The effect of lower body negative pressure on phase 1 cardiovascular responses at exercise onset in healthy humans

We tested the hypothesis that vagal withdrawal and increased venous return interact in determining the rapid cardiac output response (Phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood dislocation to the heart by muscle pump action and simultaneously reduce resting vagal activity. At exercise start, we expected larger response amplitude for stroke volume and smaller for heart rate at progressively stronger LBNP levels, so that the cardiac output response would remain unchanged. Ten subjects performed 50 W exercise supine in Control condition and during -45 mmHg LBNP exposure. On single beat basis, we measured heart rate (HR), stroke volume (SV), and we calculated cardiac output (CO). We computed Phase I response amplitudes (A1) using an exponential model. SV A1 was higher under LBNP than in Control (p < 0.05). Conversely, the A1 of HR, was 23 ± 56 % lower under LBNP than in Control (although NS). Since these changes tended to compensate each other, the A1 for CO was unaffected by LBNP. The rapid SV kinetics at exercise onset is compatible with an effect of increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR kinetics. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, as hypothesized, one acting on SV, the other on H

Clinical effectiveness of Enneking appropriate versus Enneking inappropriate procedure in patients with primary osteosarcoma of the spine: a systematic review with meta-analysis

Purpose Primary osteosarcoma of the spine is a rare osseous tumour. En bloc resection, in contrast to intralesional resection, is the only procedure able to provide Enneking appropriate (EA) margins, which has improved local control and survival of patients with primary osteosarcoma of the spine. The objective of this study is to compare the risk of local recurrence, metastases development and survival in patients with primary osteosarcoma of the spine submitted to Enneking appropriate (EA) and Enneking inappropriate (EI) procedures. Methods A systematic search was performed on EBSCO, PubMed and Web of Science, between 1966 and 2018, to identify studies evaluating patients submitted to resection of primary osteosarcoma of the spine. Two reviewers independently assessed all reports. The outcomes were local recurrence, metastases development and survival at 12, 24 and 60 months. Results Five studies (108 patients) were included for systematic review. These studies support the conclusion that EA procedure has a lower local recurrence rate (RR 0.33, 95% CI 0.17-0.66), a lower metastases development rate (RR 0.39, 95% CI 0.17-0.89) and a higher survival rate at 24 months (RR 1.78, 95% CI 1.24-2.55) and 60 months (RR 1.97, 95% CI 1.14-3.42) of follow-up; however, at 12 months, there is a non-significant difference. Conclusions EA procedure increases the ratio of remission and survival after 24 months of follow-up. Multidisciplinary oncologic groups should weigh the morbidity of an en bloc resection, knowing that in the first year the probability of survival is the same for EA and EI procedures. Graphic abstract These slides can be retrieved under Electronic Supplementary Material

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n=3,083) suffered mostly from fatigue (25.5%), headache (10.0%), difficulty concentrating (7.9%), exhaustion/burnout (7.1%), insomnia (6.2%), myalgia (6.7%) and arthralgia (6.3%). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n=3,556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Treating pulmonary hypertension in pediatrics.

INTRODUCTION: Pulmonary hypertension is a hemodynamic condition occurring rarely in pediatrics. Nevertheless, it is associated with significant morbidity and mortality. When characterized by progressive pulmonary vascular structural changes, the disease is called pulmonary arterial hypertension (PAH). It results in increased pulmonary vascular resistance and eventual right ventricular failure. In the vast majority of cases, pediatric PAH is idiopathic or associated with congenital heart disease, and, contrary to adult PAH, is rarely associated with connective tissue, portal hypertension, HIV infection or thromboembolic disease. AREAS COVERED: This article reviews the current drug therapies available for the management of pediatric PAH. These treatments target the recognized pathophysiological pathways of PAH with endothelin-1 receptor antagonists, prostacyclin analogs and PDE type 5 inhibitors. New treatments and explored pathways are briefly discussed. EXPERT OPINION: Although there is still no cure for PAH, quality of life and survival have been improved significantly with specific drug therapies. Nevertheless, management of pediatric PAH remains challenging, and depends mainly on results from adult clinical trials and pediatric experts. Further research on PAH-specific treatments in the pediatric population and data from international registries are needed to identify optimal therapeutic strategies and treatment goals in the pediatric population

Effects of prolonged bed rest on the cardiopulmonary response to postural changes in humans

In order to gain a better understanding of the cardio-pulmonary impairment induced by prolonged bed rest, we measured steady-state oxygen uptake (V\u2019O2) and carbon dioxide output (V\u2019CO2), by Gr\uf8nlund\u2019s algorithm on a breath-by-breath basis, cardiac output (Q\u2019), by open circuit acetylene washout, heart rate (HR), by electrocardiography, and mean arterial pressure (MAP), by fingertip plethysmography, on 18 male subjects (33.1 years \ub1 0.9; 71.1 kg \ub1 1.1; 1.75 m \ub1 0.01) before (BB) and after (AB) 90 days of head down tilt bed rest, in the following conditions : upright and supine posture, both at rest and at the 50 W exercise. The stroke volume (SV) was calculated as the ratio of Q\u2019 to HR. The total peripheral resistance (TPR) was calculated as the ratio of MAP to Q\u2019. V\u2019O2 was lower (p<0.01) supine than upright (0.43 l/min vs 0.52 l/min at rest; 1.06 l/min vs 1.27 l/min at 50W) in BB. In AB, V\u2019O2 was 0.81 l/min at rest and 1.61 l/min at 50W upright, whereas supine it was 0.74 l/min at rest and 1.54 l/min at 50W. All the values in AB were significantly higher than the corresponding values in BB. V\u2019CO2 followed the same patterns as V\u2019O2, so that the gas exchange ratio was the same in all conditions. In BB, Q\u2019 was the same supine and upright. In AB, Q\u2019 was significantly higher supine than upright at rest (6.11 l/min vs 5.40 l/min). All Q\u2019 values observed in AB were significantly higher than the corresponding values in BB (rest: 5.40 vs 4.50 upright; 6.11 vs 5.05 supine. 50 W exercise 8.26 vs 6.99 upright and 9.18 vs 7.38 supine). SV was higher supine than upright (71.2 ml vs 51.2 ml BB, 78.6 vs 55.4 ml AB at rest; 76.9 ml vs 67.2 ml BB, 87.5 ml 70.8 ml AB at 50W). HR was lower supine (70.3 bpm at rest, 95.2 at 50W) than upright (87.8 bpm at rest, 104.7 at 50 W) in BB, and was (77.3 bpm at rest, 103.9 at 50W) and (97.7 bpm at rest, 116.8 at 50 W) in AB. SV was the same in AB as in BB, whereas HR was higher in AB than in BB. MAP was lower supine than upright in AB (94.3 mmHg vs 105.4 mmHg at rest; 101.6 mmHg vs 115.4 mmHg at 50W). In supine posture, MAP was lower in AB than in BB, both at rest and at exercise. TPR was lower supine than upright in AB (17.8 mmHg*min/l vs 21.6 mmHg*min/l at rest; 12.8 mmHg*min/l vs 16 mmHg*min/l at 50W). In supine posture, TPR was lower in AB than in BB, both at rest and at exercise. These results suggest that the cardio-pulmonary system adjusts to reduced blood volume and increased venous compliance essentially by increasing HR, perhaps modulated by increase in sympathetic output tone. The HR increase is larger than the drop in SV, so that Q' is increased in AB. This is coherent with the higher V\u2019O2 levels in AB than in BB at the same power. The V\u2019O2 increase could be mainly due to an impairment of the motor control system after 90 days of bed rest

Effects of prolonged bed rest on the cardiopulmonary response to postural changes in humans

none8In order to gain a better understanding of the cardio-pulmonary impairment induced by prolonged bed rest, we measured steady-state oxygen uptake (V’O2) and carbon dioxide output (V’CO2), by Grønlund’s algorithm on a breath-by-breath basis, cardiac output (Q’), by open circuit acetylene washout, heart rate (HR), by electrocardiography, and mean arterial pressure (MAP), by fingertip plethysmography, on 18 male subjects (33.1 years ± 0.9; 71.1 kg ± 1.1; 1.75 m ± 0.01) before (BB) and after (AB) 90 days of head down tilt bed rest, in the following conditions : upright and supine posture, both at rest and at the 50 W exercise. The stroke volume (SV) was calculated as the ratio of Q’ to HR. The total peripheral resistance (TPR) was calculated as the ratio of MAP to Q’. V’O2 was lower (p<0.01) supine than upright (0.43 l/min vs 0.52 l/min at rest; 1.06 l/min vs 1.27 l/min at 50W) in BB. In AB, V’O2 was 0.81 l/min at rest and 1.61 l/min at 50W upright, whereas supine it was 0.74 l/min at rest and 1.54 l/min at 50W. All the values in AB were significantly higher than the corresponding values in BB. V’CO2 followed the same patterns as V’O2, so that the gas exchange ratio was the same in all conditions. In BB, Q’ was the same supine and upright. In AB, Q’ was significantly higher supine than upright at rest (6.11 l/min vs 5.40 l/min). All Q’ values observed in AB were significantly higher than the corresponding values in BB (rest: 5.40 vs 4.50 upright; 6.11 vs 5.05 supine. 50 W exercise 8.26 vs 6.99 upright and 9.18 vs 7.38 supine). SV was higher supine than upright (71.2 ml vs 51.2 ml BB, 78.6 vs 55.4 ml AB at rest; 76.9 ml vs 67.2 ml BB, 87.5 ml 70.8 ml AB at 50W). HR was lower supine (70.3 bpm at rest, 95.2 at 50W) than upright (87.8 bpm at rest, 104.7 at 50 W) in BB, and was (77.3 bpm at rest, 103.9 at 50W) and (97.7 bpm at rest, 116.8 at 50 W) in AB. SV was the same in AB as in BB, whereas HR was higher in AB than in BB. MAP was lower supine than upright in AB (94.3 mmHg vs 105.4 mmHg at rest; 101.6 mmHg vs 115.4 mmHg at 50W). In supine posture, MAP was lower in AB than in BB, both at rest and at exercise. TPR was lower supine than upright in AB (17.8 mmHg*min/l vs 21.6 mmHg*min/l at rest; 12.8 mmHg*min/l vs 16 mmHg*min/l at 50W). In supine posture, TPR was lower in AB than in BB, both at rest and at exercise. These results suggest that the cardio-pulmonary system adjusts to reduced blood volume and increased venous compliance essentially by increasing HR, perhaps modulated by increase in sympathetic output tone. The HR increase is larger than the drop in SV, so that Q' is increased in AB. This is coherent with the higher V’O2 levels in AB than in BB at the same power. The V’O2 increase could be mainly due to an impairment of the motor control system after 90 days of bed rest.Autore/i del volume: HOPPELER H., REALLY T., TSOLAKIDIS E., GFELLER L., KLOSSNER S.mixedE. Tam; N. Fagoni; M. A. Kenfack; M. Cautero; F. Lador ; C. Moia; C. Capelli; G. FerrettiE. Tam; N. Fagoni; M. A. Kenfack; M. Cautero; F. Lador ; C. Moia; C. Capelli; G. Ferrett

From Local to Global: A Holistic Lung Graph Model

Lung image analysis is an essential part in the assessment of pulmonary diseases. Through visual inspection of CT scans, radiologists detect abnormal patterns in the lung parenchyma, aiming to establish a timely diagnosis and thus improving patient outcome. However, in a generalized disorder of the lungs, such as pulmonary hypertension, the changes in organ tissue can be elusive, requiring additional invasive studies to confirm the diagnosis. We present a graph model that quantifies lung texture in a holistic approach enhancing the analysis between pathologies with similar local changes. The approach extracts local state-of-the-art 3D texture descriptors from an automatically generated geometric parcellation of the lungs. The global texture distribution is encoded in a weighted graph that characterizes the correlations among neighboring organ regions. A data set of 125 patients with suspicion of having a pulmonary vascular pathology was used to evaluate our method. Three classes containing 47 pulmonary hypertension, 31 pulmonary embolism and 47 control cases were classified in a one vs. one setup. An area under the curve of up to 0.85 was obtained adding directionality to the edges of the graph architecture. The approach was able to identify diseased patients, and to distinguish pathologies with abnormal local and global blood perfusion defects