Brain dysfunction is a frequent complication of sepsis. Most likely, sepsis-associated brain dysfunction (SABD) results from the interaction between multiple factors: neurodegeneration due to microglial activation, altered neurotransmission, neuroinflammation and impairment of cerebral macro- and microcirculation. Altered brain perfusion might results from several mechanism: global or regional alterations in cerebral blood flow (CBF); reduced cerebral perfusion pressure - which is the driving force propelling blood through cerebral blood vessels - due to systemic hypotension; global or regional vasoconstriction; dysfunction of the intrinsic regulatory mechanisms of CBF, such as cerebral autoregulation and cerebrovascular reactivity; endothelial and blood-brain barrier dysfunction; autonomic nervous system dysfunction and metabolic uncoupling. Disorders of brain perfusion and CBF regulation are frequently observed in humans with sepsis, and intracranial hemodynamics monitoring can potentially be useful in clinical management of septic patients. The aim of this review is to provide an update of the current knowledge on alterations in brain hemodynamics associated with sepsis, along with physiological and methodological considerations intended to help the reader navigate the diverse results from published literature and a practical guide to apply non-invasive intracranial hemodynamics monitoring to septic patients in clinical practice.

Sepsis is an increasing cause of decompensation in patients with chronic heart failure with reduced or preserved ejection fraction. Sepsis and decompensated heart failure results in a mixed septic-cardiogenic shock that poses several therapeutic dilemmas: Rapid fluid resuscitation is the cornerstone of sepsis management, while loop diuretics are the main stay of decompensated heart failure treatment. Whether inotropic therapy with dobutamine or inodilators improves microvascular alterations remains unsettled in sepsis. When to resume loop diuretic therapy in patients with sepsis and decompensated heart failure is unclear. In the absence of relevant guidelines, we review vasopressor therapy, the timing and volume of fluid resuscitation, and the need for inotropic therapy in patients who, with sepsis and decompensated heart failure, present with a mixed septic-cardiogenic shock.

PURPOSE:Leukocyte adhesion to vascular and matrix Metalloproteinase-8 (MMP8) expression is increased in sepsis and associated with poor prognosis in sepsis patients. This study aimed to investigate the role of MMP8 in sepsis serum mediated leukocyte adhesion. METHODS:Bioinformatics analysis of GSE64457 and GSE65682 was performed to evaluate the role of MMP8 in the progression of sepsis. Expression of MMP8 in blood samples from patients with sepsis was detected by qRT-PCR and ELISA. Human umbilical vein endothelial cells (HUVECs) were treated with sepsis serum, control serum, and MMP8 inhibitor. Expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by qRT-PCR and ELISA, respectively. The protein expression of total p38, phosphorylated-p38, ERK1/2, and p-ERK1/2 was detected by Western blotting. Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) were incubated with the treated HUVECs to calculate leukocyte adhesion. RESULTS:Four hundred and twenty-nine differentially expressed genes (DEGs) and seven hub genes between sepsis patients and healthy controls were identified. GO function analysis of DEGs and hub genes indicated that the DEGs and hub genes were mainly enriched in neutrophil activation. MMP8 was selected as a key gene with an unfavorable prognosis in sepsis patients. The mRNA and protein expression of MMP8 in blood from sepsis patients were significantly higher than controls. Leukocyte adhesion and mRNA and protein expression of VCAM-1 and ICAM-1 were significantly increased in the sepsis serum group compared to that in the control group, as was the protein expression of p-p38 and p-ERK1/2. However, the MMP8 inhibitor suppressed the leukocyte adhesion promoted by sepsis serum by decreasing the expression of VCAM-1, ICAM-1, p-p38, and p-ERK1/2. CONCLUSION:Our study indicated that MMP8 acts as a key gene in the development of sepsis, and sepsis serum promotes leukocyte adhesion to HUVECs via MMP8, which suggest that MMP8 might be a potential therapeutic target for sepsis.

BACKGROUND:Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis. METHODS:Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated. RESULTS:Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs' chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs' chemotaxis and phagocytosis functions. CONCLUSIONS:The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low- and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease the overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming, and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants have been used for the diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices, and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes. IMPACT: Reviews the clinical relevance of currently available diagnostic tests for sepsis. Summarizes the diagnostic accuracy of novel biomarkers for neonatal sepsis. Outlines future strategies including the use of omics technology, personalized medicine, and point of care tests.

PURPOSE OF REVIEW:Sepsis is a leading cause of death worldwide. Groundbreaking international collaborative efforts have culminated in the widely accepted surviving sepsis guidelines, with iterative improvements in management strategies and definitions providing important advances in care for patients. Key to the diagnosis of sepsis is identification of infection, and whilst the diagnostic criteria for sepsis is now clear, the diagnosis of infection remains a challenge and there is often discordance between clinician assessments for infection. RECENT FINDINGS:We review the utility of common biochemical, microbiological and radiological tools employed by clinicians to diagnose infection and explore the difficulty of making a diagnosis of infection in severe inflammatory states through illustrative case reports. Finally, we discuss some of the novel and emerging approaches in diagnosis of infection and sepsis. SUMMARY:While prompt diagnosis and treatment of sepsis is essential to improve outcomes in sepsis, there remains no single tool to reliably identify or exclude infection. This contributes to unnecessary antimicrobial use that is harmful to individuals and populations. There is therefore a pressing need for novel solutions. Machine learning approaches using multiple diagnostic and clinical inputs may offer a potential solution but as yet these approaches remain experimental.

In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies.

BACKGROUND:Mortality and other clinical outcomes between culture-negative and culture-positive septic patients have been documented inconsistently and are very controversial. A systematic review and meta-analysis was performed to compare the clinical outcomes of culture-negative and culture-positive sepsis or septic shock. METHODS:We searched the PubMed, Cochrane and Embase databases for studies from inception to the 1st of January 2021. We included studies involving patients with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality and clearly compared culture-negative versus culture-positive patients with clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, mechanical ventilation requirements, mechanical ventilation duration and renal replacement requirements). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS:Seven studies including 22,655 patients were included. The primary outcome of this meta-analysis showed that there was no statistically significant difference in the all-cause mortality between two groups (OR = 0.95; 95% CI, 0.88 to 1.01; P = 0.12; Chi- = 30.71; I = 80%). Secondary outcomes demonstrated that there was no statistically significant difference in the ICU length of stay (MD = - 0.19;95% CI, - 0.42 to 0.04; P = 0.10;Chi- = 5.73; I = 48%), mechanical ventilation requirements (OR = 1.02; 95% CI, 0.94 to 1.11; P = 0.61; Chi = 6.32; I = 53%) and renal replacement requirements (OR = 0.82; 95% CI, 0.67 to 1.01; P = 0.06; Chi- = 1.21; I = 0%) between two groups. The hospital length of stay of culture-positive group was longer than that of the culture-negative group (MD = - 3.48;95% CI, - 4.34 to - 2.63; P < 0.00001;Chi- = 1.03; I = 0%). The mechanical ventilation duration of culture-positive group was longer than that of the culture-negative group (MD = - 0.64;95% CI, - 0.88 to - 0.4; P < 0.00001;Chi- = 4.86; I = 38%). CONCLUSIONS:Culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. Furthermore, culture-positive septic patients had similar ICU length of stay, mechanical ventilation requirements and renal replacement requirements as those culture-negative patients. The hospital length of stay and mechanical ventilation duration of culture-positive septic patients were both longer than that of the culture-negative patients. Further large-scale studies are still required to confirm these results.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B, B, B, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

Sepsis is a host immune disorder induced by infection. It can lead to multiple organ dysfunction syndrome (MODS), which has high morbidity and mortality. There has been great progress in the clinical diagnosis and treatment of sepsis, such as improvements in pathogen detection technology, innovations regarding anti-infection drugs, and the development of organ function support. Abnormal immune responses triggered by pathogens, ranging from excessive inflammation to immunosuppression, are recognized to be an important cause of the high mortality rate. However, no drugs have been approved specifically for treating sepsis. Here, we review the recent research progress on immune responses in sepsis to provide a theoretical basis for the treatment of sepsis. Constructing and optimizing a dynamic immune system treatment regimen based on anti-infection treatment, fluid replacement, organ function support, and timely use of immunomodulatory interventions may improve the prognosis of sepsis patients.

The complex pathophysiology of sepsis makes it a syndrome with limited therapeutic options and a high mortality rate. Gram-negative bacteria containing lipopolysaccharides (LPS) in their outer membrane correspond to the most common cause of sepsis. Since the gut is considered an important source of LPS, intestinal damage has been considered a cause and a consequence of sepsis. Although important in the maintenance of the intestinal epithelial cell homeostasis, the microbiota has been considered a source of LPS. Recent studies have started to shed light on how sepsis is triggered by dysbiosis, and an increased inflammatory state of the intestinal epithelial cells, expanding the understanding of the gut-liver axis in sepsis. Here, we review the gut-liver interaction in Gram-negative sepsis, exploring the mechanisms of LPS inactivation, including the recently described contribution of an isoform of the cholesteryl-ester transfer protein (CETPI). Although several key questions remain to be answered when the pathophysiology of sepsis is reviewed, new contributions coming to light exploring the way LPS might be inactivated in vivo, suggest that new applications might soon reach the clinical setting.

BACKGROUND:Procalcitonin (PCT) has been widely investigated as an infection biomarker. The study aimed to prove that serum PCT, combining with other relevant variables, has an even better sepsis-detecting ability in critically ill patients. METHODS:We conducted a retrospective cohort study in a regional teaching hospital enrolling eligible patients admitted to intensive care units (ICU) between July 1, 2016, and December 31, 2016, and followed them until March 31, 2017. The primary outcome measurement was the occurrence of sepsis. We used multivariate logistic regression analysis to determine the independent factors for sepsis and constructed a novel PCT-based score containing these factors. The area under the receiver operating characteristics curve (AUROC) was applied to evaluate sepsis-detecting abilities. Finally, we validated the score using a validation cohort. RESULTS:A total of 258 critically ill patients (70.9±16.3 years; 55.4% man) were enrolled in the derivation cohort and further subgrouped into the sepsis group (n = 115) and the non-sepsis group (n = 143). By using the multivariate logistic regression analysis, we disclosed five independent factors for detecting sepsis, namely, "serum PCT level," "albumin level" and "neutrophil-lymphocyte ratio" at ICU admission, along with "diabetes mellitus," and "with vasopressor." We subsequently constructed a PCT-based score containing the five weighted factors. The PCT-based score performed well in detecting sepsis with the cut-points of 8 points (AUROC 0.80; 95% confidence interval (CI) 0.74-0.85; sensitivity 0.70; specificity 0.76), which was better than PCT alone, C-reactive protein and infection probability score. The findings were confirmed using an independent validation cohort (n = 72, 69.2±16.7 years, 62.5% men) (cut-point: 8 points; AUROC, 0.79; 95% CI 0.69-0.90; sensitivity 0.64; specificity 0.87). CONCLUSIONS:We proposed a novel PCT-based score that performs better in detecting sepsis than serum PCT levels alone, C-reactive protein, and infection probability score.

Sepsis has been characterized as a dysregulated host response to infection, and the role of the microbiome as a key influencer of this response is emerging. Disruption of the microbiome while treating sepsis with antibiotics can itself result in immune dysregulation. Alterations in the gut microbiome resulting from sepsis and its treatment have been implicated in organ dysfunction typical of sepsis across multiple tissues including the lung, kidney, and brain. Multiple microbiota-directed interventions are currently under investigation in the setting of sepsis, including fecal transplant, the administration of dietary fiber, and the use of antibiotic scavengers that attenuate the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. The emerging evidence shows that the gut microbiome interacts with various elements of the septic response, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.

Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". Contrary to the older definitions, the current one not only focuses on inflammation, but points to systemic disturbances in homeostasis, including metabolism. Sepsis leads to sepsis-induced dysfunction and mitochondrial damage, which is suggested as a major cause of cell metabolism disorders in these patients. The changes affect the metabolism of all macronutrients. The metabolism of all macronutrients is altered. A characteristic change in carbohydrate metabolism is the intensification of glycolysis, which in combination with the failure of entering pyruvate to the tricarboxylic acid cycle increases the formation of lactate. Sepsis also affects lipid metabolism-lipolysis in adipose tissue is upregulated, which leads to an increase in the level of fatty acids and triglycerides in the blood. At the same time, their use is disturbed, which may result in the accumulation of lipids and their toxic metabolites. Changes in the metabolism of ketone bodies and amino acids have also been described. Metabolic disorders in sepsis are an important area of research, both for their potential role as a target for future therapies (metabolic resuscitation) and for optimizing the current treatment, such as clinical nutrition.

Sepsis still remains a big challenge in patients admitted to intensive care units (ICUs) despite stellar advances made in the field of medicine. We can achieve better clinical outcomes in patients by diagnosing sepsis earlier. Procalcitonin (PCT), an inflammatory biomarker, has shown promising results in this regard. Therefore, this systematic review was done to assess the use of PCT in diagnosing and predicting severe outcomes in patients admitted to ICU and to assess if introducing PCT as a routine biochemical tool in hospitals would be helpful to achieve better clinical course in ICU patients. To identify relevant articles, we searched PubMed, Google Scholar, and references of included articles. Eligible studies were identified by two investigators independently and data were extracted. Original articles that evaluated the diagnostic and prognostic value of serum PCT levels in predicting sepsis, the severity of sepsis, and mortality among adult patients admitted to ICU were included in this study. A total of 2,063 citations were identified by the search, among which 10 studies (five prospective cohort, three retrospective cohort, one cross-sectional, and one case-control study) met the inclusion criteria. Most studies showed moderate-to-low risk of bias which was evaluated using the Quality in Prognosis Studies tool. All studies showed a positive correlation between initial PCT levels and detecting mortality resulting from sepsis, six studies found PCT helpful in detecting sepsis, and four studies evaluated the role of PCT in detecting severity in patients with sepsis. One study found area under the curve of serum PCT level for predicting 28-day mortality to be 0.82 (95% confidence interval [CI]: 0.70-0.94; p < 0.001) in adults and 0.83 (95% CI: 0.73-0.92; p < 0.001) in the elderly having an optimal cut-off level of serum PCT of 0.2 ng/mL in both the adult and elderly groups, with a sensitivity of 81 and 75% and specificity of 81.7 and 80.4%, respectively. PCT has shown promising results in detecting sepsis and its clinical course. For early diagnosis and management of sepsis, severe sepsis, and mortality in patients admitted to the ICU for a more favorable clinical outcome, PCT can be used.

BACKGROUND Hyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear. MATERIAL AND METHODS Information about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality. RESULTS A total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis. CONCLUSIONS Higher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

Sepsis as life-threatening organ dysfunction caused by microorganisms represents a dreadful challenge for the immune system. The role of the complement system as major column of innate immunity has been extensively studied in various sepsis models, but its translational value remains in the dark. Complement activation products, such as C3a and C5a, and their corresponding receptors provide useful diagnostic tools and promising targets to improve organ function and outcome. However, a monotherapeutic complement intervention irrespective of the current immune function seems insufficient to reverse the complex sepsis mechanisms. Indeed, sepsis-induced disturbances of cross talking complement, coagulation, and fibrinolytic cascades lead to systemic 'thromboinflammation', ultimately followed by multiple-organ failure. We propose to reliably monitor the complement function in the patient and to re-establish the immune balance by patient-tailored combined therapies, such as complement and Toll-like receptor inhibition. Our working hypothesis aims at blocking the 'explosive' innate immune recognition systems early on before downstream mediators are released and the inflammatory response becomes irreversible, a strategy that we name 'upstream approach'.

BACKGROUND:Little is known about the accuracy of the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS) in identifying sepsis patients with a history of hypertension on anti-hypertensive agents, which affect vital signs as components of the scoring systems. We aimed to examine the ability of qSOFA and NEWS to predict sepsis among anti-hypertensive agent users by comparing them with non-users. METHODS:We retrospectively identified adult patients (aged ≥18years) with suspected infection who presented to an emergency department (ED) of a large tertiary medical center in Japan between April 2018 and March 2020. Suspected infection was defined based on the chief complaint of fever, high body temperature, or the clinical context on arrival at the ED. We excluded patients who had trauma or cardiac arrest, those who were transported to other hospitals after arrival at the ED, and those whose vital signs data were mostly missing. The predictive performances of qSOFA and NEWS based on initial vital signs were examined separately for sepsis, ICU admission, and in-hospital mortality and compared between anti-hypertensive agent users and non-users. RESULTS:Among 2900 patients with suspected infection presenting to the ED, 291 (10%) had sepsis, 1023 (35%) were admitted to the ICU, and 188 (6.5%) died. The prediction performances of qSOFA and NEWS for each outcome among anti-hypertensive agent users were lower than that among non-users (e.g., c-statistics of qSOFA for sepsis, 0.66 vs. 0.71, p = 0.07; and for ICU admission, 0.70 vs. 0.75, p = 0.01). For identifying sepsis, the sensitivity and specificity of qSOFA ≥2 were 0.43 and 0.77 in anti-hypertensive agent users and 0.51 and 0.82 in non-users. Similar associations were observed for identifying ICU admission and in-hospital mortality. Regardless of the use of anti-hypertensive agents, NEWS had better prediction abilities for each outcome than qSOFA. CONCLUSION:The clinical performance of qSOFA and NEWS for identifying sepsis among anti-hypertensive agent users was likely lower than that among non-users.

Despite continuous advances in burn care, sepsis is still the main cause of death in burn patients. Procalcitonin (PCT) has been reported as an accurate sepsis biomarker and also as a fair predictor of death. The aim of this study was to assess PCT kinetics in the first week postburn regarding sepsis diagnosis and death prognosis. Sample included 142 patients with ≥15% TBSA, admitted from January 2011 to December 2014 at Coimbra Burns Unit, Portugal. Sepsis diagnosis was done according to American Burn Association criteria. PCT range and median values in the first 7 days after burns were statistically analyzed for its potential for sepsis diagnosis and death prognosis. A subanalysis was done regarding TBSA, sex, age, and inhalation injury. First week PCT range and median were significant for sepsis diagnosis and death prognosis, but the median area under the curve was greater in the last case. TBSA influenced PCT accuracy, which was greater for TBSA less than 40% either for diagnosis or prognosis. Age was inversely related to the accuracy, being better in younger than 40 years in both cases. PCT diagnostic accuracy was not affected by sex, opposing to the prognostic one which is better in women. Inhalation injury had no effect on diagnostic accuracy, but it happens with prognostic accuracy. PCT levels' variation is related to sepsis evolution and outcome. Its median performs better than its range. Always coupled with clinical examination, monitoring PCT levels kinetics may help early sepsis detection, potentially reducing morbidity and mortality, being also useful for death prognosis.

Sepsis-associated encephalopathy causes long-term health problems in patients with sepsis. This review explores the pathogenesis of sepsis-associated encephalopathy, including its effects on the blood-brain barrier, microglia activation, mitochondrial dysfunction, the inflammatory medium and neurotransmitters and its roles in amino acid balance disorders, hyperammonemia, and intestinal flora imbalance. Understanding the etiology of sepsis-associated encephalopathy may allow the development of adjunctive therapies targeting its underlying mechanism and help develop preventative strategies.

BACKGROUND:The benefits of early antibiotics for sepsis have recently been questioned. Evidence for this mainly comes from observational studies. The only randomized trial on this subject, the Prehospital Antibiotics Against Sepsis (PHANTASi) trial, did not find significant mortality benefits from early antibiotics. That subgroups of patients benefit from this practice is still plausible, given the heterogeneous nature of sepsis. RESEARCH QUESTION:Do subgroups of sepsis patients experience 28-day mortality benefits from early administration of antibiotics in a prehospital setting? And what key traits drive these benefits? STUDY DESIGN AND METHODS:We used machine learning to conduct exploratory partitioning cluster analysis to identify possible subgroups of sepsis patients who may benefit from early antibiotics. We further tested the influence of several traits within these subgroups, using a logistic regression model. RESULTS:We found a significant interaction between age and benefits of early antibiotics (P = .03). When we adjusted for this interaction and several other confounders, there was a significant benefit of early antibiotic treatment (OR, 0.07; 95% CI, 0.01-0.79; P = .03). INTERPRETATION:An interaction between age and benefits of early antibiotics for sepsis has not been reported before. When validated, it can have major implications for clinical practice. This new insight into benefits of early antibiotic treatment for younger sepsis patients may enable more effective care.

BACKGROUND:The extent of the damage following surgery has been subject of study for several years. Numerous surgical complications can impact postoperative quality of life of patients and even can cause mortality. Although these complications are generally due to multifactorial mechanisms, oxidative stress plays a key pathophysiological role. Moreover, oxidative stress could be an unavoidable effect derived even from the surgical procedure itself. METHODS:A systematic review was performed following an electronic search of Pubmed and ScienceDirect databases. Keywords such as sepsis, oxidative stress, organ dysfunction, antioxidants, outcomes in postoperative complications, among others, were used. Review articles were preferably used between the years 2015 onwards, not excluding older ones. RESULTS:The vast majority point to the role of oxidative stress in generating greater damage and worse prognosis in postoperative patients without the necessary care and precautions, taking importance on the use of antioxidants to prevent this problem. DISCUSSIONS:Oxidative stress represents a common final pathway related to pathological processes such as inflammation or ischemia-reperfusion, among others. The expression of greater severity of these complications can result in multiple organ dysfunction or sepsis. The aim of this study was to present an update of the role of oxidative stress on surgical postoperative complications.

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.

Children with hypoplastic left heart syndrome (HLHS) must undergo multiple surgical stages to reconstruct the anatomy to a sustainable single ventricle system. Stage I palliation, or the Norwood procedure, provides circulation to both pulmonary and systemic vasculature. The aorta is reconstructed and attached to the right ventricle and a fraction of systemic flow is redirected to the pulmonary arteries (PAs) through a systemic-to-PA shunt. Despite abundant hemodynamic data available 4-5 months after Norwood palliation, data is very scarce immediately following stage I. This data is critical in determining post-operative success. In this work, we combined population data and computational fluid dynamics (CFD) to characterize hemodynamics immediately following stage I (post-stage I) and prior to stage II palliation (pre-stage II). A patient-specific model was constructed as a baseline geometry, which was then scaled to reflect population-based morphological data at both time-points. Population-based hemodynamic data was then used to calibrate each model to reproduce blood flow representative of HLHS patients. The post-stage I simulation produced a PA pressure of 22 mmHg and high-frequency oscillations within the flow field indicating highly disturbed hemodynamics. Despite PA mean pressure dropping to 14 mmHg, the pre-stage II model also produced high-frequency flow components and PA wall shear stress increases. These suboptimal conditions may be necessary to ensure adequate PA flow throughout the pre-stage II period, as the shunt becomes relatively smaller compared to the patient's somatic growth. In the future, CFD can be used to optimize shunt design and minimize these suboptimal conditions.

BACKGROUND:Quick Sepsis-related Organ Failure Assessment (qSOFA) is recommended for use by the most recent international sepsis definition taskforce to identify suspected sepsis in patients outside the intensive care unit (ICU) at risk of adverse outcomes. Evidence of its comparative effectiveness with existing sepsis recognition tools is important to guide decisions about its widespread implementation. AIM:To compare the performance of qSOFA with the adult sepsis pathway (ASP), a current sepsis recognition tool widely used in NSW hospitals and systemic inflammatory response syndrome criteria in predicting adverse outcomes in adult patients on general wards. METHODS:A retrospective observational cohort study was conducted which included all adults with suspected infections admitted to a Sydney teaching hospital between December 2014 and June 2016. The primary outcome was in-hospital mortality with two secondary composite outcomes. RESULTS:Among 2940 patients with suspected infection, 217 (7.38%) died in-hospital and 702 (23.88%) were subsequently admitted to ICU. The ASP showed the greatest ability to correctly discriminate in-hospital mortality and secondary outcomes. The area under the receiver-operating characteristic curve for mortality was 0.76 (95% confidence interval (CI): 0.74-0.78), compared to 0.64 for the qSOFA tool (95% CI: 0.61-0.67, P < 0.0001). Median time from the first ASP sepsis warning to death was 8.21 days (interquartile range (IQR): 2.29-16.75) while it was 0 days for qSOFA (IQR: 0-2.58). CONCLUSIONS:The ASP demonstrated both greater prognostic accuracy and earlier warning for in-hospital mortality for adults on hospital wards compared to qSOFA. Hospitals already using ASP may not benefit from switching to the qSOFA tool.

OBJECTIVE:Expand upon the priorities of fluid resuscitation and vasopressor therapy research priorities identified by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES:Original article, literature search. STUDY SELECTION:Several members of the original task force with expertise specific to the area of fluid resuscitation and vasopressor therapy. DATA EXTRACTION:None. DATA SYNTHESIS:None. CONCLUSION:In the second of a series of manuscripts subsequent to the original article, members with expertise in the subjects expound upon the three identified priorities related to fluid resuscitation and vasopressor therapies. This analysis summarizes what is known and what were identified as ongoing and future research.

OBJECTIVE:To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN:A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS:Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction? CONCLUSIONS:While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

The Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 provides updated recommendations, rationales, and evidence tables for best care of patients with sepsis. "Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock (sepsis-3) is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality than with sepsis alone." Sepsis and septic shock are major health care problems, affecting millions of people around the world each year. Early identification and management of sepsis and septic shock in the initial hours after sepsis develops, improves outcomes.

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

A new update of the sepsis bundle was published by the Surviving Sepsis Campaign (SSC) in April 2018. The original 3 h and 6 h bundles have been restructured and combined into a 1‑h bundle. The recommendations comprehensively focus on diagnostic and therapeutic measures which should be carried out within 1 h after recognition of sepsis. This article presents the background and discusses criticisms of the new recommendations.

Implantation of bacteria embedded in a fibrin clot allows for successful establishment of sepsis in preclinical models. This model allows the investigator to modulate the strain of bacteria as well as the bacterial load delivered. As it allows for a slow release of standardized bacteria, the use of a fibrin clot model may be considered in studying the initial and later phases of sepsis and the host response to infection. Here we describe methods for performing the fibrin clot model of sepsis.

PURPOSE:This study aimed to investigate the incidence and effect of quality of life (QOL) change in Korean sepsis survivors. MATERIALS AND METHODS:Using the National Health Insurance claim database of South Korea, we included adult sepsis survivors who were primarily diagnosed with sepsis between 2010 and 2018 and survived for more than 1 year after diagnosis. QOL change was defined using three criteria: decrease in annual income level, newly acquired disability, and increase in underlying comorbidities after sepsis. RESULTS:A total of 119,660 sepsis survivors were included in the final analysis. Overall, worsening QOL was observed in 92,096 (77.0%) of the survivors. Specifically, compared with that of before sepsis diagnosis, 9778 sepsis survivors (8.2%) had a decrease in annual income level, and 10,648 (8.9%) were newly registered as having a disability. Additionally, 74,528 (62.3%) and 79,142 (66.1%) sepsis survivors showed an increase in the Charlson and Elixhauser comorbidity indices, respectively. Among sepsis survivors, post-sepsis disability and increase in comorbidity indices were associated with a higher risk of 3-year all-cause mortality. CONCLUSIONS:We found that most sepsis survivors experienced a worsening in their QOL, which was associated with a higher risk of long-term mortality.

Sepsis is one of the most serious problems in modern medicine. Long-term outcomes in septic shock patients are very discouraging: 75% individuals who survived sepsis and septic shock demonstrate signs of organ failure and experience persistent functional deficit. Acute sepsis and its management in an intensive care unit (ICU) to a great extent determine the pathogenesis of further complications. We believe that the concept of phenoptosis proposed by Prof. Skulachev deserves a special attention from anesthesiologists and ICU doctors. According to this concept, septic shock is a suicidal mechanism of programmed organism death, which protects human population from dangerously infected individuals. The article suggests a potential approach to the sepsis treatment based on the notion that septic shock can be prevented by identification and blockade of receptors involved in the processing of phenoptotic signal induced by lipopolysaccharide and other substances that initiate septic shock. In view of this, the search for agents that can block molecular mechanisms of the phenoptotic signal transmission seems very promising.

BACKGROUND:Septic shock is a life-threatening infection frequently responsible for hospital admissions or may be acquired as nosocomial infection in hospitalized patients with resultant significant morbidity and mortality . There is a dearth of data on a résumé and meta-analysis on the global epidemiology of this potentially deadly condition. Therefore, we propose the first systematic review to synthesize existing data on the global incidence, prevalence and case fatality rate of septic shock worldwide. METHODS:We will include cross-sectional, case-control and cohort studies reporting on the incidence, and case fatality rate of septic shock. Electronic databases including PubMed, Embase, WHO Global Health Library and Web of Science will be searched for relevant records published between 1 January 2000 and 31 August 2019. Independents reviewers will perform study selection and data extraction, as well as assessment of methodological quality of included studies. Appropriate meta-analysis will then be used to pool studies judged to be clinically homogenous. Egger's test and funnel plots will be used to detect publication bias. Findings will be reported and compared by human development level of countries. ETHICS AND DISSEMINATION:Being a review, ethical approval is not required as it was obtained in the primary study which will make up the review. This review is expected to provide relevant data to help in evaluating the burden of septic shock in the general population. The overall findings of this research will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER:CRD42019129783.

BACKGROUND:We aimed to determine if the ABO blood types carry different risks of 30-day mortality, acute kidney injury (AKI), and endothelial damage in critically ill patients with sepsis. This was a retrospective cohort study of three independent cohorts of critically ill patients from the United States and Scandinavia consisting of adults with septic shock. We compared the 30-day mortality across the blood types within each cohort and pooled the results in a meta-analysis. We also estimated the incidence of AKI and degree of endothelial damage, as measured by blood concentrations of soluble thrombomodulin and syndecan-1. RESULTS:We included 12,342 patients with severe sepsis. In a pooled analysis blood type B carried a slightly lower risk of 30-day all-cause mortality compared to non-blood type B (adjusted HR 0.88; 95%-CI 0.79-0.98; p = 0.02). There was no difference in the risk of AKI. Soluble thrombomodulin and syndecan-1 concentrations were lower in patients with blood type B and O compared to blood type A, suggesting less endothelial damage. CONCLUSION:Septic patients with blood type B had less endothelial damage, and a small reduction in mortality. The exposure is, however, unmodifiable.

BACKGROUND:The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. MAIN BODY:A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. CONCLUSION:Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.

OBJECTIVES:Antibiotic administration within 1 hour of hypotension has been shown to reduce mortality. It is unknown whether antibiotics before hypotension in children who eventually meet criteria for septic shock improves outcomes. This study assesses whether antibiotic timing from the time of meeting criteria for sepsis in children with septic shock impacts morbidity and mortality. METHODS:This is a retrospective study of children 18 years or younger presenting to a tertiary free-standing children's hospital emergency department with sepsis that subsequently progressed to septic shock and were admitted to an intensive care unit from 2008 to 2012. The time when the patient met criteria for sepsis to the time of first antibiotic administration was assessed and correlated with patient morbidity and mortality. RESULTS:Among 135 children (median age, 13.1 years), 34 (25%) were previously healthy, whereas 49 (36%) had 2 or more medical comorbidities. Twenty-seven children (20%) had positive blood cultures, 17 (13%) had positive urine cultures, and 34 (25%) had chest x-ray findings that were interpreted as pneumonia. Among the 42 (31%) with antibiotics within 1 hour from criteria for sepsis, there was higher mortality (4/42 vs 0/93, P = 0.009), more organ dysfunction, longer time on a vasoactive infusion, and increased intensive care unit and hospital lengths of stay (all P < 0.05). CONCLUSIONS:Children with criteria for sepsis who subsequently progressed to septic shock who received antibiotics within 1 hour of meeting sepsis criteria had increased mortality, length of stay, and organ dysfunction.

Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.

BACKGROUND:Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. METHODS:This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure ( = 70) and NIV success ( = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. RESULTS:The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; = .007), and initial NIV [Formula: see text] settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, = .02) or had signs of volume overload (36% vs 64%, < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], < .001), and initial [Formula: see text] on NIV (odds ratio 1.04 [95% CI 1.01-1.08, = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). CONCLUSIONS:NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial [Formula: see text] settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.

Sepsis is one of the main causes of death in burn patients, and many studies have suggested that procalcitonin (PCT) is a biomarker for the early diagnosis of sepsis, but the results are controversial. The aim of this study was to evaluate the diagnostic value of serum PCT in adult burn sepsis by conducting a meta-analysis of published studies. The PubMed, Embase, Web of Science, CNKI and China Wanfang databases were searched, and studies on PCT as a marker for the diagnosis of adult burn sepsis from the establishment of the database, to February 1, 2020 were screened. The data were analyzed using Stata v. 15.0 software. A total of 10 studies and 704 patients were included. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.67 (95% CI: 0.48-0.81), 0.87 (95% CI: 0.72-0.95), 5.20 (95% CI: 2.49-10.84), 0.38 (95% CI: 0.24-0.61) and 13.70 (95% CI: 5.72-32.82), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.85 (95% CI: 0.82-0.88), and the diagnostic threshold was the main source of heterogeneity. Results demonstrate that serum PCT may be used as a useful biomarker for the early diagnosis of burn sepsis in adults, and may be combined with other diagnostic indexes to further improve the sensitivity and specificity.

Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials.

PURPOSE OF REVIEW:Maternal sepsis is the second leading cause of maternal death in the United States. A significant number of these deaths are preventable and the purpose of this review is to highlight causes such as delays in recognition and early treatment. RECENT FINDINGS:Maternal sepsis can be difficult to diagnose due to significant overlap of symptoms and signs of normal physiological changes of pregnancy, and current screening tools perform poorly to identify sepsis in pregnant women. Surveillance should not only include during pregnancy, but also throughout the postpartum period, up to 42 days postpartum. Education and awareness to highlight this importance are not only vital for obstetric healthcare provides, but also for nonobstetric healthcare providers, patients, and support persons. SUMMARY:Through education and continual review and analysis of evidence-based practice, a reduction in maternal morbidity and mortality secondary to maternal sepsis should be attainable with dedication from all disciplines that care for obstetric and postpartum patients. Education and vigilance also extend to patients and support persons who should be empowered to escalate care when needed.