Ground truth labels challenge the validity of sepsis consensus definitions in critical illness

Background Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. Methods In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient’s condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. Results We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the “worst” working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. Conclusions GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

A comparison of scoring systems for predicting mortality and sepsis in the emergency department patients with a suspected infection

Objective We aimed to compare the modified National Early Warning Score (mNEWS), quick Sequential Organ Failure Assessment (qSOFA) score, modified Systemic Inflammatory Response Syndrome (mSIRS) score, and modified Search Out Severity (mSOS) score in predicting mortality and sepsis among patients suspected of first observed infections in the emergency department. The modified scores were created by removing variables for simplicity.Methods This was a prospective cohort study that enrolled adult patients presenting at the emergency department with signs and symptoms suggesting infection. The mNEWS, qSOFA score, mSIRS score, and mSOS score were calculated using triage data. The SOFA score was a reference standard for sepsis diagnosis. All patients were monitored for up to 30 days after the initial visit to measure each scoring system’s ability to predict 30-day mortality and sepsis.Results There were 260 patients included in the study. The 30-day mortality prediction with mNEWS ≥5 had the highest sensitivity (91.18%). The highest area under the receiver operating characteristic curve (AUC) for the 30-day mortality prediction was mNEWS (0.607), followed by qSOFA (0.605), mSOS (0.550), and mSIRS (0.423). The sepsis prediction with mNEWS ≥5 had the highest sensitivity (96.48%). The highest AUC for the sepsis prediction was also mNEWS (0.685), followed by qSOFA (0.605), mSOS (0.480), and mSIRS (0.477).Conclusion mNEWS was an acceptable scoring system screening tool for predicting mortality and sepsis in patients with a suspected infection.

Bloodstream Infections in Children With Sickle Cell Disease: 2010–2019

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS: We conducted a retrospective cohort study of children aged &lt;18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45–1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20–2.94) and chronic transfusions (OR 2.66; 95% CI 1.51–4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39–0.84). CONCLUSIONS: BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD.

An Overview of Emerging Point-of-Care Tests for Differentiating Bacterial and Viral Infections

Antimicrobial resistance is an important health concern in Canada and around the world. Although resistance arises naturally, the overuse of antibiotics, among many other behavioural, social, and economic drivers, contributes to the emergence of resistance patterns. Within health care settings, diagnostic uncertainty, a situation in which it is uncertain whether a suspected infection is due to a bacterial, viral, or other microorganism, is a regarded as a key driver that contributes to overuse of antibiotics. In these situations, antibiotics may be prescribed although the infection is viral. Emerging health technologies that can help reduce diagnostic uncertainty of acute infections at the point of care may help reduce the unnecessary use of antibiotics. If these point-of-care diagnostic devices demonstrate clinical benefit and cost-effectiveness for health systems, they may complement other interventions as part of antibiotic stewardship programs. This Horizon Scan provides an overview of new and emerging point-of-care tests that help differentiate bacterial and viral infections. Although rapid tests for identifying specific pathogens have existed for decades, these emerging tests aim to assess a wider range of possible pathogens and help inform treatment decisions. Different types of emerging devices, such as rapid molecular tests and immunoassays, are described including how they work and information about their capabilities that may influence their potential use. The report also describes the evidence about the diagnostic accuracy of certain tests and their effect on reducing antibiotic prescribing. Considerations are provided about where tests might be beneficial, such as primary care settings, and the emerging evidence base for their feasibility and acceptability. The emerging evidence suggests that point-of-care tests could be effective tools as part of antibiotic stewardship programs, but further studies assessing specific devices in randomized controlled trials are recommended by researchers and health technology assessment agencies. Monitoring the continued development of devices and the testing landscape, especially in post-pandemic health care, will be important for decision-makers.

The results of approbation of a comprehensive expert assessment of the quality of CT images of the chest obtained on low-dose scanning protocols using iterative reconstruction methods

Introduction. Сomputed tomography (CT) is associated with high individual patient doses. Hence, the process of optimization in CT examinations by developing low-dose scan protocols is important.Purpose of the study. Clinical approbation of low-dose protocols developed by the authors earlier, selection of the most promising protocol, assessment of the applicability of the developed algorithm for expert assessment of the quality of CT images.Materials and methods. The study was based on the data from 96 patients who underwent cardiac surgery with suspected infection in the lungs or sternal wound infection. CT examinations were performed using standard, low-dose and ultra-low-dose protocols (effective dose 3,5±0,9, 1,7±0,1 and 0,8±0,1 mSv, respectively) using two iterative reconstruction algorithms (IMR and iDose). The quality of the obtained data was assessed by 5 radiologists with more than 5-year experience in chest radiology.Results. In terms of the number of misinterpretations, no significant differences were estimated between the standard and lowdose protocols for all reconstruction methods. The ultra-low-dose protocol was characterized by a significantly higher number of missing lesions compared to other protocols.Conclusion. The developed method of assessment of the CT image quality has proven to be informative and reproducible and can be used to assess new scanning protocols.

The incidence, mortality and renal outcomes of acute kidney injury in patients with suspected infection at the emergency department

Background Acute kidney injury (AKI) is a major health problem associated with considerable mortality and morbidity. Studies on clinical outcomes and mortality of AKI in the emergency department are scarce. The aim of this study is to assess incidence, mortality and renal outcomes after AKI in patients with suspected infection at the emergency department. Methods We used data from the SPACE-cohort (SePsis in the ACutely ill patients in the Emergency department), which included consecutive patients that presented to the emergency department of the internal medicine with suspected infection. Hazard ratios (HR) were assessed using Cox regression to investigate the association between AKI, 30-days mortality and renal function decline up to 1 year after AKI. Survival in patients with and without AKI was assessed using Kaplan-Meier analyses. Results Of the 3105 patients in the SPACE-cohort, we included 1716 patients who fulfilled the inclusion criteria. Of these patients, 10.8% had an AKI episode. Mortality was 12.4% for the AKI group and 4.2% for the non-AKI patients. The adjusted HR for all-cause mortality at 30-days in AKI patients was 2.8 (95% CI 1.7–4.8). Moreover, the cumulative incidence of renal function decline was 69.8% for AKI patients and 39.3% for non-AKI patients. Patients with an episode of AKI had higher risk of developing renal function decline (adjusted HR 3.3, 95% CI 2.4–4.5) at one year after initial AKI-episode at the emergency department. Conclusion Acute kidney injury is common in patients with suspected infection in the emergency department and is significantly associated with 30-days mortality and renal function decline one year after AKI.

Role of Multimodal Imaging in Patients With Suspected Infections After the Bentall Procedure

Purpose: This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (99mTc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis.Methods: Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29–83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 99mTc-WBC and 49 [18F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (&lt;3 months after surgery) were imaged with both the techniques. Positive imaging was classified according to the anatomical site of increased uptake: to the aortic valve (AV), to both the AV and AV tube graft (AVTG) or to the TG, to surrounding tissue, and/or to extracardiac sites (embolic events or other sites of concomitant infection). Standard clinical workup included in all the patients having echocardiography/CT, blood culture, and the Duke criteria. Pretest probability and positive/negative likelihood ratio were calculated. Sensitivity and specificity of 99mTc labeled hexamethylpropylene amine oxime-WBC SPECT/CT (99mTc-HMPAO-WBC SPECT/CT) and [18F]FDG PET/CT imaging were calculated by using microbiology (n = 35) or clinical follow-up (n = 41) as final diagnosis. 99mTc-HMPAO-WBC scintigraphy and [18F]FDG PET/CT findings were compared with 95% CIs by using the McNemar test to those of echocardiography/CT, blood culture, and the Duke criteria.Results: Sensitivity, specificity, and accuracy of 99mTc-HMPAO-WBC were 86, 92, and 88%, respectively, with a slightly higher sensitivity for tube graft infection (TGI) as compared to isolated AV and combined AVTG. Overall, sensitivity, specificity, and accuracy of [18F]FDG PET/CT were 97, 73, and 90%, respectively. In 22 patients with suspected very early and early postsurgical infections, the two imaging modalities were concordant in 17 cases [10 true positive (TP) and 7 true negative (TN)]. [18F]FDG PET/CT presented a higher sensitivity than 99mTc-HMPAO-WBC scan. 99mTc-HMPAO-WBC scan correctly classified as negative three false-positive (FP) PET/CT findings.Conclusion: Our findings supported the use of 99mTc-HMPAO-WBC SPECT/CT and [18F]FDG PET/CT in patients with suspicion infection after the Bentall procedure early in the course of the disease onset to confirm the diagnosis and provide a comprehensive assessment of disease burden through the proposed criteria.

Delayed Presentation and Mortality in Children With Sepsis in a Public Tertiary Care Hospital in Tanzania

Background: Over 40% of the global burden of sepsis occurs in children under 5 years of age, making pediatric sepsis the top cause of death for this age group. Prior studies have shown that outcomes in children with sepsis improve by minimizing the time between symptom onset and treatment. This is a challenge in resource-limited settings where access to definitive care is limited.Methods: A secondary analysis was performed on data from 1,803 patients (28 days−14 years old) who presented to the emergency department (ED) at Muhimbili National Hospital (MNH) from July 1, 2016 to June 30, 2017 with a suspected infection and ≥2 clinical systemic inflammatory response syndrome criteria. The objective of this study was to determine the relationship between delayed presentation to definitive care (&gt;48 h between fever onset and presentation to the ED) and mortality, as well as the association between socioeconomic status (SES) and delayed presentation. Multivariable logistic regression models tested the two relationships of interest. We report both unadjusted and adjusted odds ratios and 95% confidence intervals.Results: During the study period, 11.3% (n = 203) of children who presented to MNH with sepsis died inhospital. Delayed presentation was more common in non-survivors (n = 90/151, 60%) compared to survivors (n = 614/1,353, 45%) (p ≤ 0.01). Children who had delayed presentation to definitive care, compared to those who did not, had an adjusted odds ratio for mortality of 1.85 (95% CI: 1.17–3.00).Conclusions: Delayed presentation was an independent risk factor for mortality in this cohort, emphasizing the importance of timely presentation to care for pediatric sepsis patients. Potential interventions include more efficient referral networks and emergency transportation systems to MNH. Additional clinics or hospitals with pediatric critical care may reduce pediatric sepsis mortality in Tanzania, as well as parental education programs for recognizing pediatric sepsis.

White Blood Cell Scintigraphy for Fracture-Related Infection: Is Semiquantitative Analysis of Equivocal Scans Accurate?

Purpose: White blood cell (WBC) scintigraphy is considered the gold-standard nuclear imaging technique for diagnosing fracture-related infection (FRI). Correct interpretation of WBC scans in FRI is important since a false positive or false negative diagnosis has major consequences for the patient in terms of clinical decision-making. The European Association of Nuclear Medicine (EANM) guideline for correct analysis and interpretation of WBC scans recommends semiquantitative analysis of visually equivocal scans. Therefore, this study aims to assess the diagnostic accuracy of semiquantitative analysis of visually equivocal WBC scans for diagnosing FRI. Methods: A retrospective single-center study was performed in consecutive patients who received WBC scintigraphy in the diagnostic work-up for FRI between February 2012 and January 2017. All the visually equivocal scans were analysed using semiquantitative analysis by comparing leukocyte uptake in the manually selected suspected infection focus with the contralateral bone marrow (L/R ratio). Cut-off points for a ‘positive’ scan result of >0%, >10% and >20% leukocyte increase between the early and late scans were used in separate analyses. The discriminative ability was quantified by calculating the sensitivity, specificity and diagnostic accuracy. Results: In total, 153 WBC scans were eligible for inclusion. After visual assessment of all the scans, 28 visually equivocal scans were included. Dichotomization of the ratios using the cut-off of >0% resulted in a sensitivity of 30%, a specificity of 45% and a diagnostic accuracy of 40%. The >10% cut-off point resulted in a sensitivity of 18%, a specificity of 82% and a diagnostic accuracy of 66%. The >20% cut-off point resulted in a sensitivity of 0%, a specificity of 89% and a diagnostic accuracy of 67%. Conclusion: Semiquantitative analysis of visually equivocal WBC scans is insufficient for correctly diagnosing FRI.