Coronavirus disease 2019-induced hypercoagulability and its clinical implications

Coronavirus disease 2019 is the disease produced by severe acute respiratory syndrome-coronavirus-2, which is introduced into the host’s cell thanks to the angiotensin-converting enzyme 2 receptor. Once there, it uses the cell’s machinery to multiply itself. In this process, it generates an immune response that stimulates the lymphocytes to produce cytokines and reactive oxygen species that begin to deteriorate the endothelial cell. Complement activation, through the complement attack complex and C5a, contributes to this endothelial damage. The different mediators further promote the expression of adhesion molecules on the endothelial surface, which encourages all blood cells to adhere to the endothelial surface to form small conglomerates, called clots, which obstruct the lumen of the small blood vessels. Furthermore, the mediators of clot lysis are inhibited. All this promotes a prothrombotic environment within the pulmonary capillaries that is reflected in the elevation of D-dimer. The only solution for this cascade of events seems to be the implementation of an effective anticoagulation protocol that early counteracts the changes induced by thrombi in the pulmonary circulation and reflected in the functioning of the right ventricle.

miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

Oxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

MECHANISMS OF THE THERAPEUTIC EFFECT OF HYPERBARIC OXYGEN ON THE GAS EXCHANGE FUNCTION OF THE LUNGS IN SARS-CO-2-ASSOCIATED PNEUMONIA

The article discusses some mechanisms of the therapeutic effect of hyperbaric oxygenation in COVID-19: the effect of hyperbaric oxygen on the contractility of endotheliocytes of pulmonary capillaries, thrombogenic and arthrombogenic potential of pulmonary vessels.

Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia

Pulmonary innate immunity is required for host defense; however, excessive neutrophil inflammation can cause life-threatening acute lung injury. B lymphocytes can be regulatory, yet little is known about peripheral transitional IgM+ B cells in terms of regulatory properties. Using single-cell RNA sequencing, we discovered eight IgM+ B cell subsets with unique gene regulatory networks in the lung circulation dominated by transitional type 1 B and type 2 B (T2B) cells. Lung intravital confocal microscopy revealed that T2B cells marginate in the pulmonary capillaries via CD49e and require CXCL13 and CXCR5. During lung inflammation, marginated T2B cells dampened excessive neutrophil vascular inflammation via the specialized proresolving molecule lipoxin A4 (LXA4). Exogenous CXCL13 dampened excessive neutrophilic inflammation by increasing marginated B cells, and LXA4 recapitulated neutrophil regulation in B cell–deficient mice during inflammation and fungal pneumonia. Thus, the lung microvasculature is enriched in multiple IgM+ B cell subsets with marginating capillary T2B cells that dampen neutrophil responses.

Diagnosis and endovascular management of pulmonary arteriovenous malformations

Pulmonary arteriovenous malformations (PAVM) are abnormal communication of a branch of the pulmonary artery and pulmonary vein circumventing the intervening pulmonary capillaries. This results in a right-to-left (R-L) shunt and its related manifestations, which include hampered gas exchange leading to hypoxaemia, dyspnoea, paradoxical emboli leading to stroke, cerebral abscess, myocardial infarction and pulmonary haemorrhage due to rupture of the PAVM. Endovascular transcatheter embolization of the feeding vessels with coils or occlusion devices is the current standard care of treatment and preferred treatment modality. The articles aim to provide insights into the current trends in diagnosis, the current recommendations, approach and management options for patients with PAVM.

SARS-CoV-2 Infection in Hereditary Hemorrhagic Telangiectasia Patients Suggests Less Clinical Impact Than in the General Population

At the moment of writing this communication, the health crisis derived from the COVID-19 pandemic has affected more than 120 million cases, with 40 million corresponding to Europe. In total, the number of deaths is almost 3 million, but continuously rising. Although COVID-19 is primarily a respiratory disease, SARS-CoV-2 infects also endothelial cells in the pulmonary capillaries. This affects the integrity of the endothelium and increases vascular permeability. In addition, there are serious indirect consequences, like disruption of endothelial cells’ junctions leading to micro-bleeds and uncontrolled blood clotting. The impact of COVID-19 in people with rare chronic cardiovascular diseases is unknown so far, and interesting to assess, because the virus may cause additional complications in these patients. The aim of the present work was to study the COVID-19 infection among the patients with Hereditary Hemorrhagic Telangiectasia (HHT). A retrospective study was carried out in a 138 HHT patients’ sample attending an Ear Nose and Throat (ENT) reference consult. The evaluation of the COVID-19 infection in them reveals milder symptoms; among the 25 HHT patients who were infected, only 3 cases were hospitalized, and none of them required ICU or ventilation assistance. The results are discussed in the light of macrophage immune response.

Severe covid-19 pneumonia: pathogenesis and clinical management

Severe covid-19 pneumonia has posed critical challenges for the research and medical communities. Older age, male sex, and comorbidities increase the risk for severe disease. For people hospitalized with covid-19, 15-30% will go on to develop covid-19 associated acute respiratory distress syndrome (CARDS). Autopsy studies of patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries. When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to avoid intubation, and does not increase risk for disease transmission. During invasive mechanical ventilation, low tidal volume ventilation and positive end expiratory pressure (PEEP) titration to optimize oxygenation are recommended. Dexamethasone treatment improves mortality for the treatment of severe and critical covid-19, while remdesivir may have modest benefit in time to recovery in patients with severe disease but shows no statistically significant benefit in mortality or other clinical outcomes. Covid-19 survivors, especially patients with ARDS, are at high risk for long term physical and mental impairments, and an interdisciplinary approach is essential for critical illness recovery.

Pulmonary arteriovenous malformation managed by VATS lobectomy

Introduction: Pulmonary arteriovenous malformation (PAVM) is formed by abnormal connections between pulmonary arteries and veins that bypass the pulmonary capillaries and transport deoxygenated blood through pulmonary veins to the left heart. This causes insufficient oxygenation of blood in the lungs. This condition remains symptomless for a long period of time. The most common symptoms include shortness of breath on exertion, nosebleeds, increased fatigue and a gradual development of cyanosis. Paradoxical embolism in the brain is a serious complication; it can present with a stroke or a brain abscess. Treatment of the disease consists of embolization of the pathological vascular connections, surgical resection of the affected pulmonary parenchyma and management of concomitant manifestations of the disease. PAVM in most common cases arises as a result of an autosomal dominant hereditary disorder referred to as hereditary hemorrhagic telangiectasia. Case report: In our communication, we document the diagnostic and therapeutic management in a young patient diagnosed with PAVM after falling off his bicycle. Based on comprehensive assessments, AV malformations with a 40% shunt of the pulmonary circulation were detected. An angiographic procedure was not an appropriate option considering the type and extent of the condition. Therefore, video-assisted thoracic resection of the affected pulmonary lobe was indicated. Conclusion: PAVM is a rare finding. PAVM should be ruled out in all patients with hereditary hemorrhagic telangiectasia (HHT) signs in the oral cavity. Contrast sonography of the heart and contract CT of the chest are the methods of choice for the diagnosis. Conservative or pharmacological treatment fails to improve the patient’s status. The condition is usually managed by embolization. Cases where PAVM is rather extensive or diffuse, where endovascular management would be inappropriate, can be well managed using endoscopic resection adequate to the extent of the condition.

A Novel Mathematical Equation for a Noninvasive Determination of the Number of Alveoli of the Human Lung

Background: There had always been a spirited effort in understanding the transport of air or molecular oxygen plus other gases from alveolar air space into the pulmonary capillaries and from the latter back into the former using mathematical models; the determination of the number of alveoli using cadaver and invasive and partially noninvasive methods have been made. There is a need for a noninvasive method of mathematical nature, with evaluative, diagnostic, and prognostic application. Objectives: The objectives of this research were to derive a mathematical equation for the noninvasive determination of the number of alveoli during rest and physical activity and elucidate the usefulness and advantage of the model over known methods. Methods: Theoretical and computational (calculational) methods; data in the literature were substituted into the model mathematical equation for the computation of the number of alveoli in the human lungs. Results and Discussion: The computed number (Nalv) of alveoli differed from one country or subcontinental region to another. The Nalv for the male were expectedly larger than for the female subjects. Conclusion: The mathematical equation for totally noninvasive determination by computation is derivable and was derived. The total number (Nalv) of alveoli mobilised for function is a function of the width (d) of the nares (d 22/15), rate (Rv) of gas flow , and radius (ralv) of a functional alveolus . The equation has the potential to be of diagnostic, evaluative and prognostic value in medical practice. This new computational approach could be faster than other known approaches for the determination of the Nalv. A noninvasive approach by computation, relying on other noninvasively determined respiratory parameters, can eliminate the possibility of tissue damage.

The vascular nature of COVID-19

A potential link between mortality, D-dimer values and a prothrombotic syndrome has been reported in COVID-19 patients. The National Institute for Public Health of the Netherlands published a report for guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19 with a new vascular disease concept. The analysis of all available current medical, laboratory and imaging data on COVID-19 confirms that symptoms and diagnostic tests can not be explained by impaired pulmonary ventilation. Further imaging and pathological investigations confirm that the COVID-19 syndrome is explained by perfusion disturbances first in the lung, but consecutively in all organs of the body. Damage of the microvasculature by SARS 1 and SARS 2 (COVID-19) viruses causes microthrombotic changes in the pulmonary capillaries and organs leading to macrothrombosis and emboli. Therefore anticoagulant profylaxis, close lab and CT imaging monitoring and early anticoagulant therapy are indicated.