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Abstract The coronavirus disease 2019 (COVID-19) pandemic has led to the worldwide implementation of unprecedented public protection measures. On the 17th of March, the French government announced a lockdown of the population for 8 weeks. This monocentric study assessed the impact of this lockdown on the musculoskeletal injuries treated at the emergency department as well as the surgical indications. We carried out a retrospective study in the Emergency Department and the Surgery Department of Nantes University Hospital from 18 February to 11 May 2020. We collected data pertaining to the demographics, the mechanism, the type, the severity, and inter-hospital transfer for musculoskeletal injuries from our institution. We compared the 4-week pre-lockdown period and the 8-week lockdown period divided into two 4-week periods: early lockdown and late lockdown. There was a 52.1% decrease in musculoskeletal injuries among patients presenting to the Emergency Department between the pre-lockdown and the lockdown period (weekly incidence: 415.3 ± 44.2 vs. 198.5 ± 46.0, respectively, p 16) between the pre-lockdown and the early lockdown period (2 (1.1%) vs. 7 (7.2%), respectively, p = .010) as well as between the pre-lockdown and the late lockdown period (2 (1.1%) vs. 10 (8.3%), respectively, p = .004). We observed a significant increase in the weekly emergency department patient admissions between the early and the late lockdown period (161.5 ± 22.9, 235.5 ± 27.7, respectively, p = .028). A pronounced decrease in the incidence of musculoskeletal injuries was observed secondary to the lockdown measures, with emergency department patient admissions being halved and surgical indications being reduced by a third. The increase in musculoskeletal injuries during the late confinement period and the higher incidence of severe trauma highlights the importance of maintaining a functional trauma center organization with an inter-hospital transfer policy in case of a COVID-19s wave lockdown.

Abstract Background Rapid access to emergency medical communication centers (EMCCs) is pivotal to address potentially life-threatening conditions. Maintaining public access to EMCCs without delay is crucial in case of disease outbreak despite the significant increased activity and the difficulties to mobilize extra staff resources. The aim of our study was to assess the impact of two-level filtering on EMCC performance during the COVID-19 outbreak. Methods A before-after monocentric prospective study was conducted at the EMCC at the Nantes University Hospital. Using telephone activity data, we compared EMCC performance during 2 periods. In period one (February 27th to March 11th 2020), call takers managed calls as usual, gathering basic information from the caller and giving first aid instructions to a bystander on scene if needed. During period two (March 12th to March 25th 2020), calls were answered by a first-line call taker to identify potentially serious conditions that required immediate dispatch. When a serious condition was excluded, the call was immediately transferred to a second-line call taker who managed the call as usual so the first-line call taker could be rapidly available for other incoming calls. The primary outcome was the quality of service at 20 s (QS20), corresponding to the rate of calls answered within 20 s. We described activity and outcome measures by hourly range. We compared EMCC performance during periods one and two using an interrupted time series analysis. Results We analyzed 45,451 incoming calls during the two study periods: 21,435 during period 1 and 24,016 during period 2. Between the two study periods, we observed a significant increase in the number of incoming calls per hour, the number of connected call takers and average call duration. A linear regression model, adjusted for these confounding variables, showed a significant increase in the QS20 slope (from − 0.4 to 1.4%, p = 0.01), highlighting the significant impact of two-level filtering on the quality of service. Conclusions We found that rapid access to our EMCC was maintained during the COVID-19 pandemic via two-level filtering. This system helped reduce the time gap between call placement and first-line call-taker evaluation of a potentially life-threatening situation. We suggest implementing this system when an EMCC faces significantly increased activity with limited staff resources.

In emergency situations, timely contact with emergency medical communication centers (EMCCs) is critical for patient outcomes. Increasing call volumes and economic constraints are challenging many countries, necessitating organizational changes in EMCCs. This study uses a simulation-based digital twin approach, creating a virtual model of EMCC operations to assess the impact of different organizational scenarios on accessibility. Specifically, we explore two decompartmentalized scenarios where traditionally isolated call centers are reorganized to enable more flexible call distribution. The primary measure of accessibility was service quality within 30 s of call reception. Our results show that decompartmentalization improves service quality by 17% to 21%. This study demonstrates that reducing regional isolation in EMCCs can enhance performance and accessibility with a simulation-based digital twin approach providing a clear and objective method to quantify the benefits.", Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Oral microbial dysbiosis has been associated with periodontitis in studies using 16S rRNA gene sequencing analysis. However, this technology is not sufficient to consistently separate the bacterial species to species level, and reproducible oral microbiome signatures are scarce. Obtaining these signatures would significantly enhance our understanding of the underlying pathophysiological processes of this condition and foster the development of improved therapeutic strategies, potentially personalized to individual patients. Here, we sequenced newly collected samples from 24 patients with periodontitis, and we collected available oral microbiome data from 24 samples in patients with periodontitis and from 214 samples in healthy individuals ( n = 262). Data were harmonized, and we performed a pooled analysis of individual patient data. By metagenomic sequencing of the plaque microbiome, we found microbial signatures for periodontitis and defined a periodontitis-related complex, composed by the most discriminative bacteria. A simple two-factor decision tree, based on Tannerella forsythia and Fretibacterium fastidiosum , was associated with periodontitis with high accuracy (area under the curve: 0.94). Altogether, we defined robust oral microbiome signatures relevant to the pathophysiology of periodontitis that can help define promising targets for microbiome therapeutic modulation when caring for patients with periodontitis., Importance: Oral microbial dysbiosis has been associated with periodontitis in studies using 16S rRNA gene sequencing analysis. However, this technology is not sufficient to consistently separate the bacterial species to species level, and reproducible oral microbiome signatures are scarce. Here, using ultra-deep metagenomic sequencing and machine learning tools, we defined a simple two-factor decision tree, based on Tannerella forsythia and Fretibacterium fastidiosum , that was highly associated with periodontitis. Altogether, we defined robust oral microbiome signatures relevant to the pathophysiology of periodontitis that can help define promising targets for microbiome therapeutic modulation when caring for patients with periodontitis., Competing Interests: The authors declare no conflict of interest.

In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients., (© 2024. The Author(s).)

Background: Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7., Methods: CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489)., Findings: Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates., Interpretation: Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis., Funding: French Ministry of Health., Competing Interests: Declaration of interests AP reports receiving personal fees from Daiichi, Bayer, Bristol Myers Squibb, Pfizer, Stago, Alnylam, Sanofi, Viatris, Boehringer, and Leo Pharma. SL reports receiving personal fees from Brahms. TD reports receiving personal fees from Sanofi Aventis. TM reports receiving personal fees from Bristol Myers Squibb. P-MR reports receiving personal fees from Aspen, Bayer, Boehringer Ingelheim, Sanofi Aventis, Pfizer, Bristol Myers Squibb, and Viatis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Point-of-care ultrasound (POCUS) curriculum varies among countries. However, the length of training required for physicians is still under debate. We investigated the impact of different training methods: short hands-on courses (STS), long academic training sessions (LTS), or both (mixed training [MTS]), for POCUS daily use and self-reported confidence overall and specific to specific clinical situations. This was a descriptive study conducted over a 3-month period through a Web-based survey designed to assess the influence of different methods of POCUS training among physicians and residents on their daily practice. The survey was sent to 1212 emergency physicians with prior POCUS training; 515 answers (42%) could be analyzed. Participants in the STS group performed POCUS less frequently than physicians in the LTS or MTS group. Daily use in the STS group was 51% versus 82% in the LTS group and 83% in the MTS group ( P < 0.01). The overall self-reported confidence in POCUS was lower in the STS group ( P < 0.01) in all studied clinical situations. There was no significant difference between LTS and MTS groups ( P > 0.05). Method of POCUS training significantly influenced POCUS daily use. Physicians who underwent long training sessions used POCUS more frequently in their routine practice and were significantly more confident in their ability to perform and interpret a POCUS examination., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Abdominal pain is common in patients visiting the emergency department (ED). The aim of this study was to assess the diagnostic contribution of point-of-care ultrasound (POCUS) in patients presenting to the ED with acute abdominal pain., Methods: We designed an interventional randomized, controlled, open label, parallel-group, trial in two French EDs. We included adult patients presenting to the ED with acute abdominal pain. Exclusion criteria were a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients were randomized in the experimental group (i.e., workup including POCUS) or control group (usual care). The primary objective of the study was to assess the added value of POCUS on diagnostic pathway in the ED, according to the diagnostic established a posteriori by an adjudication committee. The primary endpoint was the proportion of exact preliminary diagnosis between the 2 groups. The preliminary diagnosis made after clinical examination and biological results with POCUS (intervention arm) or without POCUS (usual care) was considered exact if it was similar to the adjudication committee diagnosis., Results: Between June 2021 11th and June 2022 23th, 256 patients were randomized, but five were not included in the primary analysis, leaving 125 patients in the POCUS group and 126 patients in the usual care group (130 women and 121 men, median [Q1-Q3] age: 42 [30;57]). There was no difference for exact diagnosis between the two groups (POCUS 70/125, 56% versus control 78/126 (62%), RD 1.23 [95% CI 0.74-2.04]). There was no difference in the accuracy for the diagnosis of non-specific abdominal pain nor number of biological or radiological exams. Diagnostic delays and length of stay in the ED were also similar., Conclusions: In this trial, systematic POCUS did not improve the rate of diagnostic accuracy in unselected patients presenting to the ED with acute abdominal pain. However, as it was a safe procedure, further research should focus on patients with suspected etiologies where POCUS is particularly useful., Trial Registration:  This trial was registered on ClinicalTrials.gov on 2022/07/20 ( https://clinicaltrials.gov/study/NCT04912206?id=NCT04912206&rank=1 ) (NCT04912206)., (© 2024. The Author(s).)

Background: Hospitalized patients with acute shortness of breath (SOB) could benefit from an enhanced focused cardiac ultrasound (eFoCUS) with Doppler measurements to reassess treatment and diagnosis., Methods: This was a retrospective observational study performed in a medical ward. Included patients were those hospitalized for acute SOB. The objectives were to assess therapeutic and diagnosis changes associated with eFoCUS. The primary endpoint of the analysis was a composite of introduction or discontinuation of diuretics, antibiotics or anticoagulation following eFoCUS., Results: Between January 2018 and July 2021, 119 patients were included, 67 women and 52 men, mean age 84 ± 11 years old. The eFoCUS was performed within a median time of 55 h (1st-3rd IQ: 21-107) following hospital admission. Overall, eFoCUS was associated with a change in diagnostic in 40 patients (34% [CI 95%: 25%-43%], p < 10 -4 ) and a change in treatment in 53 patients (45% [CI 95%: 35%-54%], p < 10 -4 ). Diuretics were prescribed in 94 patients before eFoCUS and in 56 after (p = 10 -4 ), antibiotics in 34 before and 27 after and anticoagulation in 30 before and 40 after., Conclusion: eFoCUS was associated with both therapeutic and diagnostic changes in patients with SOB. Such results should be confirmed in multicentric prospective studies., (© 2023 Wiley Periodicals LLC.)

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain., Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain., Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units., Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123)., Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen., Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention., Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain., Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.

Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL- E. coli ). The combination of inulin and pantoprazole (IP) significantly reduced ESBL- E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL- E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli . The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.

Importance: Tracheal intubation is recommended for coma patients and those with severe brain injury, but its use in patients with decreased levels of consciousness from acute poisoning is uncertain., Objective: To determine the effect of intubation withholding vs routine practice on clinical outcomes of comatose patients with acute poisoning and a Glasgow Coma Scale score less than 9., Design, Setting, and Participants: This was a multicenter, randomized trial conducted in 20 emergency departments and 1 intensive care unit (ICU) that included comatose patients with suspected acute poisoning and a Glasgow Coma Scale score less than 9 in France between May 16, 2021, and April 12, 2023, and followed up until May 12, 2023., Intervention: Patients were randomized to undergo conservative airway strategy of intubation withholding vs routine practice., Main Outcomes and Measures: The primary outcome was a hierarchical composite end point of in-hospital death, length of ICU stay, and length of hospital stay. Key secondary outcomes included adverse events resulting from intubation as well as pneumonia within 48 hours., Results: Among the 225 included patients (mean age, 33 years; 38% female), 116 were in the intervention group and 109 in the control group, with respective proportions of intubations of 16% and 58%. No patients died during the in-hospital stay. There was a significant clinical benefit for the primary end point in the intervention group, with a win ratio of 1.85 (95% CI, 1.33 to 2.58). In the intervention group, there was a lower proportion with any adverse event (6% vs 14.7%; absolute risk difference, 8.6% [95% CI, -16.6% to -0.7%]) compared with the control group, and pneumonia occurred in 8 (6.9%) and 16 (14.7%) patients, respectively (absolute risk difference, -7.8% [95% CI, -15.9% to 0.3%])., Conclusions and Relevance: Among comatose patients with suspected acute poisoning, a conservative strategy of withholding intubation was associated with a greater clinical benefit for the composite end point of in-hospital death, length of ICU stay, and length of hospital stay., Trial Registration: ClinicalTrials.gov Identifier: NCT04653597.

Respiratory microbial dysbiosis is associated with acute respiratory distress syndrome (ARDS) and hospital-acquired pneumonia (HAP) in critically ill patients. However, we lack reproducible respiratory microbiome signatures that can increase our understanding of these conditions and potential treatments. Here, we analyze 16S rRNA sequencing data from 2,177 respiratory samples collected from 1,029 critically ill patients (21.7% with ARDS and 26.3% with HAP) and 327 healthy controls, sourced from 17 published studies. After data harmonization and pooling of individual patient data, we identified microbiota signatures associated with ARDS, HAP and prolonged mechanical ventilation. Microbiota signatures for HAP and prolonged mechanical ventilation were characterized by depletion of a core group of microbes typical of healthy respiratory samples, and the ARDS microbiota signature was distinguished by enrichment of potentially pathogenic respiratory microbes, including Pseudomonas and Staphylococcus. Using machine learning models, we identified clinically informative, three- and four-factor signatures that predicted ARDS, HAP and prolonged mechanical ventilation with relatively high accuracy (area under the curve of 0.751, 0.72 and 0.727, respectively). We validated the signatures in an independent prospective cohort of 136 patients on mechanical ventillation and found that patients with microbiome signatures associated with ARDS, HAP or prolonged mechanical ventilation had longer times to successful extubation than patients lacking these signatures (hazard ratios of 1.56 (95% confidence interval (CI) 1.07-2.27), 1.51 (95% CI 1.02-2.23) and 1.50 (95% CI 1.03-2.18), respectively). Thus, we defined and validated robust respiratory microbiome signatures associated with ARDS and HAP that may help to identify promising targets for microbiome therapeutic modulation in critically ill patients., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background Emergency tracheal intubation is routinely performed in the prehospital setting. Airway management in the prehospital setting has substantial challenges. Objective The aim of the present study was to determine risk factors predicting tracheal intubation-related complications on the prehospital field. Setting A prospective, multicentric, cohort study which was conducted in three mobile ICUs (MICUs; service mobile d'urgence et de réanimation).Outcome measures and analysis Tracheal intubation-related complications were defined as the occurrence of at least one of the following events: oxygen desaturation (SpO2 < 90%) during tracheal intubation, aspiration (regurgitation visualized during laryngoscopy), and vomiting. Difficult intubation was defined as more than two failed direct laryngoscopic attempts, or the need for any alternative tracheal intubation method. Multivariate logistic regressions were used. Results During the 5-year study period, 1915 consecutive patients were intubated in the MICUs participating in the study. Overall, 1287 (70%) patients were successfully intubated after the first laryngoscopic attempt, with rates of 90, 74, 42, and 30% for Cormack-Lehane grade 1, 2, 3, and 4, respectively. Tracheal intubation was difficult in 663 cases (36%). Tracheal intubation-related complications occurred in 267 (14%) patients. In the multivariate analysis, we found that the leading risk factors for tracheal intubation-related complications were Cormack and Lehane grade 3 and 4 [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.05-2.61; and OR = 2.79; 95% CI, 1.56-4.98, respectively], a BMI of more than 30 (OR = 1.61; 95% CI, 1.13-2.28), when intubation was difficult (OR = 1.72; 95% CI, 1.15-2.57), and when tracheal intubation required more than one operator (OR = 2.30; 95% CI, 1.50-3.49).Conclusions In this prospective study, we found that Cormack and Lehane more than grade 2, BMI >30, difficult intubation, and tracheal intubation requiring more than one operator were all independent predictors of tracheal intubation-related complications in the prehospital setting. When these risk factors are identified on scene, adapted algorithms that anticipate the use of a bougie should be generalized to reduce morbidity on the prehospital field., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recently, validated clinical decision rules have been developed that avoid unnecessary use of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE) in the emergency department (ED)., Objective: To measure any resulting change in CTPA use for suspected PE., Design: Retrospective analysis., Setting: 26 European EDs in 6 countries., Patients: Patients with CTPA performed for suspected PE in the ED during the first 7 days of each odd month between January 2015 and December 2019., Measurements: The primary end points were the CTPAs done for suspected PE in the ED and the number of PEs diagnosed in the ED each year adjusted to an annual census of 100 000 ED visits. Temporal trends were estimated using generalized linear mixed regression models., Results: 8970 CTPAs were included (median age, 63 years; 56% female). Statistically significant temporal trends for more frequent use of CTPA (836 per 100 000 ED visits in 2015 vs. 1112 in 2019; P  < 0.001), more diagnosed PEs (138 per 100 000 in 2015 vs. 164 in 2019; P  = 0.028), a higher proportion of low-risk PEs (annual percent change [APC], 13.8% [95% CI, 2.6% to 30.1%]) with more ambulatory management (APC, 19.3% [CI, 4.1% to 45.1%]), and a lower proportion of intensive care unit admissions (APC, -8.9% [CI, -17.1% to -0.3%]) were observed., Limitation: Data were limited to 7 days every 2 months., Conclusion: Despite the recent validation of clinical decision rules to limit the use of CTPA, an increase in the CTPA rate along with more diagnosed PEs and especially low-risk PEs were instead observed., Primary Funding Source: None specific for this study., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3116.

Background: In emergency medicine, pain is a frequent reason for consultation. However, there is a great variation in its management which is often insufficient. The use intravenous morphine alone or multimodal analgesia with paracetamol is recommended for severe pain. But robust data are lacking to justify the association of paracetamol with morphine versus morphine alone for pain management in the emergency room (ER). The aim of our study is therefore to assess if in patients with acute pain of moderate to severe intensity with a numerical verbal scale (NVS) ≥5 in the ER, the intravenous administration of morphine alone is not inferior to the administration of intravenous morphine combined with paracetamol at 30 min from the first administration of the study drug., Methods: ADAMOPA is a prospective, non-inferiority, multicenter, placebo-controlled, parallel-group, randomized (1:1), double-blind trial. Subjects will be enrolled in the ER if they experience moderate to severe, acute, non-traumatic, and traumatic pain, defined as an NVS ≥5. The primary endpoint will be the between-group difference in mean change in NVS pain scores among patients receiving the combination of intravenous morphine plus paracetamol or intravenous morphine given alone, measured from the time before administration of the study medication to 30 min later., Discussion: This trial will determine the clinical utility of the association of paracetamol with morphine for pain management in the emergency room. The ADAMOPA trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practices., Trial Registration: EudraCT number: 2019-002149-39., Clinicaltrials: gov identifier: NCT04148495. Date of trial registration: November 1, 2019., (© 2022. The Author(s).)

Background: Abdominal pain is frequent in patients consulting in emergency departments. The aim of this study is to determine the diagnosis efficacy of point-of-care ultrasound (POCUS) in patients consulting in the ED for acute abdominal pain by comparing the rate of exact diagnostic between the two arms (with or without POCUS), according to the index diagnostic established by an adjudication committee., Methods: It is a randomized, controlled, open and interventional study in two emergency departments. The included patients will be adults admitted for acute abdominal pain. Exclusion criteria will be a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients will be randomized in intervention (POCUS) or control groups. POCUS will only be performed by trained physicians and will be added to the diagnosis procedure in the intervention group. In the control group, the diagnosis will be established after clinical examination and reception of biological analysis results. In the interventional group, the diagnosis will be established after a clinical exam, biological analysis reception and POCUS. An adjudication committee will review all data from case report forms and will determine the index diagnosis which will be used for the analysis. The primary endpoint will be the comparison of the rate of exact diagnostic between the two arms according to the adjudication committee diagnostic. Secondary endpoints will be the comparison between the two groups for diagnostic delay, duration of ED stay, diagnostic performances for non-specific abdominal pain and hospitalization rate. The primary endpoint will be compared between the two groups using a mixed model taking into account the recruiting centre. Delays will be compared by a mixed linear generalized model. Diagnostic performances will be estimated with their 95% confidence intervals. For a correct diagnostic rate of 57% in the control group and 74% in the intervention group with a 0.05 alpha risk and a 80% power, 244 patients will be required., Discussion: POCUS diagnostic abilities have been mainly demonstrated in monocentric studies but the level of evidence of its diagnostic efficacy remains controversial in particular in Europe. The aim of this study is to address this question with a rigorous methodology., Trial Registration: ClinicalTrials.gov NCT04912206. Registered on June 3, 2021., (© 2022. The Author(s).)

Rationale: Brain injury induces systemic immunosuppression, increasing the risk of viral reactivations and altering neurological recovery. Objectives: To determine if systemic immune alterations and lung replication of herpesviridae are associated and can help predict outcomes after brain injury. Methods: We collected peripheral blood mononuclear cells in patients with severe brain injury requiring invasive mechanical ventilation. We systematically searched for respiratory herpes simplex virus (HSV) replications in tracheal aspirates. We also performed chromatin immunoprecipitation sequencing, RNA-sequencing, and in vitro functional assays of monocytes and CD4 T cells collected on Day 1 to characterize the immune response to severe acute brain injury. The primary outcome was the Glasgow Outcome Scale Extended at 6 months. Measurements and Main Results: In 344 patients with severe brain injury, lung HSV reactivations were observed in 39% of the 232 patients seropositive for HSV and independently associated with poor neurological recovery at 6 months (hazard ratio, 1.90; 95% confidence interval, 1.08-3.57). Weighted gene coexpression network analyses of the transcriptomic response of monocytes to brain injury defined a module of 721 genes, including PD-L1 and CD80, enriched for the binding DNA motif of the transcriptional factor Zeb2 and whose ontogenic analyses revealed decreased IFN-γ-mediated and antiviral response signaling pathways. This monocyte signature was preserved in a validation cohort and predicted the neurological outcome at 6 months with good accuracy (area under the curve, 0.786; 95% confidence interval, 0.593-0.978). Conclusions: A specific monocyte signature is associated with HSV reactivation and predicts poor recovery after brain injury. The alterations of the immune control of herpesviridae replication are understudied and represent a novel therapeutic target.

Recent observations suggest that Gal antigen content in gut microbiota and anti-Gal antibody response may influence inflammation in immune related disorders. In this review we summarized the current knowledge on antibody response to the Gal epitope in various immune disorders. We discuss the origin of Gal antigen associated to gut microbiota. In multiple sclerosis, the possible mechanisms by which the altered microbiota and/or circulating anti-Gal level could affect the immune response in this disease are presented., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The growing resistance of bacteria to antibiotics is a major global public health concern. An important reservoir of this resistance is the gut microbiota. However, limited data are available on the ability of phage therapy to reduce the digestive carriage of multidrug-resistant bacteria., Materials and Methods: Four novel lytic phages were isolated in vitro for efficacy against an extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strain also resistant to carbapenems through a carbapenemase OXA-48. The first step was to develop models of ESBL E. coli digestive carriage in mice. The second step was to test the efficacy of an oral and rectal phage therapy (a cocktail of four phages or microencapsulated phage) to reduce this carriage., Results: The two most intense models of digestive carriage were obtained by administering amoxicillin (0.5 g·L -1 ) continuously in the drinking water (Model 1) or pantoprazole (0.1 g·L -1 ) continuously in the drinking water, combined with amoxicillin (0.5 g·L -1 ), for the first 8 days (Model 2). Oral administration of the phage cocktail to Model 1 resulted in a transient reduction in the concentration of ESBL E. coli in the faeces 9 days after the bacterial challenge (median = 5.33 × 10 8 versus 2.76 × 10 9 CFU·g -1 , p = 0.02). In contrast, in Model 2, oral or oral + rectal administration of this cocktail did not alter the bacterial titre compared to the control (area under the curve, AUC, 3.49 × 10 9 ; 3.41 × 10 9 and 3.82 × 10 9 for the control, oral and oral + rectal groups, respectively; p -value > 0.8 for each two-by-two group comparison), as well as the administration of an oral microencapsulated phage in Model 1 (AUC = 8.93 × 10 9 versus 9.04 × 10 9 , p = 0.81)., Conclusions: Oral treatment with amoxicillin promoted digestive carriage in mice, which was also the case for the addition of pantoprazole. However, our study confirms the difficulty of achieving efficacy with phage therapy to reduce multidrug-resistant bacterial digestive carriage in vivo.

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases. However, aHSCT procedures are limited by potentially life-threatening complications, and one of the most serious complications is acute graft-versus-host disease (GVHD). During the last decades, DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states. Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease, they may be useful for diagnosis, prevention and therapy in aHSCT recipients. Here, we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors who contributed their efforts in this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Importance: Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds., Objective: To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold., Design, Settings, and Participants: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020., Interventions: Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold., Main Outcomes and Measures: The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months., Results: Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9])., Conclusions and Relevance: Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events., Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be associated with myocardial injury. Identification of at-risk patients and mechanisms underlying cardiac involvement in COVID-19 remains unclear. During hospitalization for COVID-19, high troponin level has been found to be an independent variable associated with in-hospital mortality and a greater risk of complications. Electrocardiographic (ECG) abnormalities could be a useful tool to identify patients at risk of poor prognostic. The aim of our study was to assess if specific ECGs patterns could be related with in-hospital mortality in COVID-19 patients presenting to the ED in a European country., Methods: From February 1st to May 31st, 2020, we conducted a multicenter study in three hospitals in France. We included adult patients (≥ 18 years old) who visited the ED during the study period, with ECG performed at ED admission and diagnosed with COVID-19. Demographic, comorbidities, drug exposures, signs and symptoms presented, and outcome data were extracted from electronic medical records using a standardized data collection form. The relationship between ECG abnormalities and in-hospital mortality was assessed using univariate and multivariable logistic regression analyses., Results: An ECG was performed on 275 patients who presented to the ED. Most of the ECGs were in normal sinus rhythm (87%), and 26 (10%) patients had atrial fibrillation/flutter on ECG at ED admission. Repolarization abnormalities represented the most common findings reported in the population (40%), with negative T waves representing 21% of all abnormalities. We found that abnormal axis (adjusted odds ratio: 3.9 [95% CI, 1.1-11.5], p = 0.02), and left bundle branch block (adjusted odds ratio: 7.1 [95% CI, 1.9-25.1], p = 0.002) were significantly associated with in-hospital mortality., Conclusions: ECG performed at ED admission may be useful to predict death in COVID-19 patients. Our data suggest that the presence of abnormal axis and left bundle branch block on ECG indicated a higher risk of in-hospital mortality in COVID-19 patients who presented to the ED. We also confirmed that ST segment elevation was rare in COVID-19 patients., (© 2021. The Author(s).)

Periodontitis is a common condition characterized by an exacerbated pro-inflammatory response, which leads to tissue destruction and, ultimately, alveolar bone loss. In this pilot study, we assess the microbiota composition and cytokine profile changes in patients with stage III/IV, grade B/C periodontitis, specifically by comparing healthy and diseased sites in the same oral cavity. Overall, we found that microbiota architecture was significantly disrupted between diseased and healthy sites, and that the clustering was driven, in part, by the increased relative abundances of Synergistetes in diseased sites, as well as the increased abundances of Firmicutes in healthy sites. We also observed that diseased sites were enriched in Synergistetes, TM7, SR1, Spirochaetes, Bacteroidetes and Fusobacteria, and depleted in Firmicutes, Proteobacteria, Tenericutes and Actinobacteria compared to healthy sites. We found that Interleukin-1b, Interleukin-4, Interleukin-10, and Interleukin-17A were significantly overexpressed in diseased sites, whereas Interleukin-6 and TNF-alpha do not differ significantly between healthy and diseased sites. Here, we observed concomitant changes in the subgingival plaque microbiota and cytokines profile, suggesting that this combined alteration could contribute to the pathobiology of periodontitis.

The SARS-CoV2 has now spread worldwide causing over four million deaths. Testing strategies are highly variable between countries and their impact on mortality is a major issue. Retrospective multicenter study with a prospective database on all inpatients throughout mainland France. Using fixed effects models, we exploit policy discontinuities at region borders in France to estimate the effect of testing on the case fatality rate. In France, testing policies are determined at a regional level, generating exogenous variation in testing rates between departments on each side of a region border. We compared all contiguous department pairs located on the opposite sides of a region border. The increase of one percentage point in the test rate is associated with a decrease of 0.0015 percentage point in the death rate, that is, for each additional 2000 tests, we could observe three fewer deaths. Our study suggests that COVID-19 population testing could have a significant impact on the mortality rate which should be considered in decision-making. As concern grows over the current second wave of COVID-19, our findings support the implementation of large-scale screening strategies in such epidemic contexts., (© 2021. The Author(s).)

Background: Out-of-hospital cardiac arrest (OHCA) in children is associated with a low survival rate. Conclusions in the literature are conflicting regarding the best way to handle ventilation. The purpose of this study was to assess the impact of two airway management strategies, endotracheal intubation (ETI) vs. supraglottic procedure, during cardiopulmonary resuscitation (CPR) on 30-day survival in paediatric OHCA., Methods: This was a retrospective, observational, multicentre, registry-based study conducted from July 2011 to March 2018. All paediatric OHCA patients under 18 years of age and managed by a mobile intensive care unit were included. The primary endpoint was 30-day survival in a weighted population (based on propensity scores)., Results: Of 1579 children, 1355 (85.8%) received ETI and 224 (14.2%) received supraglottic ventilation during CPR. We observe a lower 30-day survival in the ETI group compared to the supraglottic group (7.7% vs. 14.3%, absolute difference, 6.6 percentage points; 95% confidence interval [CI], 2.3-12.0; propensity-adjusted odds ratio [paOR], 0.39; 95% CI, 0.25-0.62; p < 0.001), and also a poorer neurological outcome (paOR, 0.32; 95% CI, 0.19-0.54; p < 0.001). However, we did not identify any significant association between airway management strategy and return of spontaneous circulation (paOR, 1.15; 95% CI, 0.80-1.65; p = 0.46)., Conclusions: The findings of this large cohort study suggest that ETI in paediatric OHCA, although performed by trained physicians, is associated with a worse outcome, regardless of traumatic or non-traumatic aetiology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: According to guidelines and bystander skill, two different methods of cardiopulmonary resuscitation (CPR) are feasible: standard CPR (S-CPR) with mouth-to-mouth ventilations and chest compression-only CPR (CO-CPR) without rescue breathing. CO-CPR appears to be most effective for cardiac causes, but there is a lack of evidence for asphyxial causes of out-of-hospital cardiac arrest (OHCA). Thus, the aim of our study was to compare CO-CPR versus S-CPR in adult OHCA from medical etiologies and assess neurologic outcome in asphyxial and non-asphyxial causes. Methods: Using the French National OHCA Registry (RéAC), we performed a multicenter retrospective study over a five-year period (2013 to 2017). All adult-witnessed OHCA who had benefited from either S-CPR or CO-CPR by bystanders were included. Non-medical causes as well as professional rescuers as witnesses were excluded. The primary end point was 30-day neurological outcome in a weighted population for all medical causes, and then for asphyxial, non-asphyxial and cardiac causes. Results: Of the 8 541 subjects included for all medical causes, 6 742 had a non-asphyxial etiology, including 5 904 of cardiac causes, and 1 799 had an asphyxial OHCA. Among all subjects, 8.6%; 95% CI [8.1-9.3] had a good neurological outcome (i.e. cerebral performance category of 1 or 2). Bystanders who performed S-CPR began more often immediately (89.0%; 95% CI [87.3-90.5] versus 78.2%; 95% CI [77.2-79.2]) and in younger subjects (64.1 years versus 65.7; p < 0.001). In the weighted population, subjects receiving bystander-initiated CO-CPR had an adjusted relative risk (aRR) of 1.04; 95% CI [0.79-1.38] of having a good neurological outcome at 30 days for all medical causes, 1.28; 95% CI [0.92-1.77] for asphyxial etiologies, 1.08; 95% CI [0.80-1.46] for non-asphyxial etiologies and 1.09; 95% CI [0.93-1.28] for cardiac-related OHCA. Conclusions: We observed no significant difference in neurological outcome when lay bystanders of adult OHCA initiated CO-CPR or S-CPR, whether the cause was asphyxial or not.

In patients visiting the emergency department (ED), a potential association between electrolytes disturbance and coronavirus disease 2019 (COVID-19) has not been well studied. We aim to describe electrolyte disturbance and explore risk factors for COVID-19 infection in patients visiting the ED. We carried out a case-control study in three hospitals in France, including adult ED inpatients (≥ 18 years old). A total of 594 ED case patients in whom infection with COVID-19 was confirmed, were matched to 594 non-COVID-19 ED patients (controls) from the same period, according to sex and age. Hyponatremia was defined by a sodium of less than 135 mmol/L (reference range 135-145 mmol/L), hypokalemia by a potassium of less than 3.5 mmol/L (reference range 3.5-5.0 mmol/L), and hypochloremia by a chloride of less than 95 mmol/L (reference range 98-108 mmol/L). Among both case patients and controls, the median (IQR) age was 65 years (IQR 51-76), and 44% were women. Hyponatremia was more common among case patients than among controls, as was hypokalemia and hypochloremia. Based on the results of the multivariate logistic regression, hyponatremia, and hypokalemia were associated with COVID-19 among case patients overall, with an adjusted odds ratio of 1.89 [95% CI 1.24-2.89] for hyponatremia and 1.76 [95% CI 1.20-2.60] for hypokalemia. Hyponatremia and hypokalemia are independently associated with COVID-19 infection in adults visiting the ED, and could act as surrogate biomarkers for the emergency physician in suspected COVID-19 patients., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method., Research Question: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely?, Study Design and Methods: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment., Results: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26)., Interpretation: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications., Trial Registry: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung ultrasound (LUS) can help clinicians make a timely diagnosis of community-acquired pneumonia (CAP)., Objectives: To assess if LUS can improve diagnosis and antibiotic initiation in emergency department (ED) patients with suspected CAP., Design: A prospective observational study., Settings: Four EDs., Participants: The study included 150 patients older than 18 years with a clinical suspicion of CAP, of which 2 were subsequently excluded (incorrect identification), leaving 148 patients (70 women and 78 men, average age 72±18 years). Exclusion criteria included a life-threatening condition with do-not-resuscitate-order or patient requiring immediate intensive care., Interventions: After routine diagnostic procedure (clinical, radiological and laboratory tests), the attending emergency physician established a clinical CAP probability according to a four-level Likert scale (definite, probable, possible and excluded). An LUS was then performed, and another CAP probability was established based on the ultrasound result. An adjudication committee composed of three independent experts established the final CAP probability at hospital discharge., Primary and Secondary Outcome Measures: Primary objective was to assess concordance rate of CAP diagnostic probabilities between routine diagnosis procedure or LUS and the final probability of the adjudication committee. Secondary objectives were to assess changes in CAP probability induced by LUS, and changes in antibiotic treatment initiation., Results: Overall, 27% (95% CI 20 to 35) of the routine procedure CAP classifications and 77% (95% CI 71 to 84) of the LUS CAP classifications were concordant with the adjudication committee classifications. Cohen's kappa coefficients between routine diagnosis procedure and LUS, according to adjudication committee, were 0.07 (95% CI 0.04 to 0.11) and 0.61 (95% CI 0.55 to 0.66), respectively. The modified probabilities for the diagnosis of CAP after LUS resulted in changes in antibiotic prescriptions in 32% (95% CI 25 to 40) of the cases., Conclusion: In our study, LUS was a powerful tool to improve CAP diagnosis in the ED, reducing diagnostic uncertainty from 73% to 14%., Trial Registration Number: NCT03411824., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The gut microbiota is composed of trillions of microbial cells and viruses that interact with hosts. The composition of the gut microbiota is influenced by several factors including age, diet, diseases, or medications. The impact of drugs on the microbiota is not limited to antibiotics and many non-antibiotic molecules significantly alter the composition of the intestinal microbiota., Areas Covered: This review focuses on the impact of four of the most widely prescribed non-antibiotic drugs in the world: Proton-pump inhibitors, metformin, statins, and non-steroidal anti-inflammatory. We conducted a systematic review by searching online databases including Medline, Web of science, and Scopus for indexed articles published in English until February 2021. We included studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, statins, and nonsteroidal anti-inflammatory drugs (NSAIDs). Only studies using culture-independent molecular techniques were included., Expert Opinion: The taxonomical signature associated with non-antibiotic drugs are not yet fully described, especially in the field of metabolomic. The identification of taxonomic profiles associated a specific molecule provides information on its mechanism of action through interaction with the intestinal microbiota. Many side effects could be related to the dysbiosis induced by these molecules.

Background and Importance: Early identification of the cause of shock is associated with better prognosis., Objective: The aim of this study was to explore the performances of an ultrasound protocol (echoSHOCK) to diagnose the cause of shock in the emergency department (ED)., Design, Settings and Participants: This was a prospective study performed in two EDs. Included patients were older than 18 years admitted with shock. After routine workup strategy, the suspected cause of shock and the planned treatment were reported. The echoSHOCK protocol, using only B mode, was then performed. After performing echoSHOCK, the investigator reported the same two items., Intervention: echoSHOCK protocol that assessed: compressive pericardial effusion (tamponade), right ventricle dilatation and flattening of the septum, left ventricle dimension and systolic function, indices of hypovolemia., Outcomes Measure and Analysis: We defined four different causes for shock (tamponade, acute cor pulmonale, cardiogenic and hypovolemia). The primary endpoint was the degree of agreement of the routine workup and echoSHOCK with an expert panel., Main Results: 85 patients [mean age of 73 (14) years] were included. Kappa coefficients between routine strategy and echoSHOCK for the cause of shock, with the expert panel were 0.33 (95% CI, 0.26-0.4) and 0.88 (95% CI, 0.83-0.93), respectively. Likewise, for the planned treatment, kappa were 0.21 (95% CI, 0.14-0.28) and 0.9 (95% CI, 0.85-0.94), respectively. The physician's confidence increased from 3.9 (2.1) before echoSHOCK to 9.3 (1.1) after, (P < 0.001)., Conclusion: This study suggested that echoSHOCK significantly increased the ability to determine the cause of undifferentiated shock in the ED., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre-LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes., Methods and Results: Overall, 254 LVAD patients were retrospectively categorized based on pre-LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre-LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre-LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre-LVAD BSIs were independent predictors of 1-year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre-LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post-LVAD infections exhibited decreased microbial diversity (P < 0.05)., Conclusions: Pre-LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre-LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation., (© 2021 European Society of Cardiology.)

Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies., (© 2021. The Author(s).)

Introduction: Seizures are one of the most common neurological reasons for emergency department (ED) visits. The benefit of ED-initiated, short-course outpatient benzodiazepine (BZD) treatment to prevent early recurrent seizure is unknown. This study assesses the risk of early seizure recurrence in patients who were or were not started with outpatient BZD in the ED., Methods: This was a multicenter retrospective study conducted in eight French EDs between January 1 and December 31, 2019. All patients admitted for seizure were retrospectively screened and those discharged home from the ED were included. Patients with a history of chronic alcohol intoxication or chronic BZD therapy were excluded. Baseline characteristics, type of seizure, and 30-day outcome were retrospectively collected from the electronic health records. The primary endpoint was a return visit for seizure recurrence within 30 days. Independent factors associated with a seizure recurrence were identified using a multivariable binary logistic regression., Results: A total of 2,218 patients were included and 1,820 were analyzed. The median age was 39 years and 60% were men. Among them 82% of patients had a generalized tonic-clonic seizure and 47% of seizures were idiopathic. BZD treatment was started in 773 (42%) patients. A total of 154 (8%) patients had an early recurrence at 30 days: 68 (9%) in patients who were treated with BZD versus 86 (8%) in patients who were not (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.71 to 1.43). In multivariable analysis, two factors were independently associated with the primary endpoint: chronic epileptic treatment (adjusted OR = 2.58, 95% CI = 1.55 to 4.37) and having had a focal seizure (adjusted OR = 2.16, 95% CI = 1.56 to 4.37)., Conclusion: BZD therapy was started in 42% of patients who were discharged home after ED visit for a seizure. This treatment was not an independent factor associated with the risk of return visit for seizure recurrence at 30 days., (© 2021 by the Society for Academic Emergency Medicine.)