Tocilizumab reduces hypercoagulation in COVID-19 - Perspectives from the coagulation and immunomodulation Covid assessment (Coag-ImmCovA) clinical trial.

Background: Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality.

Long-term Mortality and Hospital Readmissions Among Survivors of Sepsis in Sweden: A Population-Based Cohort Study.

Background: Survivors of sepsis may experience long-term risk of increased morbidity and mortality, but estimations of cause-specific effects beyond 1 year after a sepsis episode are lacking.

Method: This nationwide population-based cohort study linked data from national registers to compare patients aged ≥18 years in Sweden admitted to an intensive care unit from 2008 to 2019 with severe community-acquired sepsis. Patients were identified through the Swedish Intensive Care Registry, and randomly selected population controls were matched for age, sex, calendar year, and county of residence.

Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial.

Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.

Methods: The study was conducted June 2020 to March 2021.

Plasma calprotectin as an indicator of need of transfer to intensive care in patients with suspected sepsis at the emergency department.

Background: Deciding whether to transfer patients with sepsis from the emergency department (ED) to intensive care units (ICUs) is challenging. We hypothesised that the new biomarker plasma calprotectin (p-calprotectin) could be used to aid the selection of patients for intensive care transfer, since it has been shown to be a promising tool for the determination of sepsis severity in critical care.

Methods: This prospective study was performed on consecutive sepsis alert patients in the ED of Karolinska University Hospital Huddinge.

Correlation of clinical sepsis definitions with microbiological characteristics in patients admitted through a sepsis alert system; a prospective cohort study.

Background: Sepsis was recently redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. With this redefinition (Sepsis-3), clinical and microbiological characteristics of patients with sepsis may differ from the patients fulfilling the previous definition (Sepsis-2).

Purpose: To describe differences in clinical and microbiological characteristics of sepsis episodes between Sepsis-3 and Sepsis-2.

Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria.

Objectives: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality.

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021.

Prognostic significance of body temperature in the emergency department vs the ICU in Patients with severe sepsis or septic shock: A nationwide cohort study.

Background: Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various combinations of BT-ED and BT-ICU, and; compared degree of fever in the ED and ICU and associated quality of care.

Methods: 2385 adults who were admitted to an ICU within 24 hours of ED arrival with severe sepsis or septic shock were included.

Single-Sampling Strategy vs. Multi-Sampling Strategy for Blood Cultures in Sepsis: A Prospective Non-inferiority Study.

Background: Optimal sampling is critical for the performance of blood cultures (BCs). Most guidelines recommend collecting 40 ml of blood, divided between two venipuncture sites, i.e.

Sex-based differences in ED management of critically ill patients with sepsis: a nationwide cohort study.

Purpose: To compare management and outcomes for critically ill women and men with sepsis in the emergency medical services (EMS), the emergency department (ED) and the ICU.

Methods: We used two prospectively compiled Swedish national quality registers, the National Quality Sepsis Registry and the Swedish Intensive Care Registry to identify a nationwide cohort of 2720 adults admitted to an ICU within 24 h of arrival to any of 32 EDs, with a diagnosis of severe sepsis or septic shock between 2008 and 2015.

Results: Patients were 44.

Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection.

The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression.

Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis.

Background: A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis.

Methods: Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704).

Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU.

Objectives: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU.

Design: Observational cohort study from the Swedish national quality register for sepsis.

Setting: Thirty ICU's in Sweden.

Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality.

Introduction And Aims: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators.

Methods: 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study.

Short- and long-term mortality in severe sepsis/septic shock in a setting with low antibiotic resistance: a prospective observational study in a Swedish university hospital.

Background: There is little epidemiologic data on sepsis, particularly in areas of low antibiotic resistance. Here we report a prospective observational study of severe sepsis and septic shock in patients admitted to the Intensive Care Unit (ICU) at Karolinska University Hospital, Sweden. We aimed to evaluate short- and long-term mortality, and risk factors for sepsis-related death.

Metabolic profiling for detection of Staphylococcus aureus infection and antibiotic resistance.

Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

Introduction: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed.

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock.

Introduction: Rapid detection of, and optimized treatment for, severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in the plasma of patients with severe sepsis and septic shock in the ICU.

Neutrophil-derived hyperresistinemia in severe acute streptococcal infections.

The concept of neutrophil activation and degranulation as important contributors to disease pathology in invasive group A streptococcal infections has recently been emphasized. This study focuses on two of the most severe streptococcal manifestations, toxic shock syndrome and necrotizing fasciitis, and the newly described proinflammatory molecule resistin, known to derive from adipocytes and monocytes. We demonstrate for the first time that these conditions are characterized by hyperresistinemia in circulation as well as at the local site of infection.

Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock.

Objective: Resistin induces insulin resistance in mice. In humans, recent data suggest that resistin functions as a proinflammatory cytokine. Here, we studied resistin up to 2 wks after admission in patients with septic shock and/or severe sepsis.

The role of high mobility group box-1 protein in severe sepsis.

Purpose Of Review: Despite medical advances, mortality in severe sepsis remains high. As our understanding of the innate immune system has expanded, clinical trials have focused on inhibiting cytokines present early in the infectious process such as interleukin-1 and tumor necrosis factor-alpha, although with disappointing results. There is evidence that the nuclear protein high mobility group box-1 protein, when released extracellularly, acts as a persistent mediator of sepsis and is therefore a promising candidate for therapeutic intervention.

Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock.

Objective: To study the systemic release and kinetics of high mobility group box-1 protein (HMGB1) in relation to clinical features in a population of patients with severe sepsis or septic shock and to compare these with the kinetics of the cytokines interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha.

Design: Prospective study of two cohorts of patients.

Setting: Intensive care unit and infectious disease clinic at Karolinska University Hospital Huddinge.