Correction to: Gr-MDSC-linked asset as a potential immune biomarker in pretreated NSCLC receiving nivolumab as second-line therapy.

Acknowledgements section was missing.

Gr-MDSC-linked asset as a potential immune biomarker in pretreated NSCLC receiving nivolumab as second-line therapy.

PURPOSE: Immunotherapy is a new standard first-line treatment for non-small cell lung cancers (NSCLC) with high programmed cell death-ligand 1 (PD-L1) expression (≥ 50%) and second-line treatment regardless of PD-L1 status, though not all patients benefit from this approach. Much effort is ongoing to identify robust prognostic and predictive biomarkers of response to immune checkpoint inhibitors, overcoming PD-L1 that appears limited in its ability to discriminate patient candidates to this new class of anticancer agents. The purpose of this research study is to identify potential new biomarkers for immunotherapy in lung cancer. METHODS: Fifty-three consecutive patients with advanced NSCLC treated with nivolumab were enrolled in the study. All the patients received a blood analysis looking for the relationship between different populations of baseline white blood cells and granulocytic myeloid-derived suppressor cells (Gr-MDSC) detected by flow cytometry, to identify and characterize patients with poor likelihood of benefit from nivolumab in NSCLC second-line setting, regardless of clinical feature and PDL1 expression. RESULTS: Univariate analysis showed that high baseline levels of Gr-MDSC and low baseline CD8/Gr-MDSC ratio are associated with significantly better (P = 0.02) response to immunotherapy treatment. Log-rank tests suggested a significant improvement in OS and PFS with high baseline levels of Gr-MDSC levels (≥ 6 cell/µl), low absolute neutrophil count (< 5840/µl), high eosinophil count (> 90 /µl), and NLR < 3. The multivariate analysis showed a statistically significant improvement for PFS (P = 0.003) and OS (P = 0.05) in favour of the identified good prognostic Gr-MDSC-linked asset group, compared with the poor prognosis group. CONCLUSION: The role of Gr-MDSC appears interesting as a potential biomarker in NSCLC patients receiving immune-checkpoint inhibitors. Further analyses are needed to confirmed and study in deep the role of these particular cells and their role in cancer response and progression during ICI therapy.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review.

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.

Effects of continuous vs interval exercise training on oxygen uptake efficiency slope in patients with coronary artery disease.

The oxygen uptake efficiency slope (OUES) is a submaximal index incorporating cardiovascular, peripheral, and pulmonary factors that determine the ventilatory response to exercise. The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease. Thirty-five patients (59.3±1.8 years old; 28 men, 7 women) with coronary artery disease were randomly divided into two groups: continuous exercise training (n=18) and interval exercise training (n=17). All patients performed graded exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold (VAT), respiratory compensation point, and peak oxygen consumption (peak VO2). The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation. After the interventions, both groups showed increased aerobic fitness (P<0.05). In addition, both the continuous exercise and interval exercise training groups demonstrated an increase in OUES (P<0.05). Significant associations were observed in both groups: 1) continuous exercise training (OUES and peak VO2 r=0.57; OUES and VO2 VAT r=0.57); 2) interval exercise training (OUES and peak VO2 r=0.80; OUES and VO2 VAT r=0.67). Continuous and interval exercise training resulted in a similar increase in OUES among patients with coronary artery disease. These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.

Effects of continuous vs interval exercise training on oxygen uptake efficiency slope in patients with coronary artery disease

The oxygen uptake efficiency slope (OUES) is a submaximal index incorporating cardiovascular, peripheral, and pulmonary factors that determine the ventilatory response to exercise. The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease. Thirty-five patients (59.3±1.8 years old; 28 men, 7 women) with coronary artery disease were randomly divided into two groups: continuous exercise training (n=18) and interval exercise training (n=17). All patients performed graded exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold (VAT), respiratory compensation point, and peak oxygen consumption (peak VO2). The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation. After the interventions, both groups showed increased aerobic fitness (P<0.05). In addition, both the continuous exercise and interval exercise training groups demonstrated an increase in OUES (P<0.05). Significant associations were observed in both groups: 1) continuous exercise training (OUES and peak VO2 r=0.57; OUES and VO2 VAT r=0.57); 2) interval exercise training (OUES and peak VO2 r=0.80; OUES and VO2 VAT r=0.67). Continuous and interval exercise training resulted in a similar increase in OUES among patients with coronary artery disease. These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms.

A análise neuropsicológica da escrita em cadernos escolares / Neuropsychological analysis of writing in school notebooks

Apresenta uma nova modalidade semiológica para a compreensäo das dificuldades encontradas nos portadores de distúrbios específicos de aprendizagem, sobretudo nas sindromes relacionadas com a linguagem: disgrafia, dislexia, (diseidética e disfonética), disortografia e dissintaxia (afasia sintática). Como essas síndromes se refletem na escrita, analisa cadernos escolares por documentarem de forma exaustiva os vários sinais patológicos que se manifestam nas 3 modalidades de escrita: cópia, ditado e redaçäo. Utiliza o método de análise de tarefa (task analysis) procurando correlacionar a escrita a organizaçäo cerebral. Fundamenta a pesquisa com os seguintes quadros teóricos: organizaçäo do sistema nervoso; niveis hierárquicos da experiência cognitiva e tipos de aprendizagem, de Myklebust; análise da tarefa: escrita de Luria. Elabora um protocolo de avaliaçäo da escrita em cadernos escolares, onde estabelece uma correlaçäo entre os sintomas e as regiöes cerebrais correspondentes, entre cujas consequências mais imediatas e eficazes está a organizaçäo de propostas terapêuticas de inspiraçäo neuropsicológica