One-year survival of aneurysmal subarachnoid hemorrhage after airplane transatlantic transfer - a monocenter retrospective study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is preferentially treated by prompt endovascular coiling, which is not available in Guadeloupe. Subsequently, patients are transferred to Paris, France mainland, by commercial airplane (6751 km flight) after being managed according to guidelines. This study describes the characteristics, management and outcomes related to these patients. METHODS: Retrospective observational cohort study of 148 patients admitted in intensive care unit for a suspected aSAH and transferred by airplane over a 10-year period (2010-2019). RESULTS: The median [interquartile range] age was 53 [45-64] years and 61% were female. On admission, Glasgow coma scale was 15 [13-15], World Federation of Neurological Surgeons (WFNS) grading scale was 1 [1-3] and Fisher scale was 4 [2-4]. External ventricular drainage and mechanical ventilation were performed prior to the flight respectively in 42% and 47% of patients. One-year mortality was 16% over the study period. By COX logistic regression analysis, acute hydrocephalus (hazard ratio [HR] 2.34, 95% confidence interval [CI] 0.98-5.58) prior to airplane transfer, WFNS grading scale on admission (HR 1.53, 95% CI 1.16-2.02) and age (OR 1.03, 95% 1.00-1.07) were associated with one-year mortality. CONCLUSION: When necessary, transatlantic air transfer of patients with suspected aSAH after management according to local guidelines seems feasible and safe.

MPox virus: an unusual aetiology of peritonitis.

We describe a rare case of severe disseminated monkeypox (MPox) virus infection complicated by peritonitis in a 44-year-old man living with well-controlled HIV. The patient was successfully treated with tecovirimat without requiring surgery. MPox should be considered in the differential diagnosis of non-bacterial peritonitis in patients at risk of infection.

24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management.

OBJECTIVES: We aimed to evaluate the impact of an uninterrupted workflow regarding blood cultures on turnaround time and antibiotic prescription. METHODS: Monomicrobial episodes of bacteremia were retrospectively evaluated before and after a continuous 24/7 workflow was implemented in our clinical microbiology laboratory (pre- and post-intervention periods; PREIP and POSTIP). Primary outcome was the time from specimen collection to the first change in antibiotic therapy. Secondary outcomes included the time from specimen collection to effective antibiotic therapy and to antibiotic susceptibility testing results (or turnaround time), as well as hospital length of stay and all-cause mortality at 30 days. RESULTS: A total of 548 episodes of bacteremia were included in the final analysis. There was no difference in PREIP and POSTIP regarding patient characteristics and causative bacteria. In POSTIP, the mean time to the first change in antibiotic therapy was reduced by 10.4 h (p<0.001). The time to effective antibiotic therapy and the turnaround time were respectively reduced by 4.8 h (p<0.001) and 5.1 h (p=0.006) in POSTIP. There was no difference in mean hospital length of stay or mortality between the two groups. CONCLUSIONS: Around the clock processing of blood cultures allows for a reduction in turnaround time, which in turn reduces the delay until effective antibiotic therapy prescription.

Cefoxitin versus carbapenems as definitive treatment for extended-spectrum ß-lactamase-producing Klebsiella pneumoniae bacteremia in intensive care unit: a propensity-matched retrospective analysis.

BACKGROUND: Despite cefoxitin's in vitro resistance to hydrolysis by extended-spectrum beta-lactamases (ESBL), treatment of ESBL-producing Klebsiella pneumoniae (KP) infections with cefoxitin remains controversial. The aim of our study was to compare the clinical efficacy of cefoxitin as definitive antibiotic therapy for patients with ESBL-KP bacteremia in intensive care unit, versus carbapenem therapy. METHODS: This retrospective study included all patients with monomicrobial bacteremia hospitalized in intensive care unit between January 2013 and January 2023 at the University Hospital of Guadeloupe. The primary outcome was the 30-day clinical success defined as a composite endpoint: 30-day survival, absence of relapse and no change of antibiotic therapy. Cox regression including a propensity score (PS) and PS-based matched analysis were performed for endpoint analysis. RESULTS: A total of 110 patients with bloodstream infections were enrolled. Sixty-three patients (57%) received definitive antibiotic therapy with cefoxitin, while forty-seven (43%) were treated with carbapenems. 30-day clinical success was not significantly different between patients treated with cefoxitin (57%) and carbapenems (53%, p = 0.823). PS-adjusted and PS-matched analysis confirmed these findings. Change of definitive antibiotic therapy was more frequent in the cefoxitin group (17% vs. 0%, p = 0.002). No significant differences were observed for the other secondary endpoints. The acquisition of carbapenem-resistant Pseudomonas aeruginosa was significantly higher in patients receiving carbapenem therapy (5% vs. 23%, p = 0.007). CONCLUSIONS: Our results suggest that cefoxitin as definitive antibiotic therapy could be a therapeutic option for some ESBL-KP bacteremia, sparing carbapenems and reducing the selection of carbapenem-resistant Pseudomonas aeruginosa strains.

Accurate Detection of SARS-CoV-2 by Next-Generation Sequencing in Low Viral Load Specimens.

As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the city of Nice (France) over a period of 32 weeks (from 19 July 2021 to 11 February 2022). In total, 76% of cases were identified with a low viral load (Ct ≥ 32, and ≤200 copies/µL). The NGS analysis was successful in 91% of cases, among which 57% of cases harbored the Delta variant, and 34% the Omicron BA.1.1 variant. Only 9% of cases had unreadable sequences. There was no significant difference in the viral load in patients infected with the Omicron variant compared to the Delta variant (Ct values, p = 0.0507; copy number, p = 0.252). We show that the NGS analysis of the SARS-CoV-2 genome provides reliable detection of the Delta and Omicron SARS-CoV-2 variants in low viral load samples.

Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]).

OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a before-and-after, propensity-matched cohort study in a Caribbean intensive care unit.

BACKGROUND: High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). METHODS: We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. RESULTS: The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p < 0.01), treatment duration was shorter (5 vs. 6 days; p < 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%; p < 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%; p < 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16-21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 [95% CI 0.575-0.968]; p = 0.02, and hazard ratio 0.751 [95% CI 0.578-0.977]; p = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p < 0.01). CONCLUSIONS: Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.

Critical care medicine in the French Territories in the Americas: Current situation and prospects.

Hospitals in the French Territories in the Americas (FTA) work according to international and French standards. This paper aims to describe different aspects of critical care in the FTA. For this, we reviewed official information about population size and intensive care unit (ICU) bed capacity in the FTA and literature on FTA ICU specificities. Persons living in or visiting the FTA are exposed to specific risks, mainly severe road traffic injuries, envenoming, stab or ballistic wounds, and emergent tropical infectious diseases. These diseases may require specific knowledge and critical care management. However, there are not enough ICU beds in the FTA. Indeed, there are 7.2 ICU beds/100 000 population in Guadeloupe, 7.2 in Martinique, and 4.5 in French Guiana. In addition, seriously ill patients in remote areas regularly have to be transferred, most often by helicopter, resulting in a delay in admission to intensive care. The COVID-19 crisis has shown that the health care system in the FTA is unready to face such an epidemic and that intensive care bed capacity must be increased. In conclusion, the critical care sector in the FTA requires upgrading of infrastructure, human resources, and equipment as well as enhancement of multidisciplinary care. Also needed are promotion of training, research, and regional and international medical and scientific cooperation.

Los hospitales en los territorios franceses de la Región de las Américas funcionan según las normas francesas e internacionales. El objetivo de este artículo es describir distintos aspectos de los cuidados intensivos en los territorios franceses. Para ello, hemos revisado los datos oficiales sobre el tamaño de la población y el número de camas de las unidades de cuidados intensivos (UCI), así como la bibliografía sobre algunos aspectos específicos de las UCI, en los territorios franceses. Las personas que viven en los territorios franceses, o que están de visita en ellos, están expuestas a riesgos específicos: principalmente traumatismos graves causados por el tránsito, envenenamiento por mordeduras, heridas de bala o por apuñalamiento, y enfermedades infecciosas tropicales emergentes. La atención de estos traumatismos y enfermedades puede requerir conocimientos específicos y cuidados intensivos. Sin embargo, no hay suficientes camas de UCI en los territorios franceses. De hecho, hay 7,2 camas de UCI por 100 000 habitantes en Guadalupe, 7,2 en Martinica y 4,5 en Guayana Francesa. Además, los pacientes gravemente enfermos que viven en zonas remotas a menudo tienen que ser trasladados, normalmente por helicóptero, lo que retrasa su ingreso en la unidad de cuidados intensivos. La crisis de la COVID-19 ha puesto de manifiesto que el sistema de atención de salud en los territorios franceses no está preparado para enfrentarse a una epidemia de estas dimensiones y que debe aumentarse la capacidad hospitalaria de las unidades de cuidados intensivos. En conclusión, el sector de los cuidados intensivos en los territorios franceses tiene que mejorar su infraestructura, recursos humanos y equipamiento, así como perfeccionar la atención multidisciplinaria. También es necesario promover la capacitación, la investigación y la cooperación médica y científica, tanto regional como internacional.

Os hospitais nos territórios ultramarinos franceses nas Américas funcionam segundo os padrões franceses e internacionais. O objetivo deste artigo é descrever os diversos aspectos da atenção intensiva nesta região. Analisamos os dados oficiais relativos ao tamanho da população e ao número de leitos de unidade de terapia intensiva (UTI) nestes territórios junto com uma revisão da literatura científica sobre as características particulares destes centros de terapia intensiva. Os residentes locais ou visitantes dos territórios ultramarinos franceses nas Américas são expostos a riscos específicos, sobretudo acidentes de trânsito graves, envenenamentos por animais peçonhentos, ferimentos por armas brancas ou armas de fogo e doenças infecciosas tropicais emergentes que requerem conhecimento especializado e atenção intensiva. Porém, não há leitos suficientes de UTI nos territórios ultramarinos franceses nas Américas: são 7,2 leitos de UTI por 100.000 habitantes em Guadalupe, 7,2 na Martinica e 4,5 na Guiana Francesa. Ademais, em áreas remotas, os pacientes em estado crítico frequentemente precisam ser transferidos por helicóptero, o que causa demora na internação em UTI. A crise da COVID-19 demonstra o despreparo do sistema de saúde para enfrentar a pandemia e a necessidade de aumentar o número de leitos de UTI nestes territórios. Em conclusão, é imprescindível modernizar a infraestrutura e os equipamentos, capacitar melhor os recursos humanos e melhorar a atenção multidisciplinar. Incentivar a formação profissional, pesquisa e cooperação médico-científica regional e mundial é também fundamental.

Three New Cases of Melioidosis, Guadeloupe, French West Indies.

Melioidosis has been detected in the Caribbean, and an increasing number of cases has been reported in the past few decades, but only 2 cases were reported in Guadeloupe during the past 20 years. We describe 3 more cases that occurred during 2016-2017 and examine arguments for increasing endemicity.

First isolation of Clostridium indolis in a patient with chronic osteitis: a case report and literature review of human infections related to Clostridium saccharolyticum group species.

Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice.

Caloric restriction (CR) is proposed to decrease tumorigenesis through a variety of mechanisms including effects on glycolysis. However, the understanding of how CR affects the response to cancer therapy is still rudimentary. Here, using the Eµ-Myc transgenic mouse model of B-cell lymphoma, we report that by reducing protein translation, CR can reduce expression of the prosurvival Bcl-2 family member Mcl-1 and sensitize lymphomas to ABT-737-induced death in vivo. By using Eµ-Myc lymphoma cells lacking p53, we showed that CR mimetics such as 2-deoxyglucose led to a decrease in Mcl-1 expression and sensitized lymphoma cells to ABT-737-induced death independently of p53. In keeping with this, Eµ-Myc lymphoma cells lacking the BH3-only proapoptotic members Noxa, Puma, or Bim were also sensitized by CR mimetics to ABT-737-induced death. Remarkably, neither the loss of both Puma and Noxa, the loss of both Puma and Bim, nor the loss of all three BH3-only proteins prevented sensitization to ABT-737 induced by CR mimetics. Thus, CR can influence Mcl-1 expression and sensitize cells to BH3 mimetic-induced apoptosis, independently of the main BH3-only proteins and of p53. Exploiting this may improve the efficiency of, or prevent resistance to, cancer therapy.

Synergistic Inhibition of ß2-adrenergic Receptor-mediated Alveolar Epithelial Fluid Transport by Interleukin-8 and Transforming Growth Factor-ß.

BACKGROUND: Patients with acute respiratory distress syndrome who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. The release of endogenous catecholamines associated with shock or the administration of ß2-adrenergic receptor (ß2AR) agonists enhances AFC via a 3'-5'-cyclic adenosine monophosphate-dependent mechanism. The authors have previously reported that transforming growth factor-ß1 (TGF-ß1) and interleukin-8 (IL-8), two major mediators of alveolar inflammation associated with the early phase of acute respiratory distress syndrome, inhibit AFC upregulation by ß2AR agonists via a phosphoinositol-3-kinase (PI3K)-dependent mechanism. However, whether TGF-ß1 and IL-8 cause an additive or synergistic inhibition of AFC is unclear. Thus, the central hypothesis of the study was to determine whether they synergistically inhibit the ß2AR-stimulated AFC by activating two different isoforms of PI3K. METHODS: The effects of TGF-ß1 or IL-8 on ß2AR agonist-stimulated net alveolar fluid transport were studied using short-circuit current studies. Molecular pathways of inhibition were confirmed by pharmacologic inhibitors and Western blotting of p-Akt, G-protein-coupled receptor kinase 2, protein kinase C-ζ, and phospho-ß2AR. Finally, our observations were confirmed by an in vivo model of AFC. RESULTS: Combined exposure to TGF-ß1 and IL-8/cytokine-induced neutrophil chemoattractant-1 caused synergistic inhibition of ß2AR agonist-stimulated vectorial Cl across alveolar epithelial type II cells (n = 12 in each group). This effect was explained by activation of different isoforms of PI3K by TGF-ß1 and IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Furthermore, the inhibitory effect of TGF-ß1 on 3'-5'-cyclic adenosine monophosphate-stimulated alveolar epithelial fluid transport required the presence of IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each group). Inhibition of cytokine-induced neutrophil chemoattractant-1 prevented TGF-ß1-mediated heterologous ß2AR downregulation and restored physiologic ß2AR agonist-stimulated AFC in rats (n = 6 in each group). CONCLUSIONS: TGF-ß1 and IL-8 have a synergistic inhibitory effect on ß2AR-mediated stimulation of pulmonary edema removal by the alveolar epithelium. This result may, in part, explain why a large proportion of the patients with acute respiratory distress syndrome have impaired AFC.

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response.

Most DNA-damaging agents are weak inducers of an anticancer immune response. Increased glycolysis is one of the best-described hallmarks of tumor cells; therefore, we investigated the impact of glycolysis inhibition, using 2-deoxyglucose (2DG), in combination with cytotoxic agents on the induction of immunogenic cell death. We demonstrated that 2DG synergized with etoposide-induced cytotoxicity and significantly increased the life span of immunocompetent mice but not immunodeficient mice. We then established that only cotreated cells induced an efficient tumor-specific T-cell activation ex vivo and that tumor antigen-specific T cells could only be isolated from cotreated animals. In addition, only when mice were immunized with cotreated dead tumor cells could they be protected (vaccinated) from a subsequent challenge using the same tumor in viable form. Finally, we demonstrated that this effect was at least partially mediated through ERp57/calreticulin exposure on the plasma membrane. These data identify that the targeting of glycolysis can convert conventional tolerogenic cancer cell death stimuli into immunogenic ones, thus creating new strategies for immunogenic chemotherapy.

Effect of sedative premedication on patient experience after general anesthesia: a randomized clinical trial.

IMPORTANCE: Sedative premedication is widely administered before surgery, but little clinical evidence supports its use. OBJECTIVE: To assess the efficacy of sedative premedication on perioperative patient experience. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, the PremedX study, enrolled 1062 adult patients who were younger than 70 years and had been scheduled for various elective surgeries under general anesthesia at 5 French teaching hospitals (in Marseille, Montpellier, Nimes, and Nice) between January 2013 and June 2014. Neurosurgery, obstetrical, cardiac, and outpatient surgery were excluded. INTERVENTIONS: Patients were randomized to 3 groups of 354 participants each to receive 2.5 mg of lorazepam, no premedication, or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was perioperative patient experience assessed 24 hours after surgery with a validated questionnaire (Evaluation du Vécu de l'Anesthésie Generale; EVAN-G) describing 6 domains of satisfaction and a global index (score range, 0-100; high scores represent high satisfaction); secondary outcomes included time to extubation and early cognitive recovery. A subgroup analysis was planned a priori in patients with a high level of preoperative anxiety. RESULTS: Premedication with lorazepam did not improve the EVAN-G mean global index for overall level of patient satisfaction (72 [95% CI, 70-73]; n = 330) compared with no premedication (73 [95% CI, 71-74]; n = 319) or placebo (71 [95% CI, 70-73]; n = 322) (P = .38). Among patients with heightened preoperative anxiety, there were no significant differences found in the EVAN-G mean global index between the lorazepam group (68 [95% CI, 65-72]; n = 87) and the no premedication group (73 [95% CI, 69-77]; n = 57) or the placebo group (70 [95% CI, 67-72]; n = 87) (P = .18). Time to extubation was 17 minutes (95% CI, 14-20 minutes) in the lorazepam group, 12 minutes (95% CI, 11-13 minutes) for the no premedication group, and 13 minutes (95% CI, 12-14 minutes) for the placebo group (P < .001) and the rate of early cognitive recovery was 51% (95% CI, 45%-56%), 71% (95% CI, 66%-76%), and 64% (95% CI, 59%-69%), respectively (P < .001). CONCLUSIONS AND RELEVANCE: Among patients undergoing elective surgery under general anesthesia, sedative premedication with lorazepam compared with placebo or no premedication did not improve the self-reported patient experience the day after surgery, but was associated with modestly prolonged time to extubation and a lower rate of early cognitive recovery. The findings suggest a lack of benefit with routine use of lorazepam as sedative premedication in patients undergoing general anesthesia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01901003.

IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism.

Patients with acute lung injury (ALI) who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. Experimental and small clinical studies have shown that ß2-adrenergic receptor (ß2AR) agonists enhance AFC via a cAMP-dependent mechanism. However, two multicenter phase 3 clinical trials failed to show that ß2AR agonists provide a survival advantage in patients with ALI. We hypothesized that IL-8, an important mediator of ALI, directly antagonizes the alveolar epithelial response to ß2AR agonists. Short-circuit current and whole-cell patch-clamping experiments revealed that IL-8 or its rat analog CINC-1 decreases by 50% ß2AR agonist-stimulated vectorial Cl(-) and net fluid transport across rat and human alveolar epithelial type II cells via a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis. This reduction was mediated by heterologous ß2AR desensitization and down-regulation (50%) via the G-protein-coupled receptor kinase 2 (GRK2)/PI3K signaling pathway. Inhibition of CINC-1 restored ß2AR agonist-stimulated AFC in an experimental model of ALI in rats. Finally, consistent with the experimental results, high pulmonary edema fluid levels of IL-8 (>4000 pg/ml) were associated with impaired AFC in patients with ALI. These results demonstrate a novel role for IL-8 in inhibiting ß2AR agonist-stimulated alveolar epithelial fluid transport via GRK2/PI3K-dependent mechanisms.-Roux, J., McNicholas, C. M., Carles, M., Goolaerts, A., Houseman, B. T., Dickinson, D. A., Iles, K. E., Ware, L. B., Matthay, M. A., Pittet, J.-F. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism.

Heat-shock response increases lung injury caused by Pseudomonas aeruginosa via an interleukin-10-dependent mechanism in mice.

BACKGROUND: The heat-shock response (HSR) protects from insults, such as ischemia-reperfusion injury, by inhibiting signaling pathways activated by sterile inflammation. However, the mechanisms by which the HSR activation would modulate lung damage and host response to a bacterial lung infection remain unknown. METHODS: HSR was activated with whole-body hyperthermia or by intraperitoneal geldanamycin in mice that had their lungs instilled with Pseudomonas aeruginosa 24 h later (at least six mice per experimental group). Four hours after instillation, lung endothelial and epithelial permeability, bacterial counts, protein levels in bronchoalveolar lavage fluid, and lung myeloperoxidase activity were measured. Mortality rate 24 h after P. aeruginosa instillation was recorded. The HSR effect on the release of interleukin-10 and killing of P. aeruginosa bacteria by a mouse alveolar macrophage cell line and on neutrophil phagocytosis was also examined. RESULTS: HSR activation worsened lung endothelial (42%) and epithelial permeability (50%) to protein, decreased lung bacterial clearance (71%), and increased mortality (50%) associated with P. aeruginosa pneumonia, an effect that was not observed in heat-shock protein-72-null mice. HSR-mediated decrease in neutrophil phagocytosis (69%) and bacterial killing (38%) by macrophages was interleukin-10 dependent, a mechanism confirmed by increased lung bacterial clearance and decreased mortality (70%) caused by P. aeruginosa pneumonia in heat-shocked interleukin-10-null mice. CONCLUSIONS: Prior HSR activation worsens lung injury associated with P. aeruginosa pneumonia in mice via heat-shock protein-72- and interleukin-10-dependent mechanisms. These results provide a novel mechanism for the immunosuppression observed after severe trauma that is known to activate HSR in humans.

The open latarjet procedure is more reliable in terms of shoulder stability than arthroscopic bankart repair.

BACKGROUND: Arthroscopic Bankart repair and open Latarjet bone block procedure are widely considered mainstays for surgical treatment of recurrent anterior shoulder instability. The choice between these procedures depends mainly on surgeon preference or training rather than published evidence. QUESTIONS/PURPOSES: We compared patients with recurrent posttraumatic anterior shoulder instability treated with arthroscopic Bankart or open Latarjet procedure in terms of (1) frequency and timing of recurrent instability, (2) risk factors for recurrent instability, and (3) patient-reported outcomes. METHODS: In this retrospective comparative study, we paired 93 patients undergoing open Latarjet procedures with 93 patients undergoing arthroscopic Bankart repairs over the same period for posttraumatic anterior shoulder instability by one of four surgeons at the same center. Both groups were comparable except that patients in the Latarjet group had more glenoid lesions and more instability episodes preoperatively. Minimum followup was 4 years (mean, 6 years; range, 4-10 years). Patients were assessed with a questionnaire, including stability, Rowe score, and return to sports. Recurrent instability was defined as at least one episode of recurrent dislocation or subluxation. Return to sports was evaluated using a 0% to 100% scale that patients completed after recovery from surgery. Various risk factors for recurrent instability were also analyzed. RESULTS: At latest followup, 10% (nine of 93) in the Latarjet group and 22% (20 of 93) in the Bankart group demonstrated recurrent instability (p = 0.026; odds ratio, 0.39; 95% CI, 0.17-0.91). Ten recurrences in the Bankart group (50%) occurred after 2 years, compared to only one (11%) in the Latarjet group. Reoperation rate was 6% and 7% in the Bankart and Latarjet groups, respectively. In both groups, patients younger than 20 years had higher recurrence risk (p = 0.019). In the Bankart group, independent factors predictive for recurrence were practice of competitive sports and shoulder hyperlaxity (ie, passive external rotation > 85° in the contralateral uninjured shoulder). Although return to sports was not different between groups, the mean Rowe score was higher in the Latarjet group (78 versus 68, p = 0.018). CONCLUSIONS: Patients who had the open Latarjet procedure had less recurrent instability and better Rowe scores over a mean 6-year followup. We now perform isolated arthroscopic Bankart repair for carefully selected patients, including patients with an Instability Severity Index Score of 3 or less. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Arthroscopic Bristow-Latarjet combined with bankart repair restores shoulder stability in patients with glenoid bone loss.

BACKGROUND: Arthroscopic Bankart repair alone cannot restore shoulder stability in patients with glenoid bone loss involving more than 20% of the glenoid surface. Coracoid transposition to prevent recurrent shoulder dislocation according to Bristow-Latarjet is an efficient but controversial procedure. QUESTIONS/PURPOSES: We determined whether an arthroscopic Bristow-Latarjet procedure with concomitant Bankart repair (1) restored shoulder stability in this selected subgroup of patients, (2) without decreasing mobility, and (3) allowed patients to return to sports at preinjury level. We also evaluated (4) bone block positioning, healing, and arthritis and (5) risk factors for nonunion and coracoid screw pullout. METHODS: Between July 2007 and August 2010, 79 patients with recurrent anterior instability and bone loss of more than 20% of the glenoid underwent arthroscopic Bristow-Latarjet-Bankart repair; nine patients (11%) were either lost before 2-year followup or had incomplete data, leaving 70 patients available at a mean of 35 months. Postoperative radiographs and CT scans were evaluated for bone block positioning, healing, and arthritis. Any postoperative dislocation or any subjective complaint of occasional to frequent subluxation was considered a failure. Physical examination included ROM in both shoulders to enable comparison and instability signs (apprehension and relocation tests). Rowe and Walch-Duplay scores were obtained at each review. Patients were asked whether they were able to return to sports at the same level and practice forced overhead sports. Potential risk factors for nonhealing were assessed. RESULTS: At latest followup, 69 of 70 (98%) patients had a stable shoulder, external rotation with arm at the side was 9° less than the nonoperated side, and 58 (83%) returned to sports at preinjury level. On latest radiographs, 64 (91%) had no osteoarthritis, and bone block positioning was accurate, with 63 (90%) being below the equator and 65 (93%) flush to the glenoid surface. The coracoid graft healed in 51 (73%), it failed to unite in 14 (20%), and graft osteolysis was seen in five (7%). Bone block nonunion/migration did not compromise shoulder stability but was associated with persistent apprehension and less return to sports. Use of screws that were too short or overangulated, smoking, and age higher than 35 years were risk factors for nonunion. CONCLUSIONS: The arthroscopic Bristow-Latarjet procedure combined with Bankart repair for anterior instability with severe glenoid bone loss restored shoulder stability, maintained ROM, allowed return to sports at preinjury level, and had a low likelihood of arthritis. Adequate healing of the transferred coracoid process to the glenoid neck is an important factor for avoiding persistent anterior apprehension. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Efficacy of an antimicrobial stewardship intervention for early adaptation of antibiotic therapy in high-risk neutropenic patients.

BACKGROUND: The 4th European Conference on Infections in Leukemia recommends early adaptation of empirical antibiotic therapy (EAT) for febrile neutropenia in stable patients. OBJECTIVES: To assess the efficacy of an antimicrobial stewardship (AMS) intervention promoting early de-escalation and discontinuation of EAT in high-risk neutropenic patients. METHODS: This before-after study was conducted in the hematology department of the University Hospital of Nice, France. The AMS intervention included the development of clinical decision support algorithms, a twice-weekly face-to-face review of all antibiotic prescriptions and monthly feedback on the intervention. The primary endpoint was overall antibiotic consumption during hospital stay, expressed as days of therapy (DOT). RESULTS: A total of 113 admissions were included: 56 during the pre-intervention period and 57 during the intervention period. Induction chemotherapy and conditioning for allogeneic stem cell transplantation were the most frequent reasons for admission. In the intervention period, there was a significant decrease in overall antibiotic consumption (median DOT 20 vs. 28 days, p = 0.006), carbapenem consumption (median DOT 5.5 vs. 9 days, p = 0.017) and anti-resistant Gram-positive agents consumption (median DOT 8 vs. 11.5 days, p = 0.017). We found no statistical difference in the rates of intensive care unit admission (9% in each period) and 30-day mortality (5% vs. 0%, p = 0.243). Compliance with de-escalation and discontinuation strategies was significantly higher in the intervention period (77% vs. 8%, p < 0.001). CONCLUSION: A multifaceted AMS intervention led to high compliance with early de-escalation and discontinuation of EAT and lower overall antibiotic consumption, without negatively affecting clinical outcomes.