Sensitivity and specificity of monocyte distribution width (MDW) in detecting patients with infection and sepsis in patients on sepsis pathway in the emergency department.

PURPOSE: Monocyte distribution width (MDW) is a biomarker for the early identification of sepsis. We assessed its accuracy in patients presenting with suspected sepsis in the emergency department (ED). METHODS: This was a single gate, single centre study in consecutive adults (≥ 18 years) admitted to the ED with suspected sepsis and clinical history compatible with infection, between 01 January and 31 December 2020 (n = 2570). RESULTS: The overall median MDW was 22.0 (IQR 19.3, 25.6). Using Sepsis-3 (qSOFA) to define sepsis, the Area Under Curve (AUC) for a receiver operator characteristic (ROC) relationship was 0.59 (95% CI 0.56, 0.61). Discrimination was similar using other clinical scores, and to that of C-reactive protein. At an MDW cutoff of 20.0, sensitivity was 0.76 (95% CI 0.73, 0.80) and specificity 0.35 (95% CI 0.33, 0.37) for Sepsis-3. MDW showed better performance to discriminate infection, with AUC 0.72 (95% CI 0.69, 0.75). At MDW 20.0, sensitivity for infection was 0.72 (95% CI 0.70, 0.74) and specificity 0.64 (95% CI 0.59, 0.70). A sensitivity analysis excluding coronavirus disease (COVID-19) admissions (n = 552) had no impact on the AUC. MDW distribution at admission was similar for bacteraemia and COVID-19. CONCLUSIONS: In this population of ED admissions with a strong clinical suspicion of sepsis, MDW had a performance to identify sepsis comparable to that of other commonly used biomarkers. In this setting, MDW could be a useful additional marker of infection

The REDS score: a new scoring system to risk-stratify emergency department suspected sepsis: a derivation and validation study.

OBJECTIVE: To derive and validate a new clinical prediction rule to risk-stratify emergency department (ED) patients admitted with suspected sepsis. DESIGN: Retrospective prognostic study of prospectively collected data. SETTING: ED. PARTICIPANTS: Patients aged ≥18 years who met two Systemic Inflammatory Response Syndrome criteria or one Red Flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted. PRIMARY OUTCOME MEASURE: In-hospital all-cause mortality. METHOD: The data were divided into derivation and validation cohorts. The simplified-Mortality in Severe Sepsis in the ED score and quick-SOFA scores, refractory hypotension and lactate were collectively termed 'component scores' and cumulatively termed the 'Risk-stratification of ED suspected Sepsis (REDS) score'. Each patient in the derivation cohort received a score (0-3) for each component score. The REDS score ranged from 0 to 12. The component scores were subject to univariate and multivariate logistic regression analyses. The receiver operator characteristic (ROC) curves for the REDS and the components scores were constructed and their cut-off points identified. Scores above the cut-off points were deemed high-risk. The area under the ROC (AUROC) curves and sensitivity for mortality of the high-risk category of the REDS score and component scores were compared. The REDS score was internally validated. RESULTS: 2115 patients of whom 282 (13.3%) died in hospital. Derivation cohort: 1078 patients with 140 deaths (13%). The AUROC curve with 95% CI, cut-off point and sensitivity for mortality (95% CI) of the high-risk category of the REDS score were: derivation: 0.78 (0.75 to 0.80); ≥3; 85.0 (78 to 90.5). VALIDATION: 0.74 (0.71 to 0.76); ≥3; 84.5 (77.5 to 90.0). The AUROC curve and the sensitivity for mortality of the REDS score was better than that of the component scores. Specificity and mortality rates for REDS scores of ≥3, ≥5 and ≥7 were 54.8%, 88.8% and 96.9% and 21.8%, 36.0% and 49.1%, respectively. CONCLUSION: The REDS score is a simple and objective score to risk-stratify ED patients with suspected sepsis

Prognostic performance of the REDS score, SOFA score, NEWS2 score, and the red-flag, NICE high-risk, and SIRS criteria to predict survival at 180 days, in emergency department patients admitted with suspected sepsis - An observational cohort study.

BACKGROUND: Patients admitted to hospital with sepsis are at persistent risk of poor outcome after discharge. Many tools are available to risk-stratify sepsis patients for in-hospital mortality. This study aimed to identify the best risk-stratification tool to prognosticate outcome 180 days after admission via the emergency department (ED) with suspected sepsis. METHODS: A retrospective observational cohort study was performed of adult ED patients who were admitted after receiving intravenous antibiotics for the treatment of a suspected sepsis, between 1st March and 31st August 2019. The Risk-stratification of ED suspected Sepsis (REDS) score, SOFA score, Red-flag sepsis criteria met, NICE high-risk criteria met, the NEWS2 score and the SIRS criteria, were calculated for each patient. Death and survival at 180 days were noted. Patients were stratified in to high and low-risk groups as per accepted criteria for each risk-stratification tool. Kaplan-Meier curves were plotted for each tool and the log-rank test performed. The tools were compared using Cox-proportional hazard regression (CPHR). The tools were studied further in those without the following specified co-morbidities: Dementia, malignancy, Rockwood Frailty score of 6 or more, long-term oxygen therapy and previous do-not-resuscitate orders. RESULTS: Of the 1,057 patients studied 146 (13.8%) died at hospital discharge and 284 were known to have died within 180 days. Overall survival proportion was 74.4% at 180 days and 8.6% of the population was censored before 180 days. Only the REDS and SOFA scores identified less than 50% of the population as high-risk. All tools except the SIRS criteria, prognosticated for outcome at 180 days; Log-rank tests between high and low-risk groups were: REDS score p < 0.0001, SOFA score p < 0.0001, Red-flag criteria p = 0.001, NICE high-risk criteria p = 0.0001, NEWS2 score p = 0.003 and SIRS criteria p = 0.98. On CPHR, the REDS [Hazard ratio (HR) 2.54 (1.92-3.35)] and SOFA [HR 1.58 (1.24-2.03)] scores out-performed the other risk-stratification tools. In patients without the specified co-morbidities, only the REDS score and the SOFA score risk-stratified for outcome at 180 days. CONCLUSION: In this study, all the risk-stratification tools studied were found to prognosticate for outcome at 180 days, except the SIRS criteria. The REDS and SOFA scores outperformed the other tools

Treatment variables associated with outcome in emergency department patients with suspected sepsis.

BACKGROUND: Early treatment is advocated in the management of patients with suspected sepsis in the emergency department (ED). We sought to understand the association between the ED treatments and outcome in patients admitted with suspected sepsis. The treatments studied were: (i) the time to antibiotics, where time zero is the time the patient was booked in which is also the triage time; (ii) the volume of intravenous fluid (IVF); (iii) mean arterial pressure (MAP) after 2000 ml of IVF and (iv) the final MAP in the ED. METHODS: We performed a retrospective analysis of the ED database of patients aged ≥ 18 year who met two SIRS criteria or one red flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted between 8th February 2016 and 31st August 2017. The primary outcome measure was all-cause in-hospital mortality. The four treatments stated above were controlled for severity of illness and subject to multivariate logistic regression and Cox proportional-hazard regression to identify independent predictors of mortality. RESULTS: Of the 2,066 patients studied 272 (13.2%) died in hospital. The median time to antibiotics was 48 (interquartile range 30-82) minutes. The time to antibiotics was an independent predictor of mortality only in those who developed refractory hypotension (RH); antibiotics administered more than 55 mins after arrival was associated with an odds ratio (OR) for mortality of 2.75 [95% confidence interval (CI) 1.22-6.14]. The number-needed-to-treat was 4. IVF > 2000 ml (95% CI > 500- > 2100), except in RH, and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality. The OR for mortality of IVF > 2,000 ml in non-RH was 1.80 (95% CI 1.15-2.82); Number-needed-to-harm was 14. The OR for morality for a MAP ≤ 66 mmHg after 2000 ml of IVF was 3.42 (95% CI 2.10-5.57). A final MAP  2000 ml (except in RH) and a MAP ≤ 66 mmHg after 2000 ml of IVF were also independent predictors of mortality

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites