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Brain function relies on sufficient blood flow and oxygen supply. Changes in cerebral oxygenation during exercise have been linked to brain activity and central command. Isometric- and dynamic-resistance exercise-(RE) may elicit differential responses in systemic circulation, neural function and metabolism; all important regulators of cerebral circulation. We examined whether (i) cerebral oxygenation differs between isometric- and dynamic-RE of similar exercise characteristics and (ii) cerebral oxygenation changes relate to cardiovascular adjustments occurring during RE. Fourteen men performed, randomly, an isometric-RE and a dynamic-RE of similar characteristics (bilateral-leg-press, 2-min×4-sets, 30% of maximal-voluntary-contraction, equivalent tension-time-index/workload). Cerebral-oxygenation (oxyhaemoglobin-O2Hb; total haemoglobin-tHb/blood-volume-index; deoxyhemoglobin-HHb) was assessed by NIRS and beat-by-beat haemodynamics via photoplethysmography. Cerebral-O2Hb and tHb progressively increased from the 1st to 4th set in both RE-protocols (p < 0.05); HHb slightly decreased (p < 0.05). Changes in NIRS-parameters were similar between RE-protocols within each exercise-set (p = 0.91–1.00) and during the entire protocol (including resting-phases) (p = 0.48–0.63). O2Hb and tHb changes were not correlated with changes in systemic haemodynamics. In conclusion, cerebral oxygenation/blood-volume steadily increased during multiple-set RE-protocols. Isometric- and dynamic-RE of matched exercise characteristics resulted in similar prefrontal oxygenation/blood volume changes, suggesting similar cerebral haemodynamic and possibly neuronal responses to maintain a predetermined force. [ABSTRACT FROM AUTHOR]

Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin–angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD. [ABSTRACT FROM AUTHOR]

Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001–0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). Methods We first tested SARS-CoV-2–specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19–infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)–positive subjects, vaccinated individuals, non–intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. Results We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2–specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2–specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. Conclusions Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients. [ABSTRACT FROM AUTHOR]

Summary: Patients with kidney failure often present with reduced cardiovascular functional reserve and exercise tolerance. Previous studies on cardiorespiratory fitness examined with cardiopulmonary exercise testing (CPET) in kidney transplant recipients (KTR) had variable results. This is a systematic review and meta‐analysis of studies examining cardiovascular functional reserve with CPET in KTR in comparison with patients with kidney failure (CKD‐Stage‐5 before dialysis, hemodialysis or peritoneal dialysis), as well as before and after kidney transplantation. Literature search involved PubMed, Web‐of‐Science and Scopus databases, manual search of article references and grey literature. From a total of 4,944 identified records, eight studies (with 461 participants) were included in quantitative analysis for the primary question. Across these studies, KTR had significantly higher oxygen consumption at peak/max exercise (VO2peak/VO2max) compared to patients with kidney failure (SMD = 0.70, 95% CI [0.31, 1.10], I2 = 70%, P = 0.002). In subgroup analyses, similar differences were evident among seven studies comparing KTR and hemodialysis patients (SMD = 0.64, 95% CI [0.16, 1.12], I2 = 65%, P = 0.009) and two studies comparing KTR with peritoneal dialysis subjects (SMD = 1.14, 95% CI [0.19, 2.09], I2 = 50%, P = 0.16). Across four studies with relevant data, oxygen consumption during peak/max exercise showed significant improvement after kidney transplantation compared to pretransplantation values (WMD = 2.43, 95% CI [0.01, 4.85], I2 = 68%, P = 0.02). In conclusion, KTR exhibit significantly higher cardiovascular functional reserve during CPET compared to patients with kidney failure. Cardiovascular reserve is significantly improved after kidney transplantation in relation to presurgery levels. [ABSTRACT FROM AUTHOR]

Introduction: Patients with idiopathic pulmonary fibrosis (IPF) have reduced exercise capacity and often present exertional dyspnea and desaturation. The role of autonomic nervous system (ANS) as a pathogenetic contributor to this dysfunction has not been evaluated. Objective: To evaluate whether improvement of arterial oxygen saturation (SpO2) via oxygen supplementation results to ANS function improvement, during steady state submaximal exercise. Methods: This is a secondary analysis of a single‐blind, randomized, placebo‐controlled, cross‐over trial, including 12 IPF patients, with isolated exertional desaturation. Following a maximal cardiopulmonary test, participants underwent two submaximal steady state tests during which they received either supplementary oxygen or medical air. Continuous beat‐to‐beat blood pressure measurements were recorded (Finapres Medical Systems, Amsterdam, The Netherlands). Autonomic function was assessed non‐invasively by heart rate variability (HRV); root mean square of successive differences (RMSSD) and standard‐deviation‐Poincare‐plot (SD1) were used as indices of parasympathetic output. Entropy and detrended fluctuation analysis (DFA) were also used. Results: During rest, oxygen supplementation did not significantly alter RMSSD and SD1. During exercise, subjects presented no significant alterations compared with baseline, in most HRV indices examined. There was no improvement of this behavior with O2‐supplementation. Approximate‐entropy increased during exercise, with no differences between protocols. Conclusions: IPF patients presented an inadequate adaptive response of their ANS to exercise and recovery. Although oxygen supplementation significantly prolonged exercise duration and prevented the substantial exertional desaturation, the blunted vagal response to steady‐state exercise in these patients was not improved, suggesting that acute oxygen supplementation does not sufficiently improve ANS dysfunction in these patients. [ABSTRACT FROM AUTHOR]

Background: The Human Coronavirus Disease 2019 (COVID‐19) is a highly contagious respiratory disorder that may result in acute respiratory distress syndrome. The aim of this review was to investigate the incidence and type of respiratory function abnormalities during the follow‐up of patients who recovered from COVID‐19. Methods: A systematic search of MEDLINE was conducted, utilising various term combinations. Studies that assessed any respiratory function parameter during the re‐evaluation of patients who recovered from COVID‐19 and were published as full‐text articles in English are included in this review. Results: Amongst 183 articles initially retrieved, 8 fulfilled the criteria and were included in this review; they involved a total of 341 adult patients. Four were retrospective studies, one was a prospective cohort study, one was a randomised control trial and two were case reports/case series. The follow‐up time ranged from 1 month since symptom onset to 3 months after discharge. The most frequent abnormality was reduced lung diffusion for carbon monoxide (DLCO), followed by a restrictive pattern. Other findings are the lack of resting hypoxemia, the reduced respiratory muscle strength and the decreased exercise capacity, although relative data are extremely limited. Conclusion: Patients who recovered from COVID‐19 present with abnormal respiratory function at short‐term follow‐up, mainly with reduced lung diffusion and a restrictive pattern. However, results are currently very limited in order safe conclusions to be made, regarding the exact incidence of these abnormalities and whether they may be temporary or permanent. [ABSTRACT FROM AUTHOR]

Background: In patients with idiopathic pulmonary fibrosis (IPF) with isolated exertional desaturation, there are limited data regarding the effectiveness of oxygen supplementation during exercise training; the underlying mechanisms that contribute to these responses are unknown. Objectives: To examine in these IPF patients the effects of oxygen supplementation during submaximal exercise (vs. medical air) on cerebral/skeletal muscle oxygenation and systemic hemodynamics. Methods: In this randomized, cross-over, placebo-controlled trial, IPF patients (n = 13; 63.4 ± 9.6 years) without resting hypoxemia but a significant desaturation during maximal cardiopulmonary exercise testing underwent 2 steady-state exercise trials (65% peak-work-load), breathing either oxygen-enriched or medical air. Cerebral/skeletal muscle oxygenation (near-infrared spectroscopy) and beat-by-beat hemodynamics (photoplethysmography) were monitored. Results: In the air protocol, from the initial minutes of submaximal exercise, patients exhibited a marked decline in cerebral oxygenated hemoglobin (O2Hb) and an abrupt rise in deoxygenated hemoglobin (HHb). Oxygen supplementation alleviated desaturation, lessened dyspnea, and prolonged exercise duration (p < 0.01). Oxygen supplementation during exercise (i) attenuated cerebral deoxygenation (cerebral-HHb: 0.7 ± 1.9 vs. 2.5 ± 1.5 μmol/L, O2 and air protocol; p = 0.009) and prevented cerebral-Hbdifference decline (2.1 ± 2.7 vs. −1.7 ± 2.0 μmol/L; p = 0.001), (ii) lessened the decline in muscle O2-saturation index, and (iii) at isotime exercise, it resulted in lower muscle-HHb (p = 0.05) and less leg fatigue (p < 0.05). No differences between protocols were observed in exercise cardiac output and vascular resistance. Conclusions: IPF patients with isolated exertional hypoxemia exhibit an inability to increase/maintain cerebral oxygenation during submaximal exercise. Correcting desaturation with O2 supplementation prevented the decline in brain oxygenation, improved muscle oxygenation, and lessened dyspnea, suggesting an efficacy of acute oxygen supplementation during exercise training in protecting brain hypoxia in these IPF patients. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is characterized by high cardiovascular risk, which is further amplified during acute COPD exacerbations (AECOPD). Endothelial dysfunction has been previously suggested as one of the potential pathogenetic mechanisms. In order to study the effects of AECOPD on endothelial function assessed by available functional methods, we performed a literature search involving Pubmed and Scopus databases. Eligible studies were those that included adult patients with COPD and evaluated endothelial damage via semi-invasive or noninvasive functional methods, during AECOPD and after recovery or in stable condition. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Endothelial function was significantly impaired during AECOPD compared to recovery/stable condition (SMD: −0.87, 95%CI [−1.19, −0.55]). Patients during AECOPD presented a significantly worse response in endothelium-dependent (flow-mediated dilatation WMD: −2.59, 95%CI [−3.75, −1.42]) and independent vasodilation (nitroglycerine-mediated dilatation WMD: −3.13, 95%CI [−5.18, −1.09]) compared to recovery. Sensitivity analyses confirmed the above results. In conclusion, endothelium-dependent and independent vasodilation is worse during AECOPD compared to the stable condition. Endothelial dysfunction could play a role in the high cardiovascular risk during AECOPD. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease is a debilitating disorder, characterized by airflow limitation, exercise impairment, reduced functional capacity and significant systemic comorbidity, which complicates the course of the disease. The critical inspiratory constraint to tidal volume expansion during exercise (that may be further complicated by the presence of dynamic hyperinflation), abnormalities in oxygen transportation and gas exchange abnormalities are the major pathophysiological mechanisms of exercise intolerance in COPD patients, and thus, exercise testing has been traditionally used for the functional evaluation of these patients. Compared to various laboratory and field exercise tests, cardiopulmonary exercise testing (CPET) provides a thorough assessment of exercise physiology, involving the integrative respiratory, cardiovascular, muscle and metabolic responses to exercise. This review highlights the clinical utility of CPET in COPD patients, as it provides important information for the determination of the major factors that limit exercise among patients with several comorbidities, allows the assessment of the severity of dynamic hyperinflation, provides valuable prognostic information and can be used to evaluate the response to several therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Most studies evaluating predictors of renal replacement therapy (RRT) following cardiac surgery use arbitrary defined limits of preoperative serum creatinine. The aim of this study was to evaluate the effect of preoperative renal function using either estimated-glomerular filtration rate (eGFR) derived using Chronic Kidney Disease-Epidemiology (CKD-EPI) or serum creatinine alone as a predictor for RRT after cardiac surgery.Methods: In this prospective cohort study, baseline, intraoperative, and postoperative data of all patients who underwent an elective, urgent, or emergency cardiac surgery between 2012 and 2016 in a single center were analyzed in order to identify multivariate parameters determining the need for RRT after surgery. For preoperative renal function, we used serum creatinine levels and eGFR-derived CKD-EPI equation. We also divided our cohort into eGFR groups following the thresholds of the currently proposed CKD classification.Results: From the 1,614 patients (mean age: 65.4 ± 10.6 years; male: 77.6%) that constituted the study population, 42 (2.6%) underwent RRT postoperatively. EUROSCORE II, cardiopulmonary bypass time, cross clamp time, red blood cell (RBC) units transfused, type and urgency of surgery, combined/non combined operation, peripheral vascular disease, heart failure, chronic obstructive pulmonary disease, dyslipidemia, and preoperative renal function were all univariately associated with RRT use. Multivariate regression with bootstrap utilization indicated that CKD-EPI eGFR (OR 0.979; 95% CI 0.956-0.998), heart failure with the New York Heart Association class ≥2 (OR 4.695; 95% CI 1.756-14.061) and RBC units transfused (OR 1.287; 95% CI 1.081-1.850) were independently associated with RRT need. When serum creatinine (OR 2.920, 95% CI1.056-8.074) was used in the model, the associations with RRT were also significant.Conclusion: Preoperative renal function, defined by serum creatinine or eGFR by CKD-EPI, NYHA class II-IV, and the number of blood units transfused were all independent predictors of RRT postoperatively. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction leading to unbalanced vasoconstriction and ischemia of renal parenchyma is increasingly proposed as an alternative pathway of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However, human studies investigating the evolution of such phenomena are limited. This study investigated the levels of emerging biomarkers of endothelial function, angiogenesis and hypoxia, in ADPKD patients with different renal function.Methods: The study population consisted of three groups: 26 ADPKD patients with impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45-70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B; eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of renal disease. Circulating levels of endocan (endothelial cell-specific molecule-1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by enzyme-linked immunosorbent assay techniques.Results: Patients in Group A had significantly higher levels of endocan (7.17 ± 0.43 ng/mL), angiopoietin-2 (5,595.43 ± 3,390), and HIF-1a (163.68 ± 37.84 pg/mL) compared to patients in Group B (6.86 ± 0.59 ng/mL, p = 0.017, 3,854.41 ± 3,014.30, p = 0.018, 136.84 ± 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 ± 0.69 ng/mL, 1,069 ± 427.88 pg/mL, 70.20 ± 17.49 pg/mL, p < 0.001 for all comparisons). Of note, patients in Group B had also higher levels of all markers compared to controls (p < 0.001) despite having similar renal function. In correlation analyses within ADPKD patients, we noted strong correlations of all studied markers with asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest correlations with eGFR.Conclusions: This study suggests that endothelial dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia, may come early in the course of ADPKD and could be a key regulator of renal injury progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Respiratory complications remain a major cause of morbidity in cardiac surgery patients. This study aimed to determine the prognostic parameters associated with the application of noninvasive ventilation (NIV) for the treatment of acute respiratory failure, along with the possible predictors associated with NIV failure, among the subjects who underwent cardiac surgery. METHODS: This was a retrospective cohort study. Data on all adult patients who underwent cardiac surgery in a single center between May 2012 and December 2016 were analyzed. Multivariate regression analysis with bootstrapping was used to identify which baseline and intraoperative parameters were associated with the application of NIV to treat acute postoperative respiratory failure. A univariate analysis was also applied to identify potential variables associated with NIV failure. P < .05 was considered significant. RESULTS: A total of 1,657 subjects (mean ± SD age 65.2 ± 10.7 y; 21.7% females) constituted the study population, 145 (8.8%) of whom were treated with NIV due to acute postoperative respiratory failure. Body mass index adjusted odds ratio 1.02, bias-corrected 95% CI 1.01-1.04), EuroSCORE (European System for Cardiac Operative Risk Evaluation) II (adjusted odds ratio 1.11, bias-corrected 95% CI 1.02-1.32), COPD (adjusted odds ratio 4.004, bias-corrected 95% CI 2.53-8.93), and preoperative estimated glomerular filtration rate (adjusted odds ratio 0.99, bias-corrected 95% CI 0.98-0.99) independently predicted NIV application. NIV treatment failed in 16 of the 145 subjects (11%) and age, EuroSCORE II, COPD, heart failure, renal replacement therapy, and postoperative stroke were all univariately associated with the outcome. CONCLUSIONS: NIV successfully treated acute respiratory failure in the vast majority of cardiac surgery subjects and COPD, EuroSCORE II, body mass index, and preoperative renal function were independently associated with its application. [ABSTRACT FROM AUTHOR]

Background/Aims: The pathophysiology of renal disease progression in autosomal dominant polycystic disease (ADPKD) is largely unknown. Recent evidence suggests microvascular dysfunction leading to renal ischemia, as an additional pathway for renal function decline. This study examined the levels of serum Fas ligand (FasL), serum myostatin and urine transforming growth factor-beta 1 (TGF-β1) and their association with markers of endothelial dysfunction, in ADPKD patients with preserved or impaired renal function. Methods: Seventy-eight participants were enrolled in the study, divided in three groups: Group A consisted of 26 ADPKD patients with impaired renal function (eGFR 45-70 ml/min/1.73m2), Group B of 26 ADPKD patients with preserved renal function (eGFR > 70 ml/min/1.73m2), and Group C of 26 age- and sex- matched controls with no history of renal disease. Serum FasL, myostatin and urine levels of TGF-β1 were measured as biomarkers of vascular dysfunction, apoptosis and fibrosis with ELISA techniques. Results: Group A patients had significantly higher levels of FasL (13.12±1.69 ng/mL), myostatin (4.62±0.59 ng/mL) and urine logTGF-β1 (3.56±0.49 ng/24h) compared to Group B (9.6±1.28 ng/mL, 3.06±0.35, and 2.09±0.37, respectively, p< 0.001 for all comparisons) or controls (6.59±1.17 ng/mL, 2.18±0.45 ng/ml, and 1.58±0.21, respectively, p< 0.001 for all comparisons). Patients in Group B had also higher levels of all markers compared to controls (p< 0.001), despite having similar renal function. In ADKPD patients negative associations of eGFR with FasL (r=-0.799, p< 0.001), myostatin (r=-0.856, p< 0.001) and TGF-β1 (r=-0.476, p< 0.001) but positive correlations of these markers with asymmetric dimethylarginine (ADMA) (r=0.825; r=0.749; and r=0.599, respectively p< 0.001) were noted. Multivariate analysis demonstrated that FasL was independently associated with high urine TGF-β1 (OR 3.774, 95%CI 1.180-12.072, p=0.025). Conclusions: ADPKD patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-β1 than controls. These results indicate that an interplay between endothelial dysfunction and renal ischemia with mechanisms linked to apoptosis and fibrosis may be present even in early stages of ADPKD. [ABSTRACT FROM AUTHOR]