Sepsis-related Death Research Articles

Epidemiological Trend of Sepsis in Patients with Hospital Admissions Related to Hepatitis C in Spain (2000-2015): A Nationwide Study.

Background: Hepatitis C virus (HCV) infection predisposes patients to other infectious diseases, such as sepsis. We aimed to analyze epidemiological trends of sepsis-related admissions, deaths, and costs in hospital admissions with chronic hepatitis C who had a hospital admission in Spain. Methods: We performed a retrospective study of all hospitalizations involving chronic hepatitis C in the Spanish Minimum Basic Data Set (MBDS) between 2000 and 2015. This period was divided into four calendar periods (2000–2004, 2005–2007, 2008–2011, and 2012–2015). Results: We selected 868,523 hospital admissions of patients with chronic hepatitis C over 16 years in the Spanish MBDS. Among them, we found 70,976 (8.17%) hospital admissions of patients who developed sepsis, of which 13,915 (19.61%) died during admission. We found an upward trend, from 2000–2003 to 2012–2015, in the rate of sepsis-related admission (from 6.18% to 10.64%; p < 0.001), the risk of sepsis-related admission (from 1.31 to 1.55; p < 0.001), and the sepsis-related cost per hospital admission (from 7198€ to above 9497€; p < 0.001). However, we found a downward trend during the same study period in the sepsis case-fatality rate (from 21.99% to 18.16%; p < 0.001), the risk of sepsis-related death (from 0.81 to 0.56; p < 0.001), and the length of hospital stay (LOHS) (from 16.9 to 13.9; p < 0.001). Moreover, the rate of bacterial Gram-positive and candidiasis infections decreased, while Gram-negative microorganisms increased from 2000–2003 to 2012–2015. Conclusions: Sepsis, in chronic hepatitis C patients admitted to the hospital, has increased the period 2000–2015 and has been an increasing burden for the Spanish public health system. However, there has also been a significant reduction in lethality and LOHS during the study period. In addition, the most prevalent specific microorganisms have also changed in this period.

Milk Allergen Detection: Sensitive Label-Free Voltammetric Immunosensor Based on Electropolymerization

We present in this work, first time in literature, a voltammetric label-free biosensor for detection of alpha lactalbumin (α-LB) in meal samples. Food allergy concern necessitates strict regulations in food labelling and innovative monitoring strategies for prevention of sepsis-related death. As major food allergens, dietary samples often contain whey proteins, including α-LB as one of the key allergenic. Available detection methods for α-LB are based on successive labelling steps and hence have long assay times with limited sensitivity. The new detection method presented here is based on capturing of α-LB via entrapped α-LB antibody (α-LB-Ab) through electropolymerization of polypyrrole (PPy) and then measuring the conductivity decrease by differential pulse voltammetry (DPV). This new label-free voltammetric biosensor for α-LB exhibits the best limit of detection (0.19 fg/mL) published so far in literature, with high selectivity and capability to quantify α-LB in real milk samples too.

Low dose of propranolol treatment is associated with better survival in cirrhotic patients with hepatic encephalopathy.

The use of nonselective beta blockers in cirrhotic patients experiencing complications is controversial. We aimed to investigate the association between propranolol treatment and outcomes for cirrhotic patients with hepatic encephalopathy. Using data from the Taiwan National Health Insurance Research Database, we identified 4754 cirrhotic patients newly diagnosed with hepatic encephalopathy between 2001 and 2010. Among them, 519 patients received propranolol treatment and the other 519 patients without exposure to propranolol were enrolled into our study, both of which were matched by sex, age, and propensity score. The Kaplan-Meier method and time-dependent-modified Cox proportional hazards models were employed for survival and multivariate-stratified analyses. The median overall survival (OS) was significantly longer in the propranolol-treated cohort than in the untreated cohort (3.46 versus 1.88 years, P < 0.001). A dose-dependent increase in survival was observed (median OS: 4.49, 3.29, and 2.46 years in patients treated with propranolol more than 30 , 20-30 , and less than 20 mg/day, respectively [P < 0.001, P = 0.001, and P = 0.079 versus the untreated group]). In addition to reduce the risk of mortality (adjusted hazard ratio, 0.58; P < 0.001), propranolol also diminished the risk of sepsis-related death (adjusted hazard ratio, 0.31; P = 0.006) according to the multivariate analysis. However, the risk of circulatory or hepatic failure was nonsignificantly altered by propranolol treatment. Low dose of propranolol treatment was associated with a better OS in cirrhotic patients with hepatic encephalopathy and its effects were dose dependent.

Intraoperative Hemoadsorption in Patients With Native Mitral Valve Infective Endocarditis

Cardiac surgery in patients with infective endocarditis is associated with high mortality owing to postoperative septic multiorgan failure. Hemoadsorption therapy may improve surgical outcomes by reducing the circulating cytokines. We aimed to evaluate the clinical effects of intraoperative hemoadsorption in patients with mitral valve endocarditis. Eligible candidates were patients with infective endocarditis of the native mitral valve undergoing cardiac surgery between January 2014 and July 2018. Patients with intraoperative hemoadsorption (hemoadsorption) were compared with surgery without hemoadsorption (control). The end points were the incidence of postoperative sepsis, sepsis-associated death, and 30-day mortality. Furthermore, postoperative need for epinephrine and norepinephrine and systemic vascular resistance were evaluated. A total of 58 consecutive patients were included: 30 in the hemoadsorption group and 28 in the control group. Postoperative sepsis occurred in 5 patients in the hemoadsorption group and in 11 in the control group (P= .05). No sepsis-associated death occurred in the hemoadsorption group, whereas five septic patients in the control group died (P= .02). Thirty-day mortality was 10% in the hemoadsorption group versus 18% in the control group (P= .39). On intensive care unit admission, the cumulative need for epinephrine and norepinephrine was 0.15 versus 0.24 μg/kg body weight/min (P= .01) and the median systemic vascular resistance was 1413 versus 1010 dyn·s·cm-5 (P= .02) in the hemoadsorption versus control group, respectively. Intraoperative hemoadsorption might reduce the incidence of postoperative sepsis and sepsis-related death. In addition, patients with intraoperative hemoadsorption showed greater hemodynamic stability. These data suggest that intraoperative hemoadsorption may improve surgical outcome in patients with mitral valve endocarditis.

The influence of atrial fibrillation on the mortality of incident ESRD patients undergoing maintenance hemodialysis.

BackgroundAtrial fibrillation (AF) is highly prevalent, occurring in 1%–2% of the adult population, increasing the risk of stroke, and resulting in considerable healthcare costs. While stroke is a major complication of AF, end-stage renal disease (ESRD) patients also have a high risk of stroke, suggesting that AF is a possible risk factor for mortality of ESRD patients. However, whether the existence of AF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients remains to be defined.MethodsThis retrospective cohort study was performed at Wanfang Hospital from January 2004 to May 2018. The end points were mortality of patients or the end of the study. Incident ESRD patients who were on maintenance hemodialysis for more than 3 months were eligible for inclusion. Cox proportional regression and Kaplan–Meier survival curves were used to determine the association between predictors and mortality. The association between AF and echocardiographic parameters, causes of death were also investigated.ResultsOf the 393 incident ESRD patients at initiation of hemodialysis, 57 (14.5%) had AF and the median age was 71 years. Patients with AF were significantly older; showed significantly higher C-reactive protein levels, more heart failure, chronic obstructive pulmonary disease and mortality. Multivariate Cox regression showed that AF had a hazard ratio of 4.1 (95% confidence interval: 2.4–7.0) for mortality. Age-specific analysis showed that AF was significantly associated with mortality in all age groups. Echocardiography measurements including ejection fraction and left ventricular hypertrophy (LVH) were similar in AF and non-AF patients. Cause-specific analysis showed that AF significantly associated with overall cardiovascular death and death due to acute myocardial infarction/coronary artery disease and sepsis.ConclusionsAF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients regardless of age. The systolic function and degree of LVH were similar in AF and non-AF patients. The association between AF and sepsis-related death suggested the role of systemic inflammation on the pathogenesis of AF.

Real-world outcomes of stem cell transplantation for severe aplastic anemia: A single-center experience in Northern India.

Stem cell transplantation is the cornerstone of therapy for transplant-eligible patients with severe aplastic anemia. Patients with severe aplastic anemia undergoing stem cell transplantation (including matched haplo-identical related donors) with a standard conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were analyzed. High-risk patients were identified as having undergone >20 pre-transplant transfusions, having febrile neutropenia at the time of transplantation, or having undergone failed immunosuppressive therapy. A total of 111 patients underwent stem cell transplantation, with a median age of 17 years. Seventy-six patients received matched related donor (MRD) transplants, and 35 received haplo-identical donor (HID) transplants. Among all patients, 65.7% were high-risk patients, with a significantly higher proportion among those receiving HID transplants (38% for MRD vs. 83% for HID). Acute GVHD grades 2-4 was observed in 9% of patients, and chronic GVHD in 16.2% of patients. Primary graft rejection was more common in 9.9% of patients (21% for HID, 5% for MRD). The 2-year overall survival and disease-free survival were 67% and 66%, respectively, with better outcomes for MRD and low-risk HID transplants than for high-risk HID transplants. The most common cause of mortality was sepsis-related death (accounting for 27% of the total deaths). Sepsis-related early deaths were significantly more common among high-risk patients who received HID transplants. We conclude that MRDs remain the preferred donor source for allogeneic stem cell transplants in patients with aplastic anemia; however, HIDs can be considered as a life-saving treatment for patients with aplastic anemia.

2321 Treatment of Hepatitis C in an Immunosuppressed Patient With Malignancy

INTRODUCTION: The prevalence of hepatitis C (HCV) is estimated to be 1-1.5% in patients with cancer. Direct-acting antivirals (DAA’s) have been shown to be a safe and effective option for treatment of HCV in patients with concurrent malignancy. However evidence for the use of DAAs in combination with b-cell depleting agents is lacking. We present a complicated case of a patient with lymphoma and HCV, who was treated simultaneously with rituximab and DAA therapy. CASE DESCRIPTION/METHODS: A 57-year-old male presented with recurrent angioedema due to acquired C1 esterase deficiency. Workup led to a bone marrow biopsy showing marginal zone lymphoma (MZL). He was pulsed with dexamethasone with plan to start rituximab. HCV screening was negative. Just prior to rituximab dose, he was found to have jaundice. Labs revealed an AST 2195, ALT 4828, total bili 5.1, alk phos 120, platelets 9k. Liver ultrasound showed hepatomegaly. He reported recent high risk sexual behavior. Initial workup revealed negative hepatitis A/B/C antibodies, ferritin 10.6k, negative autoimmune workup, and an HCV viral load of 31 million copies. His liver tests improved and he was seen in clinic where liver elastography showed a kPa of 17.7 (IQR 21%). He was started on a 12-week course of glecaprevir/pibrentasvir. Follow up HCV antibody was positive three weeks later. His clinical course was further complicated by ITP treated with IVIG, dexamethasone, rituximab and ultimately splenectomy. Course was also complicated by renal failure due to secondary minimal change disease and neuropathy due to AIDP/CIDP. He received additional dexamethasone and IVIG for these conditions. One month later he completed DAA therapy, LFTs normalized, and his HCV viral load was &lt; 12. Two days after completing HCV therapy he was admitted to the ICU with septic shock of unclear etiology, ultimately resulting in death. DISCUSSION: Our patient’s workup was suggestive of acute HCV given initial negative antibody with eventual seroconversion. A 12-week course of glecaprevir/pibrentasvir was chosen, as there was uncertainty regarding whether or not cirrhosis was present. Aggressive immunosuppression was given concomitantly for the MZL, as well as other immune-mediated diseases. His sepsis-related death was felt to be due to prolonged hospitalization in an immunosuppressed state rather than DAA therapy. Larger scale studies are needed to further inform optimal treatment of HCV in patients receiving immunosuppressive therapy, in the setting of malignancy.

Immunohistochemistry in the Postmortem Diagnosis of Sepsis: A Systematic Review.

It is not uncommon for the forensic pathologist to question whether a deceased person had experienced sepsis that could have either been the cause of or contributed to the person's death. Often, the missing typical pathologic factors or lack of clinical and circumstantial information on the death render the autopsy of a sepsis-related death a difficult task for the forensic pathologist. Several authors emphasize on how an immunohistochemical analysis could help in diagnosing death related to sepsis. The research we carried out analyzes the main scientific studies in the literature, primarily the tracing of 21 immunohistochemical antigens evaluated to help diagnose death related to sepsis. The purpose of this review was to analyze and summarize the markers studied until now and to consider the limitations of immunohistochemistry that currently exist with regard to this particular field of forensic pathology. Immunohistochemistry provided interesting and promising results, but further studies are needed in order for them to be confirmed, so that they may be applied in standard forensic practice.

Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease

Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

Presepsin: A potential superior diagnostic biomarker for the postmortem differentiation of sepsis based on the Sepsis-3 criteria

Diagnosis of sepsis-related death by autopsy is often a complex process. Presepsin (PSEP) is typically used as a marker for diagnosing sepsis after death; however, its efficacy remains unclear. In the present study, we compared the levels of PSEP, C-reactive protein (CRP), and procalcitonin (PCT) in the postmortem serum of femoral blood to determine their efficacies as biomarkers for the postmortem differentiation of sepsis. Patients (n = 93; 48 males, 45 females with a mean age: 62.8 ± 19.2 years) who were admitted to and died in hospitals were screened for sepsis based on the sequential organ failure assessment score, and those with clinically confirmed sepsis were assessed in this study. All patients underwent autopsy within 48 h (n = 44 patients) or 48–96 h (n = 49 patients) of death. The cadavers were divided into two groups using the Sepsis-3 criteria: control group (n = 74) comprising patients without clinically diagnosed sepsis, and the group of patients who were clinically diagnosed with sepsis (n = 19). The area under the curve values (AUCs) for CRP, PCT, and PSEP levels in the sepsis group were 0.83, 0.817, and 0.977, respectively, with optimal cutoff levels of 7 mg/dL (sensitivity: 78.9%, specificity: 77.0%) for CRP, 0.07 ng/mL (sensitivity: 84.2%, specificity: 68.9%) for PCT, and 1250 pg/mL (sensitivity: 100.0%, specificity: 91.9%) for PSEP. No significant differences were noted for PSEP levels for gender, age, elapsed time after death, and the presence or absence of postmortem trauma. The present study demonstrated that compared to CRP and PCT, PSEP is a superior biomarker for the postmortem differentiation of sepsis and that a concentration >1250 pg/mL is highly likely to indicate sepsis within 96 h of death. This is the first report confirming the superiority of PSEP for diagnosing sepsis after death.

Red-flag sepsis and SOFA identifies different patient population at risk of sepsis-related deaths on the general ward.

Controversy exists regarding the best diagnostic and screening tool for sepsis outside the intensive care unit (ICU). Sequential organ failure assessment (SOFA) score has been shown to be superior to systemic inflammatory response syndrome (SIRS) criteria, however, the performance of "Red Flag sepsis criteria" has not been tested formally.The aim of the study was to investigate the ability of Red Flag sepsis criteria to identify the patients at high risk of sepsis-related death in comparison to SOFA based sepsis criteria. We also investigated the comparison of Red Flag sepsis to quick SOFA (qSOFA), SIRS, and national early warning score (NEWS) scores and factors influencing patient mortality.Patients were recruited into a 24-hour point-prevalence study on the general wards and emergency departments across all Welsh acute hospitals. Inclusion criteria were: clinical suspicion of infection and NEWS 3 or above in-line with established escalation criteria in Wales. Data on Red Flag sepsis and SOFA criteria was collected together with qSOFA and SIRS scores and 90-day mortality.459 patients were recruited over a 24-hour period. 246 were positive for Red Flag sepsis, mortality 33.7% (83/246); 241 for SOFA based sepsis criteria, mortality 39.4% (95/241); 54 for qSOFA, mortality 57.4% (31/54), and 268 for SIRS, mortality 33.6% (90/268). 55 patients were not picked up by any criteria. We found that older age was associated with death with OR (95% CI) of 1.03 (1.02-1.04); higher frailty score 1.24 (1.11-1.40); DNA-CPR order 1.74 (1.14-2.65); ceiling of care 1.55 (1.02-2.33); and SOFA score of 2 and above 1.69 (1.16-2.47).The different clinical tools captured different subsets of the at-risk population, with similar sensitivity. SOFA score 2 or above was independently associated with increased risk of death at 90 days. The sequalae of infection-related organ dysfunction cannot be reliably captured based on routine clinical and physiological parameters alone.

The most common causative bacteria in maternal sepsis-related deaths in Japan were group A Streptococcus: A nationwide survey

The present retrospective study provides an in-depth analysis of the maternal sepsis-related deaths reported in Japan, and aims to guide future care regarding maternal sepsis. This is a nationwide, retrospective, descriptive cohort study. Data were retrospectively analyzed on all maternal death cases related to sepsis reported in Japan from 2010 through 2016. A total of 7,347,727 births and 317 maternal deaths were reported during the study period. The cause of maternal death was sepsis in 24 women (7.5%). Causative bacteria were Streptococcus pyogenes (54.2%), Chlamydia psittaci (8.3%), Mycobacterium tuberculosis (8.3%), Escherichia coli (4.2%), Neisseria meningitidis (4.2%), Epstein-Barr virus (4.2%), and unknown (16.6%). In maternal death due to S.pyogenes (13 women), onset periods ware antepartum in 10 women (76.9%) and postpartum in 3 (23.1%); death within 24h after hospital admission occurred in 7 women (53.8%); and the median time from hospital admission to death was 12h (6-744h). The most common causative bacteria in to maternal sepsis-related death were GAS. When encountering severe sepsis during the peripartum period, we recommend considering severe GAS infection and early intervention.

PS01.213: COMPARISON OF MANUAL VERSUS MECHANICAL INTRA-THORACIC ESOPHAGO-GASTRIC ANASTOMOSIS IN RADICAL 2-STAGE MINIMALLY INVASIVE ESOPHAGECTOMY FOR CANCER

Abstract Background While in open esophagectomy a plethora of studies comparing outcomes of mechanical (circular or linear stapler) versus hand-sewn intra-thoracic anastomosis have been published, little evidence exists regarding 2-stage minimally invasive esophagectomy; In the majority of published studies the mechanical anastomosis is favored. Construction of the intra-thoracic esophago-gastric anastomosis in minimally invasive esophagectomy is the procedure's rate limiting step. We aim to present our results of hand-sewn versus mechanical anastomosis in 2-stage minimally invasive esophagectomy. Methods Data of 113 consecutive patients over a 20-month period that underwent 2-stage minimally invasive esophagectomy for cancer in our institution were analyzed. Inclusion criteria included only 2-stage and only minimally invasive esophagectomies for cancer. 43 cases underwent fully minimally invasive esophagectomy and 70 had laparoscopic-assisted hybrid esophagectomy. A fully hand-sewn anastomosis with 3/0 v-lock barbed suture was formed in 38% of cases and a mechanical anastomosis with a 25mm or 28mm circular stapler was formed in 62% of cases. Comparison between anastomotic techniques was assessed through Chi-Square and Log-Rank analysis. Results Median age was 68(IQR,47–82) in manual anastomosis group and 65(IQR,31–81) in circular stapler group. Of the manual anastomosis group, 74% received neo-adjuvant treatment versus 20% of the mechanical anastomosis group. In the manual anastomosis group n = 3(6.97%) developed a leak; of these, n = 2 were stented and n = 1 was subclinical requiring no intervention. There was one sepsis-related death; 30-day mortality was 2.3%. In the mechanical anastomosis group n = 2(2,8%) developed anastomotic leak (one combined with tracheo-esophageal fistula) and both were stented and eventually resulted in mortality. 30-day mortality was 2.8%. No conduit necrosis was noticed. Anastomotic strictures requiring dilatation were seen in n = 4(9.3%) in the manual anastomosis group versus n = 5(7.1%) in the mechanical anastomosis group. No statistically significant difference was found between the groups in terms of leak (P = 0.312), stricture (P = 0.698) and mortality rate (P &gt; 0.005). Median length of stay was 11 days (7–70) in the manual anastomosis group and 12 days (7–51) in mechanical anastomosis group. Conclusion Outcomes between manual and mechanical intra-thoracic anastomosis in minimally invasive esophagectomy show no difference within our study group. Both are equally safe and efficient, with surgeon's preference taking priority. Disclosure All authors have declared no conflicts of interest.

Understanding the Cellular Origin of the Mononuclear Phagocyte System Sheds Light on the Myeloid Postulate of Immune Paralysis in Sepsis.

Sepsis, in essence, is a serious clinical condition that can subsequently result in death as a consequence of a systemic inflammatory response syndrome including febrile leukopenia, hypotension, and multiple organ failures. To date, such life-threatening organ dysfunction remains one of the leading causes of death in intensive care units, with an increasing incidence rate worldwide and particularly within the rapidly growing senior population. While most of the clinical trials are aimed at dampening the overwhelming immune response to infection that spreads through the bloodstream, based on several human immunological investigations, it is now widely accepted that susceptibility to nosocomial infections and long-term sepsis mortality involves an immunosuppressive phase that is characterized by a decrease in some subsets of dendritic cells (DCs). Only recently substantial advances have been made in terms of the origin of the mononuclear phagocyte system that is now likely to allow for a better understanding of how the paralysis of DCs leads to sepsis-related death. Indeed, the unifying view of each subset of DCs has already improved our understanding of the pivotal pathways that contribute to the shift in commitment of their progenitors that originate from the bone marrow. It is quite plausible that this anomaly in sepsis may occur at the single level of DC-committed precursors, and elucidating the immunological basis for such a derangement during the ontogeny of each subset of DCs is now of particular importance for restoring an adequate cell fate decision to their vulnerable progenitors. Last but not least, it provides a direct perspective on the development of sophisticated myelopoiesis-based strategies that are currently being considered for the treatment of immunosenescence within different tissue microenvironments, such as the kidney and the spleen.

Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis-related death.

The post-mortem assessment of sepsis-related death can be carry out by many methods recently suggested as microbiological and biochemical investigations. In these cases, the cause of death is a multiple organ dysfunction due to a dysregulated inflammatory response occurring after the failure of infection control process. It was highlighted also that the heart can be a target organ in sepsis which determines the so-called septic cardiomyopathy characterized by myocardial depression. Several mechanisms to explain the pathophysiology of septic cardiomyopathy were suggested, but very few studies about the structural alterations of cardiac cells responsible for myocardial depression were carried out. The aim of this study was to evaluate whether sarcoglycans (SG) were involved in septic cardiac damage analyzing their expression in sepsis-related deaths and, particularly, if these proteins can be used as markers of septic myocardial dysfunction. Cases of septic-related death confirmed by clinical and autopsy records were investigated and compared to a control group of traumatic deaths. Indirect immunofluorescence analysis was performed to analyze α-SG, β-SG, δ-SG, ζ-SG, ε-SG, and γ-SG. Decrease of fluorescence staining pattern for all tested sarcoglycans was observed in the septic-related deaths compared to normal fluorescence staining pattern of control group. These results provide new findings about the myocytes structural alterations due to sepsis and suggest that these proteins could be used in forensic assessment of septic cardiomyopathy.

Unique transcriptomic response to sepsis is observed among patients of different age groups.

Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with and without sepsis. Nine public whole-blood gene expression datasets (636 patients) were employed. Age impacted the transcriptomic host response to sepsis. Gene expression from septic neonates and adults was more dissimilar whereas infants and children were more similar. Neonates showed reductions in inflammatory recognition and signaling pathways compared to all other age groups. Likewise, adults demonstrated decreased pathogen sensing, inflammation, and myeloid cell function, as compared to children. This may help to explain the increased incidence of sepsis-related organ failure and death in adults. The number of dysregulated genes in septic patients was proportional to age and significantly differed among septic adults, children, infants, and neonates. Overall, children manifested a greater transcriptomic intensity to sepsis as compared to the other age groups. The transcriptomic magnitude for adults and neonates was dramatically reduced as compared to children and infants. These findings suggest that the transcriptomic response to sepsis is age-dependent, and diagnostic and therapeutic efforts to identify and treat sepsis will have to consider age as an important variable.

Sepsis-related mortality in 497 cases with blood culture-positive sepsis in an emergency department

Few studies have sought to establish how often death after sepsis is related to the sepsis and how often underlying diseases have a major role in case fatality. In this retrospective cohort study, data were collected on 497 cases with blood culture-positive sepsis in an emergency department (ED). Sepsis was categorized as severe in 31% of cases; 7% had septic shock. The quick Sepsis-related Organ Failure Assessment score was positive in 136 out of 473 cases (29%). Ninety-eight patients died by day 90; in 16 of these cases (16%) the death was sepsis-related in a patient without a rapidly fatal underlying disease, in 45 cases (46%) the death was sepsis-related in a patient with a rapidly fatal underlying disease, and in 37 cases (38%) the death was unrelated to sepsis. Sepsis-related death occurred in 58 out of 61 cases (95%) by day 28. Underlying diseases were found to have a considerable role in the death of patients suffering from blood culture-positive sepsis in an ED of a developed country, as only 16% of the deaths by day 90 occurred where death was sepsis-related and the patient had a life-expectancy of more than 6 months. Improving the outcome of sepsis with new treatments is thus challenging. It is possible that day 7+day 28 mortality is a more appropriate endpoint than day 90 mortality when studying the outcome of sepsis, as this time-span includes most of the patients whose death was related to sepsis.

Successful emergency department interventions that reduce time to antibiotics in febrile pediatric cancer patients

Children with cancer and fever are at high risk for sepsis related death. Rapid antibiotic delivery (< 60 minutes) has been shown to reduce mortality.We compared patient outcomes and describe...

AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol

IntroductionSepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis...

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation.

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.