Efficacy of an inulin-based treatment on intestinal colonization by multidrug-resistant E. coli: insight into the mechanism of action.

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.

Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study.

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.

Impact of emergency physician performed ultrasound in the evaluation of adult patients with acute abdominal pain: a prospective randomized bicentric trial.

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).

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.

Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

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.

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.

Impact of Different Training Methods on Daily Use of Point-of-Care Ultrasound: Survey on 515 Physicians.

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.

Robust airway microbiome signatures in acute respiratory failure and hospital-acquired pneumonia.

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.

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.

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.

Factors associated with tracheal intubation-related complications in the prehospital setting: a prospective multicentric cohort study.

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.

Intravenous acetaminophen with morphine versus intravenous morphine alone for acute pain in the emergency room: protocol for a multicenter, randomized, placebo-controlled, double-blinded study (ADAMOPA).

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.

Impact of emergency physician-performed ultrasound for the evaluation of patients with acute abdominal pain, prospective randomized dual Centre study: study protocol for a diagnostic trial.

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.

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.

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.