André Luis Pereira de Albuquerque

Background: Long‐term survivors of breast cancer (BC) treated with doxorubicin and trastuzumab‐based chemotherapy are at increased risk of developing cardiovascular disease. However, the physiological mechanisms associated with increased cardiovascular disease risk are completely unknown. We hypothesized that long‐term survivors of BC, compared with controls, exhibit sympathetic neural hyperactivity, vascular dysfunction, cardiac morphofunctional changes, exercise intolerance, and alterations in the circulating milieu. Methods: Twenty‐three survivors of BC (age: 48.9±1.3 years; body mass index: 25.2±0.8 kg/m ² ) and 18 (age: 46.4±1.3 years; body mass index: 26.8±0.8 kg/m ² ) well‐matched controls were studied. Muscle sympathetic nerve activity (microneurography), brachial artery flow‐mediated dilation (ultrasound‐Doppler), carotid‐femoral pulse wave velocity (tonometry), left ventricular ejection fraction and global longitudinal strain (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), endothelial cell‐derived extracellular vesicles (flow cytometry), and plasma metabolome (mass spectrometry) were assessed. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. Results: Survivors of breast cancer were tested ⁓8 years after cancer treatment completion. Muscle sympathetic nerve activity was higher and brachial artery flow‐mediated dilation and peak oxygen uptake were lower in survivors than controls. Survivors of breast cancer exhibited higher circulating endothelial cell‐derived extracellular vesicles, higher reactive oxygen species bioactivity, and lower acetylcholine‐evoked nitrics oxide production in plasma‐treated human umbilical vein endothelial cells. Twenty‐eight plasma metabolites differed in survivors versus controls. Peak oxygen uptake was inversely related to muscle sympathetic nerve activity or positively to brachial artery flow‐mediated dilation. No differences in carotid‐femoral pulse wave velocity, left ventricular ejection fraction, and left ventricular global longitudinal strain were observed. Conclusions: Our findings demonstrate that long‐term survivors of breast cancer exhibit sympathetic overdrive, vascular dysfunction, and exercise intolerance, which may contribute to increased cardiovascular disease risk in this population.

The latest pulmonary function guideline from the Brazilian Thoracic Association was published in 2002, since which there have been updates to international guidelines (mainly those from the European Respiratory Society and the American Thoracic Society), as well as new national and international publications on various aspects of the performance, interpretation, and clinical implications of spirometry. Despite those updates, a careful analysis of what applies to the reality in Brazil is essential, because there have been studies that evaluated individuals who are representative of our population and who could show responses different from those of individuals in other regions of the world. This document is the result of the work of a group of specialists in pulmonary function who evaluated relevant scientific articles that could be applicable to the population of Brazil. After the discussions, new spirometry guidelines were drawn up, covering various aspects such as its technical parameters and performance; its indications and contraindications; its interpretation; concepts of normality and their related variability; reference values; classification of functional severity; and response to an inhaled bronchodilator. Finally, the guidelines emphasize the need to always interpret spirometry results in the context of the clinical condition of the patient and of the pretest probability.

Background: Long COVID-19 has been characterized by the presence of symptoms lasting longer than 4 weeks after the acute infection. The pathophysiology of clinical manifestations still lacks knowledge. Objective: The objective of this paper was to evaluate metabolite abundance in the saliva of long COVID patients 60 days after hospital discharge. Methods: A convenience sample was composed of 30 post-discharge patients with long COVID and seven non-COVID-19 controls. All COVID-19 patients were evaluated by demographic characteristics, spirometry, 6 min walk test (6mWT), Saint George Respiratory Questionnaire (SGRQ), and body composition. Metabolomics was performed on saliva. Results: The long COVID-19 patients were 60.4 ± 14.3 years-old, and 66% male. Their lean body mass was 30.7 ± 7.3 kg and fat mass, 34.4 ± 13.7 kg. Spirometry evaluation showed forced vital capacity (FVC) of 3.84 ± 0.97 L with 96.0 ± 14.0% of the predicted value, and forced expiratory volume in the first second (FEV₁) of 3.11 ± 0.83 L with 98.0 ± 16.0 of the predicted value. The long COVID-19 patients had reduced maximal inspiratory (90.1 ± 31.6 cmH₂O) and maximal expiratory (97.3 ± 31.0 cmH₂O) pressures. SGRQ showed domain symptoms of 32.3 ± 15.2, domain activities of 41.9 ± 25.6, and domain impact 13.7 ± 11.4, with a mean of 24.3 ± 14.9%. Physical capacity measured by distance covered in the 6mWT was 418.2 ± 130 m with a 73.3% (22.3–98.1) predictive value. The control group consisted of 44.1 ± 10.7-year-old men with a body mass index of 26.5 ± 1.66 Kg/m². Metabolomics revealed 19 differentially expressed metabolites; expression was lower in 16 metabolites, and 2 metabolites were absent in the COVID-19 patients compared to controls. Calenduloside G methyl ester (p = 0.03), Gly Pro Lys (p = 0.0001), and creatine (p = 0.0001) expressions were lower in patients than controls. Conclusions: Long COVID-19 patients present less abundance of calenduloside G methyl ester, Gly Pro Lys, and creatine in saliva than healthy controls. Lower creatine abundance may be related to reduced physical capacity and fatigue

There's limited evidence of the potential benefits of cardiopulmonary and metabolic rehabilitation (CPMR) in patients with heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) and coronary artery disease (CAD). The aim of this study was to investigate the impact of CPMR on the myocardial ischemia response (MIR), exercise-induced arrhythmias (EIA), New York Heart Association (NYHA) functional class, heart rate recovery (HRR), Borg CR10 perceived symptoms, and the SF-36 physical and mental health summary scores. A prospective cohort study was conducted with 106 patients undergoing 12 weeks of CPMR who completed two exercise tests pre- and post-CPMR: 1) maximum incremental test (CPX) and 2) submaximal constant load test (SUB). After CPMR, the effects on MIR, EIA, NYHA functional class, and HRR during both tests were analyzed. There was a significant change in NYHA functional classes after CPMR, with 96% of the patients in class I (vs 62% pre-CPMR, Pvs 32%), and none in class III (vs 6%). There was a significant reduction in the frequency of EIA (P<0.05) and MIR (P<0.001) and a significantly improved performance on both CPX and SUB tests (P<0.0001). Lastly, there was significant progress in the recovery metrics like HRR (P<0.0001), the Borg CR10 (P<0.0001), and the SF-36 summary scores (P<0.0001). The CPMR resulted in a significant decrease in EIA, delayed ischemia threshold in CPX and SUB tests, increased functional capacity, and improved quality of life.

Mechanical ventilation (MV) is a life-saving respiratory support therapy, but MV can lead to diaphragm muscle injury (myotrauma) and induce diaphragmatic dysfunction (DD). DD is relevant because it is highly prevalent and associated with significant adverse outcomes, including prolonged ventilation, weaning failures, and mortality. The main mechanisms involved in the occurrence of myotrauma are associated with inadequate MV support in adapting to the patient’s respiratory effort (over- and under-assistance) and as a result of patient-ventilator asynchrony (PVA). The recognition of these mechanisms associated with myotrauma forced the development of myotrauma prevention strategies (MV with diaphragm protection), mainly based on titration of appropriate levels of inspiratory effort (to avoid over- and under-assistance) and to avoid PVA. Protecting the diaphragm during MV therefore requires the use of tools to monitor diaphragmatic effort and detect PVA. Diaphragm ultrasound is a non-invasive technique that can be used to monitor diaphragm function, to assess PVA, and potentially help to define diaphragmatic effort with protective ventilation. This review aims to provide clinicians with an overview of the relevance of DD and the main mechanisms underlying myotrauma, as well as the most current strategies aimed at minimizing the occurrence of myotrauma with special emphasis on the role of ultrasound in monitoring diaphragm function.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Computer-aided detection algorithms applied to CT lung imaging have the potential to objectively quantify pulmonary pathology. We aim to develop an automatic classification method based on textural features able to classify healthy and pathological patterns on CT lung images and to quantify the extent of each disease pattern in a group of patients with chronic hypersensitivity pneumonitis (cHP), in comparison to pulmonary function tests (PFTs).27 cHP patients were scanned via high resolution CT (HRCT) at full-inspiration. Regions of interest (ROIs) were extracted and labeled as normal (NOR), ground glass opacity (GGO), reticulation (RET), consolidation (C), honeycombing (HB) and air trapping (AT). For each ROI, statistical, morphological and fractal parameters were computed. For automatic classification, we compared two classification methods (Bayesian and Support Vector Machine) and three ROI sizes. The classifier was therefore applied to the overall CT images and the extent of each class was calculated and compared to PFTs. Better classification accuracy was found for the Bayesian classifier and the 16x16 ROI size: 92.1±2.7%. The extent of GGO, HB and NOR significantly correlated with forced vital capacity (FVC) and the extent of NOR with carbon monoxide diffusing capacity (DLCO).Clinical Relevance— Texture analysis can differentiate and objectively quantify pathological classes in the lung parenchyma and may represent a quantitative diagnostic tool in cHP.