression of SIMD, whereas exogenous H2S alleviates SIMD by inhibiting inflammation via the TLR4-NLRP3 pathway suppression.
- MeSH
- funkce levé komory srdeční MeSH
- kardiomyopatie * MeSH
- lipopolysacharidy toxicita MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- poranění srdce * MeSH
- protein NLRP3 MeSH
- sepse * chemicky indukované komplikace farmakoterapie MeSH
- sulfan * farmakologie terapeutické užití MeSH
- tepový objem MeSH
- TNF-alfa MeSH
- toll-like receptor 4 metabolismus MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Diseminovaná intravaskulárna koagulácia (DIC) je častou a život ohrozujúcou komplikáciou sepsy. Sepsa asociovaná s DIC je charakterizovaná ako systémová aktivácia pri koagulácii s potlačenou fibrinolýzou, ktorá vedie k dysfunkcii orgánov v kombinácii so systémovým intravaskulárnym zápalom. V tomto procese zohrávajú kľúčovú úlohu trombín, neutrofily, trombocyty, endotel a molekulárne vzorce spojené s poškodením ako súčasť imunotrombózy. Nedávne pokroky v chápaní patofyziológie umožnili diagnostikovať DIC spojenú so sepsou v skoršom načasovaní a s lepšou presnosťou. Pokrok v liečbe je však stále obmedzený a vyžaduje nové terapeutiká pre DIC spojenú so sepsou.
Disseminated intravascular coagulation (DIC) is a common and life-threatening complication in sepsis. Sepsis-associated DIC is recognized as the systemic activation in coagulation with suppressed fibrinolysis that leads to organ dysfunction in combination with systemic intravascular inflammation. In this proces, thrombin, neutrophils, platelets, endothelium and damage-associated molecular patterns play a key role as part of immunothrombosis. Recent advances in the understanding of pathophysiology have made it possible to diagnose sepsis-associated DIC at earlier timing and with better accuracy. However, progress in the treatment is still limited, and requires new therapeutics for sepsis-associated DIC.
Úvod: Cílem této studie bylo porovnat hodnoty interleukinu-6 v pupečníkové a periferní krvi novorozence. Klinickým cílem bylo zjistit, zda lze vyšetřením krve z pupečníku nahradit brzký postnatální odběr periferní krve. Pacienti a metody: Do studie byli zahrnuti novorozenci (< 35. týden gestace) narození v roce 2016–2018 ve Fakultní nemocnici Olomouc. U těchto novorozenců se zároveň podařilo odebrat dostatečné množství krve z pupečníku. Výsledky: Párový odběr se zdařil u 73 novorozenců. Mezi pupečníkovou a periferní hodnotou interleukinu-6 byl zjištěn významný rozdíl (p < 0,001). Medián prvního měření (pupečníková krev) byl 6,5 ng/l, medián druhého měření (periferní krev) 56 ng/l. Nárůst je téměř desetinásobný. Závěr: Hodnoty interleukinu-6 z pupečníkové krve a z časného postnatálního odběru se podstatně liší. Na tuto skutečnost je nutné myslet při jeho klinickém využití.
Introduction: The aim of this study was to compare interleukin-6 values in umbilical cord and peripheral blood of newborns. The clinical goal was to determine whether the examination of cord blood can replace early postnatal peripheral blood collection. Patients and methods: Study included premature newborns (< 35th week of gestation) born in 2016-2018 at Olomouc University Hospital. At the same time, it was possible to collect a sufficient amount of blood from the umbilical cord in these newborns. Results: Paired sampling was successful in 73 of these newborns. A significant difference (p < 0,001) was found between the umbilical cord and peripheral interleukin-6 values. The median of the first measurement (cord blood) was 6,5 ng/l, the median of the second measurement (peripheral blood) was 56 ng/l. The increase is almost ten times bigger. Conclusion: The difference of values between interleukin-6 from umbilical cord blood and from early postnatal collection are significantly different and it is necessary to keep it in mind during its clinical use.
- MeSH
- fetální krev imunologie MeSH
- interleukin-6 * analýza izolace a purifikace krev MeSH
- krev imunologie MeSH
- lidé MeSH
- novorozenec nedonošený imunologie krev MeSH
- novorozenec MeSH
- novorozenecká sepse diagnóza etiologie imunologie prevence a kontrola MeSH
- prospektivní studie MeSH
- pupečník imunologie krevní zásobení MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- COVID-19 * diagnóza patofyziologie terapie MeSH
- heparin aplikace a dávkování terapeutické užití MeSH
- intravenózní imunoglobuliny aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- methylprednisolon aplikace a dávkování terapeutické užití MeSH
- syndrom systémové zánětlivé reakce * etiologie farmakoterapie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
INTRODUCTION: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs). METHOD: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis). RESULTS: Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively. DISCUSSION: A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.
- MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- kojenecká mortalita MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká sepse * diagnóza MeSH
- randomizované kontrolované studie jako téma MeSH
- sepse diagnóza terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
- MeSH
- ECHO virové infekce * diagnóza epidemiologie komplikace MeSH
- lidé MeSH
- masivní nekróza jater MeSH
- novorozenec MeSH
- novorozenecká sepse MeSH
- vertikální přenos infekce MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Geografické názvy
- Francie MeSH
- Itálie MeSH
