Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

EQ-5D in Central and Eastern Europe : 2000-2015

Objective: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. Methods: An electronic database search was performed up to July 1, 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. Results: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n=11), Bulgaria (n=6), Czech Republic (n=18), Hungary (n=47), Poland (n=51), Romania (n=2), Slovakia (n=3) and Slovenia (n=14). Cardiovascular (20%), neurologic (16%), musculoskeletal (15%) and endocrine/nutritional/metabolic diseases (14%) were the most frequently studied clinical areas. Overall 112 (78%) of the studies reported EQ VAS results and 86 (60%) EQ-5D index scores, of which 27 (31%) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. Conclusions: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened

Use the Lower Limit of Normal, Not 80% Predicted, in Judging Eligibility for Lung Resection

Background: Impaired lung function (LF) is a well-known risk factor for perioperative complications in patients qualified for lung resection surgery. The recent European guidelines recommend using values below 80% predicted as indicating abnormal LF rather than the lower limit of normal (LLN). Objectives: To assess how the choice of a cut-off point (80% predicted vs. LLN at -1.645 SD) affects the incidence of functional disorders and postoperative complications in lung cancer patients referred for lung resection. Methods: Preoperative spirometry and the transfer factor for carbon monoxide (T-L,T-CO) were retrospectively analysed in 851 consecutive lung cancer patients after resectional surgery. Results: Airway obstruction was diagnosed in 369 (43.4%), and a restrictive pattern in 41 patients (4.8%). The forced expiratory volume in 1 s (FEV1) or T-L,T-CO was below the LLN in 503 patients (59.1%), whereas the FEV1 or T-L,T-CO was <80% predicted in 620 patients (72.9%; chi(2) test: p < 0.0001). In all, 117 out of 851 patients had LF indices <80% predicted but not below the LLN. Odds ratios (ORs) for perioperative complications were higher in patients with impaired LF indices defined as below the LLN (1.59, p = 0.0005) with the exception of large resections (>5 segments). In patients with test results above the LLN and <80% predicted, the OR for perioperative complications was not different (1.14, p = 0.5) from that in patients with normal LF. Conclusions: LF impairments are common in candidates for lung resection. Using the LLN instead of 80% predicted diminishes the prevalence of respiratory impairment by 14% and allows for safe resectional surgery without additional function testing. (C) 2016 S. Karger AG, Base

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking

Amnon Ariel,1 Alan Altraja,2,3 Andrey Belevskiy,4 Piotr W Boros,5 Edvardas Danila,6 Matjaz Fležar,7 Vladimir Koblizek,8 Zvi G Fridlender,9 Kosta Kostov,10 Alvils Krams,11 Branislava Milenkovic,12 Attila Somfay,13 Ruzena Tkacova,14 Neven Tudoric,15 Ruxandra Ulmeanu,16 Arschang Valipour17 1Emek Medical Center, Clalit Healthcare Services, Afula, Israel; 2Department of Pulmonary Medicine, University of Tartu, 3Lung Clinic, Tartu University Hospital, Tartu, Estonia; 4Department of Pulmonology, Russian National Research Medical University, Moscow, Russia; 5Lung Pathophysiology Department, National TB and Lung Diseases Research Institute, Warsaw, Poland; 6Clinic of Infectious Chest Diseases, Dermatovenereology, and Allergology, Vilnius University, Centre of Pulmonology and Allergology, Vilnius University Hospital, Vilnius, Lithuania; 7University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; 8Department of Pneumology, University Hospital, Hradec Králové, Czech Republic; 9Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem, Israel; 10Clinic of Pulmonary Diseases, Military Medical Academy, Sofia, Bulgaria; 11Medical Faculty of Latvian University, Riga East University Hospital, Riga, Latvia; 12Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 13Department of Pulmonology, University of Szeged, Deszk, Hungary; 14Department of Respiratory Medicine and Tuberculosis, Faculty of Medicine, PJ Safarik University, Košice, Slovakia; 15School of Medicine, Dubrava University Hospital, Zagreb, Croatia; 16Marius Nasta Institute of Pneumology, Bucharest, Romania; 17Department of Respiratory and Critical Care Medicine, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria Abstract: COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups. Keywords: dual bronchodilation, inhaled corticosteroid, LAMA, LABA, tiotropium, anticholinergic&nbsp

International consensus on lung function testing during the COVID-19 pandemic and beyond.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required