Pierre Bouzat

Background: Community-acquired intra-abdominal infections (CA-IAIs) exhibit significant clinical heterogeneity. However, most studies focusing on CA-IAIs do not stratify comparisons by infection site. Methods: This post hoc analysis of the prospective multicenter PERICOM cohort (13 French university hospitals, April 2018 to February 2019) included adult patients with CA-IAIs requiring surgical management. We compared clinical characteristics, microbiology, and outcomes between appendicular and non-appendicular sites. Secondary analyses assessed the impact of Enterococcus spp., Pseudomonas aeruginosa, or fungal documentation, and the theoretical coverage of empirical antibiotic regimens. Results: Of the 205 patients, 86 (42%) had appendicular and 119 (58%) had non-appendicular CA-IAIs. Appendicular CA-IAIs involved younger patients with fewer comorbidities and were followed by fewer major postoperative complications (Clavien-Dindo score ≥ 3: 10% versus 43%, p < 0.001) and no deaths (0% versus 12%, p < 0.001). Among 118 culture-positive patients, appendicular CA-IAIs showed higher rates of non-fermenting Gram-negative bacilli (25% versus 10%, p = 0.046) and anaerobes (53% versus 28%, p = 0.008) and were more often polymicrobial (76% versus 55%, p = 0.020). Conversely, Staphylococcus spp. (0% versus 9%, p = 0.036) and fungal co-infection (0% versus 12%, p = 0.010) were confined to non-appendicular CA-IAIs. Furthermore, Enterococcus spp. documentation (24/118, 20%) identified patients with greater admission severity and higher 28-day mortality (33% versus 2%, p < 0.001). Amoxicillin-clavulanic acid plus gentamicin covered the isolates of 92% of patients versus 61% for third-generation cephalosporin plus metronidazole (p < 0.001), a difference identical in both appendicular and non-appendicular sites. Conclusions: Appendicular and non-appendicular CA-IAIs appear to be distinct entities, supporting stratified management. Future guidelines should consider site-specific strategies, therapeutic individualization, and the integration of CA-IAI ecology.

Introduction: Blunt chest trauma is frequently associated with rib fractures, and inadequate pain control may lead to respiratory complications and prolonged ventilatory support. In spontaneously breathing patients, pain impairs coughing and secretion clearance, promoting atelectasis and respiratory failure, while in mechanically ventilated patients, it may delay weaning. Current French guidelines recommend intravenous multimodal analgesia as first-line therapy followed by thoracic epidural or paravertebral block if pain remains uncontrolled. However, these techniques have limited applicability in the trauma setting. The erector spinae plane (ESP) block is a simpler ultrasound-guided regional analgesia technique with fewer contraindications. Although retrospective data suggest potential respiratory benefits, its efficacy has not been evaluated in randomised controlled trials. This study aims to assess whether early initiation of a continuous ESP block reduces ventilatory support duration after blunt chest trauma. Methods and analysis: The EffecT of eARly analGesia with ErecTor spinae plane block (TARGET) trial is a multicentre, superiority, randomised controlled trial including adult patients (≥18 years) with blunt chest trauma and at least three rib fractures on thoracic CT scan requiring intensive care unit admission. Participants are randomised to receive either early continuous ESP block initiated within 6 hours of admission or standard intravenous multimodal analgesia with escalation to thoracic epidural or paravertebral block if indicated. The primary outcome is the number of days alive and free from invasive or non-invasive curative ventilation within 30 days after randomisation or hospital discharge. Randomisation is stratified by centre and age (CPP Sud-Ouest IV on 17 April 2023 (approval number 23.00675.000144). The study began on 22 October 2023. Results will be disseminated through publication in a peer-reviewed international medical journal. Trial registration: ClinicalTrials.gov: NCT05920109 .

L'œdème cérébral et l'hypoxie cérébrale post-traumatiques sont les acteurs principaux de l'apparition des lésions ischémiques secondaires. L'erythropoïétine (Epo) sous sa forme recombinante humaine possède une activité anti-oedémateuse dans un modèle expérimental de TC diffus. Son action sur l'hypoxie cérébrale post-traumatique reste néammoins méconnue. De plus, les effets indésirables hématologiques de l'Epo ont conduit à la synthèse de dérivés de l'Epo ne possèdant pas d'activité hématopoïétique comme l'érythropoïetine carbamylée (CEpo). Dans ce contexte, mon travail de thèse a eu pour but d'évaluer les propriétés de l'Epo et de la CEpo dans le modèle de TC diffus. Un traitement intraveineux par CEpo à la dose de 50 µg/Kg a ainsi permis de diminuer précocemment l'œdème cérébral post-traumatique évalué in vivo par IRM de diffusion et ex vivo par gravimétrie spécifique. Cette propriété a impliqué l'inhibition de la phosphorylation de la voie Erk et s'est accompagnée de l'amélioration des fonctions motrices et cognitives jusqu'à 10 jours après le TC. Après une étude de validation sur des rats sains soumis à différentes conditions d'oxygénation, une méthode de mesure IRM de la saturation locale en oxygène (lSO2) cérébrale combinant l'effet BOLD avec la mesure du volume sanguin cérébral a montré une diminution de l'oxygénation cérébrale post-traumatique. Cette hypoxie cérébrale n'était pas en lien avec une diminution du débit sanguin cérébral attestée par méthode de premier passage d'un agent de constraste. Un collapsus des capillaires cérébraux était par ailleurs retrouvé en microscopie électronique. L'Epo à la dose de 5000 UI/Kg a été capable de restaurer l'oxygénation cérébrale en diminuant l'œdème astrocytaire péricapillaire. L'ensemble de ce travail a permis d'établir les bénéfices d'un traitement par Epo ou par CEpo sur l'œdème cérébral et l'hypoxie cérébrale post-traumatiques.

Introduction: The management of severe traumatic brain injury (sTBI) in the intensive care unit (ICU) is focused on preventing secondary brain insults, by ensuring adequate cerebral perfusion, oxygenation and substrate delivery. Despite optimisation of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) using evidence-based guidelines, brain tissue hypoxia can still occur and is strongly associated with adverse functional outcomes post sTBI. Methods and analysis: The Brain Oxygen Neuromonitoring in Australia and New Zealand Assessment – Global Trial (BONANZA-GT) is an international, two-arm, open-label, parallel group, randomised controlled trial comparing sTBI management incorporating early brain tissue oxygen (PbtO ₂ ) monitoring and optimisation, with ICP/CPP-based management alone. A total of 860 adults admitted to participating institutions with non-penetrating sTBI and requiring insertion of an ICP monitor (as determined by the treating neurosurgeon) will be enrolled. The primary outcome is the proportion of patients with favourable neurological outcomes, as defined by a Glasgow Outcome Score-Extended (GOS-E) >4, at 6 months following injury. Key secondary outcomes include all-cause mortality at ICU discharge, hospital discharge, adverse events, as well as hospital and ICU length of stay and GOS-E at 12 months. The BONANZA-GT will determine whether a protocolised therapeutic strategy guided by continuous PbtO ₂ monitoring in addition to ICP/CPP targets results in improved neurological outcomes when compared with standard care using ICP/CPP-guided management alone. Ethics and dissemination: Approval has been obtained from relevant ethics boards in every jurisdiction that is participating in the trial. Inclusion of adults who lack capacity for informed consent will be governed in accordance with the legal requirements of each participating site. Study findings will be presented at scientific meetings and disseminated via peer-review publications. Trial registration number: Australian and New Zealand Clinical Trials Registry (ACTRN 12619001328167).

After mild traumatic brain injury (TBI), discharge from the emergency department (ED) relies on clinical examination and brain imaging, but triaging of these patients can be challenging in specific situations. Transcranial Doppler (TCD) after mild TBI may rule out early neurologic worsening. We hypothesize that patients with mild TBI and normal TCD can be safely discharged home immediately after the ED. This is a prospective, open-label, multisite, randomized controlled noninferiority trial. Eligible patients are mild TBI patients (Glasgow Coma Scale, GCS, 13–15 on admission) with minor lesions on brain CT scan or normal CT scan but one of the following risk factors: (1) GCS = 14 after CT scan; (2) alcoholic intoxication, (3) ongoing treatment with anticoagulants or anti-platelet therapy; (4) persisting nausea, vomiting, and/or headaches; or (5) early initial CT scan (< 4 h after TBI). Patients randomized in the intervention group have TCD within 12 h after TBI and can be immediately discharged from the ED if TCD is normal (diastolic flow velocity higher than 25 cm/s and pulsatility index lower than 1.25). Discharge of patients in the control group relies on clinical examination and brain imaging only. The primary outcome is the 3-month neurological outcome measured with the Extended Glasgow Outcome Scale (GOS-E). Secondary outcomes are the GOS-E at 1 month, the QOLIBRI (Quality of life after TBI) and EQ-5D-5L questionnaires at 1 month and 3 months after TBI, the Rivermead Post-Concussion Symptoms questionnaire at 1 month and 3 months after TBI, mortality within the first 3 months, the number of cerebral CT scans, length of stay in hospital, the number of thromboembolic events or diagnosed nosocomial infections, and the number of patients re-admitted to hospital in relation with the initial TBI. Inclusions have started in February 2020 and are expected to be complete by June 2025. Transcranial Doppler in mild TBI patients may help immediate discharge from the ED after CT scanning. This study has been prospectively registered on clinical trial on June 14, 2019, NCT03989999.

BACKGROUND: Red blood cell transfusions are commonly administered to anemic patients with spontaneous intracerebral hemorrhage (ICH); however, the optimal hemoglobin threshold to initiate transfusion is uncertain in this population. Therefore, we aimed to assess the impact of 2 different hemoglobin thresholds to guide transfusion on the neurological outcome of anemic critically ill patients with ICH. METHODS: This is a secondary analysis of a prospective, multicenter, phase 3 randomized study conducted in 72 intensive care units across 22 countries from 2017 to 2022. Eligible patients for the original trial had an acute brain injury, hemoglobin values ≤9 g/dL within the first 10 days after admission, and an expected intensive care unit stay of at least 72 hours; in this study, only patients with spontaneous ICH were assessed. Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤7 g/dL) or a liberal (transfusion triggered by hemoglobin ≤9 g/dL) strategy over a 28-day period. The primary outcome was the occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5, at 180 days following randomization. RESULTS: A total of 144 patients with spontaneous ICH were analyzed: 45.8% of them were men with a mean age of 58.4 (SD, 13.4). Mean Glasgow Coma Scale on admission was 7.3 (SD, 3.3), and 75.7% of patients had a volume of hematoma >30 mL. Among all patients, 73 were randomized to the restrictive transfusion strategy, while 71 to the liberal one. Baseline characteristics were comparable between the 2 groups. At 180 days after randomization, patients assigned to the liberal transfusion strategy had a nonsignificant decrease in the probability of unfavorable neurological outcome (71.8 versus 84.7%; risk ratio, 0.85 [95% CI, 0.71–1.01]; P =0.06). Also, the occurrence of the composite outcome (mortality and organ failure at day 28) was significantly lower in the liberal group (71.8% versus 87.7%, risk ratio, 0.82 [95% CI, 0.69–0.97]; P =0.02). CONCLUSIONS: A liberal transfusion strategy was associated with a lower risk of mortality and organ failure, but not of unfavorable outcome in patients presenting with spontaneous ICH, compared with a restrictive strategy. However, the study cohort might have been underpowered to detect clinically relevant differences between the 2 interventions.