Clinical spectrum and prognostic impact of cancer in critically ill patients with HIV: a multicentre cohort study.

BACKGROUND: Both AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU). METHODS: All PLHIV admitted over the 2015-2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer. RESULTS: Amongst the 939 included PLHIV (median age, 52 [43-59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07-12.05) and ADC (aOR, 3.11; 95% CI 1.76-5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)-organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001). CONCLUSIONS: NADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission.

Spontaneous pneumomediastinum: a surrogate of P-SILI in critically ill COVID-19 patients.

Spontaneous pneumomediastinum (SP) has been described early during the COVID-19 pandemic in large series of patients with severe pneumonia, but most patients were receiving invasive mechanical ventilation (IMV) at the time of SP diagnosis. In this retrospective multicenter observational study, we aimed at describing the prevalence and outcomes of SP during severe COVID-19 with pneumonia before any IMV, to rule out mechanisms induced by IMV in the development of pneumomediastinum.Among 549 patients, 21 patients (4%) developed a SP while receiving non-invasive respiratory support, after a median of 6 days [4-12] from ICU admission. The proportion of patients requiring IMV was similar. However, the time to tracheal intubation was longer in patients with SP (6 days [5-13] vs. 2 days [1-4]; P = 0.00002), with a higher first-line use of non-invasive ventilation (n = 11; 52% vs. n = 150; 28%; P = 0.02). The 21 patients who developed a SP had persisting signs of severe lung disease and respiratory failure with lower ROX index between ICU admission and occurrence of SP (3.94 [3.15-5.55] at admission vs. 3.25 [2.73-4.02] the day preceding SP; P = 0.1), which may underline potential indirect signals of Patient-self inflicted lung injury (P-SILI).In this series of critically ill COVID-19 patients, the prevalence of SP without IMV was not uncommon, affecting 4% of patients. They received more often vasopressors and had a longer ICU length of stay, as compared with their counterparts. One pathophysiological mechanism may potentially be carried out by P-SILI related to a prolonged respiratory failure, as underlined by a delayed use of IMV and the evolution of the ROX index between ICU admission and the day preceding SP.

Diagnosis and prognosis of acute respiratory distress syndrome related to diffuse pneumonic-type adenocarcinoma: a single-center case series study.

Background: The absence of diagnosis of acute respiratory distress syndrome (ARDS) concerns 20% of cancer patients and is associated with poorer outcomes. Diffuse pneumonic-type adenocarcinoma (P-ADC) is part of these difficult-to-diagnose ARDS, but only limited data are available regarding critically ill patients with diffuse P-ADC. We sought to describe the diagnosis process and the prognosis of P-ADC related ARDS patients admitted to the intensive care unit (ICU). Methods: Single-center observational case series study. All consecutive patients admitted to the ICU over a two-decade period presenting with (I) histologically or cytologically proven adenocarcinoma of the lung and (II) ARDS according to Berlin definition were included. Clinical, biological, radiological and cytological features of P-ADC were collected to identify diagnostic clues. Multivariate logistic regression analyses were performed to assess factors associated with ICU and hospital mortality. Results: Among the 24 patients included [70 (61-75) years old, 17 (71%) males], the cancer diagnosis was performed during the ICU stay in 19 (79%), and 17 (71%) required mechanical ventilation. The time between the first symptoms and the diagnosis of P-ADC was 210 days (92-246 days). A non-resolving pneumonia after 2 (2 to 3) antibiotics lines observed in 23 (96%) patients with a 34 mg/L (19 to 75 mg/L) plasma C-reactive protein level at ICU admission. Progressive dyspnea, bronchorrhea, salty expectoration, fissural bulging and compressed bronchi and vessels were present in 100%, 83%, 69%, 57% and 43% of cases. Cytological examination of sputum or broncho-alveolar lavage provided a 75% diagnostic yield. The ICU and hospital mortality rates were 25% and 63%, respectively. The time (in days) between first symptoms and diagnosis [odds ratio (OR) 1.02, 95% confidence interval (95% CI): 1.00-1.03, P=0.046] and the Simplified Acute Physiology Score II (OR 1.16, 95% CI: 1.01-1.33, P=0.040) were independently associated with ICU mortality. Conclusions: Non-resolving pneumonia after several antibiotics lines without inflammatory syndrome, associated with progressive dyspnea, salty bronchorrhea, and lobar swelling (i.e., fissural bulging, compressed bronchi and vessels) were suggestive of P-ADC. Delayed diagnosis of diffuse P-ADC seemed an independent prognostic predictor and disease timely recognition may contribute to prognosis improvement.

Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients.

The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30-4.41] vs. 9.53 [2.56-19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.

Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity.

BACKGROUND: A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. METHODS: By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. RESULTS: At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets-both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. CONCLUSIONS: These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.

Endotracheal intubation rate is lower with additional face-mask noninvasive ventilation for critically-ill SARS-CoV-2 patients requiring high-flow nasal oxygen: a retrospective bicentric cohort with propensity score analysis.

BACKGROUND: SARS-CoV-2 pneumonia is responsible for unprecedented numbers of acute respiratory failure requiring invasive mechanical ventilation (IMV). This work aimed to assess whether adding face-mask noninvasive ventilation (NIV) to high-flow nasal oxygen (HFNO) was associated with a reduced need for endotracheal intubation. METHODS: This retrospective cohort study was conducted from July 2020 to January 2021 in two tertiary care intensive care units (ICUs) in Paris, France. Patients admitted for laboratory confirmed SARS-CoV-2 infection with acute hypoxemic respiratory failure requiring HFNO with or without NIV were included. The primary outcome was the rate of endotracheal intubation. Secondary outcomes included day-28 mortality, day-28 respiratory support and IMV free days, ICU and hospital length-of-stay. Sensitivity analyses with both propensity score matching and overlap weighting were used. RESULTS: One hundred twenty-eight patients were included, 88 (69%) received HFNO alone and 40 (31%) received additional NIV. Additional NIV was associated with a reduced rate of endotracheal intubation in multivariate analysis (53 [60%] vs. 15 [38%], HR=0.46 [95% CI: 0.23-0.95], P=0.04). Sensitivity analyses by propensity score matching (HR=0.45 [95% CI: 0.24-0.84], P=0.01) and overlap weighting (HR=0.52 [95% CI: 0.28-0.94], P=0.03) were consistent. Day-28 mortality was 25 (28%) in the HFNO group and 8 (20%) in the NIV group (HR=0.75 [95% CI: 0.15-3.82], P=0.72). NIV was associated with higher IMV free days (20 [0-28] vs. 28 [14-28], P=0.015). All sensitivity analyses were consistent regarding secondary outcomes. CONCLUSIONS: Need for endotracheal intubation was lower in critically-ill SARS-CoV-2 patients receiving face-mask noninvasive mechanical ventilation in addition to high-flow oxygen therapy.

Infectious aetiologies of severe acute chest syndrome in sickle-cell adult patients, combining conventional microbiological tests and respiratory multiplex PCR.

Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.

Pain and dyspnea control during awake fiberoptic bronchoscopy in critically ill patients: safety and efficacy of remifentanil target-controlled infusion.

PURPOSE: Flexible fiberoptic bronchoscopy is frequently used in intensive care unit, but is a source of discomfort, dyspnea and anxiety for patients. Our objective was to assess the feasibility and tolerance of a sedation using remifentanil target-controlled infusion, to perform fiberoptic bronchoscopy in awake ICU patients. MATERIALS, PATIENTS AND METHODS: This monocentric, prospective observational study was conducted in awake patients requiring fiberoptic bronchoscopy. In accordance with usual practices in our center, remifentanil target-controlled infusion was used under close monitoring and adapted to the patient's reactions. The primary objective was the rate of successful procedures without additional analgesia or anesthesia. The secondary objectives were clinical tolerance and the comfort of patients (graded from "very uncomfortable" to "very comfortable") and operators (numeric scale from 0 to 10) during the procedure. RESULTS: From May 2014 to December 2015, 72 patients were included. Most of them (69%) were hypoxemic and admitted for acute respiratory failure. No additional medication was needed in 96% of the patients. No severe side-effects occurred. Seventy-eight percent of patients described the procedure as "comfortable or very comfortable". Physicians rated their comfort with a median [IQR] score of 9 [8-10]. CONCLUSION: Remifentanil target-controlled infusion administered to perform awake fiberoptic bronchoscopy in critically ill patients is feasible without requirement of additional analgesics or sedative drugs. Clinical tolerance as well as patients' and operators' comfort were good to excellent. This technique could benefit patients' experience.

Bacterial coinfection in critically ill COVID-19 patients with severe pneumonia.

Severe 2019 novel coronavirus infectious disease (COVID-19) with pneumonia is associated with high rates of admission to the intensive care unit (ICU). Bacterial coinfection has been reported to be rare. We aimed at describing the rate of bacterial coinfection in critically ill adult patients with severe COVID-19 pneumonia. All the patients with laboratory-confirmed severe COVID-19 pneumonia admitted to the ICU of Tenon University-teaching hospital, from February 22 to May 7th, 2020 were included. Respiratory tract specimens were obtained within the first 48 h of ICU admission. During the study period, 101 patients were referred to the ICU for COVID-19 with severe pneumonia. Most patients (n = 83; 82.2%) were intubated and mechanically ventilated on ICU admission. Overall, 20 (19.8%) respiratory tract specimens obtained within the first 48 h. Staphylococcus aureus was the main pathogen identified, accounting for almost half of the early-onset bacterial etiologies. We found a high prevalence of early-onset bacterial coinfection during severe COVID-19 pneumonia, with a high proportion of S. aureus. Our data support the current WHO guidelines for the management of severe COVID-19 patients, in whom antibiotic therapy directed to respiratory pathogens is recommended.

Severe COVID-19 with acute respiratory distress syndrome (ARDS) in a sickle cell disease adult patient: case report.

BACKGROUND: Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known. CASE PRESENTATION: We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital. CONCLUSIONS: This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19.

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study).

INTRODUCTION: Acute respiratory failure is the main reason for admission to the intensive care unit (ICU) in HIV-infected adults. There is little data about the epidemiology of respiratory viruses in this population. METHODS: HIV-infected adults admitted to two intensive care units over a 6-year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mPCR) were retrospectively selected. Objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome. RESULTS: A total of 123 episodes were included. An HIV infection was newly diagnosed in 9% of cases and 72% of the population were on antiretroviral therapy. Real-time mPCR tests identified at least one respiratory virus in the respiratory tract of 33 (27%) patients, but with a non-viral copathogen in two-thirds of cases. Rhinovirus was predominant, documented in 15 patients, followed by Influenza and Respiratory Syncytial Viruses (both n = 6). The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL (n = 13 (20%) vs. n = 2 (4%), p < 0.01). In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis. CONCLUSIONS: Viruses are frequently identified in the respiratory tract of HIV-infected patients with acute respiratory failure that requires ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.

An unusual community-acquired invasive and multi systemic infection due to ExoU-harboring Pseudomonas aeruginosa strain: Clinical disease and microbiological characteristics.

Community-acquired Pseudomonas aeruginosa infections are rare. Most cases involve patients either with underlying immunosuppression or structural chronic lung diseases. We report here an atypical case of a severe community-acquired invasive infection due to a hypervirulent ExoU-producing strain, in an immunocompetent patient.

Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.