Life-threatening Respiratory Failure Research Articles

Thermal Helium-Oxygen Mixture as Part of a Treatment Protocol for Patients with COVID-19

Background. The paper discusses the use of a thermal helium-oxygen mixture (t-Не/О2 ), a novel technology, in treating patients with the 2019-nCoV acute respiratory disease (COVID-19) who develop life-threatening respiratory failure.
 Aim to evaluate the safety and efficacy of t-Не/О2 inhalation combined with standard therapy in the treatment of acute respiratory failure in patients with COVID-19.
 Materials and Methods. This was a single-center, randomized, prospective study of 70 patients with COVID-19. All patients were divided into two groups: in Group 1 (n = 38) patients received t-He/О2 in addition to the standard COVID-19 treatment; and in Group 2 (n = 32) patients were given the standard treatment in accordance with the Clinical Treatment Guidelines for patients with COVID-19, developed by the Ministry of Health of the Russian Federation. The male/female ratio was 18/20 in Group 1 and 18/14 in Group 2. The mean age of the patients in the study was 53.5 years (43; 62): 56 years (42; 64) in Group 1 and 52 years (43; 66) in Group 2. All patients had computed tomography (CT) signs of lung injury: ground-glass opacities and areas of consolidation. SARS-CoV-2 RNA was detected in 30 Group 1 patients and 28 Group 2 patients. The patients were matched by sex, age, body mass index (BMI), area of pulmonary involvement, and laboratory findings. All patients provided voluntary informed consent to participate in the study and signed a consent form.
 Results. Inhalation of thermal helium-oxygen mixture combined with standard therapy did not cause any procedure-related side effects in any of the patients. The following changes were observed in all patients: pO2 /FiO2 , SpO2 , and lymphocyte counts increased, C-reactive protein (CRP) levels decreased, and D-dimer and ferritin levels returned to normal. In Group 1 statistically significant changes in the above-mentioned parameters were seen within three days, while in Group 2 the same changes were observed between Days 7 and 10 of treatment. In Group 1 patients cleared SARS-CoV-2 within 4872 hours after initiation of inhalation, which was confirmed by polymerase chain reaction (PCR), and in Group 2 virus elimination was achieved within 72168 hours.
 Conclusion. The addition of inhalation of a thermal gas mixture of helium and oxygen (t-He/О2 ) to the standard therapy for patients with SARS-CoV-2 infection, CT signs of pneumonia (grades СT2 or CT3), and acute respiratory failure improves gas exchange, contributes to a more rapid virus elimination, and indirectly reduces inflammation.

Rare Surgical Lung Biopsy Findings of Metastatic Pulmonary Calcification Associated with Chronic Renal Failure

Abstract Introduction/Objective Metastatic pulmonary calcification is a metabolic lung disease characterized by depositions of calcium in lung parenchyma. Depositions of calcium salts are usually caused by hypercalcemia and are associated with end-stage renal disease, primary and secondary hyperparathyroidism, and hemodialysis. It is mostly asymptomatic and clinically silent but can lead to life-threatening respiratory failure. Methods We present a case of a 53-year-old woman, with a failed renal transplant and on hemodialysis, admitted with cough and shortness of breath. Computed tomography showed extensive diffuse bilateral groundglass and nodular opacities. Bronchoscopy was unremarkable. BAL results were negative for infection. The initial differential diagnosis included pneumonitis, interstitial lung disease, and chronic obstructive pulmonary disease. VATS lung wedge resection was performed. Results Microscopically there were numerous interstitial, peribronchial and perivascular calcifications highlighted by Van Kossa stain. Calcifications were associated with a marked interstitial fibrosis confirmed by trichrome stain. There was no evidence of significant acute and chronic inflammation, granulomas, fibroblastic foci and vasculitis. Conclusion Metastatic pulmonary calcification is found in 60–80% of autopsies of patients undergoing dialysis treatment. It is rarely diagnosed during their lifetime, because patients are usually asymptomatic, or the imaging findings are negative. The diagnosis of metastatic pulmonary calcification in our patient prompt further evaluation for repeat kidney transplant and the patient is being considered for parathyroidectomy for her tertiary hyperparathyroidism.

Congenital Aortic Vascular Ring: In-Utero Sonographic Assessment ofTracheal Patency and Postnatal Outcome.

Congenital aortic vascular ring may present after birth with variable degrees of respiratory distress due to tracheal compression. The aim of this study was to prospectively evaluate in utero tracheal patency in correlation with postnatal outcome. During an eight-year period, fetuses with aortic arch abnormality encircling the trachea and forming a complete ring were recruited for the study. Tracheal patency was classified as: no compression, partial compression, or complete compression. Postnatal MRI/CTangio studies were performed and outcome data was retrospectively analyzed from the medical records. Among the 46 fetuses recruited to the study, 38 had right aortic arch (RAA), and 8 presented with double aortic arch (DAA). In the RAA group 35 (92.1 %) of the fetuses presented no compression and 34 (97.1 %) of them were asymptomatic in the long-term follow-up. Three fetuses (7.9 %) in this group presented in utero compression: one was terminated at 16 weeks of gestation due to associated ominous findings, and the other two had mild respiratory symptoms around 12months of age and underwent surgery with a good outcome. In the DAA group, all fetuses presented in utero with tracheal compression. Seven showed partial and one complete compression. Among the seven with partial compression, six were symptomatic and underwent surgery. The case with severe airway occlusion had emergency tube insertion in the delivery room and underwent surgery at 7 days but died from severe respiratory complications. This is the first study to evaluate in utero tracheal patency in cases with vascular ring. It allows better prenatal and postnatal workup and follow-up including potentially life-threatening respiratory failure.

A CASE OF LIFE-THREATENING NON-INFECTIOUS PNEUMONITIS IN A PATIENT TREATED WITH EVEROLIMUS FOR METASTATIC NON-SMALL CELL LUNG CANCER

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Everolimus, an oral inhibitor of mTOR, is a targeted anti-neoplastic therapy for advanced NSCLC. We present a case of non-infectious pneumonitis (NIP) in a patient being treated with everolimus. Prompt recognition and management is essential. CASE PRESENTATION: 64-year-old male with Stage IV NSCLC, recently started on 6th line salvage therapy with everolimus, presented with 4 days of dyspnea, fatigue, intermittent chills, productive cough, and scant hemoptysis. On arrival, patient was afebrile, tachycardiac and hypoxic to 88% on room air. He was found to have mild anemia and elevated LDH without leukocytosis or thrombocytopenia. CT chest showed increase in RUL perihilar mass and new peribronchovascular airspace disease in all lobes. Differential diagnosis included infectious and noninfectious findings of new airspace disease. Everolimus was discontinued and patient was started on oxygen supplementation to maintain oxygen saturation >88%, along with 60 mg IV solumedrol q24 hours, broad-spectrum antibiotic coverage with piperacillin-tazobactam, linezolid, and azithromycin. Bronchoalveolar lavage (BAL) was negative for mycobacterium, fungal or bacterial pathogens. Patient improved symptomatically after starting steroids along with reduction in oxygen requirement. DISCUSSION: Everolimus is used in select cases of advanced NSCLC. NIP is a potentially fatal adverse effect of mTOR inhibitors, more frequently seen in NSCLC as compared to other solid malignancies and in patients with baseline interstitial lung disease. Severe or life-threatening symptoms requiring discontinuation of therapy, as seen in our patient, are uncommon and require prompt diagnosis and treatment. Common presentation includes cough, dyspnea, and hypoxemia. Hemoptysis, as seen in our patient, is rare. Radiographic changes in everolimus associated NIP include, lower lobe predominant ground-glass and reticular opacities, focal parenchymal consolidations, and rarely, pleural effusions. Pulmonary function tests can show a restrictive pattern or abnormally low DLCO. Histological testing including BAL, lung biopsy, and sputum cultures help exclude infection, granulomatous disease or malignancy. Management is guided by grade of pneumonitis, and includes close clinical observation, dose reduction or discontinuation. Systemic steroids can be given to patients with grade ≥2 pneumonitis until symptoms improve to grade ≤1. CONCLUSIONS: Patients on everolimus therapy for advanced NSCLC are at high risk of developing NIP, that can sometimes lead to life-threatening hypoxic respiratory failure. Urgent diagnosis and guideline directed management of this adverse effect is highly important. Reference #1: Alvarez RH, Bechara RI, Naughton MJ, Adachi JA, Reuben JM. Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer. Oncologist. 2018;23(6):660-669. Reference #2: Grünwald V, Weikert S, Pavel M, et al. Practical Management of Everolimus-Related Toxicities in Patients with Advanced Solid Tumors. Onkologie. 2013;36:295-302. Reference #3: White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH. Characterization of Pneumonitis in Patients with Advanced Non-small Cell Lung Cancer Treated with Everolimus (RAD001). Journal of Thoracic Oncology. 2009;4(11):1357-1363. DISCLOSURES: No relevant relationships by zainub ajmal, source=Web Response No relevant relationships by Sana Ghalib, source=Web Response No relevant relationships by Boris Shkolnik, source=Web Response No relevant relationships by Fatima Tuz Zahra, source=Web Response

A Rapid and International Applicable Diagnostic Device for Cobra (Genus Naja) Snakebites.

Cobra snakes (genus Naja) are some of the most dangerous snake species in Asia and Africa, as their bites cause severe life-threatening respiratory failure and local tissue destruction, especially in the case of late diagnosis. The differential diagnosis of snakebite envenomation still mainly relies upon symptomatology, the patient’s description, and the experience of physicians. We have designed a rapid test, immunochromatographic test of cobra (ICT-Cobra), which obtained fair results in improving the diagnosis and treatment of Naja (N.) atra snakebites in Taiwan. In this study, we further investigated the feasibility of applying the kit for the detection of other cobra venoms based on the potential interspecies similarity. We firstly demonstrated the cross-reactivity between eight venoms of medically important cobra species and the rabbit anti-N. atra IgG that was used in ICT-Cobra by Western blotting and sandwich enzyme-linked immunosorbent assay. Then, ICT-Cobra was used to detect various concentrations of the eight venoms to elucidate its performance. Noticeable correlations between the cross-reactivity of venoms from genus Naja snakes and existing geographical characteristics were found. ICT-Cobra could detect venoms from other Asian cobras with variable detection limits comparable to those observed for N. atra, but the kit was less successful in the detection of venom from African cobras. The similar but slightly different venom components and the interaction between venom and rabbit anti-N. atra IgG led to variations in the detection limits. The transcontinental usage of ICT-Cobra might be possible due to the cross-reactivity of antibodies and similarities among the larger-sized proteins. This study showed that the close immunological relationships in the genus Naja could be used to develop a venom detection kit for the diagnosis of cobra envenomation in both Asian and African regions. Additional clinical studies and technical adjustments are still needed to improve the efficacy and broadening the application of ICT-Cobra in the future.

Etiologies of delayed diagnosis and six-month outcome of patients with newly diagnosed advanced lung cancer with respiratory failure at initial presentation.

BackgroundThis study aimed to evaluate the characteristics of patients with newly diagnosed advanced lung cancer who initially presented with respiratory failure.MethodsThis was a retrospective study which analyzed patients in the intensive care unit (ICU) with newly diagnosed advanced lung cancer who were placed on mechanical ventilation (MV). We defined newly diagnosed lung cancer as pathological or molecular results for treatment decisions not yet determined when the patient was admitted to ICU.ResultsDuring the 14‐year inclusion period, 845 lung cancer patients requiring MV were screened. A total of 56 newly diagnosed extensive lung cancer patients were analyzed. Cancer‐related to central airway obstruction (n = 29, 51.8%) was the leading cause of respiratory failure. The significant etiologies of delay in the diagnosis of lung cancer were diagnostic error, mistaking cancer for tuberculosis, and missed hilar lesions. The six‐month survival rate was only 7.1% (n = 4). The sequential organ failure assessment (SOFA) score was significantly associated with mortality (HR = 1.142, 95% CI = 1.012–1.288, P = 0.031). The six‐month survival rate in patients receiving suitable targeted therapy and accepting chemotherapy and best supportive care was 40% (2/5), 0% (0/7), and 4.5% (2/44), respectively.ConclusionsPatients with newly diagnosed advanced lung cancer with acute life‐threatening respiratory failure have poor outcomes. Cancer‐related to central airway obstruction is a leading cause of respiratory failure. Diagnostic errors such as tuberculosis and missed hilar lesions are the two main etiologies of a delay in diagnosis. The SOFA score is correlated with mortality. Targeted therapy can raise the six‐month survival rates in patients with oncogenic mutation adenocarcinoma, who survive after presentation in a critical condition.

Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy

SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired.

Machine learning for COVID-19—asking the right questions

COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has put health-care systems worldwide into crisis.1 The speed with which health-care resources have been consumed has in some countries exceeded supply of personal protective equipment and ventilators, the unprecedented need for the latter as a result of life-threatening respiratory failure that characterises severe disease.

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making.

The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1β/neutrophil extracellular traps feedback loop

Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5–10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, coagulopathy and multiorgan failure is not known. SARS-CoV-2 is an envelope virus with S (spike), M (membrane), N (nucleocapsid) and E (envelop) proteins. In a closely related coronavirus (SARS-CoV), the transmembrane E protein exerts an important role in membrane-ionic transport through viroporins, deletion of which reduced levels of IL-1β and a remarkably reduced lung edema compared to wild type. IL-1β is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1β. Expiring neutrophils undergo “NETosis”, producing thread-like extracellular structures termed neutrophil extracellular traps (NETs), which protect against mild infections and microbes. However, uncontrolled NET production can cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), coagulopathy, multiple organ failure, and autoimmune disease. Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19. Considering such assertions, we propose potential drug candidates that could be used to alleviate such pathologies. Considering that recent efforts to ascertain effective treatments of COVID-19 in severe patients has been less than successful, investigating novel avenues of treating this virus are essential.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Emergence, history, basic and clinical aspects.

In late December 2019, the world woke to a reality of a pandemic of Coronavirus Disease (COVID-19), elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which belongs to a group of β-coronavirus. The potential to cause life-threatening respiratory failure and rapid transmission puts COVID-19 in the list of Public Health Emergency of International Concern (PHEIC). In the last two decades, this is the 3rd deadliest Coronavirus pandemic, following SARS which lasted between 2002 and 2003 and Middle East Respiratory Syndrome (MERS) from 2012 till date. Globally and as of April 23rd 2020, COVID-19 has affected 2,544,792 individuals in over 200 countries, causing 175,694 fatalities. While the SARS-CoV-2 originated in China with 84,302 confirmed cases and 4642 deaths as at the time of writing this review, the rapid transmission of SARS-CoV-2 has resulted in exponential increase in the number of cases outside of China to about 10 times the report case and death in mainland China. SARS-CoV-2 is suspected to be zoonotic in nature as genetic studies have shown sequence similarity to viruses originating from bats. Extreme precautionary measures, such as curfew, shutting of borders and quarantining of individuals suspected to be infected have been instituted with immediate effect; however, due to individuals that are asymptomatic, uncontrolled human-to-human transmission has resulted in exponential infection rate and numerous loss of lives even with this lockdown measures. This review article summarizes the developing situation surrounding the SARS-CoV-2 pandemic with respect to its epidemiology, unique genomic structure, possible origins, transmission, pathogenesis, comparison with other deadly species of Coronaviruses (CoV) and emerging treatment strategies built on informed literature.

Vaping-Associated Respiratory Distress Syndrome: Case Classification and Clinical Guidance.

Center from Disease Control, Departments of Public Health, MEDLINE (via PubMed), and the Cochrane Library. Cases, series, and public health reports of cases that met the Centers for Disease Control and Prevention case definition of vaping-associated respiratory disease were extracted by an author with perfect verification by a second. Cases were classified on the basis of toxin exposure, symptoms, oxygen saturation, progression to respiratory failure, and pathologic features, and a clinically actionable system of classification was based on expert opinion. The reported spectrum of vaping-associated respiratory diseases allows clinical classification of cases into groups with distinct evaluation, management, and recommendations for prevention and follow-up. Clinical stratification also identifies a small proportion of vaping-exposed patients who are at risk for progression to hypoxemic respiratory failure and an acute respiratory distress syndrome-like illness.

Dysphonia as the main presenting symptom of COVID-19: a case report

The spectrum of illness associated with COVID-19 is wide, ranging from asymptomatic infection to life-threatening respiratory failure. Herein, the authors are presenting a case in which the main symptoms expressed by a patient infected with SARS-CoV-2 were simultaneous gradual change of voice with loss of olfaction but without nasal obstruction.

Ventilator-induced lung injury in children: a reality?

Mechanical ventilation (MV) is inextricably linked to the care of critically ill patients admitted to the paediatric intensive care unit (PICU). Even today, little evidence supports best MV practices for life-threatening acute respiratory failure in children. However, careful attention must be paid because this life-saving technique induces pulmonary inflammation that aggravates pre-existing lung injury, a concept that is known as ventilator-induced lung injury (VILI). The delivery of too large tidal volumes (Vt) (i.e., volutrauma) and repetitive opening and closure of alveoli (i.e., atelectrauma) are two key mechanisms underlying VILI. Despite the knowledge of these mechanisms, the clinical relevance of VILI in critically ill children is poorly understood as almost all of our knowledge has been obtained from studies in adults or experimental studies mimicking the adult critical care situation. This leaves the question if VILI is relevant in the paediatric context. In fact, limited paediatric experimental data showed that the use of large, supraphysiologic Vt resulted in less inflammation and injury in paediatric animal models compared to adult models. Furthermore, the association between large Vt and adverse outcome has not been confirmed and the issue of setting positive end-expiratory pressure (PEEP) to prevent atelectrauma has hardly been studied in paediatric clinical studies. Hence, even today, the question whether or not there VILI is relevant in pediatric critical remains to be answered. Consequently, how MV is used remains thus based on institutional preferences, personal beliefs and clinical data extrapolated from adults. This signifies the need for clinical and experimental studies in order to better understand the use and effects of MV in paediatric patients with or without lung injury.

Pulmonary Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review

Background The syndrome of drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with anticonvulsants, sulfonamides, and allopurinol. The reaction commonly manifests as a febrile skin eruption with lymphadenopathy and malaise between two and eight weeks following drug exposure. Internal organ involvement occurs in close to 90 percent of patients, and multiple organs may be involved in approximately half of those affected (most commonly the liver, kidney, and lung). Its long latency period and its variable clinical pattern of presentation have earned it the moniker of “the great mimicker,” with delays in diagnosis leading to higher morbidity and mortality. Although less commonly affected in DRESS syndrome, lung involvement is associated with more severe clinical course and potentially worse outcome. Pulmonary symptoms may precede development of the other more common symptoms and signs of the syndrome, or they might develop later in the course of the disease. Lung involvement in DRESS presents with a plethora of manifestations from mild cough or dyspnea with nonspecific interstitial changes on chest imaging to acute respiratory distress syndrome (ARDS) with life-threatening hypoxic respiratory failure. Methods We performed a systematic review of literature from the PubMed database and selected cases of definite DRESS syndrome as defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) with a score of 6 or more who also had pulmonary involvement. Demographic data, pattern of lung involvement, culprit medication, latency period, laboratory findings, therapy, and outcome were described and compared with the literature. Results The most common pulmonary radiographic findings in DRESS were interstitial infiltrates in 50% of cases, followed by acute respiratory distress syndrome (ARDS) 31%. Symptoms of cough and shortness of breath (SOB) were present in 72% of patients at the time of presentation. SOB was the more common presenting symptom (81%) compared to cough (19%). In 95% of cases, another visceral organ was involved (most commonly liver or kidneys). 45% of cases were initially misdiagnosed as pneumonia and were treated with empiric antimicrobials. In a multivariate regression, a latency of 30 days or less and an age of 60 or less were associated with development of ARDS. Gender and eosinophil count were not associated with severity of pulmonary manifestations. All patients recovered, and in the vast majority of cases (95%), parenteral steroids were used for treatment in addition to supportive care and symptomatic management. Conclusion Albeit rare, DRESS is a potentially life-threatening syndrome which may present with a myriad of pulmonary signs and symptoms. Pulmonary manifestations are less common but are typically seen in more severe cases. Pulmonary manifestations may be a presenting sign of DRESS, and timely recognition is important in order to stop offending medication and decrease morbidity and mortality.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD.

While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode. Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

A Time-to-Death Analysis of Older Adults after Emergency Department Intubation.

Background: Older adults frequently report a preference to "trial" intubation and mechanical ventilation (MV) if faced with life-threatening respiratory failure. Understanding the anticipated outcome of unplanned MV is key to structuring a time-limited trial of treatment. Objective: To characterize the time-to-death (TTD) among adults 65 years of age and older, who undergo emergency intubation and MV. Design: Retrospective cohort study. Setting/Subjects: All patients 65 years of age and older, who underwent emergency department (ED) intubation from 2008 to 2015, from 417 hospitals were included. Measurements: The primary outcome was TTD after emergency intubation. Results: We identified 41,463 ED encounters. The median TTD was three days (interquartile range, IQR, 1-8). There was a statistically significant change in the median TTD by age decile, with the shortest TTD, two days, in the oldest age group (p < 0.001). TTD was shortest among those with myocardial infarction (one day, IQR 4) and sepsis (two days, IQR 5). Bivariate analysis comparing TTD by Charleston Comorbidity Index (CCI) revealed a trend of increasing TTD with increasing CCI score among decedents. Patients with a CCI of 0 had a median TTD of one day (IQR 4), whereas the median TTD among those with a CCI >4 was four days (IQR 9). Conclusions: In a large, nationally representative cohort of older adults undergoing ED intubation, the median time from intubation to death was short; however, the length of time between intubation and death varied considerably by principal diagnosis. This information will help guide providers' prognostication after emergency intubation and enhance serious illness conversations by informing expectations. Tweet: Thirty-five percent of older adults die after ED intubation-most only survive two or three days after intubation.

Principlism and Personalism. Comparing Two Ethical Models Applied Clinically in Neonates Undergoing Extracorporeal Membrane Oxygenation Support

Extracorporeal membrane oxygenation (ECMO) is a technology used to temporarily assist critically ill patients with acute and reversible life-threatening cardiac and/or respiratory failure. This technology can often be lifesaving but is also associated with several complications that may contribute to reduced survival. Currently, neonates supported with ECMO are complex and bear an increased risk of mortality. This means that clinicians must be particularly prepared not only to deal with complex clinical scenarios, but also ethical issues associated with ECMO. In particular, clinicians should be trained to handle unsuccessful ECMO runs with attention to high quality end of life care. Within this manuscript we will compare and contrast the application of two ethical frameworks, used in the authors' institutions (Toronto and Rome). This is intended to enhance a broader understanding of cultural differences in applied ethics which is useful to the clinician in an increasingly multicultural and diverse patient mix.

The use of extracorporeal membrane oxygenation in severe closed chest injury

The clinical case of successful cure of the victim with severe closed chest injury is presented, as a result of which the life-threatening acute respiratory failure could not be compensated by artificial lung ventilation and, in connection with which the use of extracorporeal membrane oxygenation as a «life-saving technology» was required.

The Contribution of Host Cells to Pneumocystis Immunity: An Update.

Pneumocystis is a ubiquitous atypical fungus that is distributed globally. The genus comprises morphologically similar but genetically heterogeneous species that have co-evolved with specific mammalian hosts as obligate intra-pulmonary pathogens. In humans, Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP) in immunocompromised individuals, a serious illness frequently leading to life-threatening respiratory failure. Initially observed in acquired immunodeficiency syndrome (AIDS) patients, PCP is increasingly observed in immunocompromised non-AIDS patients. The evolving epidemiology and persistently poor outcomes of this common infection will require new strategies for diagnosis and treatment. A deeper understanding of host immune responses and of the cells that mediate them will improve the chance of developing new treatment strategies. This brief review provides an update on recent studies on the role of host immunity against Pneumocystis.