Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype

Cardiopulmonary exercise testing in patients with asthma: What is its clinical value?

Asthma is one of the most common respiratory disorders, characterized by fully or largely reversible airflow limitation. Asthma symptoms can be triggered or magnified during exertion, while physical activity limitation is often present among asthmatic patients. Cardiopulmonary exercise testing (CPET) is a dynamic, non-invasive technique which provides a thorough assessment of exercise physiology, involving the integrative assessment of cardiopulmonary, neuromuscular and metabolic responses during exercise. This review summarizes current evidence regarding the utility of CPET in the diagnostic work-up, functional evaluation and therapeutic intervention among patients with asthma, highlighting its potential role for thorough patient assessment and physician clinical desicion-making. © 2020 Elsevier Lt

Massive chest wall resection and reconstruction for malignant disease

Christophoros N Foroulis,1 Athanassios D Kleontas,1 George Tagarakis,1 Chryssoula Nana,1 Ioannis Alexiou,1 Vasilis Grosomanidis,1 Paschalis Tossios,1 Elena Papadaki,2 Ioannis Kioumis,2 Sofia Baka,3 Paul Zarogoulidis,2 Kyriakos Anastasiadis11Department of Cardiothoracic Surgery, Aristotle University School of Medicine, AHEPA University Hospital, 2Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, 3Oncology Department, European Interbalkan Medical Center, Thessaloniki, GreeceObjective: Malignant chest wall tumors are rare neoplasms. Resection with wide-free margins is an important prognostic factor, and massive chest wall resection and reconstruction are often necessary. A recent case series of 20 consecutive patients is reported in order to find any possible correlation between tumor histology, extent of resection, type of reconstruction, and adjuvant treatment with short- and long-term outcomes.Methods: Twenty patients were submitted to chest wall resection and reconstruction for malignant chest wall neoplasms between 2006 and 2014. The mean age (ten males) was 59±4 years. The size and histology of the tumor, the technique of reconstruction, and the short- and long-term follow-up records were noted.Results: The median maximum diameter of tumors was 10 cm (5.4–32 cm). Subtotal sternal resection was performed in nine cases, and the resection of multiple ribs was performed in eleven cases. The median area of chest wall defect was 108 cm2 (60–340 cm2). Histology revealed soft tissue, bone, and cartilage sarcomas in 16 cases (80%), most of them chondrosarcomas. The rest of the tumors was metastatic tumors in two cases and localized malignant pleural mesothelioma and non-Hodgkin lymphoma in one case. The chest wall defect was reconstructed by using the “sandwich technique” (propylene mesh/methyl methacrylate/propylene mesh) in nine cases of large anterior defects or by using a 2 mm polytetrafluoroethylene (e-PTFE) mesh in nine cases of lateral or posterior defects. Support from a plastic surgeon was necessary to cover the full-thickness chest wall defects in seven cases. Adjuvant oncologic treatment was administered in 13 patients. Local recurrences were observed in five cases where surgical reintervention was finally necessary in two cases. Recurrences were associated with larger tumors, histology of malignant fibrous histiocytoma, and initial incomplete resection or misdiagnosis made by nonthoracic surgeons. Three patients died during the study period because of recurrent disease or complications of treatment for recurrent disease.Conclusion: Chest wall tumors are in their majority mesenchymal neoplasms, which often require major chest wall resection for their eradication. Long-term survival is expected in low-grade tumors where a radical resection is achieved, while big tumors and histology of malignant fibrous histiocytoma are connected with the increase rate of recurrence.Keywords: chest wall tumors, chest wall resection, chest wall reconstruction, soft tissue sarcomas, sternal tumors, chondrosarcoma&nbsp

Clinical experimentation with aerosol antibiotics: current and future methods of administration [Corrigendum]

Zarogoulidis P, Kioumis I, Porpodis K, Spyratos D, Tsakiridis K, Huang H, Li Q, Turner JF, Browning R, Hohenforst-Schmidt W, Zarogoulidis K. Drug Des Devel Ther. 2013;7:1115–1134.Throughout the paper Microsprayer should have been cited as MicroSprayer® Aerosolizer (Penn-Century, Inc., Wyndmoor, PA, USA).On page 1127 and 1128 the paragraph on Azithromycin should not have been included in the paper.Read the original article

Clinical differences between H3N2 and H1N1 influenza 2012 and lower respiratory tract infection found using a statistical classification approach

Background: Influenza A H1N1 and H3N2 are two influenza waves that have been identified in past years. Methods: Data from 77 inpatients from three tertiary hospitals were included and statistical analysis was performed in three different clusters. Results: Thirty-four patients (44.2%) had respiratory distress upon admission, 31.2% had a smoking history or were active smokers, 37.7% manifested disease symptoms, and 7.8% were obese (body mass index > 41). The mean age of patients was 51.1 years. Cough was the most common symptom observed in 77.9% of the patients, accompanied by sputum production (51.9%) and fatigue (42.9%). Hemoptysis and vomiting were rarely recorded in the patients (9.1% and 16.9%, respectively). Oseltamivir administration varied between 0 and 10 days, giving a mean value of 2.2 days. In particular, 19 patients received no drug, 31 patients received drug for only for 1 day, 19 patients for 5 days, and 8 patients from 2 to 10 days. Conclusion: Clusters of symptoms can be used to identify different types of influenza and disease severity. Patients with vaccination had pneumonia, whereas patients without vaccination had influenza A. Patients more than 54.5 years old had H3N2 and patients less than 54.5 years had H1N1. White blood cell count values increased from normal to elevated in H3N2 patients but still remained abnormal in lower tract infection and H1N1 patients. © 2014 Petridis et al. This work is published by Dove Medical Press Limited

Vitamin D in asthma and future perspectives

Haidong Huang,1 Konstantinos Porpodis,2 Paul Zarogoulidis,2,3 Kalliopi Domvri,2 Paschalina Giouleka,2 Antonis Papaiwannou,2 Stella Primikyri,2 Efi Mylonaki,2 Dionysis Spyratos,2 Wolfgang Hohenforst-Schmidt,4 Ioannis Kioumis,2 Konstantinos Zarogoulidis2 1Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 2Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg–Essen, Essen, Germany; 4II Medical Clinic, “Coburg” Hospital, University of Würzburg, Coburg, Germany Abstract: Humans have the ability to synthesize vitamin D during the action of ultraviolet (UV) radiation upon the skin. Apart from the regulation of calcium and phosphate metabolism, another critical role for vitamin D in immunity and respiratory health has been revealed, since vitamin D receptors have also been found in other body cells. The term “vitamin D insufficiency” has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with a wide range of pulmonary diseases, including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. This review focuses on the controversial relationship between vitamin D and asthma. Also, it has been found that different gene polymorphisms of the vitamin D receptor have variable associations with asthma. Other studies investigated the vitamin D receptor signaling pathway in vitro or in experimental animal models and showed either a beneficial or a negative effect of vitamin D in asthma. Furthermore, a range of epidemiological studies has also suggested that vitamin D insufficiency is associated with low lung function. In the future, clinical trials in different asthmatic groups, such as infants, children of school age, and ethnic minorities are needed to establish the role of vitamin D supplementation to prevent and/or treat asthma. Keywords: vitamin D, asthma, immunomodulation, anti-inflammatio

Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients

Konstantinos Porpodis,1 Kalliopi Domvri,1 Paul Zarogoulidis,1 Dimitrios Petridis,2 Katerina Tsirgogianni,1 Antonis Papaioannou,1 Olga Hatzizisi,3 Ioannis Kioumis,1 Alexandra Liaka,3 Violeta Kikidaki,3 Sofia Lampaki,1 John Organtzis,1 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, 3Pulmonary Department, Immunology and Histocompatibility Laboratory, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Background: A new approach to the treatment of COPD includes controlling inflammation because of its important role in exacerbation of the disease. Recently, roflumilast has been added as a therapeutic option for COPD. Roflumilast is an oral phosphodiesterase-4 inhibitor that targets inflammatory cells involved in triggering exacerbations of COPD. The objective of the current study was to evaluate roflumilast for its contribution to phagocytic activity in COPD patients.Methods: Twenty-one patients diagnosed with COPD received roflumilast once daily for 6 months in combination with fluticasone (an inhaled corticosteroid), salmeterol (a long-acting β2-agonist), and tiotropium (a long-acting muscarinic antagonist) or combinations of these agents. The main inclusion criterion was stable disease for at least the previous 30 days. Neutrophils and spirometric changes, ie, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were measured in the COPD patients at indicated time points. The first sample was taken before receiving roflumilast, the second 3 months later, and the third after 6 months. Examination of defective phagocytosis was done by flow cytometry using a FagoFlowEx® kit. The statistical analysis was performed using Statistica software. Results: Our results indicate that phagocytic activity was increased after 3 and 6 months of treatment when compared with baseline (P<0.001). Similarly, FVC and FEV1 were also increased during the 6-month period, but only FVC differed significantly from baseline (P<0.001).Conclusion: Although the number of patients in this study was limited, our results indicate that roflumilast induces phagocytic activity, which improves lung function. Keywords: COPD, roflumilast, phosphodiesterase-4 inhibitor

Clinical differences between H3N2 and H1N1 influenza 2012 and lower respiratory tract infection found using a statistical classification approach

Dimitris Petridis,1 Paul Zarogoulidis,2,3 Anastasios Kallianos,4 Ioannis Kioumis,2 Georgia Trakada,5 Dionysios Spyratos,2 Antonis Papaiwannou,2 Konstantinos Porpodis,2 Haidong Huang,6 Aggeliki Rapti,4 Wolfgang Hohenforst-Schmidt,7 Konstantinos Zarogoulidis2 1Department of Food Technology, Alexander Technological Educational Institute of Thessaloniki, Thessaloniki, Greece; 2Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 42nd Pulmonary Department, "Sotiria" Hospital for Chest Diseases, Athens, Greece; 5Department of Clinical Therapeutics, Division of Pneumonology, Medical School, National University of Athens, Athens, Greece; 6Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China; 7II Medical Department, "Coburg" Regional Clinic, University of Wüerzburg, Coburg, Germany Background: Influenza A H1N1 and H3N2 are two influenza waves that have been identified in past years. Methods: Data from 77 inpatients from three tertiary hospitals were included and statistical analysis was performed in three different clusters. Results: Thirty-four patients (44.2%) had respiratory distress upon admission, 31.2% had a smoking history or were active smokers, 37.7% manifested disease symptoms, and 7.8% were obese (body mass index >41). The mean age of patients was 51.1 years. Cough was the most common symptom observed in 77.9% of the patients, accompanied by sputum production (51.9%) and fatigue (42.9%). Hemoptysis and vomiting were rarely recorded in the patients (9.1% and 16.9%, respectively). Oseltamivir administration varied between 0 and 10 days, giving a mean value of 2.2 days. In particular, 19 patients received no drug, 31 patients received drug for only for 1 day, 19 patients for 5 days, and 8 patients from 2 to 10 days. Conclusion: Clusters of symptoms can be used to identify different types of influenza and disease severity. Patients with vaccination had pneumonia, whereas patients without vaccination had influenza A. Patients more than 54.5 years old had H3N2 and patients less than 54.5 years had H1N1. White blood cell count values increased from normal to elevated in H3N2 patients but still remained abnormal in lower tract infection and H1N1 patients. Keywords: H3N2, H1N1, influenza outbreak, respiratory infection, vaccinatio