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Background Sepsis and septic shock remain drivers for mortality in critically ill patients. The heterogeneity of the syndrome hinders the generation of reproducible numbers on mortality risks. Consequently, mortality rates range from 15 to 56%. We aimed to update and extend the existing knowledge from meta-analyses and estimate 30- and 90-day mortality rates for sepsis and septic shock separately, stratify rates by region and study type and assess mortality rates across different sequential organ failure assessment (SOFA) scores. Methods We performed a systematic review of articles published in PubMed or in the Cochrane Database, between 2009 and 2019 in English language including interventional and observational studies. A meta-analysis of pooled 28/30- and 90-day mortality rated separately for sepsis and septic shock was done using a random-effects model. Time trends were assessed via Joinpoint methodology and for the assessment of mortality rate over different SOFA scores, and linear regression was applied. Results Four thousand five hundred records were identified. After title/abstract screening, 783 articles were assessed in full text for eligibility. Of those, 170 studies were included. Average 30-day septic shock mortality was 34.7% (95% CI 32.6–36.9%), and 90-day septic shock mortality was 38.5% (95% CI 35.4–41.5%). Average 30-day sepsis mortality was 24.4% (95% CI 21.5–27.2%), and 90-day sepsis mortality was 32.2% (95% CI 27.0–37.5%). Estimated mortality rates from RCTs were below prospective and retrospective cohort studies. Rates varied between regions, with 30-day septic shock mortality being 33.7% (95% CI 31.5–35.9) in North America, 32.5% (95% CI 31.7–33.3) in Europe and 26.4% (95% CI 18.1–34.6) in Australia. A statistically significant decrease of 30-day septic shock mortality rate was found between 2009 and 2011, but not after 2011. Per 1-point increase of the average SOFA score, average mortality increased by 1.8–3.3%. Conclusion Trends of lower sepsis and continuous septic shock mortality rates over time and regional disparities indicate a remaining unmet need for improving sepsis management. Further research is needed to investigate how trends in the burden of disease influence mortality rates in sepsis and septic shock at 30- and 90-day mortality over time.

Background Septic shock is the most severe form of sepsis, in which profound underlying abnormalities in circulatory and cellular/metabolic parameters lead to substantially increased mortality. A clear understanding and up-to-date assessment of the burden and epidemiology of septic shock are needed to help guide resource allocation and thus ultimately improve patient care. The aim of this systematic review and meta-analysis was therefore to provide a recent evaluation of the frequency of septic shock in intensive care units (ICUs) and associated ICU and hospital mortality. Methods We searched MEDLINE, Embase, and the Cochrane Library from 1 January 2005 to 20 February 2018 for observational studies that reported on the frequency and mortality of septic shock. Four reviewers independently selected studies and extracted data. Disagreements were resolved via consensus. Random effects meta-analyses were performed to estimate pooled frequency of septic shock diagnosed at admission and during the ICU stay and to estimate septic shock mortality in the ICU, hospital, and at 28 or 30 days. Results The literature search identified 6291 records of which 71 articles met the inclusion criteria. The frequency of septic shock was estimated at 10.4% (95% CI 5.9 to 16.1%) in studies reporting values for patients diagnosed at ICU admission and at 8.3% (95% CI 6.1 to 10.7%) in studies reporting values for patients diagnosed at any time during the ICU stay. ICU mortality was 37.3% (95% CI 31.5 to 43.5%), hospital mortality 39.0% (95% CI 34.4 to 43.9%), and 28-/30-day mortality 36.7% (95% CI 32.8 to 40.8%). Significant between-study heterogeneity was observed. Conclusions Our literature review reaffirms the continued common occurrence of septic shock and estimates a high mortality of around 38%. The high level of heterogeneity observed in this review may be driven by variability in defining and applying the diagnostic criteria, as well as differences in treatment and care across settings and countries.

There are few studies documenting the changing epidemiology and outcomes of shock in cardiac intensive care unit (CICU) patients. We sought to describe the changes in shock epidemiology and outcomes over time in a CICU population. We included 1859 unique patients admitted to the Mayo Clinic Rochester CICU from 2007 through 2018 with an admission diagnosis of shock. Temporal trends, including mortality, were assessed across 3-year periods. Shock comprised 15.1% of CICU admissions during the study period, increasing from 8.8% of CICU admissions in 2007 to 21.6% in 2018 (P < .01 for trend). Mean age was 68 ± 14 years (38% females). Shock was cardiogenic in 65%, septic in 10% and mixed cardiogenic-septic in 15%. Concomitant diagnoses in patients with cardiogenic shock (CS) included acute coronary syndrome (ACS) in 17%, heart failure (HF) in 35% and both in 40%. There was no significant change in the prevalence of individual shock subtypes over time (P > .1). Among patients with CS, the prevalence of ACS decreased and the prevalence of HF increased over time (P < .01). Hospital mortality was highest among patients with mixed shock (39%; P = .05). Among patients with CS, hospital mortality was lower among those with HF compared to those without HF (31% vs. 40%, P < .01). Hospital mortality decreased over time among patients with shock (P < .01) and CS (P = .02). The prevalence of shock in the CICU has increased over time, with a substantial prevalence of mixed CS. The etiology of CS has changed over the last decade with HF overtaking ACS as the most common cause of CS in the CICU.

Background. Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. Methods. From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. Results. We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649–13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136–1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates. Conclusions. The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact.

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.

Background Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Discussion There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. Summary Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”.

Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality. Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.

Sepsis has been around since the dawn of time, having been described for more than 2000 years, although clinical definitions are recent. The consensus sepsis definitions have permitted worldwide epidemiological studies of sepsis to be conducted. We now recognize the common nature of sepsis and the consistency of its disease - particularly severe sepsis and septic shock. The incidence of sepsis, severe sepsis and septic shock continues to increase, and although Gram-positive bacterial pathogens remain the most common cause of sepsis, fungal organisms are increasing rapidly. We have made progress over the past half-century in identifying and treating patients with sepsis, and decreasing fatality rates reflect this progress. However, owing to the increasing incidence of sepsis, the number of people who die each year continues to increase. The mortality with sepsis, particularly related to treating organ dysfunction, remains a priority to clinicians worldwide and is deserving of greater public health attention.

We examined the risk of sepsis within 90 days after discharge from a previous hospital stay by type of antibiotic received during the previous stay. We retrospectively identified a cohort of hospitalized patients from the Truven Health MarketScan Hospital Drug Database. We examined the association between the use of certain antibiotics during the initial hospital stay, determined a priori, and the risk of postdischarge sepsis controlling for potential confounding factors in a multivariable logistic regression model. Our primary exposure was receipt of antibiotics more strongly associated with clinically important microbiome disruption. Our primary outcome was a hospital stay within 90 days of the index stay that included an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis of severe sepsis (ICD-9-CM code 995.92) or septic shock (785.52). Among 516 hospitals, we randomly selected a single stay for eligible patients. In 0.17% of these patients, severe sepsis/septic shock developed within 90 days after discharge. The risk of sepsis associated with exposure to our high-risk antibiotics was 65% higher than in those without antibiotic exposure. Our study identified an increased risk of sepsis within 90 days of discharge among patients with exposure to high-risk antibiotics or increased quantities of antibiotics during hospitalization. Given that a significant proportion of inpatient antimicrobial use may be unnecessary, this study builds on previous evidence suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, Clostridium difficile infection, and other adverse effects, but may also reduce unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock. Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled. Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels. Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.