Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial.

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.

Temporal Trends in the Use of Computed Tomographic Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department : A Retrospective Analysis.

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.

Impact of an enhanced focused cardiac ultrasound on treatment changes in a population of internal medicine patients.

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.

Monocyte Signature Associated with Herpes Simplex Virus Reactivation and Neurological Recovery after Brain Injury.

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.

Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial.

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.

Anti α1-3Gal antibodies and Gal content in gut microbiota in immune disorders and multiple sclerosis.

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.

Neurological Outcome of Chest Compression-Only Bystander CPR in Asphyxial and Non-Asphyxial Out-Of-Hospital Cardiac Arrest: An Observational Study.

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.

Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.

An Evidence-Based Narrative Review of the Emergency Department Management of Acute Hyperkalemia.

BACKGROUND: The normal range for potassium is within narrow limits. Hyperkalemia is an electrolyte disorder that frequently affects patients in the emergency department (ED), and can result in significant morbidity and mortality if not identified and treated rapidly. OBJECTIVE: This article provides an evidence-based narrative review of the management of hyperkalemia, with focused updates for the emergency clinician. METHODS: We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until May 2020. We used multiple search terms, including hyperkalemia, potassium, acute hyperkalemia, emergency department, dyskalemia, potassium disorders, kidney disease, epidemiology, electrolyte disturbance, severe hyperkalemia, and emergency management. DISCUSSION: In the ED, interventions aimed to protect patients from the immediate dangers of elevated serum potassium are divided into the following: stabilizing cardiac membrane potentials, reducing serum potassium levels through shift from the extracellular fluid to intracellular fluid, and elimination of potassium through excretion via urinary or fecal excretion. Calcium is widely recommended to stabilize the myocardial cell membrane, but additional research is necessary to establish criteria for use, dosages, and preferred solutions. Redistribution of potassium ions from the bloodstream into the cells is based on intravenous insulin or nebulized ß2-agonists. CONCLUSIONS: Hyperkalemia is a frequent electrolyte disorder in the ED. Because of the risk of fatal dysrhythmia due to cardiac membrane instability, hyperkalemia is a medical emergency. There is a lack of scientific evidence on the optimal management of hyperkalemia and more research is needed to establish optimal strategies to manage acute hyperkalemia in the emergency department.

Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial.

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.

Electrocardiographic abnormalities in COVID-19 patients visiting the emergency department: a multicenter retrospective study.

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.

US Immigration Is Associated With Rapid and Persistent Acquisition of Antibiotic Resistance Genes in the Gut.

Little is known about the effect of human migration on gut microbiome antibiotic resistance gene (ARG) carriage. Using deep shotgun stool metagenomics analysis, we found a rapid increase in gut microbiome ARG richness and abundance in women from 2 independent ethnic groups relocating from Thailand to the United States.

Unique and specific Proteobacteria diversity in urinary microbiota of tolerant kidney transplanted recipients.

Host-microbiota interactions can modulate the immune system both at local and systemic levels, with potential consequences for organ transplantation outcomes. In this study, we hypothesized that differences in the urinary microbiome following kidney transplantation would be associated with posttransplantation status: stable, minimally immunosuppressed, or tolerant. One hundred thirteen urine samples from stable (n = 51), minimally immunosuppressed (n = 19), and spontaneously tolerant (n = 16) patients, paired with age-matched controls (n = 27) were profiled and compared to each other at a taxonomic level with special interest in the immunosuppressive regimen. All comparisons and correlations were adjusted on sex and time posttransplantation. Our results highlighted a unique and specific urinary microbiota associated with spontaneous tolerance characterized by a high diversity and a clear Proteobacteria profile. Finally, we report that this profile is (1) impacted by gender, (2) inversely correlated with immunosuppressive drugs (calcineurin inhibitors and mammalian target of rapamycin inhibitors), and (3) stable in time.

Modeling the risk of fluoroquinolone resistance in non-severe community-onset pyelonephritis.

Estimating whether the individual probability of being infected by a fluoroquinolone resistant isolate is higher than 10% may help to choose the empirical treatment of pyelonephritis. We aimed to model the risk of fluoroquinolone resistance in women with community-onset pyelonephritis. Women with non-severe community-onset pyelonephritis were prospectively recruited in 4 French emergency departments of 2 districts. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated through multivariate logistic regression. Among 190 patients, 19 (10%) were infected by a fluoroquinolone resistant isolate. Fluoroquinolone resistance was more frequent in district #2 (17%) than in district #1 (3%). Independent risk factors for fluoroquinolone resistance were district (adjusted OR, 7.0 (2.2-31.9)), and in the 6 previous months, urinary tract infection (UTI, aOR, 3.9 (1.3-11.5)) and vesical catheterization (aOR, 4.7 (0.5-33.3)). A specific model was derived to identify district #2 patients with a low (10% or lower) probability of being infected by a fluoroquinolone resistant isolate. Independent risk factors were residency in long-term care facility (aOR, 3.3 (0.7-13.5)), and in the 6 previous months, UTI (adjusted OR, 3.1 (0.9-10.7)) and home nursing care (aOR, 3.4 (0.6-17.0)). For 63 (67%) patients, the predicted probability of fluoroquinolone resistance was 0.10; among these patients, 6 (10%) actually had a fluoroquinolone resistant isolate. Locally derived predictive models may be used to identify patients with a low probability of fluoroquinolone resistance and guide the empirical antimicrobial therapy of non-severe community-onset pyelonephritis.

The effects of inulin on gut microbial composition: a systematic review of evidence from human studies.

BACKGROUND: Inulin, consisting of repetitive fructosyl units linked by ß(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action. METHODS: Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019. We used multiple search terms capturing gut microbiome, gut microflora, intestinal microbiota, intestinal flora, gut microbiota, gut flora, microbial gut community, gut microbial composition, and inulin. RESULTS: Overall, nine original articles reported the effects of inulin on microbiome composition in adult humans, most of them being randomized, double-blind, placebo-controlled trials (n = 7). Studies varied significantly in design (3 studies associated inulin and oligofructose), supplementation protocols (from 5 to 20 gr per day of inulin consumed) and in microbiome assessment methods (16S sequencing, n = 7). The most consistent change was an increase in Bifidobacterium. Other concordant results included an increase in relative abundance of Anaerostipes, Faecalibacterium, and Lactobacillus, and a decrease in relative abundance of Bacteroides after inulin supplementation. CONCLUSIONS: Our systematic review assessed the evidence for the effects of inulin supplementation on the human gut microbiome. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels.

Maximum Value of End-Tidal Carbon Dioxide Concentrations during Resuscitation as an Indicator of Return of Spontaneous Circulation in out-of-Hospital Cardiac Arrest.

Background: The end-tidal carbon dioxide (ETCO2) concentration during resuscitation (CPR) of an out-of-hospital cardiac arrest (OHCA) has an increasingly well-known prognostic value. Nevertheless, few studies have investigated its maximum value in different etiologies. Methods: It was a retrospective, observational, multicentre study from the French OHCA Registry. All adult OHCA with a known maximum value of ETCO2 during CPR were included. The primary end-point was to determine the area under the receiver operating characteristic curve (AUROC) of the maximum value of ETCO2 during resuscitation for the return of spontaneous circulation (ROSC). Results: Of the 53,048 eligible subjects from 2011 to 2018, ETCO2 was known in 32,249 subjects (61%). Among them, there were 9.2% of traumatic OHCA, 37.7% of suspected cardiac etiology and 16.4% of suspected respiratory etiology. The AUROC of maximum value of ETCO2 during CPR to achieve ROSC was 0.887 95CI [0.875-0.898] in traumatic OHCA, 0.772 95CI [0.765-0.780] in suspected cardiac etiology and 0.802 95CI [0.791-0.812] in suspected respiratory etiology. The threshold with no survivors at d-30 was <10 mmHg for traumatic etiologies and <6 mmHg for suspected cardiac and respiratory causes. The probability of ROSC increased with the value of ETCO2 in the 3 etiologies studied. Conclusions: The maximum value of ETCO2 during OHCA resuscitation was strongly associated with ROSC, especially in the case of a traumatic cause. This suggests that a single elevated ETCO2 value, regardless of time, could help to predict the outcome.

Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Faecalibacterium prausnitzii, a member of the Clostridium IV group of the Firmicutes phylum that is abundant in the intestinal microbiota, has anti-inflammatory effects. The relative level of F prausnitzii is decreased in fecal samples from patients with inflammatory bowel diseases (IBDs) compared with healthy individuals. Reduced F prausnitzii was correlated with relapse of Crohn's disease after surgery. We identified, in human colonic mucosa and blood, a population of T regulatory type 1-like T regulatory (TREG) cells that express CD4 and CD8α (DP8α T cells) and are specific for F prausnitzii. We aimed to determine whether they are altered in patients with IBD. METHODS: We isolated DP8α T cells from human colon lamina propria and blood samples and used flow cytometry to detect markers of cells that are of colon origin. We quantified DP8α cells that express colon-specific markers in blood samples from 106 patients with IBD, 12 patients with infectious colitis, and 35 healthy donors (controls). We identified cells that respond to F prausnitzii. Cells were stimulated with anti-CD3, and their production of interleukin 10 was measured by enzyme-linked immunosorbent assay. We compared the frequency and reactivity of cells from patients vs controls using the 2-sided Student t test or 1-way analysis of variance. RESULTS: Circulating DP8α T cells that proliferate in response to F prausnitzii express the C-C motif chemokine receptor 6 (CCR6) and C-X-C motif chemokine receptor 6 (CXCR6). These cells also have features of TREG cells, including production of IL-10 and inhibition of T-cell proliferation via CD39 activity. The proportion of circulating CCR6+/CXCR6+ DP8α T cells was significantly reduced (P < .0001) within the total population of CD3+ T cells from patients with IBD compared with patients with infectious colitis or controls. A threshold of <7.875 CCR6+/CXCR6+ DP8α T cells/10,000 CD3+ cells discriminated patients with IBD from those with infectious colitis with 100% specificity and 72.2% sensitivity. CONCLUSIONS: We identified a population of gut-derived TREG cells that are reduced in blood samples from patients with IBD compared with patients with infectious colitis or controls. These cells should be studied further to determine the mechanisms of this reduction and how it might contribute to the pathogenesis of IBD and their prognostic or diagnostic value.

Trends and prediction of antimicrobial susceptibility in urinary bacteria isolated in European emergency departments: the EuroUTI 2010-2016 Study.

OBJECTIVES: To assess recent trends in susceptibility to antibiotics among urinary isolates isolated in European emergency departments (EDs) and to identify isolates with a high (90% or more) predicted probability of susceptibility to fluoroquinolones or third-generation cephalosporins (3GCs). METHODS: In this cross-sectional study, we included urine cultures obtained from adult patients between 2010 and 2016 in 24 European EDs. Temporal trends were assessed using time-series analysis and multivariate logistic models. Multivariate logistic models were also used to predict susceptibility to fluoroquinolones or 3GCs from patient age and sex, year, month and ED. RESULTS: We included 88242 isolates. Time-series analysis found a significant increase in susceptibility to fluoroquinolones and no significant trend for susceptibility to 3GCs. Adjusting for patient age and sex, ED and organism, multivariate models showed that susceptibility to 3GCs decreased from 2014 to 2016, while susceptibility to fluoroquinolones increased in 2015 and 2016. Among isolates from 2016, multivariate models predicted high probability of susceptibility to fluoroquinolones in 11% of isolates (positive predictive value 91%) and a high probability of susceptibility to 3GCs in 35% of isolates (positive predictive value 94%). CONCLUSIONS: Susceptibility of ED urinary isolates to fluoroquinolones increased from 2014, while susceptibility to 3GCs decreased from 2015. Predictive models identified isolates with a high probability of susceptibility to fluoroquinolones or 3GCs. The ability of such models to guide the empirical treatment of pyelonephritis in the ED remains to be determined.

Inflammatory skin is associated with changes in the skin microbiota composition on the back of severe acne patients.

Acne is the most common inflammatory skin disease, affecting up to 85% of the 11-30 years old world population. Skin microbiota appears as a key player involved in several skin dermatoses physiopathology. Here, we show that inflammatory skin is associated with changes in the skin microbiota composition on the back of severe acne patients but also on the face of patients where acne was scored as mild to moderate, comparing with healthy controls. Changes were observed particularly on skin commensals Propionibacteriaceae, Staphylococcaceae and Enterococcaceae families, suggesting the importance of the balance between skin commensals to maintain skin homeostasis and control skin inflammatory process.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.