Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein.

Influenza virus infection causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we here demonstrate that influenza virus induces a major reprogramming of lung metabolism. We focused on mitochondria-derived succinate that accumulated both in the respiratory fluids of virus-challenged mice and of patients with influenza pneumonia. Notably, succinate displays a potent antiviral activity in vitro as it inhibits the multiplication of influenza A/H1N1 and A/H3N2 strains and strongly decreases virus-triggered metabolic perturbations and inflammatory responses. Moreover, mice receiving succinate intranasally showed reduced viral loads in lungs and increased survival compared to control animals. The antiviral mechanism involves a succinate-dependent posttranslational modification, that is, succinylation, of the viral nucleoprotein at the highly conserved K87 residue. Succinylation of viral nucleoprotein altered its electrostatic interactions with viral RNA and further impaired the trafficking of viral ribonucleoprotein complexes. The finding that succinate efficiently disrupts the influenza replication cycle opens up new avenues for improved treatment of influenza pneumonia.

Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study).

BACKGROUND: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors. METHODS: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate. RESULTS: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality. CONCLUSION: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.

Place of high-flow nasal oxygen in nonoperating room anesthesia.

PURPOSE OF REVIEW: This article aims to assess the utility of high-flow nasal oxygen (HFNO) therapy in nonoperating room anesthesia (NORA) settings. RECENT FINDINGS: The number of procedural interventions under deep sedation in NORA is still increasing. Administration of oxygen is recommended to prevent hypoxemia and is usually delivered with standard oxygen through nasal cannula or a face mask. HFNO is a simple alternative with a high warmed humidified flow (ranging from 30 to 70 l/min) with a precise fraction inspired of oxygen (ranging from 21 to 100%). Compared to standard oxygen, HFNO has demonstrated efficacy in reducing the incidence of hypoxemia and the need for airway maneuvers. Research on HFNO has primarily focused on its application in gastrointestinal endoscopy procedures. Yet, it has also shown promising results in various other procedural interventions including bronchoscopy, cardiology, and endovascular procedures. However, the adoption of HFNO prompted considerations regarding cost-effectiveness and environmental impact. SUMMARY: HFNO emerges as a compelling alternative to conventional oxygen delivery methods for preventing hypoxemia during procedural interventions in NORA. However, its utilization should be reserved for patients at moderate-to-high risk to mitigate the impact of cost and environmental factors.

Assessment of the pain induced by vaccination according to the injected arm (COVID-19 vaccination) / Évaluation de la douleur induite par la vaccination en fonction du bras d'injection (vaccination SARS-COV-2)

Since its discovery, the concept of vaccination has continued to improve in order to offer better efficacy and tolerance. Local or even diffuse reactions are often reported, but no study reports results on the injection side. We carried out a prospective observational study on the COVID-19 vaccination centers of the Landes regional hospital consortium (GHT) over three weeks. A questionnaire was given after the second injection, and assessed patients' feelings about the first injection. During this period, 2797 patients received their second injection and 2487 responded to the questionnaire, of which 2301 are usable. 81% of vaccinations were performed on the weak arm and 19% on the dominant arm. Local pain/discomfort was reported by 47% of patients on both arms, occurring the same day as the vaccination took place for half of the patients and the next day for the other half, with an average intensity of 3.3. Extensive pain/discomfort was present in 19% of patients, regardless of which arm was injected. The choice of the injected arm does not seem to have influence on pain.

Depuis sa découverte, la pratique de la vaccination s'est améliorée de façon continue afin d'offrir une meilleure efficacité et tolérance. Les réactions locales voire diffuses sont souvent évoquées, mais aucune étude ne rapporte de résultats en fonction du bras choisi pour l'injection. Nous avons réalisé une étude observationnelle prospective aux centres de vaccination COVID-19 du GHT des Landes pendant trois semaines. Un questionnaire était remis après la deuxième injection et évaluait les douleurs et gênes du patient lors de la première injection. Durant cette période, 2 797 patients ont reçu leur deuxième injection, 2 487 ont répondu au questionnaire dont 2 301 sont exploitables. La vaccination a été réalisée à 81 % du côté du bras non dominant et à 19 % du côté du bras dominant. Les douleurs/gênes locales ont été rapportées par 47 % des patients sur les deux bras, leur apparition étant survenue le jour même pour la moitié des personnes et le lendemain pour l'autre moitié, avec une intensité moyenne de 3,3 sur une échelle de 10. Les douleurs/gênes diffuses étaient présentes chez 19 % des personnes, quel que soit le côté. Le choix du bras pour l'injection semble ne pas avoir d'influence sur la survenue de douleurs.

High-flow nasal oxygenation or standard oxygenation for gastrointestinal endoscopy with sedation in patients at risk of hypoxaemia: a multicentre randomised controlled trial (ODEPHI trial).

BACKGROUND: We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. METHODS: This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min-1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min-1) or nasopharyngeal tube (5 L min-1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. RESULTS: In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, -23.4% [95% confidence interval (CI), -28.9 to -16.7]; P<0.001). Prolonged desaturation (>1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P<0.001). CONCLUSIONS: In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. CLINICAL TRIAL REGISTRATION: NCT03829293.

Cardiovascular magnetic resonance in heart transplant patients: diagnostic value of quantitative tissue markers: T2 mapping and extracellular volume fraction, for acute rejection diagnosis.

BACKGROUND: The diagnosis of acute rejection in cardiac transplant recipients requires invasive technique with endomyocardial biopsy (EMB) which has risks and limitations. Cardiovascular magnetic resonance imaging (CMR) with T2 and T1 mapping is a promising technique for characterizing myocardial tissue. The purpose of the study was to evaluate T2, T1 and extracellular volume fraction (ECV) quantification as novel tissue markers to diagnose acute rejection. METHODS: CMR was prospectively performed in 20 heart transplant patients providing 31 comparisons EMB-CMR. CMR was performed close to EMB. Images were acquired on a 1.5 Tesla scanner including T2 mapping (T2 prepared balanced steady state free precession) and T1 mapping (modified Look-Locker inversion recovery sequences: MOLLI) at basal, mid and apical level in short axis view. Global and segmental T2 and T1 values were measured before and 15 min (for T1 mapping) after contrast administration. RESULTS: Acute rejection was diagnosed in seven patients: six cellular rejections (4 grade IR, 2 grade 2R) and one antibody mediated rejection. Patients with acute rejection had significantly higher global T2 values at 3 levels: 58.5 ms [55.0-60.3] vs 51.3 ms [49.5-55.2] (p = 0.007) at basal; 55.7 ms [54.0-59.7] vs 51.8 ms [50.1-53.6] (p = 0.002) at median and 58.2 ms [54.0-63.7] vs 53.6 ms [50.8-57.4] (p = 0.026) at apical level. The area under the curve (AUC) for each level was 0.83, 0.79 and 0.78 respectively. Patients with acute rejection had significantly higher ECV at basal level: 34.2% [32.8-37.4] vs 27.4% [24.6-30.6] (p = 0.006). The AUC for basal level was 0.84. The sensitivity, specificity and diagnosis accuracy for basal T2 (cut off: 57.7 ms) were 71, 96 and 90% respectively; and for basal ECV: (cut off 32%) were 86, 85 and 85% respectively. Combining basal T2 and basal ECV allowed diagnosing all acute rejection and avoiding 63% of EMB. CONCLUSIONS: In heart transplant patients, a combined CMR approach using T2 mapping and ECV quantification provides a high diagnostic accuracy for acute rejection diagnosis and could potentially decrease the number of routine EMB.

High-flow nasal oxygenation versus standard oxygenation for gastrointestinal endoscopy with sedation. The prospective multicentre randomised controlled ODEPHI study protocol.

INTRODUCTION: Hypoxaemia is a major complication during gastrointestinal endoscopy (GIE) procedures (upper/lower) when performed under deep sedation in the procedure room. Standard oxygen therapy (SOT) is used to prevent hypoxaemia. Data suggest that risk factors for hypoxaemia under deep sedation during GIE are obstructive sleep apnoea syndrome, a body mass index above 30 kg/m², high blood pressure, diabetes, heart disease, age over 60 years old, high American Society of Anesthesiologists physical status class and the association of upper and lower GIE. High-flow nasal oxygenation (HFNO) may potentially improve oxygenation during GIE under deep sedation. We hypothesised that HFNO could decrease the incidence of hypoxaemia in comparison with SOT. METHODS AND ANALYSIS: The ODEPHI (High-flow nasal oxygenation versus standard oxygenation for gastrointestinal endoscopy with sedation. The prospective multicentre randomised controlled) study is a multicentre randomised controlled trial comparing HFNO to SOT during GIE (upper and/or lower) under deep sedation administered by anaesthesiologists in the procedure room. Three hundred and eighty patients will be randomised with a 1:1 ratio in two parallel groups.The primary outcome is the occurrence of hypoxaemia, defined by a pulse oximetry measurement of peripheral capillary oxygen saturation (SpO2) below or equal to 92% during the GIE procedure. Secondary outcomes include prolonged hypoxaemia, severe hypoxaemia, need for manoeuvres to maintain upper airway patency and other adverse events. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee (CPP Sud Est Paris V, France), and patients are included after informed consent. The results will be submitted for publication in peer-reviewed journals. As provided for by French law, patients participating in the study are informed that they have the possibility to ask the investigators, once the study is completed, to be informed of the overall results of the study. Thus, a summary of the results will be sent by post to the participants on request. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03829293).

Rapid detection of bacterial meningitis using a point-of-care glucometer.

BACKGROUND: In case of acute bacterial meningitis, a decision on the need for intensive care admission should be made within the first hour. The aim of this study was to assess the ability of a point-of-care glucometer to determine abnormal cerebrospinal fluid (CSF) glucose concentration at the bedside that contributes toward bacterial meningitis diagnosis. METHODS: We carried out a prospective study and simultaneously measured the glucose concentrations in CSF and blood using a central laboratory and a point-of-care glucometer. We compared CSF/blood glucose ratios obtained at the bedside with a glucometer versus those obtained by the central laboratory. We determined the performance characteristics of the CSF/blood glucose ratio provided by a glucometer to detect bacterial infection in the CSF immediately after CSF sampling. RESULTS: We screened 201 CSF collection procedures during the study period and included 172 samples for analysis. Acute bacterial meningitis was diagnosed in 17/172 (9.9%) of CSF samples. The median turnaround time for a point-of-care glucometer analysis was 5 (interquartile range 2-10) min versus 112 (interquartile range 86-154) min for the central laboratory (P<0.0001). The optimal cut-off of the CSF/blood glucose ratio calculated from a bedside glucometer was 0.46, with a sensitivity of 94.1% (95% confidence interval: 71.3-99.9%), a specificity of 91% (95% confidence interval: 85.3-95%), and a positive likelihood ratio of 10. CONCLUSION: A glucometer accurately detects an abnormal CSF/blood glucose ratio immediately after the lumbar puncture. This cheap point-of-care method has the potential to speed up the diagnostic process of patients with bacterial meningitis.

Preanalytical conditions of point-of-care testing in the intensive care unit are decisive for analysis reliability.

BACKGROUND: Point-of-care testing (POCT) systems enable a wide range of tests to be rapidly performed at the bedside and have attracted increasing interest in the intensive care unit (ICU). However, previous studies comparing the concordance of POCT with central laboratory testing have reported divergent findings. Most reported studies on POCT reliability have focused on analyzer performance rather than the preanalytical phase. The aim of this study was to assess the reliability of results provided by point-of-care analyzers according to the organization of the care units and the preanalytical process. METHODS: In three adult critical care units, 491 paired blood samples were analyzed for hemoglobin, potassium, and sodium concentrations by blood gas analyzers (identical reference) and the central laboratory. The clinical significance of agreement was assessed using Bland-Altman plots. A quality improvement program was then implemented to improve the preanalytical POCT process for one ICU where there was poor agreement. A second comparison was performed on 278 paired blood samples in this unit. RESULTS: Biases were clinically nonsignificant for potassium and sodium concentrations for all tested critical care units, relative to the reference method. However, biases [limits of agreements] for hemoglobin analyses were clearly affected by the preanalytical process: -3 [-6; 1] g/L in the operating room, -5 [-28; 17] g/L in a 10-bed ICU, and -19 [-64; 27] g/L in a 37-bed ICU. The quality approach was implemented in the 37-bed ICU and led to corrective actions that: (1) reduced the time for the POCT preanalytical phase; (2) implemented a checklist to validate the preanalytical conditions; (3) used technical innovations. The improvement of the preanalytical process resulted in a substantial decrease of the bias for hemoglobin concentration measurements: -3 [-10; 5] g/L in the 37-bed ICU. CONCLUSION: We clearly demonstrate that an identical analyzer can provide results of varying quality depending on the local constraints of the ICUs. We demonstrate that quality management focused on the preanalytical process and performed by the partners involved in the POCT can overcome these issues.