Subtyping meconium protease activities which degrade lung protective angiotensin converting enzyme-2 in human lung cells

Purpose: Meconium pneumonitis occurs due to local lung injury and inflammation in newborn with meconium aspiration. The activation of Renin Angiotensin System (RAS) plays critical role in lung injury. Angiotensin converting enzyme-2 (ACE 2) functions as a negative regulator of the angiotensin system by converting pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. Our previous study has shown that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium. However, the specific proteases in meconium that degrade ACE-2 have not yet been identified. Objective: To begin characterizing ACE-2-degrading proteases in meconium through the use of different subtypes of protease inhibitors. Methods: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium and meconium + specific protease inhibitors (PIs). Specific PIs used included chymostatin, AEBSF(Pefobloc) and leupeptin. At the end of incubation, cell lysates were collected for ACE-2 immunoblotting and enzyme activity. Results: Reduction of ACE-2 immunoreactive 100-115 kDa bands or enzymatic activity by meconium was attenuated by treatment with chymostatin, but not with the other the PIs. These data suggest the involvement of cysteine-like proteases in meconium in ACE-2 degradation, and suggest a potential therapeutic strategy of PI administration to babies aspirating meconium.

Continuation of therapeutic anticoagulation before and during hospitalization is associated with reduced mortality in COVID-19 ICU patients

Background: Literature has well established COVID-19 associated coagulopathy with resulting thrombotic complications including microthrombi as an underlying mechanism leading to severe respiratory disease. Therapeutic anticoagulation (TAC) for COVID-19 patients has therefore been widely trialed to combat COVID-19’s coagulopathic effects. However, literature has yet to define which population of patients TAC benefits; the most current randomized controlled trials (RCTs) reveal TAC to be possibly beneficial to moderately-ill hospitalized COVID-19 patients, whereas benefits did not outweigh risks in critically-ill ICU patients. Importantly, these studies excluded patients who received prehospital TAC. We examined outcomes in critically ill COVID-19 ICU patients who received TAC vs prophylactic anticoagulation (PAC) and specifically whether prehospital TAC effected outcomes. Methods: Retrospective cohort study of 132 COVID-19 ICU patients admitted March-June, 2020. Initial clinical practice provided PAC, as literature demonstrating COVID-19 associated coagulopathy and increased thromboembolic complications emerged, a TAC protocol was initiated. Results: 130 patients were included in the study, 95 of whom received TAC and 35 PAC. There was 50.8% overall mortality, with lower mortality in the TAC vs PAC group (46.3% vs 62.9%, p=0.094). There were few thromboembolic and hemorrhagic complications, with no significant difference between TAC and PAC patients. Of 24 patients anticoagulated prior to and during hospitalization, only 1 (4.2%) died, whereas the mortality was 60.6% among patients therapeutically anticoagulated during hospitalization only (p<0.001). Multivariable analysis revealed patients who received prehospital and in hospital TAC had a 92% lower risk of death (p=0.008) compared to in hospital only TAC and PAC patients. Conclusions: Overall, therapeutic anticoagulation did not result in mortality benefit to COVID-19 ICU patients compared to prophylactic anticoagulation. However, a sub-population of patients who received TAC both prior to and during hospitalization had a 12-fold lower risk of death. This suggests a protective effect of TAC when it is continued before and during hospitalization. RCTs are needed to specifically examine this subset of COVID-19 patients.

Post Covid-19 organizing pneumonia: Case series for 6 patients with post-COVID interstitial lung disease

Organizing pneumonia secondary to viral infection is well established entity in the literature. Here we describe 6 cases of organizing pneumonia secondary to COVID-19. All six cases were presented with respiratory symptoms after their initial COVID-19 infection, and they had CT changes compatible with organizing pneumonia. Steroid treatment was initiated in all cases empirically without the need for trans-bronchial biopsy. All presented cases showed significant improvement with steroid clinically and radiographically.

Huge mediastinal bronchogenic cyst revealed by hemoptysis and resected by uniportal VATS: A case report

Bronchogenic cysts are rare unusual congenital cysts, resulting from abnormal budding of the primary tracheobronchial tube and can be located either in the mediastinum or in the pulmonary parenchyma. They remain asymptomatic in most adults unless they are large to compress adjacent structures or infected. We report a case of a 43-year-old woman, who presented recurrent episodes of hemoptysis low abundance 4 months ago revealing a huge mediastinal cystic formation, initially taken as a hydatid cyst, the chest CT showed a voluminous cystic formation of 11,4x10, 9x8, 8 cm exerting a mass effect on the posterior mediastinal structures: the superior vena cava, the azygos vein, and the trachea. The diagnosis as a bronchogenic cyst is done after resected by uniportal video-assisted surgery (VATS), and histological confirmation. The patient does not present any complications or reoffending during the follow-up. The rarity of this entity and even more a rare association of this lesion with symptoms of hemoptysis led to the report of this case. This case illustrates the interest of uniportal VATS for the extirpation of the bronchogenic cyst. We recommend a complete exeresis in most cases to confirm the diagnosis, relieve symptoms, and prevent complications.

The role of airway remodeling in the pathogenesis and treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is currently considered the third leading cause of death in the world. COPD represents an important public health challenge and a socio-economical problem that is preventable and treatable. The main cause of COPD is chronic inhalation of cigarette smoke, and other harmful constituents of air pollution, which cause epithelial injury, chronic inflammation and airway remodeling. Airway remodeling is most prominent in small airways. It is due to infiltration of the airways by inflammatory cells, such as neutrophils, eosinophils, macrophages, and immune cells, including CD8+ T-cells, Th1, Th17 lymphocytes, and innate lymphoid cells group 3. Fibroblasts, myofibroblasts, and airway smooth muscle (ASM) cells also contribute to airway remodeling by depositing extracellular matrix (ECM) proteins, which increase the thickness of the airway wall. Activated inflammatory cells, and structural cells secrete cytokines, chemokines, growth factors, and enzymes which propagate airway remodeling. Airway remodeling is an active process which leads to thickness of the reticular basement membrane, subepithelial fibrosis, peribronchiolar fibrosis, and ASM cells hyperplasia and hypertrophy. It is also accompanied by submucosal glands and goblet cells hypertrophy and mucus hypersecretion, and angiogenesis. Epithelial mesenchymal transmission (EMT) plays a key role in airway remodeling. In patients with COPD and smokers, cellular reprograming in epithelial cells leads to EMT, whereby epithelial cells assume a mesencymal phenotype. Additionally, COPD is associated with increased parasympathetic cholinergic activity, which leads to ASM cells hypercontractility, increased mucus secretion, and vasodilatation. Treatment of COPD is intricate because of the heterogeneous nature of the disease, which requires specific treatment of the pathophysiological pathways, such as airway inflammation, ASM cell hypercontractility, and parasympathetic cholinergic hyperreactivity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy report recommends personalized approach for the treatment of COPD. However, some patients with COPD are unresponsive to the standards of care. They may require a triple combination of LABA/LAMA/ICS. Single-inhaler triple therapy (SITT), such as fluticasone fuorate/vilanterol/umeclidinium has been shown to significantly improve symptoms and asthma control, reduce moderate and severe exacerbations, and to improve lung function.

Pulmonary sarcomatoid carcinoma - pathohistological and immunohistochemical analysis, prognosis and complex treatment

The pulmonary sarcomatoid carcinoma (PSC) is extremely rarely lung neoplasm. A woman at the age of 55 with a local advanced pulmonary sarcomatoid carcinoma of the right lung and CT data on bilateral adrenal metastases and three brain metastases were established. Diagnosis is placed after bronchoscopy with biopsy and detailed pathochistological and immunohistochemical analysis. PSC is extremely malignant and with high risk of distant haematogenic metastases. This rare clinical case support the need for strict pathohistological and immunohistochemical analysis, a difficult pathohistological differential diagnosis with other primary malignant lung tumors and the assessment of complex treatment. In order to improve the healing results and survival of patients, timely diagnosis is required at early stage with surgical treatment and subsequent adjuvant chemotherapy and targetеd therapy after genetic analysis of surgery or biopsy tissue material.

SARS-CoV-2 infection in a patient with destination left ventricular assist device

Recipients of LVAD for destination therapy may represent a challenge in the treatment of COVID-19. We present a case of a 58 year-old male with LVAD support complicated with SARS-CoV-2 who declines for hospital admission despite interstitial pneumonia and lower O2 saturation. The patient recieved ambulatory support and treatment with anticoagulation, supplementary O2, steroids, antibiotics, ivermectin with succesful evolution and recovery.

Saddle pulmonary embolism on non-contrast CT

Background: A saddle pulmonary embolism (PE) is a large embolism that straddles the bifurcation of the pulmonary trunk. This PE extends into the right and left pulmonary arteries. There is a greater incidence in males. Common features of a PE include dyspnea, tachypnea, cough, hemoptysis, pleuritic chest pain, tachycardia, hypotension, jugular venous distension, and severe cases Kussmaul sign. The Wells criteria for PE is used as the pretest probability. Diagnostics include D-dimer levels, CT pulmonary angiography (CTPA), ventilation/perfusion scintigraphy (V/Q scan), echocardiography, lower extremity venous ultrasound, chest x-ray, pulmonary angiography, and electrocardiography (ECG). Case description: We present a 65-year-old male that presented with a two-week history of dyspnea with non-radiating intermittent chest pressure. Initial V/Q scan showed a low probability for PE, but a subsequent non-contrast CT revealed that he indeed had a saddle PE.