Clinical impact of the implementation of monocyte distribution width (MDW) measurement on time to anti-infective administration in sepsis patients in the emergency department: a before/after cohort study.

BACKGROUND: Timely recognition of sepsis in emergency department (ED) is challenging. We evaluated the impact of implementing the biomarker monocyte distribution width (MDW) at bedside, on the time to anti-infective administration. METHODS: We conducted a before-and-after cohort study in the ED of an academic hospital in Paris, to compare sepsis patients care and outcomes, before and after the implementation of point of care (POC) MDW measurement in the ED. During post-implementation period (period-2), MDW was measured with complete blood count by ED nurses with results given in 2 min: if above 21.5 units, ED physicians were asked to consider sepsis and to start an anti-infectious as soon as possible. Primary endpoint was time to anti-infectious administration (TTA) from ED arrival, and secondary endpoints were TTA from sepsis onset (TTAS), length of stay, mortality, and hospitalization rates. RESULTS: In total, 255 patients (period-1) and 180 patients (period-2) with sepsis were included. The TTA was 5.4 h (3.5-7.7) period-1 and 4.9 h (IQR 2.5-7.1) in period-2 (p = 0.06). MDW implementation significantly reduced the median TTAS from to 3.7 h (IQR 1.5-5.8) in period-1, to 2.2 h (IQR 0.5-4.5) in period-2 (p < 0.001). Mortality rates remained similar between the two periods (18% vs. 16% respectively, p = 0.4), as did hospitalization rates (93% vs. 91%, p = 0.4) and ED length of stay (7.2 h (5.3-9.8) vs 7.0 (5.4-9.4), p = 0.7). CONCLUSION: Implementing POC MDW measurement in the ED protocols enhances the timeliness of anti-infective administration from sepsis onset, meeting current sepsis management guidelines.

Biomarkers of COVID-19 short-term worsening: a multiparameter analysis within the prospective multicenter COVIDeF cohort.

BACKGROUND: During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required. OBJECTIVE: The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19. DESIGN: Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort). SETTING AND PARTICIPANTS: Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed. OUTCOME MEASURES AND ANALYSES: The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed. RESULTS: Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities. CONCLUSION: In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW. TRIAL REGISTRATION: ClinicalTrials.gov NCT04352348.

Biomarkers of COVID-19 short-term worsening: a multiparameter analysis within the prospective multicenter COVIDeF cohort.

BACKGROUND: During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required. OBJECTIVE: The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19. DESIGN: Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort). SETTING AND PARTICIPANTS: Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed. OUTCOME MEASURES AND ANALYSES: The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed. RESULTS: Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities. CONCLUSION: In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW. TRIAL REGISTRATION: ClinicalTrials.gov NCT04352348.

Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial.

PURPOSE: The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30 mL/kg crystalloid fluid for hypotension or lactate ≥ 4 mmol/L, remains controversial. METHODS: We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2 mmol/L were eligible. The intervention was the implementation of the 1-h sepsis bundle. The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24 h, acute heart failure at 24 h, SOFA score at 72 h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28 days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. RESULTS: 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40 min in the intervention group vs 113 min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3 h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. CONCLUSIONS: Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.

Point-of-care multiplex molecular diagnosis coupled with procalcitonin-guided algorithm for antibiotic stewardship in lower respiratory tract infection: a randomized controlled trial.

OBJECTIVE: We aimed to show that coupling molecular syndromic respiratory panel (RP) testing with procalcitonin (PCT) measurement in the emergency department improves antibiotic (ATB) stewardship in lower respiratory tract infection. METHODS: Open-label, prospective, randomized interventional trial, conducted from 2019 to 2022 in an adult emergency department. Patients with a suspicion of lower respiratory tract infection were randomized into an intervention arm (PCT measurement and point-of-care BIOFIRE RP2.1 plus testing, accompanied by a recommended ATB algorithm) or a standard of care (SOC) arm (PCT allowed as current practice). The primary endpoint was the duration of antibiotic exposure. RESULTS: Four hundred fifty-one patients were randomized, median age 65 years (Q1-Q3: 49-77), the hospitalization rate was 59.9% (270/451), the median length of stay 5 days (Q1-Q3: 3 - 12), and the 28-day mortality rate 5.3% (23/451). The median duration of ATB exposure was 6 days (Q1-Q3: 0-9) and 5 days (Q1-Q3: 0-9) in the SOC and interventional arm respectively (p = 0.71). ATB was started in 29.6 % (67/226) and 33.8% (76/225) respectively (p = 0.54). The BIOFIRE RP2.1 plus identified at least one viral species in 112/225 patients (49.8%) of intervention arm. Two hundred twelve out of two hundred twenty-six (93.8%) SOC patients had PCT measurement. The adherence rate to algorithm in the intervention arm was 93.3 % (210/225). CONCLUSION: Displaying PCT and real-time RP results to emergency physicians failed to significantly reduce ATB exposure in lower respiratory tract infection suspicions. However, the median ATB duration and rate of initiation were already low in the SOC arm using PCT measurement routinely.

Valorisation of Wasted Immature Tomato to Innovative Fermented Functional Foods.

In this study, the lactic fermentation of immature tomatoes as a tool for food ingredient production was evaluated as a circular economy-oriented alternative for valorising industrial tomatoes that are unsuitable for processing and which have wasted away in large quantities in the field. Two lactic acid bacteria (LAB) were assessed as starter cultures in an immature tomato pulp fermentation to produce functional food ingredients with probiotic potential. The first trial evaluated the probiotic character of Lactiplantibacillus plantarum (LAB97, isolated from immature tomato microbiota) and Weissella paramesenteroides (C1090, from the INIAV collection) through in vitro gastrointestinal digestion simulation. The results showed that LAB97 and C1090 met the probiotic potential viability criterion by maintaining 6 log10 CFU/mL counts after in vitro simulation. The second trial assessed the LAB starters' fermentative ability. Partially decontaminated (110 °C/2 min) immature tomato pulp was used to prepare the individually inoculated samples (Id: LAB97 and C1090). Non-inoculated samples, both with and without thermal treatment (Id: CTR-TT and CTR-NTT, respectively), were prepared as the controls. Fermentation was undertaken (25 °C, 100 rpm) for 14 days. Throughout storage (0, 24, 48, 72 h, 7, and 14 days), all the samples were tested for LAB and Y&M counts, titratable acidity (TA), solid soluble content (SSC), total phenolic content (TPC), antioxidant capacity (AOx), as well as for organic acids and phenolic profiles, and CIELab colour and sensory evaluation (14th day). The LAB growth reached ca. 9 log10 CFU/mL for all samples after 72 h. The LAB97 samples had an earlier and higher acidification rate than the remaining ones, and they were highly correlated to lactic acid increments. The inoculated samples showed a faster and higher decrease rate in their SSC levels when compared to the controls. A nearly two-fold increase (p < 0.05) during the fermentation, over time, was observed in all samples' AOx and TPC (p < 0.05, r = 0.93; similar pattern). The LAB97 samples obtained the best sensory acceptance for flavour and overall appreciation scores when compared to the others. In conclusion, the L. plantarum LAB97 starter culture was selected as a novel probiotic candidate to obtain a potential probiotic ingredient from immature tomato fruits.

Usefulness of serum procalcitonin and point-of-care multiplex PCR gastro-intestinal panel in acute diarrhoea or colitis in the emergency department.

INTRODUCTION: Acute infectious diarrhoea is one of the most common diseases worldwide. Procalcitonin (PCT) is useful for antibiotic stewardship in lower respiratory tract infections but has been poorly studied in infectious diarrhoea. Our objective is to describe the PCT concentrations according to diarrhoea aetiology. METHODS: This is a single-center prospective cohort study involving adults consulting the emergency department (ED) for an acute diarrhoea or colitis. Serum PCT was measured and a stool sample was tested with FilmArray® Gastro-Intestinal Panel. The primary endpoint is the PCT concentration according to each type of pathogen identified using Gastro-Intestinal-panel and/or stool cultures at ED admission. RESULTS: 125 patients were included: 80 had an acute infectious diarrhoea, 21 an acute colitis and 24 another illness causing diarrhoea. The median (interquartile ranges) PCT values (ng/ml) were 0.13 (0.08-0.28), 0.07 (0.06-0.54), 0.13 (0.09-0.26) and 0.05 (0.03-0.17), respectively if there was a bacteria (n = 41), parasite (n = 3), virus (n = 10) or no pathogen identified and 0.34 (0.13-1.03) if the diarrhoea was due to another illness (n = 24). CONCLUSION: In patients admitted to the ED with an acute infectious diarrhoea or acute colitis, PCT remained low when a bacteria was identified. It may not be informative in current practice to guide antibiotic therapy.

Influence of Air-Drying Conditions on Quality, Bioactive Composition and Sensorial Attributes of Sweet Potato Chips.

The drying process is an essential thermal process for preserving vegetables and can be used in developing dried products as healthy alternative snacks. The effects of air-drying conditions using a convection dryer with hot air at different temperatures (60°, 65°, 70°, 75°, and 80 °C, in the range 5-200 min, at a fixed air speed of 2.3 m/s) were tested on the quality of slices (2.0 ± 0.1 mm) of dried sweet potato (Bellevue PBR). For each time and temperature, drying condition, physicochemical parameters (moisture content, CIELab color, texture parameters, total phenolic and carotenoid contents) and a sensory evaluation by a panel at the last drying period (200 min) were assessed. Drying time was shown to have a more significant effect than temperature on the quality of dried sweet potato as a snack, except for carotenoid content. Given the raw tuber content, thermal degradation (p < 0.05) of total phenolic compounds (about 70%), regardless of tested conditions, contrasted with the higher stability of total carotenoids (<30%). The dried product, under optimal conditions (≥75 °C for 200 min), achieved a moisture content (≤10%) suitable for preservation, providing a crispy texture with favourable sensory acceptance and providing a carotenoid content similar to the raw product.

Nutritional Properties of Baobab Pulp from Different Angolan Origins.

The baobab tree (Adansonia digitata L.) is found widely in the forests and savannas of sub-Saharan Africa. The baobab fruit has a sour and slightly sweet taste and is widely consumed by the natives, thus containing a high nutritional value and providing a source of income for rural people. This study aimed to compare the nutritional composition of baobab fruit pulp from different localities in the Namibe province (Angola). Twenty samples of baobab pulp were collected in markets of the four municipalities of Namibe. The results obtained showed that there is some geographic location dependence on nutritional and functional composition. The municipality of Camucuio showed samples with higher fibre content (56.62 g/100 g) and vitamin C (288.9 mg/100 g). Samples from the Virei municipality stood out for their antioxidant activity (1936 mmol TE/100 g), high K content (42.4 mg/g) and higher values of protein (2.42 g/100 g). The samples collected in the municipality of Bibala stood out for their high contents of carbohydrates (28.1 g/100 g), total phenolic compounds (972 mg GAE/100 g) and Ca (3.80 mg/g). Despite the differences in origin, the high nutritional value of baobab fruit has the potential to improve the diet of thousands of people in Africa qualitatively.

Multi-Target Alternative Approaches to Promoting Fresh-Cut Carrots' Bioactive and Fresh-like Quality.

Fresh-cut fruits and vegetables, as near-fresh foods, are a quick and easy solution to a healthy and balanced diet. The rapid degradation of nutritional and sensory quality during the processing and storage of a product is critical and plant-type-dependent. The introduction of disruptive technological solutions in fresh-cut processing, which could maintain fresh-like quality with less environmental impact, is an emerging research concept. The application of abiotic stress treatments (heat shock and UV-C) induces metabolic responses and microbial effects in plant tissues, potentially slowing down several quality senescence pathways. The previously selected combined and single effects of heat shock (100 °C/45 s; in the whole root) and UV-C (2.5 kJ/m2) treatments and two packaging conditions (oriented polypropylene (OPP) vs. micro-perforated OPP films) on controlling critical degradation pathways of fresh-cut carrots and on promoting bioactive and sensory quality during storage (5 °C, 14 days) were studied. Among the tested combinations, synergistic effects on the quality retention of fresh-cut carrots were only attained for applying heat shock associated with micro-perforated OPP film packaging. Its effects on reducing (3.3 Log10 CFU/g) the initial contamination and controlling microbiological spoilage (counts below the threshold limit of 7.5 Log10 CFU/g), increasing the bioactive content (38% and 72% in total phenolic content and chlorogenic acid, respectively), and preserving fresh quality attributes prove to be a viable alternative technology for shredded carrot processing.

Influence of a heat-shock pre-treatment on wound-induced phenolic biosynthesis as an alternative strategy towards fresh-cut carrot processing.

In fresh-cut vegetables, plant tissues are often challenged by (a)biotic stresses that act in combination, and the response to combinatorial stresses differs from that triggered by each individually. Phenolic induction by wounding is a known response contributing to increase products phenolic content. Heat application is a promising treatment in minimal processing, and its interference on the wound-induced response is produce-dependent. In carrot, two-combined stress effects were evaluated: peel removal vs. shredding, and heat application (100 °C/45 s) vs. shredding, on changes in total phenolic content (TPC) during 10 days (5 °C). By applying the first stress combination, a decrease in TPC was verified on day 0 (∼50%), ascribed to the high phenolic content of peels. Recovery of initial fresh carrot levels was achieved after 7 days owing to phenolic biosynthesis induced by shredding. For the second combination, changes in TPC, phenylalanine-ammonia-lyase (PAL), and peroxidase (POD) activity of untreated (Ctr) and heat-treated (HS) peeled shredded carrot samples were evaluated during 10 days. The heat-shock did not suppress phenolic biosynthesis promoted by PAL, although there was a two-day delay in TPC increments. Notwithstanding, phenolic accumulation after 10 days exceeded raw material TPC content. Also, the decrease in POD activity (30%) could influence quality degradation during storage.

Selection of Autochthonous LAB Strains of Unripe Green Tomato towards the Production of Highly Nutritious Lacto-Fermented Ingredients.

Lactic fermentation of unripe green tomatoes as a tool to produce food ingredients is a viable alternative for adding value to industrial tomatoes unsuitable for processing and left in large quantities in the fields. Fermentation using starter cultures isolated from the fruit (plant-matrix adapted) can have advantages over allochthonous strains in obtaining fermented products with sensory acceptability and potentially probiotic characteristics. This paper details the characterisation of the unripe green tomato lactic microbiota to screen LAB strains for use as starter cultures in fermentation processes, along with LAB strains available from INIAV's collection. Morphological, biochemical (API system), and genomic (16S rDNA gene sequencing) identification showed that the dominant LAB genera in unripe green tomato are Lactiplantibacillus, Leuconostoc, and Weissella. Among nine tested strains, autochthonous Lactiplantibacillus plantarum and allochthonous Weissella paramesenteroides showed tolerance to added solanine (200 ppm) and the best in vitro probiotic potential. The results indicate that the two LAB strains are promising candidates for manufacturing probiotic fermented foods from unripe green tomatoes.

Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study.

BACKGROUND: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).