Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.

BACKGROUND: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known. METHODS: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1. RESULTS: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03). CONCLUSION: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline. CLINICALTRIALS: gov Identifier: NCT05094856.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Epidemiology and Clinical Patterns of Lung Abscesses in ICU: A French Multicenter Retrospective Study.

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses. RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality? STUDY DESIGN AND METHODS: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression. RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not. INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.

OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS. METHODS: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 106 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO2/FiO2)-ratio change between baseline (day (D) 0) and D7. RESULTS: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO2/FiO2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. CONCLUSIONS: D0-to-D7 PaO2/FiO2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. TRIAL REGISTRATION: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.

High-Emergency Lung Transplantation for Interstitial Lung Disease Associated With Anti-MDA5 Dermatomyositis: A Case Report.

BACKGROUND: Rapidly progressive interstitial lung disease (RPILD) associated with the anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5ab+) dermatomyositis (DM) is a rare but life-threatening condition despite immunosuppressive treatment. We report the case of a 44-year-old woman who was diagnosed with severe RPILD associated with anti-MDA5ab+ DM 1 week before her admission in the intensive care unit. The patient underwent a successful double-lung transplant after she failed treatment with immunosuppressive therapy, including tofacitinib. At 1-year follow-up, she had experienced no relapse of the disease. CASE REPORT: This case includes a patient recently diagnosed with RPILD for whom no treatment showed efficacy, including glucocorticoids, cyclophosphamide, plasma exchanges, tofacitinib, and tacrolimus. She was placed under mechanical ventilation and venovenous extracorporeal membrane oxygenation 2 weeks after diagnosis in a bridge-to-transplant process. She was successfully transplanted 20 days later after having been registered on the French National Lung Transplant Waiting List with high priority. One year after surgery, her pulmonary function tests were good, and she showed no sign of relapse of anti-MDA5ab+ DM. CONCLUSIONS: Lung transplantation can be a life-saving procedure in RPILD related to anti-MDA5ab+ DM. High-emergency allocation priority on the transplant list reduced the time between diagnosis and surgery. Patients without comorbidities should be promptly referred to specialized centers to rapidly assess the feasibility of transplantation in this context.

Combined use of a broad-panel respiratory multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP): a multicentre, parallel-group, open-label, individual randomised trial conducted in French intensive care units.

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.

Severe hemoptysis in post-tuberculosis bronchiectasis precipitated by SARS-CoV-2 infection.

BACKGROUND: Since the beginning of SARS-CoV-2 outbreak in China, severe acute respiratory syndrome has been widely descripted. Hemoptysis has rarely been observed in SARS-CoV-2 infection. We report here a case of severe hemoptysis in post-tuberculosis bronchiectasis precipitated by SARS-CoV-2 infection and managed in a referral center. CASE PRESENTATION: A 58-year-old man was admitted to our intensive care unit for severe hemoptysis with history of post-tuberculosis bronchiectasis. At ICU admission the patient had fever and severe acute respiratory failure requiring high flow oxygen therapy. Respiratory tract sampling was positive for SARS-CoV-2. Multi-detector computed tomography angiography pointed out localized bronchiectasis on the left lower lobe and enlarged left bronchial and phrenic arteries; bronchial arteriography with distal embolization was performed with favorable outcome and no bleeding recurrence. CONCLUSIONS: To our knowledge, this is the first case of acute exacerbation of bronchiectasis related to SARS-CoV-2 infection and complicated by severe hemoptysis. Whether the virus may play a role in the dysregulation of airway haemostasis, and contribute to episodes of hemoptysis in patients with chronic pulmonary diseases and predisposing factors might be investigated.

Increased mortality in patients with severe SARS-CoV-2 infection admitted within seven days of disease onset.

PURPOSE: Coronavirus disease 2019 (COVID-19) is creating an unprecedented healthcare crisis. Understanding the determinants of mortality is crucial to optimise intensive care unit (ICU) resource use and to identify targets for improving survival. METHODS: In a multicentre retrospective study, we included 379 COVID-19 patients admitted to four ICUs between 20 February and 24 April 2020 and categorised according to time from disease onset to ICU admission. A Cox proportional-hazards model identified factors associated with 28-day mortality. RESULTS: Median age was 66 years (53-68) and 292 (77%) were men. The main comorbidities included obesity and overweight (67%), hypertension (49.6%) and diabetes (30.1%). Median time from disease onset (i.e., viral symptoms) to ICU admission was 8 (6-11) days (missing for three); 161 (42.5%) patients were admitted within a week of disease onset, 173 (45.6%) between 8 and 14 days, and 42 (11.1%) > 14 days after disease onset; day 28 mortality was 26.4% (22-31) and decreased as time from disease onset to ICU admission increased, from 37 to 21% and 12%, respectively. Patients admitted within the first week had higher SOFA scores, more often had thrombocytopenia or acute kidney injury, had more limited radiographic involvement, and had significantly higher blood IL-6 levels. Age, COPD, immunocompromised status, time from disease onset, troponin concentration, and acute kidney injury were independently associated with mortality. CONCLUSION: The excess mortality in patients admitted within a week of disease onset reflected greater non-respiratory severity. Therapeutic interventions against SARS-CoV-2 might impact different clinical endpoints according to time since disease onset.

Mucormycosis in intensive care unit: surgery is a major prognostic factor in patients with hematological malignancy.

BACKGROUND: Mucormycosis is an invasive fungal infection, with an increasing incidence especially in patients with hematological malignancies. Its prognosis is poor because of its high invasive power and its intrinsic low susceptibility to antifungal agents. We aimed to describe the epidemiology of mucormycosis in intensive care units (ICU) and evaluate the outcomes. We performed a retrospective multi-center study in 16 French ICUs between 2008 and 2017. We compared the patients who survived in ICU and the patients who did not to identify factors associated with ICU survival. Then, we focused on the subgroup of patients with hematological malignancies. RESULTS: Mucormycosis was diagnosed in 74 patients during the study period. Among them, 60 patients (81%) were immunocompromised: 41 had hematological malignancies, 9 were solid organ transplant recipients, 31 received long-term steroids, 11 had diabetes, 24 had malnutrition. Only 21 patients survived to ICU stay (28.4%) with a median survival of 22 days (Q1-Q3 = 9-106) and a survival rate at day 28 and day 90, respectively, of 35.1% and 26.4%. Survivors were significantly younger (p = 0.001), with less frequently hematological malignancies (p = 0.02), and less malnutrition (p = 0.05). Median survival in patients with hematological malignancies (n = 41) was 15 days (Q1-Q3 = 5-23.5 days). In this subgroup, curative surgery was a major factor associated with survival in multivariate analysis (odds ratio = 0.71, [0.45-0.97], p < 0.001). CONCLUSION: Overall prognosis of mucormycosis in ICU remains poor, especially in patients with hematological malignancies. In this subgroup of patients, a therapeutic strategy including curative surgery was the main factor associated with survival.

Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and ß-Blockers.

BACKGROUND: Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. ß-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a ß-blocker (atenolol) during murine peritonitis. METHODS: Ivabradine (3 µg/g), atenolol (3 µg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile). RESULTS: As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224). CONCLUSIONS: Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

Management of severe hemoptysis.

INTRODUCTION: Though rare, severe hemoptysis (SH) is associated with a mortality rate exceeding 50% when not managed properly. Areas covered: This paper reviews the recent epidemiological data regarding SH, the role of multidetector computed tomography angiography (MDCTA), and fiberoptic bronchoscopy (FOB) in its management, as well as the value of current treatments. Expert commentary: MDCTA is becoming an essential modality, since it allows determining the location, etiology, and mechanism of the bleeding. FOB can be delayed, except when local control of bleeding is required. Emergency treatment relies on interventional radiology. Both bronchial and non-bronchial arteries should be explored during bronchial arteriography. Surgery must be considered in all operable patients if the cause of hemoptysis persists.

Transcatheter embolotherapy of pulmonary artery aneurysms as emergency treatment of hemoptysis in Behcet patients: experience of a referral center and a review of the literature.

Hemoptysis is a life-threatening complication of Behcet's disease that is likely related to pulmonary artery aneurysm (PAA). Vascular interventional radiology may offer effective emergency therapeutic option, but has not been thoroughly investigated in this setting. A case series of a French referral center for hemoptysis combined with a literature review of case reports was conducted. Between 1995 and 2016, 12 patients were referred to our center for hemoptysis revealing or complicating the course of Behcet's disease. Pulmonary artery aneurysm (PAA) was the mechanism of hemoptysis in ten patients, nine of whom were treated by a transcatheter embolotherapy. Combining an additional 8 case reports from the literature, 17 patients treated by transcatheter embolotherapy for PAA were analyzed. The duration of the course of Behcet's disease was 22 months [IQR 3-45] at the time of PAA diagnosis. Transcatheter embolotherapy of PAA was successful for immediately controlling hemoptysis in all patients, without major complication except for one. Hemoptysis recurred in seven patients (41%) within 5 months [IQR 1-12]. The use of coils for transcatheter embolotherapy was associated with hemoptysis recurrence. A bronchosystemic hypervascularization related to the previously occluded PAA was the main mechanism of bleeding recurrence, leading to bronchosystemic artery embolization in four patients and surgery in two patients. Behcet's disease-related hemoptysis is mainly due to PAA. Transcatheter embolotherapy should be considered as the first-line emergency treatment for PAA-related hemoptysis, in association with the immunosuppressive regimen. Hemoptysis may recur in half of the cases, involving preferentially a bronchosystemic arterial mechanism.

Severe Hemoptysis Associated with Bacterial Pulmonary Infection: Clinical Features, Significance of Parenchymal Necrosis, and Outcome.

PURPOSE: Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower respiratory tract infection (LRTI) is poorly described, and the efficacy of the usual decision-making process is unknown. This study aimed at describing the clinical, radiological patterns, mechanism, and microbiological spectrum of SH related to bacterial LRTI, and assessing whether the severity of hemoptysis and the results of usual therapeutic strategy are influenced by the presence of parenchymal necrosis. METHODS: A single-center analysis of patients with SH related to bacterial LRTI from a prospective registry of consecutive patients with SH admitted to the intensive care unit of a tertiary referral center between November 1996 and May 2013. RESULTS: Of 1504 patients with SH during the study period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10), and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%) was associated with a more abundant bleeding (volume: 200 ml [70-300] vs. 80 ml [30-170]; p = 0.01) and a more frequent need for endovascular procedure (26/34; 76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the pulmonary artery vasculature was involved in 16 patients (47%), and the failure rate of endovascular treatment was up to 25% despite multiple procedures. CONCLUSIONS: Bacterial LRTI is a rare cause of SH. The presence of parenchymal necrosis is more likely associated with bleeding severity, pulmonary vasculature involvement, and endovascular treatment failure.

Prevalence of respiratory viruses among adults, by season, age, respiratory tract region and type of medical unit in Paris, France, from 2011 to 2016.

BACKGROUND: Multiplex PCR tests have improved our understanding of respiratory viruses' epidemiology by allowing their wide range detection. We describe here the burden of these viruses in hospital settings over a five-year period. METHODS: All respiratory samples from adult patients (>20 years old) tested by multiplex-PCR at the request of physicians, from May 1 2011 to April 30 2016, were included retrospectively. Viral findings are reported by season, patient age group, respiratory tract region (upper or lower) and type of clinical unit (intensive care unit, pneumology unit, lung transplantation unit and other medical units). RESULTS: In total, 7196 samples (4958 patients) were included; 29.2% tested positive, with viral co-infections detected in 1.6% of samples. Overall, two viral groups accounted for 60.2% of all viruses identified: picornaviruses (rhinovirus or enterovirus, 34.3%) and influenza (26.6%). Influenza viruses constituted the group most frequently identified in winter (34.4%), in the upper respiratory tract (32%) and in patients over the age of 70 years (36.4%). Picornavirus was the second most frequently identified viral group in these populations and in all other groups, including lower respiratory tract infections (41.3%) or patients in intensive care units (37.6%). CONCLUSION: This study, the largest to date in Europe, provides a broad picture of the distribution of viruses over seasons, age groups, types of clinical unit and respiratory tract regions in the hospital setting. It highlights the burden associated with the neglected picornavirus group. These data have important implications for the future development of vaccines and antiviral drugs.