Category Archives: Publications

Onset of androgen deprivation therapy leads to rapid deterioration of body composition, physical performance, cardiometabolic health and quality-of-life in prostate cancer patients.

Overkamp M; Houben LHP; van der Meer S; Bos R; Kokshoorn APJ; Larsen MS; van Loon LJC; Beelen M; Beijer S;

Scandinavian journal of urology [Scand J Urol] 2023 Jan 26, pp. 1-7.
Date of Electronic Publication: 2023 Jan 26.

Objectives: To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients.
Materials and Methods: Thirty-four prostate cancer patients (70 ± 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student’s paired t -tests.
Results: Over time, whole-body fat mass (from 26.2 ± 7.7 to 28.4 ± 8.3 kg, p  < 0.001) and fasting insulin (from 9.5 ± 5.8 to 11.3 ± 6.9 mU/L, p  < 0.001) increased. Declines were observed for quadriceps cross-sectional area (from 66.3 ± 9.1 to 65.0 ± 8.5 cm 2 , p  < 0.01), one-repetition maximum leg press (from 107 ± 27 to 100 ± 27 kg, p  < 0.01), peak oxygen uptake (from 23.2 ± 3.7 to 20.3 ± 3.4 mL/min/kg body weight, p  < 0.001), step count (from 7,048 ± 2,277 to 5,842 ± 1,749 steps/day, p  < 0.01) and health-related quality-of-life (from 84.6 ± 13.5 to 77.0 ± 14.6, p  < 0.001).
Conclusions: Androgen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.

Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure.

Cunha GJL; Maltês S; Rocha BML; Nina D; Aguiar C; Andrade MJ; Moreno L; Durazzo A; Mendes M; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2023 Jan 27.
Date of Electronic Publication: 2023 Jan 27.

Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.

Prediction of exercise respiratory limitation from pulmonary function tests.

Shlomi D; Beck T; Reuveny R; Segel MJ;

Pulmonology [Pulmonology] 2023 Jan 28.
Date of Electronic Publication: 2023 Jan 28.

Background: Evaluation of unexplained exercise intolerance is best resolved by cardiopulmonary exercise testing (CPET) which enables the determination of the exercise limiting system in most cases. Traditionally, pulmonary function tests (PFTs) at rest are not used for the prediction of a respiratory limitation on CPET.
Objective: We sought cut-off values on PFTs that might, a priori, rule-in or rule-out a respiratory limitation in CPET.
Methods: Patients who underwent CPET in our institute were divided into two groups according to spirometry: obstructive and non-obstructive. Each group was randomly divided 2:1 into derivation and validation cohorts respectively. We analyzed selected PFTs parameters in the derivation groups in order to establish maximal and minimal cut-off values for which a respiratory limitation could be ruled-in or ruled-out. We then validated these values in the validation cohorts.
Results: Of 593 patients who underwent a CPET, 126 were in the obstructive and 467 in the non-obstructive group. In patients with obstructive lung disease, forced expiratory volume in 1 second (FEV 1 ) ≥ 61% predicted could rule out a respiratory limitation, while FEV 1 ≤ 33% predicted was always associated with a respiratory limitation. For patients with non-obstructive spirometry, FEV 1 of ≥ 73% predicted could rule-out a respiratory limitation. Application of this algorithm might have saved up to 47% and 71% of CPETs in our obstructive and non-obstructive groups, respectively.
Conclusion: Presence or absence of a respiratory limitation on CPET can be predicted in some cases based on a PFTs performed at rest.

Impaired aerobic capacity in adolescents and young adults after treatment for cancer or non-malignant haematological disease.

Gavotto A; Dubard V; Avesani M; Huguet H; Picot MC; Abassi H; Guillaumont S; De La Villeon G; Haouy S; Sirvent N; Sirvent A; Theron A; Requirand A; Matecki S; Amedro P;

Purpose: Childhood cancer survivors are at increased risk for cardiovascular disease. Maximal oxygen uptake
(VO 2max ) is a major determinant of cardiovascular morbidity. The aim of this study was to compare aerobic capacity, measured by cardiopulmonary exercise test (CPET), of adolescents and young adults in remission with that of healthy controls and to identify the predictors of aerobic capacity in this population.
Method: This is a controlled cross-sectional study.
Results: A total of 477 subjects (77 in remission and 400 controls), aged from 6 to 25 years, were included, with a mean delay between end of treatment and CPET of 2.9 ± 2.3 years in the remission group. In this group, the mean VO 2max was significantly lower than in controls (37.3 ± 7.6 vs. 43.3 ± 13.1 mL/kg/min, P < 0.01, respectively), without any clinical or echocardiographic evidence of heart failure. The VAT was significantly lower in the remission group (26.9 ± 6.0 mL/kg/min vs. 31.0 ± 9.9 mL/kg/min, P < 0.01, respectively). A lower VO 2max was associated with female sex, older age, higher BMI, radiotherapy, and hematopoietic stem cell transplantation.
Conclusion: Impaired aerobic capacity had a higher prevalence in adolescents and young adults in cancer remission. This impairment was primarily related to physical deconditioning and not to heart failure.
Impact: In childhood cancer survivors, aerobic capacity is five times more impaired than in healthy subjects. This impairment mostly reflects early onset of physical deconditioning. No evidence of heart failure was observed in this population.

Exertional oscillatory ventilation in subjects without heart failure reporting chronic dyspnoea.

Neder JA; Rocha A; Arbex FF; Alencar MCN; Sperandio PA; Hirai DM; Berton DC;

Publisher: European Respiratory Society Country of Publication: England NLM ID: 101671641 Publication Model: eCollection Cited Medium: Print ISSN: 2312-0541 (Print) Linking ISSN: 23120541 NLM ISO Abbreviation: ERJ Open Res Subsets: PubMed not MEDLINE

Oscillatory ventilation detected on incremental cardiopulmonary exercise testing might be found in subjects without heart failure reporting exertional dyspnoea despite the best available therapy for their underlying cardiopulmonary disease

Software development to standardize the clinical diagnosis of exercise oscillatory ventilation in heart failure.

Dos Santos Ribeiro G; Beltrame T; Fernando Deresz L; Hansen D; Agostoni P; Karsten M;

Journal of clinical monitoring and computing [J Clin Monit Comput] 2023 Feb 03.
Date of Electronic Publication: 2023 Feb 03.

Background: Exercise oscillatory ventilation (EOV) is characterized by periodic oscillations of minute ventilation during cardiopulmonary exercise testing (CPET). Despite its prognostic value in chronic heart failure (HF), its diagnosis is complex due to technical limitations. An easier and more accurate way of EOV identification can contribute to a better approach and clinical diagnosis. This study aims to describe a software development to standardize the EOV diagnosis from CPET’s raw data in heart failure patients and test its reliability (intra- and inter-rater).
Methods: The software was developed in the “drag-and-drop” G-language using LabVIEW ® . Five EOV definitions (Ben-Dov, Corrà, Kremser, Leite, and Sun definitions), two alternative approaches, one smoothing technique, and some basic statistics were incorporated into the interface to visualize four charts of the ventilatory response. EOV identification was based on a set of criteria verified from the interaction between amplitude, cycle length, and oscillation time. Two raters analyzed the datasets. In addition, repeated measurements were verified after six months using about 25% of the initial data. Cohen’s kappa coefficient (κ) was used to investigate the reliability.
Results: Overall, 391 tests were analyzed in duplicate (inter-rater reliability) and 100 tests were randomized for new analysis (intra-rater reliability). High inter-rater (κ > 0.80) and intra-rater (κ > 0.80) reliability of the five EOV diagnoses were observed.
Conclusion: The present study proposes novel semi-automated software to detect EOV in HF, with high inter and intra-rater agreements. The software project and its tutorial are freely available for download.

Muscle–Organ Crosstalk: The Emerging Roles of Myokines

Severinsen, C; Pedersen, B

Endocrine Reviews, Volume 41, Issue 4, August 2020, Pages 594–609

Physical activity decreases the risk of a network of diseases, and exercise may be prescribed as medicine for lifestyle-related disorders such as type 2 diabetes, dementia, cardiovascular diseases, and cancer. During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners. Recent advances show that skeletal muscle produces myokines in response to exercise, which allow for crosstalk between the muscle and other organs, including brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin, as well as communication within the muscle itself. Although only few myokines have been allocated to a specific function in humans, it has been identified that the biological roles of myokines include effects on, for example, cognition, lipid and glucose metabolism, browning of white fat, bone formation, endothelial cell function, hypertrophy, skin structure, and tumor growth. This suggests that myokines may be useful biomarkers for monitoring exercise prescription for people with, for example, cancer, diabetes, or neurodegenerative diseases.

Graphical Abstract
Graphical Abstract

Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study.

Ostrowska M; Rzepka-Cholasińska A; Pietrzykowski Ł; Michalski P; Kosobucka-Ozdoba A; Jasiewicz M; Kasprzak M; Kryś J; Kubica A;

Journal of clinical medicine [J Clin Med] 2023 Jan 04; Vol. 12 (2).
Date of Electronic Publication: 2023 Jan 04.

Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m ( p &lt; 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 ( p &lt; 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 ( p &lt; 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 ( p &lt; 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients.

Cerebral oxygenation during cardiopulmonary exercise testing in cardiorespiratory diseases: A systematic review.

Galdino GAM; Rehder-Santos P; Linares SN; Beltrame T; Catai AM;

Heart & lung : the journal of critical care [Heart Lung] 2023 Jan 18; Vol. 59, pp. 23-32.
Date of Electronic Publication: 2023 Jan 18.

Background: Cardiopulmonary exercise testing (CPET) is the gold standard for analyzing cardiorespiratory fitness and integrating physiological responses. However, the presence of chronic diseases may compromise cerebral hemodynamic responses during CPET. In addition, the acute response of cerebral oxygenation during incremental CPET may identify abnormal behavior and ensure greater safety for patients with cardiovascular, respiratory, and metabolic diseases.
Objective: To summarize the cerebral oxygenation acute response during CPET of patients with cardiovascular, metabolic, or respiratory diseases.
Methods: From inception to 23rd September 2022, five databases (PubMed, SCOPUS, Web of Science, Embase and CINAHAL) were searched for cross-sectional studies performing incremental CPET and measuring the cerebral oxygenation acute response in cardiovascular, metabolic, or respiratory diseases compared with healthy individuals. The Downs and Black tool assessed the risk of bias of the studies.
Results: We included seven studies with 428 participants (305 men and 123 women), aged 43 to 70 years. Of these, 101 had heart failure NYHA II and III; 77 idiopathic dilated cardiomyopathy; 33 valvular disease; 25 coronary heart disease; 22 pulmonary arterial hypertension; 15 had severe obstructive sleep apnea (OSA) and 166 were apparently healthy. There was no eligible article with metabolic disease. There was a lower magnitude increase in cerebral oxygenation of cardiovascular patients compared with the healthy individuals during the CPET. Furthermore, pulmonary arterial hypertension patients presented increased cerebral oxygen extraction, differently to those with severe OSA.
Conclusion: Considering the heterogeneity of the included studies, patients with cardiovascular disease may suffer from reduced cerebral oxygen supply, and individuals with OSA presented lower brain oxygen extraction during the CPET. Future studies should aim for strategies to improve cerebral oxygenation to ensure greater safety at CPET of cardiovascular and OSA patients. An acute response pattern for metabolic and other respiratory diseases was not established.

The Association of Field Test Outcomes with Peak Oxygen Uptake in Patients with Cystic Fibrosis: A Systematic Review.

Campos NE; Vendrusculo FM; DA Costa GA; DE Almeida IS; Becker NA; Donadio MVF;

International journal of exercise science [Int J Exerc Sci] 2022 Nov 01; Vol. 15 (3), pp. 1381-1394.
Date of Electronic Publication: 2022 Nov 01 (Print Publication: 2022).

The purpose of the study was to evaluate the association of field test outcomes with peak oxygen uptake (VO 2 peak) in patients with cystic fibrosis (CF) and to describe the main prediction equations available. Data searches were performed in five databases (Pubmed, Embase, LILACs, Scopus and Web of Science) and also in the reference lists of articles included. The following inclusion criteria were used: studies including individuals with CF, presenting both a field test and a cardiopulmonary exercise testing (CPET), and describing a predictive equation or coefficient of correlation/determination. Case studies, abstracts, letters of reply, editorials and duplicate publications were excluded. The methodological quality analysis was performed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies scale. Protocol registration number: CRD42020148363. Ten studies were eligible. Five equations were found to predict VO 2 peak. Equations derived from the shuttle tests (ST) showed strong correlations with VO 2 peak ( r = 0.79 to 0.95). The six-minute walk test (6MWT) showed moderate associations with VO 2 peak in participants with moderate disease severity ( r = 0.53 to 0.65). Furthermore, patients with lower maximum heart rate on the three-minute step test tended to have a higher percent predicted VO 2 peak ( r = -0.40), and the one-minute sit-to-stand test demonstrated moderate correlations between VO 2 peak and the number of repetitions ( r = 0.52 to 0.66). In conclusion, field test outcomes correlate with oxygen consumption assessed through CPET, although only the ST seems to be valid as a predictor of VO 2 peak in patients with CF.