Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France.

Describe the characteristics of ventilation-acquired pneumonia (VAP) and potential risk factors in critically ill SARS-CoV-2 patients admitted in three French public hospitals during the first year of the COVID-19 pandemic. We conducted a monocentric retrospective study in seven Marseille intensive care units (ICUs) aiming to describe VAP characteristics and identify their risk factors. VAP patients were compared to a non-VAP control group. From March to November 2020, 161 patients admitted for viral-induced acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV) were included. This cohort was categorized in two groups according to the development or not of a VAP during their stay in ICU. 82 patients (51%) developed ventilation-acquired pneumonia. Most of them were men (77%) and 55% had hypertension. In the VAP population, 31 out of 82 patients (38%) had received dexamethasone and 47% were administered antibiotic course prior to ICU admission. An amount of 88% of respiratory infections were late VAPs with a median delay of 10 days from the onset of IMV. Gram negative bacteria were responsible for 62% of VAPs with Pseudomonas spp. being the most documented bacteria. Less than a third of the ICU-acquired infections were due to multidrug resistant (MDR) bacteria mainly displaying AmpC cephalosporin hyper production resistance phenotype. Multivariate analysis revealed that early Dexamethasone administration in ICU, male sex, older age and ROX score were risk factors for VAP whereas pre-ICU antimicrobial treatment and higher IGS 2 were protective factors. VAP is a frequent ICU-related complication affecting half of patients infected with SARS-CoV-2 and requiring IMV. It was responsible for increased morbidity due to a longer ICU and hospital stay. VAP risk factors included demographic factors such as age and sex. Dexamethasone was associated with a threefold greater risk of developing VAP during ICU stay. These results need to be comforted by large multi-centric studies before questioning the only available and effective treatment against SARS-CoV-2 in ICU patients.

Immune Checkpoint Inhibitor-Induced Myositis/Myocarditis with Myasthenia Gravis-like Misleading Presentation: A Case Series in Intensive Care Unit.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are a major breakthrough in cancer treatment. Their increasingly frequent use leads to an uprising incidence of immune-related adverse events (irAEs). Among those, myocarditis is the most reported fatal cardiovascular irAE, frequently associated with ICI-related myositis. CASE SERIES: Here, we report three cases of ICI-induced myocarditis/myositis with an extremely severe myasthenia gravis-like (MG-like) presentation, highlighting the main challenges in irAEs management. These patients were over 60 years old and presented an ongoing melanoma, either locally advanced or metastatic, treated with ICI combinations. Shortly after the first or second ICI infusion, they were admitted in an intensive care unit (ICU) for grade 3 ICI-induced MG-like symptoms leading to acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV). The initial misdiagnosis was later corrected to severe ICI-induced seronegative myocarditis/myositis upon biological results and histopathology from muscular/endomyocardial biopsies. All of them received urgent high-dose corticosteroids pulses. The oldest patient died prematurely, but the two others received targeted therapies leading to complete recovery for one of them. DISCUSSION: These cases highlight the four main challenges of irAEs, encompassing the lack of knowledge among physicians, the risk of misdiagnosis due to numerous and non-specific symptoms, the frequent overlapping forms of irAEs, and the extremely rare MG-like misleading presentation of myocarditis/myositis. The exact pathophysiology of irAEs remains unclear, although a major involvement of the lymphoid compartment (specifically T lymphocytes) was evidenced. Therapeutic management is based on urgent high-dose corticosteroids. For the severest forms of irAEs, case-by-case targeted immunosuppressive therapies should be urgently administered upon multidisciplinary meetings. CONCLUSION: These cases highlight the lack of knowledge of irAEs among physicians, aggravated by misleading overlapping forms, requiring specific management in trained units and multidisciplinary care. Severe MG-like presentation of irAEs constitutes an absolute therapeutic emergency with high-dose corticosteroids and targeted immunosuppressive therapy.

Two Venovenous Extracorporeal Membrane Oxygenation for One Gunshot.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an adjuvant treatment for severe acute respiratory distress syndrome (ARDS) with refractory hypoxemia. Contraindications to therapeutic anticoagulation must be ruled out prior to ECMO implementation. We report the case of a 17-year-old male admitted in intensive care unit (ICU) for penetrating chest trauma due to multiple gunshot wounds. The body computed tomography (body CT scan) documented right pulmonary contusions and a homolateral hemothorax. His condition rapidly deteriorated with refractory hypoxemia due to lung contusion requiring invasive mechanical ventilation (IMV) and polytransfused hemorrhagic shock. During his stay in ICU, venovenous ECMO (VV-ECMO) was implemented twice, firstly for trauma-induced ARDS and secondly after thoracic surgery. This case emphasizes the successful use of VV-ECMO in posttraumatic ARDS without increasing the risk of bleeding.

Salivary Alpha Amylase Bronchial Measure for Early Aspiration Pneumonia Diagnosis in Patients Treated With Therapeutic Hypothermia After Out-of-hospital Cardiac Arrest.

Background: Aspiration pneumonia is the most common respiratory complication following out-of-hospital cardiac arrests (OHCA). Alpha-amylase (α-amylase) in pulmonary secretions is a biomarker of interest in detecting inhalation. The main goal of this study is to evaluate the performance of bronchoalveolar levels of α-amylase in early diagnosis of aspiration pneumonia, in patients admitted to intensive care unit (ICU) after OHCA. Methods: This is a prospective single-center trial, led during 5 years (July 2015 to September 2020). We included patients admitted to ICU after OHCA. A protected specimen bronchial brushing and a mini-bronchoalveolar lavage (mini-BAL) were collected during the first 6 h after admission. Dosage of bronchial α-amylase and standard bacterial analysis were performed. Investigators confirmed pneumonia diagnosis using clinical, radiological, and microbiological criteria. Every patient underwent targeted temperature management. Results: 88 patients were included. The 34% (30 patients) developed aspiration pneumonia within 5 days following admission. The 55% (17) of pneumonias occurred during the first 48 h. The 57% of the patients received a prophylactic antibiotic treatment on their admission day. ICU mortality was 50%. Median value of bronchial α-amylase did not differ whether patients had aspiration pneumonia (15 [0-94]) or not (3 [0-61], p = 0,157). Values were significantly different concerning early-onset pneumonia (within 48 h) [19 (7-297) vs. 3 (0-82), p = 0,047]. If one or more microorganisms were detected in the initial mini-BAL, median value of α-amylase was significantly higher [25 (2-230)] than in sterile cultures (2 [0-43], p = 0,007). With an 8.5 IU/L cut-point, sensitivity and specificity of α-amylase value for predicting aspiration pneumonia during the first 2 days were respectively 74 and 62%. True positive and negative rates were respectively 44 and 86%. The area under the ROC curve was 0,654 (CI 95%; 0,524-0,785). Mechanical ventilation duration, length of ICU stay, and mortality were similar in both groups. Conclusion: In our study, dosage of bronchial α-amylase was not useful in predicting aspiration pneumonia within the first 5 days after ICU admission for OHCA. Performance in predicting early-onset pneumonia was moderate.

High Mortality of HLH in ICU Regardless Etiology or Treatment.

Background: Adult hemophagocytic lymphohistiocytosis (HLH) is highly lethal in the ICU. The diagnostic and therapeutic emergency that HLH represents is compounded by its unknown pathophysiological mechanisms. Here, we report on a large cohort of adult HLH in the ICU (ICU-HLH). We analyzed prognostic factors associated with mortality to define the diagnostic and therapeutic challenges in this specific population. Methods: This retrospective study included adult patients diagnosed with HLH in four ICUs in Marseille, France between 2010 and 2020. Patients who fulfilled the HLH-2004 criteria (≥ 4/8) and/or had an HScore ≥ 169 were diagnosed with HLH. HLH was categorized into four groups according to etiology: sepsis-associated HLH, intracellular infection-associated HLH, malignancy-associated HLH, and idiopathic HLH. Results: Two hundred and sixty patients were included: 121 sepsis-associated HLH (47%), 84 intracellular infection-associated HLH (32%), 28 malignancy-associated HLH (11%), and 27 idiopathic HLH (10%). The ICU mortality rate reached 57% (n = 147/260) without a statistical difference between etiological groups. Independent factors associated with mortality in multivariate analysis included age (OR (5 years) = 1.31 [1.16-1.48], p < 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21-1.56], p < 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28-1.70], p < 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11-24.97], p = 0.04), highly severe anemia (OR = 1.44 [1.09-1.91], p = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04-1.41], p = 0.02). Conclusions: In this large retrospective cohort study of critically ill patients, ICU-HLH in adults was associated with a 57% mortality rate, regardless of HLH etiology or specific treatment. Factors independently associated with prognosis included age, presence of hemophagocytosis in bone-marrow aspirates, organ failure at admission, and worsening organ failure during the ICU stay. Whether a rapid diagnosis and the efficacy of specific therapy improve outcome is yet to be prospectively investigated.

Case report: Ribavirin and vitamin A in a severe case of measles.

RATIONALE: Despite a vaccine being widely available, measles continues to occur frequently, with sometimes lethal consequences. PATIENTS CONCERNS: The mortality rate reaches 35% and measles represents 44% of the 1.4 million deaths which are due to preventable diseases. Severe forms of measles are reported, mainly in young, unvaccinated adults, and in specific populations. The risk factors for severe measles include no or incomplete vaccination and vitamin A deficiency. Apart from secondary measles-related infections, severe measles is mainly represented by neurological, respiratory, and digestive symptoms. DIAGNOSES: Strengthening the hypothesis that there is a link between vitamin A deficiency and severe measles in this paper we report the case of a 25-year-old unvaccinated man hospitalized for severe and complicated measles. OUTCOMES: The evolution was good after administration of intramuscular vitamin A as well as intravenous ribavirin. LESSONS: Measles remains a fatal and serious disease. The early use of ribavirin and vitamin A shows significant improvements regarding morbimortality and should be systematic in severe cases.