Comparison of physical activity and quality of life between obese individuals with obstructive sleep apnea syndrome and individuals with obesity hypoventilation syndrome.

PURPOSE: Obstructive Sleep Apnea Syndrome (OSAS) and Obesity Hypoventilation Syndrome (OHS) share common causal factors and comorbidities but may have a variable effect on physical activity and associated quality of life, due to differences in pathophysiology. The aim of this study was to compare the levels of physical activity, mental health and quality of life between matched obese patients with either OSAS or OHS, aiming to identify which of the two syndromes may impose the most severe impact on these variables, for the first time in literature. METHODS: A total of 76 obese patients (OSAS: Ν1 = 48, OHS: N2 = 26) of similar age (58.2 ± 12.2 vs. 63.6 ± 9.8; p > 0.05), BMI (37.2 ± 6.2 vs. 40.3 ± 7.3; p > 0.05), and Apnea-Hypopnea Index (AHI) under non-invasive ventilation, completed International Physical Activity Questionnaire (IPAQ), Short-Form Health Questionnaire (SF-36), Personal Well-Being (PWB) Scale and Hospital Anxiety and Depression Scale (HADS-A and HADS-D), in this cross-sectional study. RESULTS: Both groups had similar scores in SF-36, HADS-A and HADS-D, while prevalence of clinical cases of anxiety (HADS-A > 8) and depression (HADS-D > 8) were also similar. OSAS patients scored significantly higher in physical activity [absolute IPAQ values 1100.75(7753.5) for OSAS vs. 518(3806) for OHS; p = 0.029]. Group comparisons yielded significant differences in physical functioning (p < 0.05) and general health perceptions (p < 0.05), in favor of the OSAS group. CONCLUSION: Both syndromes significantly affect patients' quality of life and physical activity, with the burden being heavier for OHS patients. Daily physical activity seems to be more impaired among obese OHS patients perhaps due to daytime hypercapnia.

Meta-analysis addressing the impact of cardiovascular-acting medication on peak oxygen uptake of patients with HFpEF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E' ratio study-end values (WMD - 1.64, 95%CI - 2.42 to - 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise.

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.

Brain oxygenation during multiple sets of isometric and dynamic resistance exercise of equivalent workloads: Association with systemic haemodynamics.

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.

Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients.

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.

Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study.

BACKGROUND: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity. METHODS: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test). RESULTS: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 µm and 15.8 ± 1.9 µm vs. 11.5 ± 2.3 µm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001). CONCLUSION: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Cardiorespiratory fitness in kidney transplant recipients compared to patients with kidney failure: a systematic review and meta-analysis.

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 (VO2 peak/VO2 max) 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.

Exertional Desaturation in Idiopathic Pulmonary Fibrosis: The Role of Oxygen Supplementation in Modifying Cerebral-Skeletal Muscle Oxygenation and Systemic Hemodynamics.

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.

Vascular endothelial injury assessed with functional techniques in systemic sclerosis patients with pulmonary arterial hypertension versus systemic sclerosis patients without pulmonary arterial hypertension: a systematic review and meta-analysis.

Microvascular dysfunction is one of the hallmarks of systemic sclerosis (SSc). The presence of pulmonary-arterial-hypertension (PAH) in SSc-patients is associated with poor prognosis. This is a systematic review and meta-analysis of studies assessing microvascular and endothelial injury with functional techniques in SSc-patients with PAH (SSc-PAH) compared to those without PAH (SSc-non-PAH) (PROSPERO: CRD42021236212). Literature search involved PubMed, the-Cochrane-Library, Web-of-Science, Scopus and manual search of article references. Studies assessing microvascular function by all available functional methods were considered eligible. Preclinical studies and studies using structural nailfold-videocapillaroscopy or biomarkers were excluded. Newcastle-Ottawa-Scale (NOS) was applied to evaluate the quality of retrieved studies. From a total of 602 retrieved articles, four studies (n = 159 participants) were included in meta-analysis; three studies were of high quality (NOS ≥ 7). In pooled analysis, a marginally significant impaired microvascular function was observed in SSc-PAH compared to SSc-non-PAH patients [SMD - 0.71, 95% CI (- 1.53, 0.12)], with significant between-study heterogeneity (I2 = 80%, p = 0.002). Among the studies examining endothelium-dependent and -independent vasodilation with LDF-iontophoresis, SSc-PAH subjects had significantly impaired endothelium-dependent-vasodilation [Ach-stimulated %change WMD - 216.79, 95% CI (- 337.87, - 95.71), I2 = 0%, p = 0.40], but no significant differences in endothelium-independent-vasodilation [SNP-stimulated %change WMD 90.84, 95% CI (- 82.52, 264.19), I2 = 44%, p = 0.18] compared with SSc-non-PAH subjects. In sensitivity analysis including only studies where SSc-PAH patients were diagnosed by right-heart-catheterization, a borderline difference between the two groups was noted [SMD - 1.09, 95% CI (- 2.30, 0.13), I2 = 82%, p = 0.004]. SSc-PAH patients showed marginally impaired microvascular function in the pooled analysis, as well as impaired endothelium-dependent-vasodilation in subgroup analysis compared with SSc-non-PAH patients. Vascular endothelial dysfunction could be involved in high cardiovascular risk of patients with SSc and PAH.

Changes in the respiratory function of COVID-19 survivors during follow-up: A novel respiratory disorder on the rise?

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.

Endothelial Dysfunction during Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

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.

Serum Creatinine and Chronic Kidney Disease-Epidemiology Estimated Glomerular Filtration Rate: Independent Predictors of Renal Replacement Therapy following Cardiac Surgery.

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.

Levels of Endocan, Angiopoietin-2, and Hypoxia-Inducible Factor-1a in Patients with Autosomal Dominant Polycystic Kidney Disease and Different Levels of Renal Function.

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.

Serum Fas Ligand, Serum Myostatin and Urine TGF-ß1 Are Elevated in Autosomal Dominant Polycystic Kidney Disease Patients with Impaired and Preserved Renal Function.

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-ß1) 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-ß1 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-ß1 (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-ß1 (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-ß1 (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-ß1 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.

Phenotyping Exercise Limitation in Systemic Sclerosis: The Use of Cardiopulmonary Exercise Testing.

BACKGROUND: Exercise impairment is a common symptom of systemic sclerosis (SSc), a disorder which is frequently complicated by cardiopulmonary involvement. OBJECTIVES: This study's aims were: (a) to define the prevalence and the potential causes of limited exercise capacity and (b) to study potential differences in clinical, radiological and functional characteristics and blood serology among SSc patients with exercise limitation of different etiology. METHODS: Prospectively collected data on SSc patients who had conducted full lung function testing, blood serology, thorax high-resolution computed tomography, Doppler echocardiogram and a maximal cardiopulmonary exercise testing (CPET) were retrospectively analyzed. Using a CPET algorithm, patients were characterized as having normal or subnormal exercise capacity (N), respiratory limitation (RL), left ventricular dysfunction (LVD) or pulmonary vasculopathy (PV). Group comparisons were conducted using either one-way ANOVA or the Kruskal-Wallis test. A p value <0.05 was considered significant. RESULTS: The study population consisted of 78 patients (53.7 ± 13.7 years old; 10.3% male). PV was present in 32.1%, LVD in 25.6% and RL in 10.2%, while 32.1% of the patients constituted the N group. The presence of antisclero-70 antibodies, low anaerobic threshold and low peak exercise capacity measures could discriminate LVD from the other groups. Low end-tidal carbon dioxide pressure and its change from rest to anaerobic threshold could discriminate between the PV, LVD and N groups, while respiratory restriction along with ventilatory inefficiency indices could differentiate the RL group from the rest. CONCLUSIONS: The combined evaluation of CPET gas exchange patterns with baseline measurements could discriminate the causes of exercise limitation among SSc patients.

Resting energy expenditure in OSAS: the impact of a single CPAP application.

PURPOSE: Data on the impact of obstructive sleep apnea syndrome (OSAS) and its treatment on resting energy expenditure (REE) are currently few and conflicting. The purpose of the present study was to investigate the impact of OSAS on REE, as measured before and after sleep, and the changes in REE after a single continuous positive airway pressure (CPAP) application, for the first time in literature. METHODS: This is a nested case-control study. From the initial study population, two groups were formed, based on the results of nocturnal polysomnography: a group of male OSAS patients and a group of male, age-matched non-OSAS controls. REE was measured in both groups before and after sleep by indirect calorimetry, while patients repeated REE measurements before and after a single nasal CPAP application. RESULTS: Ninety-two male OSAS patients (45.3 ± 12.8 years old) and 19 male non-OSAS controls (50.8 ± 11.7 years old) were studied. REE/lean body mass (LBM) was higher among patients compared to controls both pre- (29.6 ± 12 vs 22.9 ± 7.9 kcal/kg; p = 0.022, correspondingly) and post-sleep (26.4 ± 9.6 vs 21.6 ± 9 kcal/kg; p = 0.047 correspondingly). REE/LBM decreased significantly after sleep in OSAS patients (p = 0.002), but not in controls; this difference was most evident among patients with more severe disease and higher desaturation. A single nasal CPAP application diminished the pre-post REE/LBM difference (30.3 ± 8.2 vs 28.3 ± 10.3 kcal/kg; p = 0.265), but only among responders. CONCLUSIONS: In OSAS patients, REE values are high and vary significantly before and after sleep. A single nasal CPAP application diminishes this difference among responders, possibly through reversal of nocturnal desaturation.

Anaemia in chronic obstructive pulmonary disease: an insight into its prevalence and pathophysiology.

Chronic obstructive pulmonary disease (COPD) is a major health problem, with increasing morbidity and mortality. There is a growing literature regarding the extra-pulmonary manifestations of COPD, which can have a significant impact on symptom burden and disease progression. Anaemia is one of the more recently identified co-morbidities, with a prevalence that varies between 4.9% and 38% depending on patient characteristics and the diagnostic criteria used. Systemic inflammation seems to be an important factor for its establishment and repeated bursts of inflammatory mediators during COPD exacerbations could further inhibit erythropoiesis. However, renal impairment, malnutrition, low testosterone levels, growth hormone level abnormalities, oxygen supplementation, theophylline treatment, inhibition of angiotensin-converting enzyme and aging itself are additional factors that could be associated with the development of anaemia. The present review evaluates the published literature on the prevalence and significance of anaemia in COPD. Moreover, it attempts to elucidate the reasons for the high variability reported and investigates the complex pathophysiology underlying the development of anaemia in these patients.