Predictors of prolonged ventilator weaning and mortality in critically ill patients with COVID-19.

OBJECTIVE: To identify factors associated with prolonged weaning and mortality in critically ill COVID-19 patients admitted to ICUs and under invasive mechanical ventilation. METHODS: Between March of 2020 and July of 2021, we retrospectively recorded clinical and ventilatory characteristics of critically ill COVID-19 patients from the day of intubation to the outcome. We classified the patients regarding the weaning period in accordance with established criteria. A logistic regression analysis was performed to identify variables associated with prolonged weaning and mortality. RESULTS: The study involved 303 patients, 100 of whom (33.0%) had a prolonged weaning period. Most of the patients were male (69.6%), 136 (44.8%) had more than 50% of pulmonary involvement on chest CT, and 93 (30.6%) had severe ARDS. Within the prolonged weaning group, 62% died within 60 days. Multivariate analysis revealed that lung involvement greater than 50% on CT and delay from intubation to the first separation attempt from mechanical ventilation were significantly associated with prolonged weaning, whereas age and prolonged weaning were significantly associated with mortality. CONCLUSIONS: Prolonged weaning can be used as a milestone in predicting mortality in critically ill COVID-19 patients. Lung involvement greater than 50% on CT and delay from intubation to the first separation attempt from mechanical ventilation were identified as significant predictors of prolonged weaning. These results might provide valuable information for healthcare professionals when making clinical decisions regarding the management of critically ill COVID-19 patients who are on mechanical ventilation.

In vitro evaluation of nanocomposites of linseed mucilage and k-carrageenan loaded with Achyrocline satureioides nanoemulsion: a gradual-release candidate of antimicrobials for the treatment of bovine mastitis.

This research paper presents the development and evaluation of pioneering nanocomposites (NCs) based on the combination of k-carrageenan and linseed mucilage. When loaded with macela extract nanoemulsion they present an innovative approach for the sustained release of antimicrobial herbal constituents, specifically tailored for bovine mastitis treatment. The NCs, encompassing various ratios of k-carrageenan and linseed mucilage polymers (8:2, 7:3, and 5:5 w/w) with 1.25 mg of macela extract/g of gel, underwent in vitro assessment, emphasizing viscosity, degradation speed, release of herbal actives from macela nanoemulsion and antimicrobial activity. The NCs exhibited thermoreversible characteristics, transitioning from liquid at 60°C to a gel at 25°C. NCs allowed a gradual release of phenolic compounds, reaching approximately 80% of total phenolics release (w/v) within 72 h. NCs inhibited the growth of MRSA (ATCC 33592) until 8 h of incubation. No toxic effect in vitro of NCs was found on MAC-T cells. Thus, the developed materials are relevant for the treatment of bovine mastitis, especially in the dry period, and the data support future evaluations in vivo.

Predictors of prolonged ventilator weaning and mortality in critically ill patients with COVID-19 / Preditores de desmame ventilatório prolongado e mortalidade em pacientes críticos com COVID-19

ABSTRACT Objective: To identify factors associated with prolonged weaning and mortality in critically ill COVID-19 patients admitted to ICUs and under invasive mechanical ventilation. Methods: Between March of 2020 and July of 2021, we retrospectively recorded clinical and ventilatory characteristics of critically ill COVID-19 patients from the day of intubation to the outcome. We classified the patients regarding the weaning period in accordance with established criteria. A logistic regression analysis was performed to identify variables associated with prolonged weaning and mortality. Results: The study involved 303 patients, 100 of whom (33.0%) had a prolonged weaning period. Most of the patients were male (69.6%), 136 (44.8%) had more than 50% of pulmonary involvement on chest CT, and 93 (30.6%) had severe ARDS. Within the prolonged weaning group, 62% died within 60 days. Multivariate analysis revealed that lung involvement greater than 50% on CT and delay from intubation to the first separation attempt from mechanical ventilation were significantly associated with prolonged weaning, whereas age and prolonged weaning were significantly associated with mortality. Conclusions: Prolonged weaning can be used as a milestone in predicting mortality in critically ill COVID-19 patients. Lung involvement greater than 50% on CT and delay from intubation to the first separation attempt from mechanical ventilation were identified as significant predictors of prolonged weaning. These results might provide valuable information for healthcare professionals when making clinical decisions regarding the management of critically ill COVID-19 patients who are on mechanical ventilation.

RESUMO Objetivo: Identificar fatores associados ao desmame prolongado e à mortalidade em pacientes críticos com COVID-19 admitidos em UTI e sob ventilação mecânica invasiva. Métodos: Entre março de 2020 e julho de 2021, registramos retrospectivamente as características clínicas e ventilatórias de pacientes críticos com COVID-19 desde o dia da intubação até o desfecho. Os pacientes foram classificados quanto ao período de desmame de acordo com critérios estabelecidos. Foi realizada análise de regressão logística para identificar variáveis associadas ao desmame prolongado e à mortalidade. Resultados: O estudo incluiu 303 pacientes, 100 dos quais (33,0%) apresentaram período de desmame prolongado. A maioria dos pacientes era do sexo masculino (69,6%), 136 (44,8%) apresentaram mais de 50% de acometimento pulmonar na TC de tórax, e 93 (30,6%) apresentaram SDRA grave. No grupo desmame prolongado, 62% foram a óbito em 60 dias. A análise multivariada revelou que o acometimento pulmonar maior que 50% na TC e a demora na primeira tentativa de retirada da ventilação mecânica após a intubação apresentaram associação significativa com o desmame prolongado, enquanto a idade e o desmame prolongado apresentaram associação significativa com a mortalidade. Conclusões: O desmame prolongado pode ser utilizado como marco na predição de mortalidade em pacientes críticos com COVID-19. O acometimento pulmonar maior que 50% na TC e a demora na primeira tentativa de retirada da ventilação mecânica após a intubação foram identificados como preditores significativos de desmame prolongado. Esses resultados podem fornecer informações valiosas para os profissionais de saúde na tomada de decisões clínicas sobre o manejo de pacientes críticos com COVID-19 e em ventilação mecânica.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

Análise espacial da mortalidade fetal por sífilis congênita no Município do Recife-PE-Brasil entre 2007 e 2016 / Análisis espacial de la mortalidad fetal por sífilis congénita en el municipio de Recife-PE-Brasil entre 2007 y 2016 / Spatial analysis of fetal mortality from congenital syphilis in the municipality of Recife-PE-Brazil between 2007 and 2016

Resumo Objetivo analisar a distribuição espacial da mortalidade fetal por sífilis congênita entre os bairros do Município do Recife-PE. Método estudo ecológico, realizado a partir do indicador epidemiológico taxa de mortalidade fetal por sífilis congênita, agregado ao nível dos bairros, em dois quinquênios: 2007 a 2011 e 2012 a 2016. O padrão de autocorrelação espacial foi determinado pelos Índices de Moran Global e Local, com significância estatística inferior a 5% e representado em mapas BoxMap e MoranMap que apontaram as áreas com taxas altas, baixas e em transição epidemiológica e os clusters de maior interesse epidemiológico. Resultados foram notificados 208 óbitos fetais. O Índice Global de Moran evidenciou autocorrelação espacial positiva em grau razoável, no primeiro quinquênio (I = 0,351 e p-valor = 0,01) e, em grau fraco, no segundo quinquênio (I = 0,189 e p-valor = 0,02). Os Distritos Sanitários I e VII obtiveram os maiores percentuais de bairros que formaram o cluster de altas taxas do indicador com 63,3% e 38,4% no primeiro e segundo quinquênios, respectivamente. Conclusões e implicações para a Prática a análise espacial apontou as áreas críticas para ocorrência do indicador, podendo contribuir para o investimento nas áreas prioritárias de prevenção da transmissão vertical da sífilis.

Resumen Objetivo Analizar la distribución espacial de la mortalidad fetal por sífilis congénita entre los barrios de Recife-PE. Método Estudio ecológico, basado en el indicador epidemiológico tasa de mortalidad fetal por sífilis congénita, agregada a nivel de barrio, en dos quinquenios: 2007 a 2011 y 2012 a 2016. El patrón de autocorrelación espacial fue determinado por los Índices Moran Global y Local, con significancia estadística menor al 5% y representados en mapas de BoxMap y MoranMap, que indicaron áreas con tasas de transición alta, baja y epidemiológica y conglomerados de mayor interés epidemiológico. Resultados Notificadas 208 muertes fetales. El Índice Global de Moran mostró un grado razonable de autocorrelación espacial positiva en el primer quinquenio (I = 0,351 y p-valor=0,01) y un grado débil en el segundo quinquenio (I = 0,189 y p-valor=0,02). Los Distritos Sanitarios I y VII presentaron los mayores porcentajes de barrios que formaron el cluster de tasas altas del indicador con 63,3% y 38,4% en el primer y segundo quinquenio, respectivamente. Conclusión e Implicación para la Práctica El análisis espacial señaló las áreas críticas para la ocurrencia del indicador, que podrían contribuir a la inversión en áreas prioritarias para la prevención de la transmisión vertical de sífilis.

Abstract Objective To analyze the spatial distribution of fetal mortality due to congenital syphilis among the neighborhoods of the city of Recife-PE. Method Ecological study, based on the epidemiological indicator fetal mortality rate due to congenital syphilis, aggregated at the neighborhood level, in two five-year periods: 2007 to 2011 and 2012 to 2016. The pattern of spatial autocorrelation was determined by the Moran Global and Local Indexes, with statistical significance lower than 5% and represented in BoxMap and MoranMap maps that indicated areas with high, low and epidemiological transition rates and clusters of greater epidemiological interest. Results It was reported 208 fetal deaths. The Moran Global Index showed a reasonable degree of positive spatial autocorrelation in the first five-year period (I = 0.351 and p-value = 0.01) and a weak degree in the second five-year period (I = 0.189 and p-value = 0.02). Sanitary Districts I and VII had the highest percentages of neighborhoods that formed the cluster of high rates of the indicator with 63.3% and 38.4% in the first and second five-year periods, respectively. Conclusions and Implications for Practice The spatial analysis pointed out the critical areas for the occurrence of the indicator, which could contribute to investment in priority areas for the prevention of vertical transmission of syphilis.

[Spatial analysis as a tool for identification of priority intervention areas for syphilis prevention]. / Análise espacial como ferramenta de identificação de áreas prioritárias de intervenção para prevenção da sífilis.

The spatial analysis of syphilis constitutes a tool capable of contributing to the establishment of guidelines for action in priority geographic areas for preventive intervention. The scope of the article was to describe the scientific evidence that used geoprocessing as a tool to identify risk areas for syphilis. This is an integrative review of the literature, carried out in the Medline/PubMed, Scopus, Web of Science, Lilacs, Ibecs, Cochrane Library Portal, SciELO, Cuiden and Bdenf databases through cross-referencing between the key words "syphilis," "spatial analysis," "geographical information system," "health education" and "geographical mapping." A total of 13 articles were analyzed and in most of them syphilis cases were distributed in a heterogeneous manner, not obeying a unique epidemiological profile in relation to the units of analysis. Discordant ecological and spatial effects between syphilis and HIV and the viability of the integrated screening of syphilis with other diseases was revealed. Efficacy and ability of spatial analysis to target specific educational interventions for each reality were revealed, avoiding investment in geographically non-priority areas for syphilis control.

A análise espacial da sífilis constitui-se numa ferramenta capaz de contribuir no estabelecimento de diretrizes de atuação nas áreas geográficas prioritárias para intervenções preventivas. O objetivo do artigo foi descrever as evidências produzidas pelos estudos que utilizaram a análise espacial para identificação das áreas prioritárias de intervenção para sífilis. Trata-se de uma revisão integrativa da literatura, realizada nas bases de dados Medline/PubMed, Scopus, Web of science, Lilacs, Ibecs, Portal da Biblioteca Cochrane, SciELO, Cuiden e Bdenf através do cruzamento entre os descritores "sífilis", "análise espacial", "sistema de informação geográfica", "educação em saúde" e "mapeamento geográfico". Foram analisados 13 artigos e na maioria deles os casos de sífilis se apresentaram distribuídos de forma heterogênea, não obedecendo um perfil epidemiológico único em relação as unidades de análise. Foi demonstrado efeito ecológico e espacial discordante entre sífilis e o HIV e a viabilidade no rastreio integrado da sífilis com outras doenças. Foi evidenciado eficácia e capacidade da análise espacial em direcionar intervencões educativas específicas para cada realidade evitando o investimento em áreas geograficamente não prioritárias para o controle da sífilis.

Adhesive strength of fiberglass posts treated with thio-urethane-based experimental silanes.

PURPOSE: The aim of this study was to evaluate the adhesive bond strength of fiberglass posts treated with experimental silanes based on thio-urethane and submitted to thermo and mechanical cycles. MATERIALS AND METHODS: Bovine roots were divided into six groups: RX-RU2 (RelyX CP + RelyX U200); PETMP-HDDI-RU2 (PETMP-HDDI + RelyX U200); PETMP-BDI-RU2 (PETMP-BDI + RelyX U200); RX-RU (RelyX CP + RelyX Ultimate); PETMP-HDDI-RU (PETMP-HDDI + RelyX Ultimate); PETMP-BDI-RU (PETMP-BDI + RelyX Ultimate). One slice from each root third (n=10) was submitted to the push-out test and the values evaluated with R Program statistical analysis, while the failure pattern assessed in percentage. RESULTS: Among root thirds, RX-RU2 promoted greater strength at the cervical and apical thirds; PETMP-HDDI-RU2 showed highest values at the three thirds; and PETMP-BDI-RU2 was strongest at the apical third. RX-RU presented higher strength at the apical third, and PETMP-HDDI-RU and PETMP-BDI-RU had similar values at the three thirds. In each root third, PETMP-HDDI-RU2 showed similar strength at all thirds, and similar strength at the apical third was observed for other associations. Mixed and adhesive failures predominated. CONCLUSION: Experimental silanes promoted different bond strength values in the adhesion of fiberglass posts to the root thirds, with better results for PETMP-HDDI silane. The root region did not influence the failure pattern and most slices showed mixed (MCDP) or adhesive (ADP) failure.

Cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension at rest and during orthostatic stress: role of the peripheral chemoreflex.

The baroreflex integrity in early-stage pulmonary arterial hypertension (PAH) remains uninvestigated. A potential baroreflex impairment could be functionally relevant and possibly mediated by enhanced peripheral chemoreflex activity. Thus, we investigated 1) the cardiac baroreflex in nonhypoxemic PAH; 2) the association between baroreflex indexes and peak aerobic capacity [i.e., peak oxygen consumption (V̇o2peak)]; and 3) the peripheral chemoreflex contribution to the cardiac baroreflex. Nineteen patients and 13 age- and sex-matched healthy adults (HA) randomly inhaled either 100% O2 (peripheral chemoreceptor inhibition) or 21% O2 (control session) while at rest and during a repeated sit-to-stand maneuver. Beat-by-beat analysis of R-R intervals and systolic blood pressure provided indexes of cardiac baroreflex sensitivity (cBRS) and effectiveness (cBEI). The PAH group had lower cBEI for all sequences (cBEIALL) at rest [means ± SD: PAH = 0.5 ± 0.2 vs. HA = 0.7 ± 0.1 arbitrary units (a.u.), P = 0.02] and lower cBRSALL (PAH = 6.8 ± 7.0 vs. HA = 9.7 ± 5.0 ms·mmHg-1, P < 0.01) and cBEIALL (PAH = 0.4 ± 0.2 vs. HA= 0.6 ± 0.1 a.u., P < 0.01) during the sit-to-stand maneuver versus the HA group. The cBEI during the sit-to-stand maneuver was independently correlated to V̇o2peak (partial r = 0.45, P < 0.01). Hyperoxia increased cBRS and cBEI similarly in both groups at rest and during the sit-to-stand maneuver. Therefore, cardiac baroreflex dysfunction was observed under spontaneous and, most notably, provoked blood pressure fluctuations in nonhypoxemic PAH, was not influenced by the peripheral chemoreflex, and was associated with lower V̇o2peak, suggesting that it could be functionally relevant.NEW & NOTEWORTHY Does the peripheral chemoreflex play a role in cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension (PAH)? Here we provide new evidence of cardiac baroreflex dysfunction under spontaneous and, most notably, provoked blood pressure fluctuations in patients with nonhypoxemic PAH. Importantly, impaired cardiac baroreflex effectiveness during provoked blood pressure fluctuations was independently associated with poorer functional capacity. Finally, our results indicated that the peripheral chemoreflex did not mediate cardiac baroreflex dysfunction among those patients.

Incidence of congenital syphilis according to inequalities and living conditions in the city of Recife, Pernambuco, Brazil / Incidência de sífilis congênita segundo as desigualdades na condição de vida no município de Recife, Pernambuco, Brasil

Abstract Objectives: to analyze the variation in the incidence rates of congenital syphilis according to the spatial distribution of Life Condition Index (LCI) among neighborhoods in the city of Recife-PE. Methods: an ecological study, developed from 3,234 cases of congenital syphilis notified in the Sistema de Informação de Agravos de Notificação (Severe Disease Notification Information System), between 2007 and 2016. LCI was built from seven variables related to the dimensions of the environment, education and income, aggregated at the neighborhood levels and spatially distributed in four strata: very high, high, low and very low. The correlation between the rates of congenital syphilis in the strata and LCI was investigated by applying the Spearman correlation coefficient and demonstrated by means of scatter graphics. Results: the mean rate on disease incidence was 6.8 cases per thousand live births. There was a higher incidence in the strata of very low and low living conditions, as well as in Districts that presented poor sanitary conditions and low schooling for the head of the family (District VII), higher proportion of illiteracy among 10 and 14 year olds (District II) and low income of the head of the household (Districts I, II and VII). Conclusions: this study showed the persistence of health inequalities in areas with worse living conditions.

Resumo Objetivos: analisar a variação das taxas de incidência de sífilis congênita segundo a distribuição espacial do Índice de Condição de Vida (ICV) entre os bairros do município do Recife-PE. Métodos: estudo ecológico, desenvolvido a partir de 3234 casos de sífilis congênita notificados no Sistema de Informação de Agravos de Notificação, entre 2007 e 2016. O ICV foi construído a partir de sete variáveis relacionadas as dimensões ambiente, educação e renda, agregadas ao nível dos bairros, e distribuído espacialmente em quatro estratos: muito alto, alto, baixo e muito baixo. A correlação entre as taxas de sífilis congênita nos estratos e o ICV foi investigada aplicando-se o coeficiente de correlação de Spearman e demonstrada por meio de gráficos de dispersão. Resultados: a taxa média de incidência da doença foi de 6,8 casos por mil nascidos vivos. Houve maior incidência nos estratos de condição de vida muito baixa e baixa bem como nos Distritos que apresentaram condições sanitárias ruins e baixa escolaridade do chefe da família (Distrito VII), maior proporção de analfabetismo entre 10 e 14 anos (Distrito II) e baixa renda do chefe do domicílio (Distritos I, II e VII). Conclusões: o estudo evidenciou a persistência das desigualdades de saúde nas áreas com piores condições de vida.

Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH. METHODS: 519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing. RESULTS: 85% of the patients were female; the median age was 34[29-42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6-1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07-0.22], p < 0.01) and ΔPA compliance (Coefficient = -2.51, Beta = -0.43, 95% CI [-4.34-(-0.68)], p = 0.01) had the best performance predicting pVO2 (R2 = 0.66). CONCLUSIONS: In conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.

Clinical utility of ventilatory and gas exchange evaluation during low-intensity exercise for risk stratification and prognostication in pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Peak oxygen consumption (pVO2 ), determined from CPET, provides a valuable indication of PAH severity and patient prognosis. However, CPET is often contraindicated in severe PAH and frequently terminated prior to achievement of a sufficient exercise effort. We sought to determine whether in PAH low-intensity [i.e. freewheeling exercise (FW)] exercise reveals abnormal VE /VCO2 and PET CO2 responses that are associated with pVO2 and serve as indices of PAH risk stratification and mortality. METHODS: Retrospective analysis of CPET from 97 PAH patients and 20 age-matched controls was undertaken. FW VE /VCO2 and PET CO2 were correlated with pVO2 % age-predicted. Prognostication analysis was conducted using pVO2 > 65% age-predicted, as known to represent a low mortality risk. Primary outcome was mortality from any cause. RESULTS: FW PET CO2 was correlated with pVO2 (P < 0.0001; r = 0.52), while FW VE /VCO2 was not (P = 0.13; r = -0.16). ROC curve analyses showed that FW PET CO2 (AUC = 0.659), but not FW VE /VCO2 (AUC = 0.587), provided predictive information identifying pVO2 > 65% age-predicted (best cut-off value of 28 mm Hg). By Cox analysis, FW PET CO2 < 28 mm Hg remained a predictor of mortality after adjusting for age and PAH aetiology (HR: 2.360, 95% CI: 1.144-4.866, P = 0.020). CONCLUSION: Low PET CO2 during FW is associated with reduced pVO2 in PAH and provides predictive information for PAH risk stratification and prognostication.

Prognostic value of six-minute walk distance at a South American pulmonary hypertension referral center.

Six-minute walk distance (6MWD) assessment is recommended for pulmonary arterial hypertension multidimensional risk stratification. However, current 6MWD cut-off values were mainly derived from North American and European pulmonary arterial hypertension registries. Therefore, it is unknown if such cut-off values broadly apply to other geographical populations. In this study, we aimed to identify 6MWD cut-off values for Brazilian pulmonary arterial hypertension patients and to contrast our findings to current international Pulmonary Hypertension guidelines recommendations. One-hundred four consecutive pulmonary arterial hypertension patients were allocated in groups according to their 6MWD, considering 50 m as a clinically relevant 6MWD difference. Next, patients were categorized into different 6MWD ranges based on similar survival rates in each group: < 250 m, 250-400 m, and >400 m. The study outcome was all-cause mortality and transplantation according to the 6MWD range. Survival was truncated at five years. Median follow-up period was 4.35 years (0.48-5.00). Survival rates at 1, 2, 3, and 5 years were 96%, 89%, 81%, and 73%, respectively. Cox analyses adjusted for age, sex, and pulmonary arterial hypertension etiology showed that 6MWD < 250 m and >400 m were associated with higher and lower risk of all-cause mortality and transplantation. According to Harrell's c-statistic, the prognostic discrimination of the 6MWD cut-off value identified by the current study was 0.70 while international Pulmonary Hypertension guidelines 6MWD cut-offs value was 0.61. In conclusion, our findings suggest that 6MWD geographical variations should be considered when assessing risk stratification in pulmonary arterial hypertension.

Modified BODE Index to Predict Mortality in Individuals With COPD: The Role of 4-Min Step Test.

BACKGROUND: The BODE (body mass index, air-flow obstruction, dyspnea, exercise capacity) index is a composite prognostic marker that predicts mortality in COPD. It includes body mass index, air-flow obstruction, dyspnea score, and exercise capacity by using the 6-min walk distance. However, a 30-m-long corridor is necessary to perform the test and this limits its use in clinical practice. Step tests may elicit distinct physiologic responses compared with the 6-min walk test but are easy to perform in the office setting. We sought to investigate whether a 4-min step test would be a suitable surrogate of the 6-min walk test, in a modified BODE step index (simplified BODE index), to predict mortality in COPD. METHODS: Individuals with COPD performed a self-paced 4-min step test, and the simplified BODE index was calculated by replacing the 6-min walk distance by the number of steps climbed. Cutoff values were determined by receiver operating characteristic curve analysis as follows: score 0 for >60 steps; score 1 for 50-60 steps; score 2 for 40-49 steps; and score 3 for <40 steps. RESULTS: A total of 186 individuals with COPD were enrolled from 2011 to 2016 (60% males; mean ± SD age, 65 ± 9 y; mean ± SD FEV1, 50 ± 17 L). There were 36 deaths among the study cohort. The simplified BODE index was a prognostic marker, independent of cardiovascular comorbidities and oxygen desaturation (HR 1.12, confidence interval (CI) [1.03-1.22]). Individuals with simplified BODE index scores ≥ 7 were at higher risk of death from any cause (P < .001, log-rank test). CONCLUSIONS: This was the first study, to our knowledge, to show that the 4-min step test as a surrogate of exercise capacity in the BODE index (simplified BODE index) is an independent predictor of mortality in COPD and may help to spread its use among practicing physicians.

Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema.

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V'E)/carbon dioxide output (V'CO2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V'E/V'CO2 ratio in the more dyspnoeic group. V'E/V'CO2 nadir >50 (OR 9.43, 95% CI 5.28-13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28-3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFEContrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased "wasted" ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension / Recomendações para o diagnóstico e tratamento da hipertensão pulmonar tromboembólica crônica da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

RESUMO A hipertensão pulmonar tromboembólica crônica (HPTEC) é uma doença grave e debilitante, causada pela oclusão do leito arterial pulmonar por êmbolos hemáticos e por material fibroso induzido pela presença desses êmbolos. Essa oclusão eleva a resistência vascular e, por consequência, a pressão do território arterial pulmonar, caracterizando a presença de hipertensão pulmonar. Esse aumento da carga imposta ao ventrículo direito leva a progressiva insuficiência do mesmo e, finalmente, ao óbito. No entanto, ao contrário das outras formas de hipertensão pulmonar, a HPTEC possui uma particularidade muito significativa: a existência de tratamento potencialmente curativo através da tromboendarterectomia pulmonar. Dessa forma, o objetivo primordial do manejo deve ser a avaliação do potencial cirúrgico do paciente em um centro de referência em HPTEC. Entretanto, nem todos os pacientes podem ser submetidos à cirurgia. Para esses pacientes outras alternativas terapêuticas viáveis são a angioplastia de artérias pulmonares e o tratamento farmacológico. Nestas recomendações, discutir-se-ão as bases fisiopatológicas para o surgimento de HPTEC, a partir da embolia pulmonar aguda, bem como o quadro clínico apresentado pelo paciente, o algoritmo diagnóstico a ser seguido e as alternativas terapêuticas disponíveis.

Trajetória profissional de treinadores no contexto do esporte paralímpico / Professional trajectory of coaches in the context of paralympic sports / Trajetoria profesional de entrenadores en el contexto del deporte paralímpico

Treinadores do esporte paralímpico apresentam diferenças na atuação comparados a outros treinadores. Assim, o objetivo do presente estudo foi analisar a trajetória profissional dos treinadores da Delegação Paralímpica Brasileira dos Jogos Rio 2016. Este estudo contou com 35 treinadores (idade: 39,7±9,4 anos, tempo de atuação: 10,7±5,4 anos) que responderam a um questionário estruturado com perguntas fechadas relacionadas à sua trajetória e formação profissional. Em relação à formação acadêmica, 97,1% dos treinadores apresentaram graduação em Educação Física, 65,7% cursaram pós-graduação lato sensu e 22,9% pós-graduação stricto sensu (mestrado) na área. Além disso, 65,7% dos treinadores realizaram alguma disciplina na universidade relacionada ao esporte paralímpico e 85% realizaram cursos de formação complementar. Concluimos que os treinadores tiveram oportunidades de aprendizado formal durante a graduação em Educação Física e em outros cursos de formação após a conclusão do curso, bem como oportunidades informais para construírem sua carreira no esporte paralímpico

Paralympic sports coaches work differently from other coaches. This study analyzed the professional trajectory of coaches working with the Brazilian Paralympic Delegation to the Rio 2016 Olympic Games. It included 35 coaches (age: 39.7±9.4; working experience: 10.7±5,4 years) who answered a structured questionnaire with closed-ended questions related to their history and professional training. As for academic training, 97.1% held degrees in Physical Education; 65.7% held specialization diplomas; and 22.9% held master's degrees in the area. In addition, 65.7% of the coaches attended some collegelevel course on Paralympic sports and 85% attended complementary training courses. We concluded that coaches had formal learning opportunities during their undergraduate training in Physical Education and other courses after that, as well as informal opportunities to build their career in Paralympic sports

Los entrenadores del deporte paralímpico presentan diferencias en su actuación en comparación a otros entrenadores. El objetivo del presente estudio fue analizar la trayectoria profesional de los entrenadores de la Delegación Paralímpica Brasileña de los Juegos Río 2016. Este estudio contó con 35 entrenadores (edad: 39,7±9,4 años, tiempo de actuación: 10,7±5,4 años) que respondieron a un cuestionario estructurado con preguntas relacionadas a su trayectoria y formación profesional. En lo referente a formación académica, el 97,1% de los entrenadores eran graduados en Educación Física, 65,7% cursó postgrado lato sensu y 22,9% posgrado strito sensu en el área. Además, 65,7% de los entrenadores realizaron alguna disciplina en la universidad relacionada deporte paralímpico y el 85% realizaron cursos de formación complementaria. Concluimos que los entrenadores tuvieron oportunidades de aprendizaje formal durante su graduación en Educación Física y en otros cursos de formación después de la conclusión del curso, así como oportunidades informales para construir su carrera en el deporte paralímpico

Does oxygen pulse trajectory during incremental exercise discriminate impaired oxygen delivery from poor muscle oxygen utilisation?

A flattened or decreasing O2 pulse trajectory during incremental CPET is commonly found in patents with low exercise stroke volume but not in those with severely impaired muscle O2 utilisation. This finding should prompt additional cardiovascular work-up. http://bit.ly/2HRE739.

Carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension.

KEY POINTS: Dysfunction of post-exercise cardiac autonomic control is associated with increased mortality risk in healthy adults and in patients with cardiorespiratory diseases. The afferent mechanisms that regulate the post-exercise cardiac autonomic control remain unclear. We found that afferent signals from carotid chemoreceptors restrain the post-exercise cardiac autonomic control in healthy adults and patients with pulmonary arterial hypertension (PAH). Patients with PAH had higher carotid chemoreflex sensitivity, and the magnitude of carotid chemoreceptor restraint of autonomic control was greater in patients with PAH as compared to healthy adults. The results demonstrate that the carotid chemoreceptors contribute to the regulation of post-exercise cardiac autonomic control, and suggest that the carotid chemoreceptors may be a potential target to treat post-exercise cardiac autonomic dysfunction in patients with PAH. ABSTRACT: Dysfunction of post-exercise cardiac autonomic control predicts mortality, but its underlying mechanisms remain unclear. We tested whether carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy adults (HA), and whether such restraint is greater in patients with pulmonary arterial hypertension (PAH) who may have both altered carotid chemoreflex and altered post-exercise cardiac autonomic control. Twenty non-hypoxaemic patients with PAH and 13 age- and sex-matched HA pedalled until 90% of peak work rate observed in a symptom-limited ramp-incremental exercise test. Recovery consisted of unloaded pedalling for 5 min followed by seated rest for 6 min. During recovery, subjects randomly inhaled either 100% O2 (hyperoxia) to inhibit the carotid chemoreceptor activity, or 21% O2 (normoxia) as control. Post-exercise cardiac autonomic control was examined via heart rate (HR) recovery (HRR; HR change after 30, 60, 120 and 300 s of recovery, using linear and non-linear regressions of HR decay) and HR variability (HRV; time and spectral domain analyses). As expected, the PAH group had higher carotid chemosensitivity and worse post-exercise HRR and HRV than HA. Hyperoxia increased HRR at 30, 60 and 120 s and absolute spectral power HRV in both groups. Additionally, hyperoxia resulted in an accelerated linear HR decay and increased time domain HRV during active recovery only in the PAH group. In conclusion, the carotid chemoreceptors restrained recovery of cardiac autonomic control from exercise in HA and in patients with PAH, with the restraint greater for some autonomic indexes in patients with PAH.