Search

Introduction: We sought to evaluate secondary infections (SIs) in patients admitted to the intensive care unit (ICU) for COVID-19 with respect to incidence, causative pathogens, and clinical outcomes. Methodology: In this two-centre retrospective study, we analysed 146 patients (96 males, 50 females; median age, 64 years) admitted to the ICU with COVID-19 between March 26 and December 31, 2020. Inclusion criteria were an ICU admission for at least 48 hours and age beyond 18 years. Patients with and without SIs were compared and the impacts of SIs and carbapenem resistance on mortality were analysed. Results: During ICU admission, 84 episodes of SIs developed in 58 patients (39.7%). A total of 104 isolates were recovered, with Gram-negative bacteria most frequent accounting for 74%. At least one carbapenem-resistant pathogen (n = 61) was recovered in 41 patients (70.1%). In multivariate analysis, the use of ECMO and an elevated procalcitonin level were significantly associated with the development of SIs. The mortality rate and the incidence of carbapenem resistance did not differ significantly in COVID-19 patients with and without SIs (p = 0.059 and p = 0.083, respectively). Conclusions: The incidences of SIs and carbapenem resistance among COVID-19 patients were alarming, emphasizing stricter infection control measures in the ICU setting. © 2022 Journal of Infection in Developing Countries. All rights reserved.

BACKGROUND: In our previous report on Turkish COVID-19 patients requiring intensive care, the 24 patients in a single ICU were elderly and mortality was high. We extended our analysis to include patients admitted to ten ICUs. OBJECTIVES: Report the demographics, clinical features, imaging findings, comorbidities, and outcomes in COVID-19 patients. DESIGN: Retrospective. SETTING: Intensive care unit. PATIENTS AND METHODS: The study includes patients with clinical and radiological confirmed or laboratory-confirmed COVID-19 infection who were admitted to ten ICUs between 15 March and 30 June 2020. MAIN OUTCOME MEASURES: Clinical outcomes, therapies, and death during hospitalization SAMPLE SIZE: 974, including 571 males (58%). RESULTS: The median age (range) was 72 (21–101) years for patients who died (n=632, 64.9%) and 70 (16–99) years for patients who lived (n=342, 35.2%) ( P P P =.013). Most (n=719, 73.8%) underwent invasive mechanical ventilation therapy. CONCLUSIONS: The majority of patients admitted to the ICU with a diagnosis of COVID-19 require respiratory support. LIMITATIONS: Although the Turkish Ministry of Health made recommendations for the treatment of COVID-19 patients, patient management may not have been identical in all ten units. CONFLICT OF INTEREST: None.

Background Although commonly used inside hospitals, no previous case report has been published on high-flow nasal oxygen (HFNO) therapy in an adult in the prehospital setting. Case Report A 46-year-old nonsmoking man presented with a cough and fever. He deteriorated suddenly 5 days later. When the basic life support team arrived, his peripheral oxygen saturation (SpO2) in ambient air was 56% and respiratory rate was 46 breaths/min. The man was weak with thoracoabdominal asynchrony. An emergency medical team with a physician was dispatched. As France was still under lockdown for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, COVID-19 (coronavirus disease 2019) was suspected. In spite of 15 L/min of oxygen delivered with a nonrebreathing mask, the patient's SpO2 tended to drop below 90% at the slightest effort and during transport from home to the ambulance. It was therefore decided to start HFNO therapy. The patient was transferred to an intensive care unit, where HFNO was continued. Why Should an Emergency Physician Be Aware of This? As the trend in emergency medical services may move toward prehospital HFNO, this case report is an opportunity to question the feasibility of HFNO therapy in the prehospital setting.

Shadi Hamouri,1 Shaher M Samrah,2 Omar Albawaih,1 Zidan Saleh,2 Mahmoud M Smadi,3 Ahmad Alhazymeh,1 Sebawe Syaj1 1Department of General Surgery and Urology, Faculty of Medicine, Jordan University of Science and Technology, King Abdullah University Hospital, Irbid, 22110, Jordan; 2Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, King Abdullah University Hospital, Irbid, 22110, Jordan; 3Department of Mathematics and Statistics, Faculty of Science and Art, Jordan University of Science and Technology, Irbid, 22110, JordanCorrespondence: Shadi HamouriDepartment of General Surgery and Urology, Faculty of Medicine, Jordan University of Science and Technology, King Abdullah University Hospital, P. O. Box 3030, Irbid, 22110, JordanTel +962 79 6266693Fax +962-2-7095010Email smhamouri@just.edu.joPurpose: This study aims to determine the incidence and outcome of COVID-19 patients who required positive pressure ventilation (PPV) and subsequently developed pulmonary barotrauma (PBT). Also, to investigate the risk factors and predictors of these complications to better understand the disease pathogenesis.Patients and Methods: This retrospective analysis enrolled all adult COVID-19 patients admitted through the period from October 1, 2020, to December 31, 2020. All patients who received any form of PPV were included. Patients were then divided into two groups based on PBT development, including subcutaneous emphysema, pneumothorax, and pneumomediastinum. Medical records of all patients were reviewed. Patients’ demographics, laboratory data on admission, respiratory support modes, surgical interventions, and outcomes were collected and analyzed.Results: In the specified period, 1095 patients were hospitalized due to COVID-19 illness. A total of 239 (21.8%) of all admitted patients received PPV. PBT accounted for 21.3% (51/239) of the study cohort. While both groups were equally exposed to the same modes of PPV, receiving invasive ventilation significantly correlated with decreased PBT odds (OR = 0.891; 95% CI, 0.803– 0.988; p=0.029). PBT patients were significantly younger (p< 0.001). Diabetes mellitus was found to have a protective effect on developing PBT (OR = 0.867; 95% CI, 0.782– 0.962), while PO2/FIO2 ratio was inversely associated with higher odds of developing PBT in both univariate and multivariate analyses (p=0.03 and p=0.019, respectively).Conclusion: COVID-19-infected patients are at a higher risk of developing PBT. Invasive positive pressure ventilation was associated with less PBT compared to noninvasive ventilation and delaying intubation does not seem to reduce the risk of pulmonary barotrauma.Keywords: COVID-19, pulmonary barotrauma, pneumothorax, pneumomediastinum, positive pressure ventilation, adult respiratory distress syndrome

Background: Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. Methods: This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. Results: Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. Conclusion: The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.

Background Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system. Methods Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles). Results Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. Conclusion In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.

This clinical review paper discusses the pathophysiology of the pulmonary and cardiovascular manifestations of a SARS-CoV-2 infection and the ensuing implications on acute cardiovascular care in patients presenting with a severe COVID-19 syndrome admitted to an intensive acute cardiac care unit. The high prevalence of old age, obesity, diabetes, hypertension, heart failure, and ischaemic heart disease in patients who develop a severe to critical COVID-19 syndrome suggests shared pathophysiological mechanisms. Pre-existing endothelial dysfunction and an impaired innate immune response promote the development by the viral infection of an acute endothelialitis in the pulmonary microcirculation complicated by abnormal vasoconstrictor responses, luminal plugging by inflammatory cells, and intravascular thrombosis. This endothelialitis extends into the systemic circulation what may lead to acute myocardial injury, myocarditis, and thromboembolic complications both in the arterial and venous circulation. Ever since the first case reports from the city of Wuhan in China in December of 2019, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues as a raging pandemic causing significant morbidity and mortality [1]. In this paper we provide a review of the epidemiological characteristics and the pathophysiology of SARS-CoV-2 infection, and formulate the hypothesis that endothelialitis may play a key role in the pathogenesis of the pulmonary and cardiovascular complications of COVID-19.

Since the appearance of the novel coronavirus (severe acute respiratory syndrome-coronavirus-2) and related coronavirus disease 2019 (COVID-19) in China in December 2019, a very high number of small and large patient series have been published in literature from around the world. Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure, and secondary bacterial sepsis, a large body of evidence suggests a plethora of other types of clinical presentation. In this exhaustive review, we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems, to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline, battling the severe pandemic.

COVID-19, a new viral disease affecting primarily the respiratory system and the lung, has caused a pandemic with serious challenges to health systems around the world. In about 20% of patients, severe symptoms occur after a mean incubation period of 5 - 6 days; 5% of patients need intensive care therapy. Morbidity is about 1 - 2%. Protecting health care workers is of paramount importance in order to prevent hospital acquired infections. Therefore, during all procedures associated with aerosol production, a personal safety equipment consisting of a FFP2/FFP3 (N95) respiratory mask, gloves, safety glasses and a waterproof overall should be used. Therapy is based on established recommendations issued for patients with acute lung injury (ARDS). Lung protective ventilation, prone position, restrictive fluid management and an adequate management of organ failures are the mainstays of therapy. In case of fulminant lung failure, veno-venous extracorporeal membrane oxygenation may be used as a rescue in experienced centres. New, experimental therapies evolve with ever increasing frequency; currently, however, there is no evidence based recommendation possible. If off-label and compassionate use of these drugs is considered, an individual benefit-risk assessment is necessary, since serious side effects have been reported.Der Übersichtsartikel ist als praktische Handreichung für alle gedacht, die COVID-19-Patienten behandeln bzw. in nächster Zeit behandeln werden, und fasst das derzeit verfügbare Wissen zu Diagnostik und Therapie zusammen. Zusätzlich werden auch neue und experimentelle Therapien bewertet, soweit dazu zumindest Einzelfallberichte vorliegen.

We report our initial experience with the management of a mixed group of patients with COVID-19 infection, admitted and treated in a designated COVID-19 centre in the Athens Metropolitan area over a 4-week period. The SARS-CoV-2 pandemic presented a huge challenge to the Greek National Healthcare System and healthcare workers. Their response so far has been miraculously effective. Since there are essentially no therapeutic guidelines yet for this disease, we relied mainly on our medical intuition, our empathy for our patients and team work to do the best possible for 49 people with this infection. We present the therapeutic algorithm we gradually developed (on the job) and applied in our patients, based on continuous creative brainstorming and monitoring of the literature.

Background Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. Methods/design This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of 9/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. Discussion If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. Trial registration ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up. The study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co‑funded by ERDF, “Una manera de hacer Europa” and Donation pro‑gram "estar preparados". UNESPA. Madrid. Spain David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041), co‑funded by the European Social Fund (ESF), “Investing in your future”. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co‑funded by European Regional European Social Fund (ESF), “Investing in your future"

Peer reviewed: True, Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation-in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality-between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16-27) vs. 14 (10.5-19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

Vaping (i.e., the use of electronic cigarettes) has been gaining popularity among people for the past few years, perhaps due to the misconception that its use is less harmful than traditional cigarettes. Although the long-term effects of these products are still unknown, it has been shown that they can be implicated in acute lung injury in healthy people. In 2019, an epidemic of severe acute lung injury was reported in the United States, and it was linked to vaping or electronic cigarette use and was referred to as e-cigarette or vaping product use-associated lung injury (EVALI). Here, we present the first case of EVALI in the state of Qatar.

Objective Coronavirus disease 2019 (COVID-19) is associated with diffuse lung injury that can progress to acute respiratory distress syndrome, multisystem-organ failure, and death. The inflammatory storm seen in many COVID-19 patients closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH) which has been described in other virus-associated severe sepsis. We sought to describe the incidence of sHLH in COVID-19 infected patients. Design In this retrospective study, we reviewed the records of critically ill COVID-19 positive patients to determine the incidence of sHLH. An H-score for sHLH diagnosis was determined for each study participant, with a score greater than 169 points needed for diagnosis. Setting A quaternary referral center in suburban Pennsylvania, USA. Patients All study participants had a positive COVID-19 test, and were deemed critically ill defined as receiving invasive mechanical ventilation and/or who expired. Measurements and Main Results Of the 246 records identified, 242 records met inclusion criteria and were reviewed. Eighty five patients were excluded from analysis due to missing H-score data parameters. Overall, 32 of 157 (20.38%, 95% CI:14.38-27.54%) patients met diagnostic criteria for sHLH. The average age was 69.42 years (standard deviation (SD) 14.81). Patients diagnosed with sHLH were more likely to be younger (61.09 years vs 69.38 years, P = 0.0036), male (71.88% vs 52.00%, P = 0.0433), and require mechanical ventilation (96.88% vs 72.80%, P = 0.0035). Conclusions Among critically ill COVID-19 positive patients, the incidence of sHLH is higher than previously reported in patients with non-COVID-19 related sepsis. Clinicians caring for COVID-19 patients should consider this secondary diagnosis and subsequent appropriate treatments, especially in those requiring mechanical ventilation.

Background Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. Objectives The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. Methods A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. Results The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. Conclusion and Relevance Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Uncontrolled bleeding has been a relative contraindication for the use of venovenous extra corporeal membrane oxygenation (VV ECMO), but current practice is relatively institution dependent. With the recent advances in circuit technology and anticoagulation practices, the ability to manage patients with ongoing bleeding with ECMO support has increased. We report the case of a 66-year-old patient with refractory hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage (DAH) from underlying anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis who was successfully supported through his acute illness with VV ECMO. ECMO is often used to manage patients with refractory hypoxemic respiratory failure but the usage in the setting of DAH is less known given the risk of bleeding while receiving anticoagulation. Our patient was successfully managed without anticoagulation during his initial ECMO course and his respiratory failure rapidly improved after cannulation. Once managed through the acute phase of his illness and treatment started for his underlying disease process, anticoagulation was started. After being de-cannulated from ECMO and a 3 week stay in the acute rehabilitation unit, our patient was discharged home with complete recovery from his illness. We highlight that patients with refractory hypoxemic respiratory failure and suspicion of DAH as an etiology, ECMO without anticoagulation should be considered as supportive salvage therapy until the underlying process can be treated.

Infusions of stem cells are increasingly being offered for a variety of diseases, including chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and cystic fibrosis. However, the potential for harm, the lack of any proven benefit, and the high fees that many of these programs charge make recommending stem cell therapy untenable. At the time of this writing (April 2019) it appears that stem cell therapy can be safely performed, although the long-term side effects remain unknown. However, the little data available show no benefit in meaningful outcomes, such as mortality, morbidity or patient well-being, for stem cell treatment of chronic lung disorders. Patients with severe, incurable diseases may be motivated to seek innovative therapies. We encourage such patients to contact their primary care physician or pulmonologist. Clinical trials in the United States and Canada investigating stem cell therapy for lung diseases can be found on the website of the National Institutes of Health at Clinicaltrials.gov. The Arizona Thoracic Society encourages regulatory agencies to protect the public health and take appropriate action against non-investigational, for-profit stem cell clinics when appropriate.

No abstract available

Background: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO­VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology. Methods: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22–89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests. Results: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either. Conclusions: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO­VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.

We comment on the study by Hirano et al. about the effect of steroids in patients with acute respiratory distress syndrome. It might be necessary to include only the existing randomized control trials and to reassess the certainty of evidence about the primary outcomes.

Introduction Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19. Methods Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. Results Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p

Pregnant patients with severe acute respiratory syndrome coronavirus 2, the virus responsible for the clinical condition newly described in 2019 as coronavirus disease 2019 (COVID-19) and illness severity to warrant intensive care have a complex disease process that must involve multiple disciplines. Guidelines from various clinical societies, along with direction from local health authorities, must be considered when approaching the care of an obstetric patient with known or suspected COVID-19. With a rapidly changing landscape, a simplified and cohesive perspective using guidance from different clinical society recommendations regarding the critically-ill obstetric patient with COVID-19 is needed. In this article, we synthesize various high-level guidelines of clinical relevance in the management of pregnant patients with severe disease or critical illness due to COVID-19. KEY POINTS: · When caring for severely ill obstetric patients with COVID-19, one must be well versed in the complications that may need to be managed including, but not limited to adult respiratory distress syndrome with need for mechanical ventilation, approach to refractory hypoxemia, hemodynamic shock, and multiorgan system failure.. · Prone positioning can be done safely in gravid patients but requires key areas of support to avoid abdominal compression.. · For the critically ill obstetric patient with COVID-19, the focus should be on supportive care as a bridge to recovery rather than delivery as a solution to recovery..

Background In late 2019, the world saw a viral outbreak of unprecedented scale that sent a significant fraction of humankind into either quarantine or lockdown. Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which was first recognized in Wuhan, China, in December 2019. Methods We created and administered a 17-item questionnaire for health care professionals (HCPs) to assess their level of knowledge towards this ongoing and evolving pandemic. It was disseminated through Web- and mobile-based social networks. The questions were sourced and created from various standard national and international guidelines available at the time of writing. Results A total of 827 medical personnel participated in the study. Among them, 65.5% scored between 60% and 79%, indicating a moderate level of knowledge. There was no statistically significant difference in the scores of doctors, nursing officers and dental surgeons (p = 0.200). Participants had good knowledge regarding clinical symptoms, mode of transmission and preventive measures. But the study identified some gaps in knowledge in the implementation of management protocols, handling of dead bodies and biomedical waste management of COVID-19 cases. Conclusion With this understanding, regular training, drills and knowledge dissemination along with skill development through learning correct practices focusing on HCP at all levels are the current needs.

In January 2020, the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported in Europe. Multiple outbreaks have since then led to a global pandemic, as well as to massive medical, economic, and social repercussions. SARS-CoV-2 pneumonia can develop into acute respiratory distress syndrome (ARDS) when mechanical ventilation (MV) is needed (3, 4). ARDS produces abnormalities in gas exchange with a variable degree of shunt (5), high dead space ventilation (dead space volume [Vd]/tidal volume [Vt] ratio) (6), diminished pulmonary compliance (7), and alterations to the pulmonary circulation (8). The cornerstone of ARDS management is to provide adequate gas exchange without further lung injury as a result of MV. To date, information regarding the characteristics of SARS-CoV-2-induced ARDS is not completely known. However, this information is crucial to better apply MV and facilitate organ support strategies. We therefore present the characteristics of gas exchange, pulmonary mechanics, and ventilatory management of 50 patients with laboratory-confirmed SARS-CoV-2 infection, who developed ARDS and underwent invasive MV (IMV). Methods: Descriptive analysis included 50 consecutive patients with laboratory-confirmed SARS-CoV-2 infection who developed ARDS (9) and underwent IMV. These patients were admitted to the SARS-CoV-2-dedicated intensive care units (ICUs) at Hospital Clinic of Barcelona, Spain, between March 7 and March 25, 2020. Upon ICU admission, epidemiological characteristics, the severity of SARS-CoV-2 infection with the Acute Physiology and Chronic Health Evaluation II score, prognostic biomarkers of SARS-CoV-2 infection (described in Reference 4), time from hospital to ICU admission, time from ICU admission to intubation, oxygen therapy or noninvasive ventilation (NIV) use, and microbiology were investigated. On the day that criteria for ARDS diagnosis were met (9) and IMV was needed, the following assessments were performed: impairment in oxygenation was analyzed with the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, and abnormalities of CO2 metabolism were studied with the ventilatory ratio (VR), a surrogate parameter of Vd/Vt. In addition, adjunctive therapies and MV parameters related with ventilation-induced lung injury (VILI) described elsewhere (11-15) were investigated. Correlations of SARS-CoV-2 prognostic biomarkers (4), pulmonary mechanics, and gas-exchange data were performed. Twenty-eight-day and hospital mortality, ventilator- and ICU-free days at Day 28, hospital and ICU lengths of stay, and need for tracheostomy were also evaluated (16). Finally, a subanalysis assessing differences before and after prone positioning was performed. For additional detail on the method, see the online supplement. Results: By March 25th, 2020, 50 patients with laboratory-confirmed SARS-CoV-2 infection and ARDS had been admitted to our hospital. Table 1 shows the demographic and clinical characteristics of these patients. The median (interquartile range [IQR]) age was 66 (57-74) years. Thirty-six patients (72%) were men. Upon ARDS diagnosis, 44% of patients were initially classified as having moderate ARDS, whereas 24% were classified as having mild ARDS and 32% were classified as having severe ARDS. The outcomes of these patients are shown in Table 1. ICU and hospital lengths of stay were prolonged, and tracheostomy was performed in 30 (60%) patients. Hospital mortality was 34%.

Introduction: ECMO provides respiratory and circulatory support in critically ill patients. In our study, we report on a single center experience with ECMO and aim to identify the prognostic markers for survival to discharge from hospital. Methods: A registry was maintained on all patients who underwent ECMO implantation from September 2012 till January 2016 at a single institution. The collected data was analyzed to identify baseline characteristics, outcomes including clinical variables predictive of poor outcome. Results: A total of 29 patients underwent ECMO implantation. The average age of patients was 42 ± 18 years. 59% were males (N = 17). 19 cases had a cardiac indication for ECMO (66%) while 10 cases had a pulmonary indication (34%). On univariate analysis; presence of Multi-organ failure, SOFA score more than 18 and hemoglobin less than 10 g/dl at baseline and after ECMO removal were associated with increased 30 day mortality. Pearson correlation with 30 day mortality showed a positive correlation with MOF (+0.562, p = 0.002) and SOFA score >18 (+0.448, p = 0.015) and a negative correlation with anemia (−0.507, p = 0.005). 15 out of the total 29 patients (52%) died within 30 days of admission. Patients with MOF (log rank: 10.926, p = 0.001), SOFA score >18 (log rank: 7.758, p = 0.005) and hemoglobin

No abstract available. Article truncated after 150 words. The Berlin definition of ARDS is: bilateral radiographic opacities (not effusion, atelectasis or nodules) of

Background: Newly approved immunotherapeutic agents, like CTLA-4 inhibitors and antibodies against PD-1, are a promising therapeutic option in cancer therapy. Case presentation: A 74-year-old man, with a history of advanced stage melanoma and treatment with ipilimumab, pembrolizumab and nivolumab, was admitted to the hospital due to respiratory failure with hypoxemia and dyspnoea. He rapidly developed severe acute respiratory distress syndrome (ARDS), which required treatment in the intensive care unit which included mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Computed tomographic imaging (CT) showed signs of a pneumonitis, with an ARDS pattern related to the use of PD-1 antibodies. Treating the patient with high-dose immunosuppressive steroids led to an overall improvement. He was transferred to a rehabilitation hospital and subsequently to his home. Discussion and conclusion: This is a unique case report of a patient suffering a grade 4 adverse event under nivolumab who survived having been treated with ECMO. It highlights the possibility of associated adverse reactions as well as the use of ECMO in palliative care patients. ECMO can be of great success even in patients with malignancies, but careful decision making should be done on a case by case basis.

Background: In this study, we present our five-year experience with venovenous extracorporeal membrane oxygenation for the treatment of acute respiratory distress syndrome. Methods: Between November 2010 and November 2015, 33 patients (24 males, 9 females; mean age: 48.6 +/- 14.7 years; range 19 to 76 years) with acute respiratory distress syndrome refractory to conventional therapy were supported with venovenous extracorporeal membrane oxygenation. The general indication for venovenous extracorporeal membrane oxygenation support was refractory hypoxia, hypercapnia, and respiratory acidosis, despite the optimization of conventional therapy. Detailed clinical data of the patients were retrospectively analyzed. Results: Cannulation was achieved via femoral-femoral veins in 24 patients (73%) and jugular-femoral veins in nine patients (27%). The median duration of venovenous extracorporeal membrane oxygenation support was 17 (range, 1 to 52) days. The most common complication was minor bleeding in six patients (18%). Eighteen patients (54.5%) were successfully weaned from venovenous extracorporeal membrane oxygenation support. Of these patients, 13 (39.4%) survived and were discharged from the hospital. Conclusion: Venovenous extracorporeal membrane oxygenation can be a life-saving treatment modality in patients with severe acute respiratory distress syndrome. Improved results may be provided with increased experience and an established standard protocol for the management of venovenous extracorporeal membrane oxygenation. Amaç: Bu çalışmada, akut solunum sıkıntısı sendromunun tedavisinde venovenöz ekstrakorporeal membran oksijenasyonuna ilişkin beş yıllık deneyimimiz sunuldu. Çalışma planı: Kasım 2010 - Kasım 2015 tarihleri arasında konvansiyonel tedaviye dirençli akut solunum sıkıntısı sendromlu 33 hastaya (24 erkek, 9 kadın; ort. yaş 48.6±14.7 yıl; dağılım 19-76 yıl) venovenöz ekstrakorporeal membran oksijenasyonu desteği uygulandı. Venovenöz ekstrakorporeal membran oksijenasyonu desteğinin genel endikasyonu, konvansiyonel tedavinin optimizasyonuna rağmen, refrakter hipoksi, hiperkapni ve solunumsal asidoz idi. Hastaların detaylı klinik verileri retrospektif olarak incelendi. Bulgular: Kanülasyon 24 hastada (%73) femoral-femoral venlerden, dokuz hastada (%27) juguler-femoral venlerden gerçekleştirildi. Ortalama venovenöz ekstrakorporeal membran oksijenasyon desteği 17 (dağılım, 1-52) gün idi. En sık görülen komplikasyon, altı hastada (%18) minör kanama idi. On sekiz hasta (%54.5) başarılı bir şekilde venovenöz ekstrakorporeal membran oksijenasyonu desteğinden ayrıldı. Bu hastaların 13’ü (%39.4) sağkaldı ve hastaneden taburcu edildi. Sonuç: Venovenöz ekstrakorporeal membran oksijenasyonu, şiddetli akut solunum sıkıntısı sendromlu hastalarda hayat kurtarıcı bir tedavi yöntemi olabilir. Sonuçların iyileşmesi, deneyimlerin artması ve venovenöz ekstrakorporeal membran oksijenasyonunun tedavisine yönelik standart bir protokolün oluşturulması ile sağlanabilir.

Rationale: Damage control is a staged surgical approach to manage polytraumatized patients. The damage control approach comprises three steps. First, bleeding is controlled and fractures are stabilized temporarily; second, vital parameters are stabilized and the child is rewarmed in the intensive care unit; and third, the child is reoperated for definitive repair of injuries. We aimed to describe the feasibility of the damage control orthopedic approach in a child. Patient concerns: An 8-year-old girl fell from the balcony of the 5th floor onto concrete pavement and was admitted to our accident and emergency ward in a stable cardiorespiratory state, but with gross deformity of the lower limbs, left thigh, and forearm. Diagnoses: The child had sustained multiple injuries with severe bilateral lung contusion, pneumothorax, fracture of first rib, liver laceration, stable spine fractures, transforaminal fracture of sacrum, pelvic ring fracture, displaced baso-cervical femoral neck fracture, displaced bilateral multifragmental growth plate fractures of both tibiae, fractures of both fibulae, displaced fracture of left forearm, and displaced supracondylar fracture of the humerus. Intervention: In the initial operation, we performed closed reduction and K-wire fixation of the right tibia, closed reduction and external fixation of the left tibia, open reduction and screw osteosynthesis of the femoral neck fracture, closed reduction and K-wire fixation of the radius, and closed reduction of the supracondylar fracture. Subsequently, we transferred the girl to the pediatric intensive care unit for hemodynamic stabilization, respiratory therapy, rewarming, and treatment of crush syndrome. In a third step, 10 days after the injury, we managed the supracondylar fracture of the humerus by closed reduction and K-wire fixation. Outcomes: Growth arrest of the left distal tibial growth plate and osteonecrosis of the femoral head and neck, slipped capital femoris epiphysis (SCFE), and coxa vara of the right femur led to balanced leg length inequality 2 years after the injury. The lesion of the left sciatic nerve improved over time and the girl walked without walking aids and took part in school sports but avoided jumping exercises. Lessons: We emphasize the importance of damage control principles when managing polytraumatized children.

A novel coronavirus disease called COVID-19 was discovered as a result of the outbreak that began in China at the end of December 2019. Common symptoms are fever, dry cough, shortness of breath and malaise. Several research are being conducted since the disease has high transmission rate even though it is not considered life-threatening. However, together with hospital and out-of-hospital care, there is a group of medications being used to fight this disease, such as hydroxychloroquine, chloroquine, remdesivir, lopinavir/ritonavir, tocilizumab, interferon beta-1b, among others. Un nuevo coronavirus, denominado COVID-19, fue descubierto por el brote iniciado en China a finales de diciembre del año 2019. Los síntomas característicos son fiebre, tos seca, dificultad respiratoria y malestar general. Muchas investigaciones se están llevando a cabo ya que, si bien no es una enfermedad considerada mortal, tiene un índice de contagio muy alto. Sin embargo, junto a los cuidados hospitalarios y extrahospitalarios, existe un grupo de fármacos que se vienen utilizando para combatir esta enfermedad, tales como hidroxicloroquina, cloroquina, remdesivir, lopinavir/ritonavir, tocilizumab, interferón beta 1B, entre otros.

SUMMARY Last year, interest in prone positioning to treat acute respiratory distress syndrome (ARDS) resurfaced with the demonstration of a reduction in mortality by a large randomized clinical trial. Reports in the literature suggest that the incidence of adverse events is significantly reduced with a team trained and experienced in the process. The objective of this review is to revisit the current evidence in the literature, discuss and propose the construction of a protocol of care for these patients. A search was performed on the main electronic databases: Medline, Lilacs and Cochrane Library. Prone positioning is increasingly used in daily practice, with properly trained staff and a well established care protocol are essencial. RESUMO No último ano, o interesse pela posição prona no tratamento da síndrome da angústia respiratória aguda (Sara) ressurgiu com a demonstração da redução da mortalidade por um grande estudo clínico randomizado. Os relatos, na literatura, sugerem que a incidência de eventos adversos é significativamente reduzida com uma equipe treinada e experiente no processo. O objetivo desta revisão é revisitar as evidências atuais, discutir e propor a construção de um protocolo de cuidados para esses pacientes. Foi realizada busca nas principais bases eletrônicas: Medline, Lilacs e Cochrane Library. A posição prona é cada vez mais utilizada na prática diária, sendo imprescindível a presença de uma equipe adequadamente treinada e um protocolo de cuidados bem estabelecido.

Diffuse alveolar haemorrhage (DAH) is defined asbleeding into alveolar spaces, and it is caused by the disruption of thealveolar-capillary basement membrane. While various diseases are associatedwith the development of DAH, we describe a rare case of alveolar haemorrhageafter a full arterial revascularisation procedure via bilateral internal mammaryarteries., Difüz alveolar hemoraji (DAH) alveolar-kapillerbazal membranın bozulmasına bağlı olarak gelişen alveolar boşluğa kanama olaraktanımlanır. Çeşitli hastalıklar DAH’ın gelişimi ile ilişkiliyken, bilateralinternal mammarian arter ile tam arteryal revaskülarizasyon sonrası gelişennadir bir alveolar hemoraji olgusu tanımladık.

Purpose: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. Conclusions: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241). © 2018, The Author(s).

Background Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS. Methods This retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality. Results The causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079–1.565, p

Rationale: The application of prone positioning for acute respiratory distress syndrome (ARDS) has evolved, with recent trials focusing on patients with more severe ARDS, and applying prone ventilation for more prolonged periods. Objectives: This review evaluates the effect of prone positioning on 28-day mortality (primary outcome) compared with conventional mechanical ventilation in the supine position for adults with ARDS. Methods: We updated the literature search from a systematic review published in 2010, searching MEDLINE, EMBASE, and CENTRAL (through to August 2016). We included randomized, controlled trials (RCTs) comparing prone to supine positioning in mechanically ventilated adults with ARDS, and conducted sensitivity analyses to explore the effects of duration of prone ventilation, concurrent lung-protective ventilation and ARDS severity. Secondary outcomes included PaO2/FIO2 ratio on Day 4 and an evaluation of adverse events. Meta-analyses used random effects models. Methodologic quality of the RCTs was evaluated using the Cochrane risk of bias instrument, and methodologic quality of the overall body of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines. Results: Eight RCTs fulfilled entry criteria, and included 2,129 patients (1,093 [51%] proned). Meta-analysis revealed no difference in mortality (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.68–1.04), but subgroup analyses found lower mortality with 12 hours or greater duration prone (five trials; RR, 0.74; 95% CI, 0.56–0.99) and for patients with moderate to severe ARDS (five trials; RR, 0.74; 95% CI, 0.56–0.99). PaO2/FIO2 ratio on Day 4 for all patients was significantly higher in the prone positioning group (mean difference, 23.5; 95% CI, 12.4–34.5). Prone positioning was associated with higher rates of endotracheal tube obstruction and pressure sores. Risk of bias was low across the trials. Conclusions: Prone positioning is likely to reduce mortality among patients with severe ARDS when applied for at least 12 hours daily. Copyright © 2017 by the American Thoracic Society.

Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for similar to 45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

Background: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function. Interferon (IFN) beta-1a up-regulates the cell surface ecto-5'-nucleotidase cluster of differentiation 73 (CD73), which increases adenosine levels, and IFN beta-1 may, therefore, be a potential treatment for ARDS. In a phase I/II, open-label study in 37 patients with acute lung injury (ALI)/ARDS, recombinant human IFN beta-1a was well tolerated and mortality rates were significantly lower in treated than in control patients. Methods/design: In this phase III, double-blind, randomized, parallel-group trial, the efficacy and safety of recombinant human IFN beta-1a (FP-1201-lyo) will be compared with placebo in adult patients with ARDS. Patients will be randomly assigned to receive 10 μg FP-1201-lyo or placebo administered intravenously once daily for 6 days and will be monitored for 28 days or until discharged from the intensive care unit. Follow-up visits will then take place at days 90, 180 and 360. The primary endpoint is a composite endpoint including any cause of death at 28 days and days free of mechanical ventilation within 28 days among survivors. Secondary endpoints include: all-cause mortality at 28, 90, 180 and 360 days; organ failure-free days; length of hospital stay; pharmacodynamic assessment including measurement of myxovirus resistance protein A concentrations; and measures of quality of life, respiratory and neurological function at 180 and 360 days. The estimated sample size to demonstrate a reduction in the primary outcome between groups from 30% to 15% is 300 patients, and the study will be conducted in 70-80 centers in nine countries across Europe. Discussion: There are no effective specific treatments for patients with ARDS and mortality rates remain high. The results from this study will provide evidence regarding the efficacy of a potential new therapeutic agent, FP-1201-lyo, in improving the clinical course and outcome for patients with moderate/severe ARDS. Trial registration: European Union Clinical Trials Register, no: 2014-005260-15. Registered on 15 July 2017., SCOPUS: ar.j, info:eu-repo/semantics/published

No abstract available. Article truncated at 150 words. Mortality has been declining in the adult respiratory distress syndrome (ARDS) (1). However, the cause of the decline in mortality is unclear. The only intervention shown to improve survival has been low tidal volume ventilation but the mortality was improving before this intervention was widely used (2). Nevertheless, it was suggested that we look at system performance regarding ARDS management from a critical appraisal standpoint. This journal club was hoped to help as a starting point in that regard. Four potential beneficial interventions were discussed: 1. Conservative fluid management; 2. Optimal PEEP as determined by esophageal pressure; 3. Prone positioning; and 4. Mechanical ventilation driving pressure. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl ...

Introduction Non-cardiogenic pulmonary edema is the hallmark of the acute respiratory distress syndrome (ARDS). The amount of fluid and which fluid should be used in these patients is controversial. Methods 43 patients with ARDS treated in the intensive care unit (ICU) of the Second Hospital, Jilin University between November 1, 2011-November 1, 2012 were prospectively analyzed and was observational. Volume and the type of fluid administered were compared to 90 day mortality and the 24 and 72 hour sequential organ failure assessment (SOFA) score, lactate level, oxygenation index (PaO2/FiO2), duration of ICU stay, total ventilator days, and need for continuous renal replacement therapy (CRRT). Results Mortality was increased when hydroxylethyl starch (HES) was used in the first day or plasma substitutes were used during the first 3 days (P3000 ml during the first 24 hours or >8000 ml during the first 72 hours were associated with higher SOFA scores at 24 and 72 hours (P

Contains fulltext : 171220.pdf (Publisher’s version ) (Closed access) PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. METHODS: The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation. RESULTS: 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. CONCLUSIONS: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.

Made available in DSpace on 2022-04-29T08:44:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-05-01 Introduction: Many experimental models using lung lavage have been developed for the study of acute respiratory distress syndrome (ARDS). The original technique has been modified by many authors, resulting in difficulties with reproducibility. There is insufficient detail on the lung injury models used, including hemodynamic stability during animal preparation and drawbacks encountered such as mortality. The authors studied the effects of the pulmonary recruitment and the use of fixed tidal volume (Vt) or fixed inspiratory pressure in the experimental ARDS model installation. Methods: Adult rabbits were submitted to repeated lung lavages with 30ml/kg warm saline until the ARDS definition (PaO 2/FiO 2≤100) was reached. The animals were divided into three groups, according to the technique used for mechanical ventilation: 1) fixed Vt of 10ml/kg; 2) fixed inspiratory pressure (IP) with a tidal volume of 10ml/kg prior to the first lung lavage; and 3) fixed Vt of 10ml/kg with pulmonary recruitment before the first lavage. Results: The use of alveolar recruitment maneuvers, and the use of a fixed Vt or IP between the lung lavages did not change the number of lung lavages necessary to obtain the experimental model of ARDS or the hemodynamic stability of the animals during the procedure. A trend was observed toward an increased mortality rate with the recruitment maneuver and with the use of a fixed IP. Discussion: There were no differences between the three study groups, with no disadvantage in method of lung recruitment, either fixed tidal volume or fixed inspiratory pressure, regarding the number of lung lavages necessary to obtain the ARDS animal model. Furthermore, the three different procedures resulted in good hemodynamic stability of the animals, and low mortality rate. © 2012 Elsevier Inc. Albert Einstein Jewish Hospital Integrated College of Bauru State University Julio de Mesquita Filho University of São Paulo Medical School Department of Pediatrics Integrated College of Bauru State University Julio de Mesquita Filho

Objectives: To describe the epidemiologic characteristics, clinical features, and outcome of severe cases of 2009 H1N1 influenza A infections who were admitted to the intensive care units (ICUs) in Damascus, Syria. Materials and Methods: Retrospectively, we collected clinical data on all patients who were admitted to the ICU with confirmed or suspected diagnosis of severe 2009 H1N1 influenza A with respiratory failure at 4 major tertiary care hospitals in Damascus, Syria. Acute Physiology and Chronic Health Evaluation (APACHE) II system was used to assess the severity of illness within the first 24 h after admission. The outcome was overall hospital mortality. Results: Eighty patients were admitted to the ICU with severe 2009 H1N1 infection. The mean age was 40.7 years; 69.8% of patients had ≥1 of the risk factors: asthmatics 20%, obesity 23.8%, and pregnancy 5%; and 72.5% had acute lung injury or adult respiratory distress syndrome, 12.5% had viral pneumonia, 42.5% had secondary bacterial pneumonia, and 15% had exacerbation of airflow disease. Mechanical ventilation was required in 73.7% of cases. The mean hospital length of stay was 11.7 days (median 8 days, range 0-77 days, IQR: 5-14 days). The overall mortality rate was 51% for a mean APACHE II score of 15.2 with a predicted mortality of 21% (standardized mortality ratio of 2.4, 95% confidence interval: 1.7-3.2, P value < 0.001). Conclusion: Critically ill patients with severe 2009 H1N1 infection in this limited resource country had a much higher mortality rate than the predicted APACHE II mortality rate or when compared with the reported mortality rates for severe cases in other countries during 2009 H1N1 pandemic.

Severe pneumonia developed in young adults who had no identifiable risk factors., We describe the clinical characteristics and outcomes of adults hospitalized with pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a general hospital in San Luis Potosí, Mexico, from April 10 through May 11, 2009, suspected to have influenza virus–associated pneumonia were evaluated. We identified 50 patients with suspected influenza pneumonia; the presence of influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1 in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were positive. Eighteen patients were treated in the intensive care unit, and 10 died. During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young adults who had no identifiable risk factors; early diagnosis and treatment of influenza virus infections may have a determinant role in outcome.

Background Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS. Methods Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment. Results In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days ( P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs ( P = 0.38), the probability of being free from mechanical ventilation at day 28 ( P = 0.63), and days without ventilation assistance ( P = 0.73). Conclusion Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.

SummaryOxidative stress has a proven role in pathophysiology of acute respiratory distress syndrome. The antioxidant drugs, especially N-acetylcysteine (NAC) have been used for years to overcome oxidative stress effects in patients. In the present study we have investigated the effects of NAC treatment (IV NAC in 150mg/kg at the first day followed by 50mg/kg/day for three days) on 27 ICU patients with ALI/ARDS considering the glutathione-S-transferase genetic variations, as an important enzyme contributing in oxidative stress pathways. The results indicated that NAC improved oxygenation (increase in PaO2/FiO2) and decreased mortality rate in treated patients compared to control group (p

Resume Introduction Chez l’adulte immunocompetent, l’Epstein Barr (EBV) entraine une maladie autolimitee spontanement resolutive. Observation Un syndrome de detresse respiratoire aigu (SDRA) compliquant une pneumonie grave a EBV est rapporte avec le recours a une ventilation artificielle prolongee. Le diagnostic etait confirme par l’usage des serologies specifiques et la recherche de la charge d’ADN virale par PCR. A part la strategie protectrice de la ventilation mecanique, le traitement medical a compris l’utilisation de l’Acyclovir et les immunoglobulines polyclonales dans la phase precoce ainsi que des corticoides systemiques dans la phase tardive. La guerison etait progressive et complete. Conclusion La pneumonie a EBV compliquee d’un SDRA chez les immunocompetents existe. Sa prise en charge est un defi diagnostique et therapeutique.