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Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI –0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, –0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93–1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54–5·22). In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved.

In extremely preterm infants, the use of cerebral oximetry monitoring to guide treatment for the first 72 hours after birth did not reduce the risk of death or severe brain injury at 36 weeks’ postmenstrual age.

In this study, patients were randomly assigned to a transfusion threshold of 9 or 7.5 g per deciliter after cardiac surgery. There was no significant between-group difference in infectious or ischemic events, but more deaths were associated with the lower threshold. Perioperative anemia is common after cardiac surgery and is associated with significant increases in morbidity and mortality. 1 – 3 The transfusion of allogeneic red cells is the preferred treatment for acute anemia and is also used in patients undergoing cardiac surgery; typically, more than 50% of patients receive a perioperative transfusion, 4 , 5 which uses a substantial proportion of blood supplies. 6 Observational studies suggest that transfusion is harmful after cardiac surgery; associations have been reported between transfusion and infection, low cardiac output, acute kidney injury, and death. 2 , 7 , 8 In contrast, randomized, controlled trials of red-cell transfusion with restrictive thresholds (i.e., transfusions . . .

Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of genes encoding for perforin or excretory granules of natural killer (NK) cells of CD8-lymphocytes. sHLH is also known as macrophage activation syndrome (MAS). Macrophage activation syndrome (MAS) in adults is poorly studied. Main features are fever, hepatosplenomegaly, hepatobiliary dysfunction (HBD), coagulopathy, cytopenia of two to three cell lineages, increased triglycerides and hemophagocytosis in the bone marrow. sHLH/MAS complicates hematologic malignancies, autoimmune disorders and infections mainly of viral origin. Pathogenesis is poorly understood and it is associated with increased activation of macrophages and NK cells. An autocrine loop of interleukin (IL)-1β over-secretion leads to cytokine storm of IL-6, IL-18, ferritin, and interferon-gamma; soluble CD163 is highly increased from macrophages. The true incidence of sHLH/MAS among patients with sepsis has only been studied in the cohort of the Hellenic Sepsis Study Group. Patients meeting the Sepsis-3 criteria and who had positive HSscore or co-presence of HBD and disseminated intravascular coagulation (DIC) were classified as patients with macrophage activation-like syndrome (MALS). The frequency of MALS ranged between 3 and 4% and it was an independent entity associated with early mortality after 10 days. Ferritin was proposed as a diagnostic and surrogate biomarker. Concentrations >4,420 ng/ml were associated with diagnosis of MALS with 97.1% specificity and 98% negative predictive value. Increased ferritin was also associated with increased IL-6, IL-18, IFNγ, and sCD163 and by decreased IL-10/TNFα ratio. A drop of ferritin by 15% the first 48 h was a surrogate finding of favorable outcome. There are 10 on-going trials in adults with sHLH; two for the development of biomarkers and eight for management. Only one of them is focusing in sepsis. The acronym of the trial is PROVIDE (ClinicalTrials.gov NCT03332225) and it is a double-blind randomized clinical trial aiming to deliver to patients with septic shock treatment targeting their precise immune state. Patients diagnosed with MALS are receiving randomized treatment with placebo or the IL-1β blocker anakinra.

Patients in the ICU were assigned to catheter insertion in the subclavian, jugular, or femoral vein. Subclavian catheterization had a lower risk of bloodstream infection and deep-vein thrombosis, and a higher risk of pneumothorax, than catheterization in the other two sites. Subclavian, jugular, and femoral central venous catheterization are associated with infectious, thrombotic, and mechanical complications. 1 Catheter-related bloodstream infection has a significant effect on morbidity, mortality, and health care costs. 2 – 4 The risk of short-term catheter-related bloodstream infection is influenced mainly by extraluminal microbial colonization of the insertion site, 5 and such colonization is also associated with thrombosis. 6 , 7 Although the importance of catheter-related deep-vein thrombosis has been debated, 1 all thromboses have the potential to embolize. In addition, catheter-related deep-vein thrombosis 7 – 9 and pulmonary embolism 10 may remain undiagnosed in critically ill patients undergoing mechanical ventilation. 11 We conducted the 3SITES multicenter study to . . .

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). MALS was diagnosed for patients scoring positive either for the hemophagocytic syndrome score and/or having both hepatobiliary dysfunction and disseminated intravascular coagulation. Logistic regression analysis was used to estimate the predictive value of MALS for 10-day mortality in both cohorts. Ferritin, sCD163, IL-6, IL-10, IL-18, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured in the blood the first 24 h; ferritin measurements were repeated in 747 patients on day 3. Results The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively. In both cohorts, MALS was an independent risk factor for 10-day mortality. A ferritin level above 4420 ng/ml was accompanied by 66.7% and 66% mortality after 28 days, respectively. Ferritin levels above 4420 ng/ml were associated with an increase of IL-6, IL-18, INF-γ, and sCD163 and a decreased IL-10/TNF-α ratio, indicating predominance of pro-inflammatory phenomena. Any less than 15% decrease of ferritin on day 3 was associated with more than 90% sensitivity for unfavorable outcome after 10 days. This high mortality risk was also validated in an independent Swedish cohort ( n  = 109). Conclusions MALS is an independent life-threatening entity in sepsis. Ferritin measurements can provide early diagnosis of MALS and may allow for specific treatment.

Background Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis. Methods This multicenter prospective study was conducted at 19 sites in China from 2020 to 2021, and 859 adult patients hospitalized with sepsis were enrolled. The advantages, challenges, knowledge gaps and privacy risks of mNGS were carefully introduced to all participants, and participants chose on their own to either receive conventional microbiological test (CMT) alone (conventional-test-only group, n  = 394) or receive mNGS test along with CMT (combined test group, n  = 465). For prognostic analysis, the primary endpoint was 28-day mortality. Secondary endpoints included 7-day mortality and average per-day hospital cost. Inverse probability of treatment weighting was used to balance covariates between groups. Concurrent CMT and mNGS results from patients in the combined test group were used for diagnostic analyses. Therapeutic impact of mNGS was evaluated based on subsequent antibiotic adjustment. Results Compared with composite reference standard, the positive percent agreement of mNGS among infected site samples was significantly higher than that of CMT (92.0% [95% CI, 88.7 to 94.5] vs. 51.1% [95% CI, 45.9 to 56.2], p  < 0.001), while the negative percent agreement of mNGS was inferior to that of CMT (39.6% [95% CI, 29.5 to 50.4] vs. 69.2% [95% CI, 58.7 to 78.5], p  < 0.001). The mNGS test identified causal microbes in 344 (74.0%) patients, and concomitant antibiotic changes occurred in 136 patients (29.2%). Death by day 7 occurred in 24 of 465 (5.2%) patients in the combined test group and in 34 of 394 (8.6%) patients in the conventional-test-only group (hazard ratio, 0.44 [95% CI, 0.26 to 0.77], p  = 0.004). However, no significant difference in 28-day mortality was observed between two study groups (hazard ratio, 0.82 [0.56 to 1.20], p  = 0.300). Conclusions The mNGS test of infected site samples exhibited 40% higher pathogen detection rate than CMT in patients with sepsis, which led to improved etiological diagnosis and tailored antibiotic therapy. Additional use of mNGS halved the risk of early death in 7 days, but did not improve 28-day survival in patients with sepsis. Trial registration chictr.org.cn Identifier: ChiCTR2000031113. Registered 22 March 2020.

Background This study aimed to evaluate the accuracy of procalcitonin (PCT) serum concentrations to diagnose Gram-negative bacteremia and the association of PCT serum concentrations with more specific pathogens and the focus of infection. Methods Secondary analysis of the prospectively collected patient-level dataset from a cluster randomized quality improvement trial was performed. The trial included sepsis patients with organ dysfunction treated in the participating intensive care units from 2011 to 2015. Test performance for the prediction of Gram-negative bacteremia was assessed by receiver operating curve analysis. Independent effects of specific pathogen groups and foci of infection on PCT concentrations were assessed by linear logistic regression models. Results Blood cultures (BC) and PCT concentrations had been taken in 4858 of 6561 documented patients. PCT was significantly higher in Gram-negative bacteremia compared to Gram-positive bacteremia or candidemia ( p  < 0.001). The area under the curve was 0.72 (95% confidence interval 0.71–0.74) for the prediction of Gram-negative bacteremia compared to all other blood culture results including negative blood cultures. The optimized cutoff value was 10 ng/ml (sensitivity 69%, specificity 35%). PCT differed significantly between specific groups of pathogens ( p  < 0.001) with highest concentrations in Escherichia coli , Streptococcus species and other Enterobacteriaceae . PCT was highest in urogenital followed by abdominal infection and lowest in respiratory infection ( p  < 0.001). In a linear regression model, Streptococci, E. coli and other Enterobacteriaceae detected from BC were associated with three times higher PCT values. Urogenital or abdominal foci of infection were associated with twofold increased PCT values independent of the pathogen. Conclusions Serum PCT concentrations are higher in patients with Gram-negative bacteremia than in patients with Gram-positive bacteremia or candidemia. However, the discriminatory power of this difference is too low to guide therapeutic decisions. Variations in PCT serum concentrations are not determined solely by Gram-negative or Gram-positive bacteria but are also affected by distinct groups of pathogens and different foci of infection. Trial registration ClinicalTrials.gov, NCT01187134 . Registered on 23 August 2010.

Background The purpose of this study was to identify the ten most frequent complications after surgery for stage I–III colon cancer and to assess the association between these complications and overall survival, conditional overall survival, and recurrences. Methods All patients who underwent surgery for stage I–III colon cancer in five hospitals in the Western region of the Netherlands were identified. Crude and adjusted Cox proportional hazards models were used to study the association between complications and 1-year overall survival, 5-year overall survival, 5-year conditional overall survival, and 5-year disease-free period. Results Data from 761 patients were used for the analyses. Complications were associated with decreased 1-year overall survival (hazard ratio (HR) 2.87, 95 % confidence interval (CI) 1.82–4.51; p  < 0.001), 5-year overall survival (HR 1.59, 95 % CI 1.25–2.04; p  < 0.001), and 5-year conditional overall survival (HR 1.34, 95 % CI 1.06–1.69; p  = 0.016), whereas an increasing number of complications had no additional impact. Anastomotic leakage, excessive blood loss, and (abdominal) sepsis were associated with reduced 1-year overall survival, anastomotic leakage, delirium, abscess, and (abdominal) sepsis with reduced 5-year overall survival, and anastomotic leakage, delirium, and abscess with reduced 5-year conditional overall survival. Anastomotic leakage, electrolyte disorders, and abscess were risk factors for recurrence within five years. Conclusions Our results demonstrate the serious impact of the most frequent complications after surgery for colon cancer on short-term and long-term outcomes. This study confirms the prolonged impact of surgery and demonstrates that complications result not only in reduced 1-year survival, but also in reduced long-term outcomes.