One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.

A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis.

PURPOSE: This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia (VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from ß-lactam including regimens. METHODS: Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received ß-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a ß-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. RESULTS: Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient's characteristics were found when the two groups were compared. CONCLUSIONS: De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with ß-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a ß-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING).

BACKGROUND: Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen desaturation during DNPs remains unknown. METHODS: A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO2) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO2 ≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO2 in the acceptable range of 90-95% during the DNP. RESULTS: Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p <  0.001). The percentage of time spent with SpO2 in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO2 in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01). CONCLUSION: AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV. TRIAL REGISTRATION: This study was registered in clinical-trial.gov ( NCT03176329 ) in June 2017.

A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia.

INTRODUCTION: Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. METHODS: A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. RESULTS: Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. CONCLUSIONS: Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.

Trimetoprim-sulfametoxazole in ventilator-associated pneumonia: a cohort study.

To evaluate the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) for treatment of ventilator-associated pneumonia (VAP). A retrospective cohort study including patients with VAP from 2011 to 2017. Two groups were analysed: TMP-SMX group, including patients who had received TMP-SMX (as first-line and as de-escalation), and No-TMP-SMX group, including patients who had not received TMP-SMX treatment. Primary clinical outcome was mortality at 30 days from starting the antibiotic treatment (T30). Secondary outcomes were mortality at end of treatment (EoT), day survival at T30, and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. Eighty cases of VAP were included and devised into two groups: No-TMP-SMX (31/80; 39%) and TMP-SMX (49/80; 61%). Univariate analysis showed no significant differences were found when the TMP-SMX group was compared with the No-TMP-SMX group, except for frequency of male gender (p = 0.025). No significant statistical correlations between mortality at T30 and individual factors were detected by the multivariate model. No cases of either severe allergy or Clostridium difficile disease were reported in the TMP-SMX and No-TMP-SMX groups. TMP-SMX treatment was not associated with higher mortality at EoT and T30 in comparison with the No-TMP-SMX group. TMP-SMX had a good safety profile, in terms of ecology (acquisition of MDR bacteria and Clostridium difficile disease) and clinical management (no allergy events).

Citrate pathophysiology and metabolism.

By chelating ionized calcium, citrate allows extracorporeal circuit anticoagulation without a bleeding risk for the patient. Citrate anticoagulation is also associated with a reduced activation of leucocytes and platelets. Citrate clearance by citric acid cycle (Krebs cycle) is not modified by renal failure, but is reduced by about 50% in patients with cirrhosis. Toxic effects of citrate result from a decrease in plasma ionized calcium of the patient. The first side effect is a prolongation of the QT interval. Clinical signs of hypocalcemia and hypotension in humans appear below 0.9mmol/L of plasma ionized calcium.

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay.

Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo.

Characteristics of Pseudomonas aeruginosa infection in intensive care unit before (2007-2010) and after (2011-2014) the beginning of an antimicrobial stewardship program.

Objectives: To investigate the factors associated with Pseudomonas aeruginosa isolates in intensive care unit (ICU) before and after an antimicrobial stewardship program. Materials: Monocentric retrospective cohort study. Patients admitted to the ICU in 2007-2014 were included. Characteristics of P. aeruginosa patients were compared to overall ICU population. Clinical and microbiological characteristics of P. aeruginosa patients before (2007-2010) and after (2011-2014) the beginning of the AMP were compared. Results: Overall, 5,263 patients were admitted to the ICU, 274/5,263 (5%) had a P. aeruginosa isolate during their staying. In 2011-2014, the percentage P. aeruginosa isolates reduced (7% vs 4%, P ≤ .0001). Patients with P. aeruginosa had higher rates of in-hospital death (43% vs 20%, P < .0001) than overall ICU population. In 2011-2014, rates of multidrug-resistant (11% vs 2%, P = .0020), fluoroquinolone-resistant (35% vs 12%, P < .0001), and ceftazidime-resistant (23% vs 8%, P = .0009) P. aeruginosa reduced. Treatments by fluoroquinolones (36% vs 4%, P ≤ .0001), carbapenems (27% vs 9%, P = .0002), and third-generation cephalosporins (49% vs 12%, P ≤ .0001) before P. aeruginosa isolation reduced while piperacillin (0% vs 13%, P < .0001) and trimethoprim-sulfamethoxazole (8% vs 26%, P = .0023) increased. Endotracheal intubation reduced in 2011-2014 (61% vs 35%, P < .0001). Fluoroquinolone-resistance was higher in patients who received endotracheal intubation (29% vs 17%, P = .0197). Previous treatment by fluoroquinolones (OR = 2.94, P = .0020) and study period (2007-2010) (OR = 2.07, P = .0462) were the factors associated with fluoroquinolone-resistance at the multivariate analysis. Conclusions: Antibiotic susceptibility in P. aeruginosa isolates was restored after the reduction of endotracheal intubation, fluoroquinolones, carbapenems, and third-generation cephalosporins and the increased use of molecules with a low ecological footprint, as piperacillin and trimethoprim-sulfamethoxazole.

Outcomes of pseudo-severe aortic stenosis under conservative treatment.

AIMS: In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment. METHODS AND RESULTS: Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease. CONCLUSION: In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

State of the Art of Cardiac Amyloidosis.

Cardiac amyloidosis is defined by extracellular deposition of misfolded proteins in the heart. The most frequent cases of cardiac amyloidosis are caused by transthyretin and light chain amyloidosis. This condition is underdiagnosed, and its incidence has been continuously rising in recent studies because of the aging of the population and the development of noninvasive multimodal diagnostic tools. Amyloid infiltration affects all cardiac tunics and causes heart failure with preserved ejection fraction, aortic stenosis, arrythmia, and conductive disorder. Innovative, specific therapeutic approaches have demonstrated an improvement in affected organs and the global survival of patients. This condition is no longer considered rare and incurable. Thus, better knowledge of the disease is mandatory. This review will provide a digest of the clinical signs and symptoms of cardiac amyloidosis, the diagnostic tools used to confirm the diagnosis, and current symptomatic and etiopathogenic management considerations according to guidelines and recommendations.

Atrial Septal Defect Associated With Right Bundle Branch Block Masking Brugada Syndrome.

A type 1 Brugada electrocardiogram pattern may be masked by typical right bundle branch block aspect. We present 2 cases (male patients, aged 18 and 22 years) of associated ostium secundum atrial septal defect with a right bundle branch block aspect and symptomatic confirmed Brugada syndrome. Both patients underwent cardiac defibrillator implantation. (Level of Difficulty: Advanced.).

Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial.

INTRODUCTION: Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients' response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids. METHODS AND ANALYSIS: RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%-10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids' effect in each subset, and (2) measure of interaction. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04280497).

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia: The ANTICOVID Randomized Clinical Trial.

Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Risk of Multidrug Resistant Bacteria Acquisition in Patients with Declared ß-Lactam Allergy during Hospitalization in Intensive Care Unit: A Retrospective Cohort Study (2007-2018).

INTRODUCTION: The risk of extended spectrum ß-lactamase (ESBL) bacterial acquisition in patients with ß-lactam allergy has been poorly investigated. In a previous study conducted over a 6-year long period (2007-2012), we found that patients with declared ß-lactam allergy had a higher risk of ESBL bacterial carriage at admission in intensive care unit (ICU), but they had not a higher risk of ESBL bacterial acquisition. We present the final results of the study which was eventually conducted over a 12-year long period (2007-2018). MATERIALS AND METHODS: The study included all patients admitted in ICU and receiving antibiotic treatment from January 2007 to December 2018. ESBL bacterial acquisition was the main clinical outcome. Mortality in ICU, multidrug resistant bacterial carriage at admission and discharge were the secondary outcomes. RESULTS: Overall, 3332 patients were included, 132/3332 (3.9%) were labelled ß-lactam allergic, while 3200/3332 (96.1%) did not presented ß-lactam allergy. No significant difference in rates of ESBL acquisition was detected (4/132, 3% vs. 78/3200, 2.4%; p = 0.17). Patients with ß-lactam allergy had higher rates of ESBL bacterial carriage at admission (19/132, 14.4% vs. 248/3200, 7.8%, p = 0.01) and at discharge (22/132, 16.7% vs. 351/3200, 11%, p = 0.04) than nonallergic patients. No differences in mortality, duration of hospitalization, and carriage of methicillin resistant Staphylococcus aureus were reported. Female gender was the only factor associated with ß-lactam allergy at the multivariate analysis. CONCLUSIONS: This study confirms that patients with declared ß-lactam allergy had not a higher risk of ESBL bacterial acquisition during hospitalization in ICU. However, they had a higher ESBL bacterial carriage at admission.

Consecutive Severe Orofacial Complications in Intensive Care Unit Patients: Quincke's Disease and Macroglossia due to Prolonged Prone Positioning for Management of Acute Respiratory Distress Syndrome.

Critically ill patients admitted into the intensive care units are susceptible to a wide array of complications that can be life-threatening, or lead to long-term complications. Some complications are inherent to the patient's condition and others are related to therapeutics or care procedure. The prolonged prone positioning and mechanical ventilation devices are the first risk factors for orofacial complications. We report the case of a 47-year-old male patient, with a history of sleep apnoea syndrome, morbid obesity (body mass index of 43 kg/m2), and gastroesophageal reflux disease, presented to the emergency department with recent otorhinolaryngological symptoms of dysphonia and exertional dyspnoea lasting two days, and complicated with Quincke's disease. First-line treatment consisted of a compilation of intravenous antihistamines and corticosteroids. The patient's condition worsened. He developed an acute respiratory distress syndrome secondary to ventilator-acquired pneumonia with prone positioning ventilation, complicated by severe macroglossia. Soaked gauze dressings were placed around his tongue. Progressively, the size of his tongue reduced. LEARNING POINTS: Intensive care unit (ICU) patients are susceptible to a wide array of life-threatening complications that can be linked.Oral severe acquired Quincke's disease is an isolated form of angioneurotic oedema that is induced by several factors including gastroesophageal reflux disease, sleep apnoea, inhalation exposure, or drug reactions. Macroglossia is rare life-threatening complication due to prolonged prone positioning of unknown pathogenesis. An experienced critical care staff with standardised protocol is needed to prevent such a complication.Because of possible consecutive severe orofacial complications, prolonged prone positioning for management of acute respiratory distress syndrome (ARDS) is not recommended in patients with inaugural oral angioedema.

The Predictive Value of Cell Blood Count Parameters to Diagnose Pulmonary Embolism in Patients with SARS-CoV-2 Infection: A Case Control Study.

Introduction: Acute pulmonary embolism (aPE) is frequently associated with coronavirus infectious disease-2019 (COVID-19) with an incidence of more than 16%. Among the new promising biomarkers of aPE, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) showed correlations with aPE prognosis. The aim of this study was to conduct an exploratory analysis to check the possible role of cell blood count (CBC) parameters as diagnostic and prognostic biomarkers of aPE in COVID-19 patients. Materials and Methods: A case control study was conducted. Two populations were compared: (i) patients hospitalised from 31 January 2020 to 30 June 2021 with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and aPE confirmed at angio computed tomography (aCT) or pulmonary scintigraphy (COVID-19 aPE group); (ii) patients hospitalised from 31 January 2017 to 30 June 2021 without SARS-CoV-2 infection whose suspicion of aPE was excluded by aCT or pulmonary scintigraphy (no-aPE group). Results: Overall, 184 patients were included in the study, 83 in COVID-19 aPE group and 101 in no-aPE group. At the univariate analysis, COVID-19 patients with aPE had higher NLR, PLR, neutrophil and lymphocyte counts than patients without aPE (p < 0.05). No significant difference was found in mean platelet volume and platelet counts. No difference in mortality rate was detected. At the multivariate analysis, neutrophil and lymphocyte counts were both associated with diagnostic of aPE while no CBC parameters were associated with mortality at day#7. Conclusions: Neutrophiland lymphocyte counts could be predictors of the early detection of aPE in COVID-19 patients. The value of CBC indices as biomarkers of aPE in daily clinical practice needs to be investigated in further studies.

Association of high SARS-CoV-2 RNAemia with diabetes and mortality in critically ill COVID-19 patients.

It has been suggested that during the period of respiratory worsening of severe COVID-19 patients, viral replication plays a less important role than inflammation. Using the droplet-based digital PCR (ddPCR) for precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia), we investigated the relationship between plasma viral load, comorbidities, and mortality of 122 critically ill COVID-19 patients. SARS-CoV-2 RNAemia was detected by ddPCR in 90 (74%) patients, ranging from 70 to 213,152 copies per mL. A high (>1 000 copies/ml) or very high (>10,000 copies/ml) SARS-Cov-2 RNAemia was observed in 46 patients (38%), of which 26 were diabetic. Diabetes was independently associated with a higher SARS-CoV-2 RNAemia. In multivariable logistic regression models, SARS-CoV-2 RNAemia was strongly and independently associated with day-60 mortality. Early initiation of antiviral therapies might be considered in COVID-19 critically ill patients with high RNAemia.

Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19: protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial.

INTRODUCTION: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely. METHODS AND ANALYSIS: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90. ETHICS AND DISSEMINATION: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04808882.