Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS2 index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS2 score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. Conclusion The 2 existing classification schemes and especially a new stroke risk index, CHADS2, can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation☆

Idarucizumab for dabigatran reversal

Interpretation of Pathological Perspective——International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26826

Role of Toll-like receptors in the pathogenesis of COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.

/pdf/harnessing-the-immune-system-to-overcome-cytokine-storm-and-3f26df8wr1.pdf

Harnessing the Immune System to Overcome Cytokine Storm and Reduce Viral Load in COVID-19: A Review of the Phases of Illness and Therapeutic Agents

Chest CT Signs in Pulmonary Disease: A Pictorial Review.

Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) By blocking these receptors and signals, the immune system can be reactivated to fight the tumor Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy PD-1 inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are currently approved by regulatory authorities for the treatment of advanced NSCLC This article provides a detailed review of these newer agents, their mechanism of action, side-effect profile, therapeutic indications and current evidence supporting their use in the management of NSCLC

/pdf/review-of-checkpoint-immunotherapy-for-the-management-of-non-57ivkbqvom.pdf

Review of checkpoint immunotherapy for the management of non-small cell lung cancer

Bleeding is one of the most feared complications of flexible bronchoscopy. Although infrequent, it can be catastrophic and result in fatal outcomes. Compared to other endoscopic procedures, the risk of morbidity and mortality from the bleeding is increased, as even a small amount of blood can fill the tracheobronchial tree and lead to respiratory failure. Patients using antithrombotic agents (ATAs) have higher bleeding risk. A thorough understanding of the different ATAs is critical to manage patients during the peri-procedural period. A decision to stop an ATA before bronchoscopy should take into account a variety of factors, including indication for its use and the type of procedure. This article serves as a detailed review on the different ATAs, their pharmacokinetics and the pre- and post-bronchoscopy management of patients receiving these medications.

https://err.ersjournals.com/content/errev/26/145/170001.full.pdf

Management of antithrombotic agents in patients undergoing flexible bronchoscopy.

Background: Critical shortages of personal protective equipment, especially N95 respirators, during the coronavirus disease 2019 (COVID-19) pandemic continues to be a source of concern. Novel methods of N95 filtering face-piece respirator decontamination that can be scaled-up for in-hospital use can help address this concern and keep healthcare workers (HCWs) safe. Methods:
 A multidisciplinary pragmatic study was conducted to evaluate the use of an ultrasonic room high-level disinfection system (HLDS) that generates aerosolized peracetic acid (PAA) and hydrogen peroxide for decontamination of large numbers of N95 respirators. A cycle duration that consistently achieved disinfection of N95 respirators (defined as ≥6 log10 reductions in bacteriophage MS2 and Geobacillus stearothermophilus spores inoculated onto respirators) was identified. The treated masks were assessed for changes to their hydrophobicity, material structure, strap elasticity, and filtration efficiency. PAA and hydrogen peroxide off-gassing from treated masks were also assessed. Results:
 The PAA room HLDS was effective for disinfection of bacteriophage MS2 and G. stearothermophilus spores on respirators in a 2,447 cubic-foot (69.6 cubic-meter) room with an aerosol deployment time of 16 minutes and a dwell time of 32 minutes. The total cycle time was 1 hour and 16 minutes. After 5 treatment cycles, no adverse effects were detected on filtration efficiency, structural integrity, or strap elasticity. There was no detectable off-gassing of PAA and hydrogen peroxide from the treated masks at 20 and 60 minutes after the disinfection cycle, respectively. Conclusion:
 The PAA room disinfection system provides a rapidly scalable solution for in-hospital decontamination of large numbers of N95 respirators during the COVID-19 pandemic.

/pdf/scalable-in-hospital-decontamination-of-n95-filtering-face-1jblnvjm2q.pdf

Shine Raju

Papers

Harnessing the Immune System to Overcome Cytokine Storm and Reduce Viral Load in COVID-19: A Review of the Phases of Illness and Therapeutic Agents

Chest CT Signs in Pulmonary Disease: A Pictorial Review.

Review of checkpoint immunotherapy for the management of non-small cell lung cancer

Management of antithrombotic agents in patients undergoing flexible bronchoscopy.

Scalable in-hospital decontamination of N95 filtering face-piece respirator with a peracetic acid room disinfection system.