Pulmonary Pathology Research Articles

Enormous Pulmonary Arteries and a Late Diagnosis of a Common Congenital Cardiac Issue: A Case Report

Background: Noonan’s syndrome is the second most common congenital cardiac syndrome after Down syndrome. Classically it is associated with pulmonary stenosis, Hypertrophic Cardiomyopathy (HCM), and Atrial Septal Defects (ASD). Late presentations, milder phenotypes and atypical presentations can occur in adult life and have cardiovascular implications. Case Summary: A 62-year-old presented to the emergency department with chest pain and atrial fibrillation with fast ventricular rate and RBBB morphology. A transthoracic echocardiogram demonstrated a massive Pulmonary Artery (PA), concerning for pulmonary hypertension and an atrial septal defect (ASD). Right heart catheterization indicated enormous coronary artery ectasia but normal PA pressures and wedge pressures. He was identified as a late presentation of Noonan’s syndrome on subsequent genetic testing. Discussion: Some series indicate a prevalence of 1 in 100 for mild Noonan’s syndrome phenotypes, highlighting the importance of understanding its cardiac presentations. In this case, we present a man with minimal symptoms but gross pathologies of his pulmonary and coronary arteries. Furthermore, pulmonary artery dilatation without pulmonary valve pathology has not been reported in the literature, and only a few reports of coronary artery ectasia are reported.

Classifier for the functional state of the respiratory system via descriptors determined by using multimodal technology

Currently, intelligent systems built on a multimodal basis are used to study the functional state of living objects. Its essence lies in the fact that a decision is made through several independent information channels with the subsequent aggregation of these decisions. The method of forming descriptors for classifiers of the functional state of the respiratory system includes the study of the spectral range of the respiratory rhythm and the construction of the wavelet plane of the monitoring electrocardiosignal overlapping this range. Then, variations in the breathing rhythm are determined along the corresponding lines of the wavelet plane. Its analysis makes it possible to select slow waves corresponding to the breathing rhythm and systemic waves of the second order. Analysis of the spectral characteristics of these waves makes it possible to form a space of informative features for classifiers of the functional state of the respiratory system. To construct classifiers of the functional state of the respiratory system, hierarchical classifiers were used. As an example, we took a group of patients with pneumonia with a well-defined diagnosis (radiography, X-ray tomography, laboratory data) and a group of volunteers without pulmonary pathology. The diagnostic sensitivity of the obtained classifier was 76% specificity with a diagnostic specificity of 82%, which is comparable to the results of X-ray studies. It is shown that the corresponding lines of the wavelet planes are correlated with the respiratory system and, using their Fourier analysis, descriptors can be obtained for training neural network classifiers of the functional state of the respiratory system.

Impact and characteristics of hospital-acquired influenza over 10 seasons in a third-level university hospital

ObjectivesTo analyze the characteristics of patients with nosocomial flu, to compare them with patients with community-acquired influenza to study possible differences and to identify possible risk factors associated with this type of flu. Patients and methodsObservational, cross-sectional and retrospective study of hospitalized patients with a microbiological confirmation of influenza in a third-level university hospital over 10 seasons, from 2009 to 2019. Nosocomial influenza was defined as that infection whose symptoms began 72h after hospital admission, and its incidence, characteristics and consequences were further analyzed. ResultsA total of 1260 hospitalized patients with a microbiological diagnosis of influenza were included, which 110 (8.7%) were nosocomial. Patients with hospital-acquired influenza were younger (71.74±16.03 years, P=0.044), had a longer hospital stay (24.25±20.25 days, P<0.001), had more frequently a history of chronic pulmonary pathologies (P=0.010), immunodeficiency (P<0.001), and were associated with greater development of bacterial superinfection (P<0.001), respiratory distress (P=0.003), and admission to the intensive care unit (ICU) (P<0.001). In the multivariate logistic regression analysis, the following characteristics were identified as independent risk factors: immunodeficiency (ORa=2.33; 95% CI: 1.47–3.60); ICU admission (ORa=4.29; 95% CI: 2.23–10.91); bacterial superinfection (ORa=1.64; 95% CI: 1.06–2.53) and respiratory distress (ORa=3.88; 95% CI: 1.23–12.23). ConclusionsNosocomial influenza is more common in patients with a history of immunodeficiency. In addition, patients with hospital-acquired influenza had an increased risk of bacterial superinfection, admission to the ICU, and development of respiratory distress.

Hypoxic Gas Therapy in Neonatology: Considerations in Practice.

Adequate oxygenation is essential for sick newborns. Each disease determines the target of oxygenation. Nevertheless, hyperoxia and hypoxia are related to adverse outcomes. Most studies related to this aspect have been conducted in preterm infants or term babies with pulmonary pathology. Congenital heart diseases may also require careful oxygenation control and management of oxygen supply. Presurgical stabilization of complex heart diseases (CHD) may be difficult, especially after the physiological decrease of pulmonary resistance, which generates pulmonary edema (due to overcirculation) and systemic hypoperfusion. Several strategies have been described to avoid this phenomenon, such as prostaglandin, vasodilators, inotropes, positive airway pressure, and even hypoxic mixture (inspired fraction of oxygen (FiO2) below 21%). The latter therapy is mainly used in single ventricular physiology heart diseases, such as the hypoplasic left heart syndrome (HLHS) or systemic ductus-dependent flow CHD (interruption of the aortic arch and coarctation of the aorta). Alveolar oxygen affects pulmonary vascular resistance modifying lung flow. This modification could help the stabilization during the presurgical period of complex CDH. Many centers use hypoxic therapy to avoid hypotension, metabolic acidosis, coronarycerebral ischemia, and liver, renal and intestinal injury. Despite the theoretical benefits, there are doubts about how tissue oxygen supply would change during hypoxic gas ventilation. It is worrisome that FiO2 < 21% causes a decrease in brain oxygenation, adding neurological injury as a complication to the already established disease of CHD and other not modifiable factors. Brain monitoring through near-infrared spectroscopy (NIRS) during hypoxic gas therapy is mandatory. Recent studies have shown that hypoxic gas ventilation therapy in patients with HLHS in the preoperative period decreases the ratio between systemic and pulmonary circulation (Qp/Qs) but does not improve regional oxygenation delivery. The use of hypoxic gas ventilation therapy continues to be controversial. It could be an option in some complex CHD, mainly HLHS.

337.6: Ultrasound Scanning in Lung Procurement. Protocol For Decision-Making With the Purpose of Increasing Transplant Eligible Lungs

Introduction: Despite having a similar population, Latin America performs 11x less lung transplant procedure than Europe. Improving brain death diagnosis and converting potential donors into real donors is key to improve these numbers. Ultrasonography (US) is common practice in Intensive Care Units. Available literature on its use in the management of brain death donors and lung procurement is extremely scarce. The selection and rejection of lungs for transplantation is usually done with chest X-rays, however US has shown better sensitivity and specificity for the diagnosis of pulmonary pathologies. Lung US allows to identify the reversible causes low PaO2/FiO2 ratio (PaFi), thus allowing to establish specific interventions which, if proved successful, could turn lungs into transplant-eligible lungs. Methods: Introducing a simple Protocol aiming at identifying and treating the main reversible causes of a low PaFi. Respiratory causes of a low PaFi ratio can be either parenchymal or pleural. Parenchymal causes: Pulmonary edema (either neurogenic or cardiogenic) determines the visualization of bilateral and symmetrical B lines. Fluid restriction prioritizing inotropic drugs to revert hypotension and usage of hypertonic solutions can reduce edema. Atelectasis, contusion and pneumonia can appear as patterns for unilateral B lines and/or consolidations. The presence of a static or dynamic air bronchogram can differentiate them. In atelectasis, fiberoptic bronchoscopy can revert the situation. In all other cases, a single lung transplant can be considered, which is a valid option in aged recipients when donors are scarce. Pneumothorax and pleural effusion are both pleural causes of a low PaFi. They can be easily diagnosed through an ultrasound scan, not there being a reason for rejection. Its resolution can turn these lungs into transplant eligible lungs. The pneumothorax —frequently anterior in ventilated patients in dorsal decubitus— may be overlooked in the chest x-ray. Diagnosis is made by the absence of pleural sliding and presence of a lung pint. Pleural effusion is anechoic, present quad sign and the sinusoid sign. The acquisition of skills to diagnose all these conditions does not require much reading and has a fast-learning curve (25 cases monitored). Results: This Protocol is currently used for donor decision-making and will be implemented prospectively by the lung transplant team to assess its ability to increase the number of lungs suitable for transplantation. Conclusions: US is a useful technique to identify reversible and treatable causes of a low PaFi, helping decision-making to increase the number of transplant eligible lungs.

Pulmonary Histopathology in Cats and Dogs with Fatal Tick Paralysis

The objective of this study was to evaluate critically the nature and prevalence of histological pulmonary lesions in dogs and cats that had died or were euthanized because of tick paralysis. A retrospective and prospective case study of 11 cats and 23 dogs was carried out. Retrospective cases were gathered from the Veterinary Laboratory Services database at The University of Queensland (UQ). Prospective cases were provided by Veterinary Specialist Services and UQ VETs Small Animal Hospital. Lung and other tissue samples were collected for histopathological analysis. All tick intoxicated animals demonstrated evidence of pulmonary parenchymal changes: alveolar oedema, interstitial and alveolar congestion and alveolar fibrin exudation. Eleven of 23 (48%) dogs exhibited mild to severe bronchopneumonia. A lower rate (18%) of bronchopneumonia was found in cats, with one case of aspiration pneumonia. A novel pulmonary histological grading scheme was developed to evaluate the correlation between clinical presentation and histopathological changes. Novel extrapulmonary lesions in cats included hepatic necrosis and acute renal tubular necrosis attributed to hypoxia. We concluded that both dogs and cats with high clinical grade tick paralysis are extremely likely to have pulmonary pathology. High-protein oedema and fibrin exudation are predicted to be present in most cases of canine and feline tick paralysis.

A Case of Secondary Spontaneous Pneumothorax in a Patient with Interstitial Lung Disease

Secondary Spontaneous Pneumothorax occurs in people with wide variety of parenchymal lung disease. These individuals have underlying pulmonary pathology that alters normal lung structure. Patients presenting with acute respiratory distress with underlying lung pathology should always be evaluated radiologically for any complications such as secondary spontaneous pneumothorax and managed accordingly. My case report of secondary spontaneous pneumothorax in a female patient with interstitial lung disease illustrates the importance of computed tomography (CT scan of Chest), insertion of intercostal drain tube and course of antibiotics for infection control and prevention. Keywords: Secondary spontaneous pneumothorax, Interstitial lung disease, Intercostal drainage tube

Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.

T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.

Modulation of TDM-induced granuloma pathology by human lactoferrin: a persistent effect in mice.

Lactoferrin (LTF), an iron binding protein, is known to exhibit immune modulatory effects on pulmonary pathology during insult-induced models of primary Mycobacterium tuberculosis (Mtb) infection. The effects of LTF correlate with modulation of the immune related development of the pathology, and altering of the histological nature of the physically compact and dense lung granuloma in mice. Specifically, a recombinant human version of LTF limits immediate progression of granulomatous severity following administration of the Mtb cell wall mycolic acid, trehalose 6,6'-dimycolate (TDM), in part through reduced pro-inflammatory responses known to control these events. This current study investigates a limited course of LTF to modulate not only initiation, but also maintenance and resolution of pathology post development of the granulomatous response in mice. Comparison is made to a fusion of LTF with the Fc domain of IgG2 (FcLTF), which is known to extend LTF half-life in circulation. TDM induced granulomas were examined at extended times post insult (day 7 and 14). Both LTF and the novel FcLTF exerted sustained effects on lung granuloma pathology. Reduction of pulmonary pro-inflammatory cytokines TNF-α and IL-1β occurred, correlating with reduced pathology. Increase in IL-6, known to regulate granuloma maintenance, was also seen with the LTFs. The FcLTF demonstrated greater impact than the recombinant LTF, and was superior in limiting damage to pulmonary tissues while limiting residual inflammatory cytokine production.

A Case of Invasive Pulmonary Aspergillosis vs. Pulmonary Aspergilloma in Immunocompromised Patient With Preexisting Lung Cavity

Subacute invasive aspergillosis (SAIA) occurs in immunocompromised patients and/or patients with preexisting pulmonary pathology. An aspergilloma is a fungus ball that occurs in preexisting lung cavities and can be relatively asymptomatic without tissue invasion. In contrast to an aspergilloma, SAIA invades local tissue and parenchyma, resulting in tissue necrosis. We present a case of a 68-year-old immunocompromised female with a past medical history of hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), stage IIIA adenocarcinoma, and a preexisting pulmonary cavity with chronic invasive aspergillosis vs. pulmonary aspergilloma treated with oral (PO) voriconazole. This case demonstrates that invasive aspergillosis should be considered in the differential diagnosis of any pulmonary lung lesion showing tissue invasion and expansion in an immunocompromised patient.

Central sleep apnea in otherwise healthy term infants.

To describe the outcomes of central sleep apnea requiring home supplemental oxygen therapy in otherwise healthy term infants. All children < 1 year of age undergoing polysomnography between 2015 and 2020 at the Queensland Children's Hospital were retrospectively studied. Children with gestational age < 37 weeks, underlying syndrome, cleft palate, those with obstructive apnea-hypopnea index > 50% of total apnea-hypopnea index, or with underlying cardiac or pulmonary parenchymal pathology were excluded. Polysomnography parameters were extracted for periods both on and off supplemental oxygenation. Fifty-two (mean [standard deviation] age at polysomnography 32.6 [34.7] days; 21 females) term infants were included. There was a statistically significant improvement in apnea-hypopnea index on supplemental oxygen (mean [standard deviation] in room air 50.2 [36.3] vs 11.6 [9], P < .001 on supplemental oxygen), in both rapid eye movement and nonrapid eye movement sleep, as well as in mean oxygen saturations (96.6% in room air to 98.9% on oxygen; P < .001). There was no statistically significant change in transcutaneous carbon dioxide levels or sleep duration. Oxygenation was prescribed for a median (interquartile range) age of 197 (127) days. Central sleep apnea in term infants who are otherwise healthy generally has a good prognosis, with oxygen therapy prescribed for around 6 months. Oxygen therapy was associated with improved saturations and decrease in apnea-hypopnea index when assessed with polysomnography. Hayashi A, Suresh S, Kevat A, Robinson J, Kapur N. Central sleep apnea in otherwise healthy term infants. J Clin Sleep Med. 2022; 18(12):2813-2817.

Frequency of occurrence of cardiovascular risk factors in patients with anthracosilicosis in combination with arterial hypertension and coronary heart disease

Introduction. Clinical and experimental studies show the adverse effect of coal-rock dust not only on the bronchopulmonary, but also on the cardiovascular system. Coal mine workers have a high incidence of arterial hypertension and coronary heart disease. The key point in the prevention of the diseases of the circulatory system is the timely detection and correction of not only the main (non-occupational), but also occupational factors of cardiovascular risk. In this regard, the study of risk factors for arterial hypertension and coronary heart disease in coal mining workers is an urgent task. The study aims to explore the frequency and reveal the most significant non-occupational and occupational factors of cardiovascular risk in patients with anthracosilicosis in combination with arterial hypertension and coronary heart disease. Materials and methods. The study involved 269 coal mine workers: 139 miners with previously diagnosed anthracosilicosis and 130 miners in the control group without lung pathology. All of them underwent a comprehensive clinical, instrumental and laboratory examination to identify arterial hypertension, coronary artery disease and risk factors for the development of the diseases of the circulatory system. Results. According to the findings of the study, a significantly higher incidence of arterial hypertension and coronary heart disease was identified in the patients with anthracosilicosis compared with the miners who worked for a long time in harmful labour conditions but did not have occupational pulmonary pathology. The most significant non-occupational risk factors for arterial hypertension in the patients with anthracosilicosis were determined: age 50 years and older, the presence of fasting hyperglycemia, hyperhomocysteinemia, abdominal type of obesity, hypersthenic constitutional-morphological type according to the Rees-Eysenck index, blood group AB (IV). Occupational risk factors for the development of arterial hypertension in the patients with anthracosilicosis were also identified: work experience in hazardous working conditions of 25 years and more, the dust level in the working area exceeding the maximum permissible concentration by 10 times and more. In the patients with anthracosilicosis, the most significant risk factors for the development of coronary heart disease were: age 45 years and older, the presence of arterial hypertension, metabolic syndrome, andromorphic constitutional-morphological type according to the Tanner index, hyperhomocysteinemia, hyperfibrinogenemia, increased levels of soluble fibrin-monomer complexes and C-reactive protein. Occupational risk factors for the development of coronary heart disease in the patients with anthracosilicosis were also identified: work experience in hazardous working conditions of 20 years and more, the presence of respiratory failure (as a complication of an occupational disease). Limitations. This study is limited to a sample of workers in the main occupations of coal mines who are examined at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. The age group of workers from 40 to 54 years old, with a long work experience in underground dusty conditions (more than 15 years) was studied. The study did not include persons with proven occupational diseases other than anthracosilicosis. Conclusions. The identified significant markers of cardiovascular risk can be applied to elaborate prognostic methods. Timely detection and elimination of cardiovascular risk factors as primary preventive measures should be used to reduce the level of cardiovascular incidence rate among individuals working in hazardous labour conditions. Ethics. This medical research involving a human was carried out in accordance with the ethical principles presented in the latest version of the Declaration of Helsinki by the World Medical Association.

Uncertainty-driven ensembles of multi-scale deep architectures for image classification

The use of automatic systems for medical image classification has revolutionized the diagnosis of a high number of diseases. These alternatives, which are usually based on artificial intelligence (AI), provide a helpful tool for clinicians, eliminating the inter and intra-observer variability that the diagnostic process entails. Convolutional Neural Network (CNNs) have proved to be an excellent option for this purpose, demonstrating a large performance in a wide range of contexts. However, it is also extremely important to quantify the reliability of the model’s predictions in order to guarantee the confidence in the classification. In this work, we propose a multi-level ensemble classification system based on a Bayesian Deep Learning approach in order to maximize performance while providing the uncertainty of each classification decision. This tool combines the information extracted from different architectures by weighting their results according to the uncertainty of their predictions. Performance is evaluated in a wide range of real scenarios: in the first one, the aim is to differentiate between different pulmonary pathologies: controls vs bacterial pneumonia vs viral pneumonia. A two-level decision tree is employed to divide the 3-class classification into two binary classifications, yielding an accuracy of 98.19%. In the second context, performance is assessed for the diagnosis of Parkinson’s disease, leading to an accuracy of 95.31%. The reduced preprocessing needed for obtaining this high performance, in addition to the information provided about the reliability of the predictions evidence the applicability of the system to be used as an aid for clinicians.

Machine Learning in Recognition of Basic Pulmonary Pathologies

Nowadays, during the diagnosis process, the doctor is able to obtain access to much information describing the patient’s condition using appropriate tools. However, there are always two sides to the coin. The doctor has certain limitations regarding the amount of data they can process at once. Information technology comes to the rescue, which with the help of computers is able to quickly and effectively separate important information from redundant information and support the doctor in making a diagnosis. In this work, a decision-making system was created to diagnose common lung pathologies in digital radiography images. Here, we consider four basic pulmonary diseases: pneumothorax, pneumonia, pulmonary consolidation, and lung lesions. Our objective is to develop a new automatic detection method of lung pathologies on chest X-ray radiographs using python programming language and its libraries. The approach uses solutions in the field of artificial intelligence, such as deep learning, convolutional neural network and segmentation to make a diagnosis that aims to help the radiologist at work. In the first sections, this work describes the fundamentals of the present form of diagnosis, a proposal to improve this process, the method of operation of the algorithms used, data acquisition, segmentation and processing methods. Then, the results of the operation of four different models and their implementation in a practical window program were presented. The best model, which detects pulmonary consolidation, achieves accuracy higher than 91%, which is a satisfactory result because they are not intended to replace radiologists but to improve their work. In the future, this type of program can be further developed by adding models that recognize other conditions.

Thoracic Splenosis in the Setting of Abdominal Trauma

The uncommon case of thoracic splenosis is presented in this paper. A patient presents to the hospital with the complaint of dyspnea on exertion. He is incidentally found to have thoracic splenosis. The case of thoracic splenosis is a vital topic to discuss in order to accurately diagnose, recognize, treat symptoms, and explore how it can exacerbate pulmonary or cardiology pathology.

HIV and Schistosoma Co-Exposure Leads to Exacerbated Pulmonary Endothelial Remodeling and Dysfunction Associated with Altered Cytokine Landscape.

HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-γ and IL-17A in CD4+ and γδ T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity.

Interpretation of Oxygen Saturation in Congenital Heart Disease: Fact and Fallacy.

Oxygen saturation is the percentage of hemoglobin that is saturated with oxygen, converting it to oxyhemoglobin. Oxygen saturation is a critical part of the physical examination of children with congenital heart disease (CHD). The expected oxygen saturation of a patient with CHD depends on their anatomical lesion, their previous surgeries, and any additional pulmonary or systemic pathology that may derange their saturation. Oxygen saturation can be noninvasively measured using pulse oximetry. Pulse oximetry is based on the differential absorption of infrared and red light by oxyhemoglobin and deoxyhemoglobin, with the former absorbing more infrared than the latter. Pulse oximetry readings may be inaccurate in settings of low cardiac output, peripheral vasoconstriction, arrhythmia, hypothermia, and venous pulsations. The use of pulse oximetry in the care of a child with CHD begins with the newborn critical CHD screen. A failed screen indicates a need for further investigation, such as repeated pulse oximetry or echocardiography. The oxyhemoglobin dissociation curve may be used to estimate the partial pressure of oxygen in the blood at various oxygen saturations. It is also a marker of the affinity of hemoglobin for oxygen, with a right-shifted curve indicating a higher oxygen tension needed to saturate hemoglobin. This is a helpful adaptation of the body to situations of stress such as fever, acidosis, and hypercapnia. An understanding of these concepts is paramount for providers caring for patients with known or potential CHD in any setting to appropriately interpret and respond to abnormal saturations for each child.

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

AbstractBronchopulmonary dysplasia (BPD) is the most common challenge in preterm neonates. Retardation of alveolar development characterizes the pulmonary pathology in BPD. In the present study, we explored the roles of the CD146-HIF-1α axis in BPD. We demonstrated that the levels of reactive oxygen species (ROS) and soluble CD146 (sCD1146) were increased in the peripheral blood of preterm neonates with BPD. In alveolar epithelial cells, hyperoxia promoted the expression of HIF-1α and CD146, which reinforced each other. In a mouse model of BPD, by exposing pups to 65% hyperoxia, HIF-1α and CD146 were increased in the pulmonary tissues. Mechanistically, CD146 hindered the migration of alveolar epithelial cells; in contrast, movement was significantly enhanced in CD146-knockout alveolar epithelial cells. As expected, CD146-knockout ameliorated alveolarization and improved BPD disease severity. Taken together, our findings imply that the CD146-HIF-1α axis contributes to alveolarization and that CD146 may be a novel candidate in BPD therapy.

Automatic scoring of COVID-19 severity in X-ray imaging based on a novel deep learning workflow

In this study, we propose a two-stage workflow used for the segmentation and scoring of lung diseases. The workflow inherits quantification, qualification, and visual assessment of lung diseases on X-ray images estimated by radiologists and clinicians. It requires the fulfillment of two core stages devoted to lung and disease segmentation as well as an additional post-processing stage devoted to scoring. The latter integrated block is utilized, mainly, for the estimation of segment scores and computes the overall severity score of a patient. The models of the proposed workflow were trained and tested on four publicly available X-ray datasets of COVID-19 patients and two X-ray datasets of patients with no pulmonary pathology. Based on a combined dataset consisting of 580 COVID-19 patients and 784 patients with no disorders, our best-performing algorithm is based on a combination of DeepLabV3 + , for lung segmentation, and MA-Net, for disease segmentation. The proposed algorithms’ mean absolute error (MAE) of 0.30 is significantly reduced in comparison to established COVID-19 algorithms; BS-net and COVID-Net-S, possessing MAEs of 2.52 and 1.83 respectively. Moreover, the proposed two-stage workflow was not only more accurate but also computationally efficient, it was approximately 11 times faster than the mentioned methods. In summary, we proposed an accurate, time-efficient, and versatile approach for segmentation and scoring of lung diseases illustrated for COVID-19 and with broader future applications for pneumonia, tuberculosis, pneumothorax, amongst others.

Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2–induced lung exudative vasculitis and predicts COVID-19 severity

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.