The effects of respiratory exercises on partial pressures of gases and anxiety in the acute phase of COVID-19 infection.

INTRODUCTION: Respiratory exercise in post-COVID-19 significantly improves pulmonary function, exercise capacity and quality of life. Our study aimed to investigate the effect of respiratory exercise on partial pressures of oxygen, carbon dioxide and oxygen saturation in arterial blood and anxiety assessed by the GAD-7 scale in the acute phase of COVID-19 infection. METHODS: The study was conducted at the Clinical Center, Kragujevac, from June to July 2020. The study was a prospective clinical trial and included 62 patients with the acute-phase of COVID-19 infection (61.3% males, mean age 60.82 ± 11.72). The duration of the comprehensive pulmonary rehabilitation program was 14 days ± 2.28 days. Oxygen saturation and heart rate were determined by using the pulse oximeter, oxygen flow, and arterial blood gas analysis values by using the gas analyzer. The anxiety assessment was measured using the Generalized Anxiety Disorder (GAD-7). RESULTS: The values of oxygen saturation significantly differed before and after the respiratory exercise sessions (95.77 vs 98.02, respectively; p < .001). After the respiratory exercise program, significantly lower values of the GAD-7 scale were observed compared to the values before the respiratory exercise program (p = .049). A significant negative correlation was observed between oxygen saturation after respiratory exercise and age and presence of chronic obstructive pulmonary disease (ρ = -0.329; p = .013; ρ = -0.334; p = .009, respectively). GAD-7 score after respiratory exercise negatively correlated with chronic obstructive pulmonary disease and malignancy (ρ = -0.285; p = .025; ρ = -0.350; p = .005, respectively). CONCLUSION: The respiratory exercise program significantly improves oxygen saturation and anxiety levels in COVID-19 patients.

Relationship of reduced cerebral blood flow and heart failure severity in elderly males.

INTRODUCTION: Brain detrimental effects are under-recognised complication of chronic heart failure (CHF). One of the major causes may be cerebral hypoperfusion. This study was designed to investigate the relationship between cerebral blood flow (CBF) and severity of CHF as well as to evaluate its determinants among different parameters of cardiac dysfunction. METHODS: Seventy-one CHF males with NYHA class II and III and 20 control subjects age ≥ 55 years were recruited. CBF was evaluated by colour duplex sonography of extracranial arteries. Echocardiography, 6-min walk test, quality of life and endothelial function were also assessed. Serum NT-pro-BNP and adipokines levels (adiponectin and leptin) were measured. RESULTS: CBF was significantly reduced in elderly patients with CHF compared to healthy controls (677 +/- 170 vs 783 +/- 128 ml/min, p=0.011). Reduced CBF was associated with reduced left ventricular ejection fraction (LVEF) (r=0.271, p=0.022), lower 6-min walk distance (r=0.339, p=0.004), deteriorated quality of life (r= -0.327, p=0.005), increased serum adiponectin (r= -0.359, p=0.002), and NT-pro-BNP levels (r= -0.375, p=0.001). In multivariate regression analysis, LVEF and adiponectin were independently associated with reduced CBF in CHF patients (R(2)=0.289). CONCLUSION: CBF was reduced in elderly males with mild-to-moderate CHF, and was associated with factors that represent the severity of CHF including high serum adiponectin and NT-pro-BNP levels, decreased LVEF, impaired physical performance, and deteriorated quality of life.

Clinical features of hemodialysis patients with intimal versus medial vascular calcifications.

BACKGROUND: Vascular calcifications (VCs) contribute to the massive mortality in hemodialysis (HD) patients. We aimed to identify prevalence and risk factors for arterial medial calcifications (AMCs) versus intimal calcifications (AICs) in a single-center HD population. METHODS: This cross-sectional study included 134 patients, mean age 56.9 +/- 9.7 years, on HD for 8.2 +/- 5.0 years. VCs were scored based on plain radiographs and ultrasonography of the common carotid arteries. RESULTS: Patients were categorized into groups I (13% without VC), II (10% with an AMC pattern), III (24% with an AIC pattern) and IV (53% with a mixed pattern). AIC and mixed patterns were associated with older age (p=0.006 and p=0.004, respectively), and mixed pattern with longer dialysis vintage (p=0.001). Pulse pressure was significantly higher in patients from group III than group IV, and intima-media thickness (IMT) was higher in both groups with AIC. By multivariate analysis, risk factors for any VC were high serum Ca, phosphate, CaxP product, low total protein, high body mass index (BMI), systolic and diastolic blood pressure, IMT and history of smoking. Elevated calcium and/or phosphate predicted an AMC pattern, and high calcium, BMI and IMT an AIC pattern. Finally, high IMT, systolic blood pressure, BMI and older age were predictors of a mixed pattern. CONCLUSION: We observed a very high prevalence of VC, mostly with a mixed AIC+AMC pattern. Apart from well-known risk factors, the data stress the importance of smoking, an under-recognized cause of AMC, and systolic blood pressure for AIC+AMC.

Risk factors for cardiovascular calcifications in non-diabetic Caucasian haemodialysis patients.

BACKGROUND/AIMS: Dialysis patients display an increased mortality which is associated with cardiovascular calcifications. Diabetes mellitus and ethnicity are known factors that affect the extent of cardiovascular calcifications. However, most studies have investigated mixed cohorts with diabetics and/or mixed ethnicity. METHODS: Cardiovascular calcifications were assessed in non-diabetic Caucasian haemodialysis patients by the semiquantitative Adragao calcification score (X-ray pelvis and hands) and a novel composite calcification score encompassing the Adragao score as well as calcifications detected by X-ray of the fistula arm, echocardiography of heart valves and carotid ultrasound. RESULTS: Using multivariate analysis, age, male gender, dialysis vintage, lower Kt/V, calcium-phosphate product, smoking and high-sensitivity CRP were independent risk factors for cardiovascular calcifications as assessed by the Adragao or the composite score. Pulse wave velocity was independently related to both calcification scores. Body mass index, cholesterol, triglycerides, iPTH and serum levels of fetuin-A and uncarboxylated matrix Gla protein were not associated with cardiovascular calcifications. CONCLUSIONS: In our cohort of non-diabetic Caucasian haemodialysis patients, age, male gender, dialysis vintage, smoking, calcium-phosphate product, high-sensitivity CRP and lower Kt/V were independent risk factors for cardiovascular calcifications. Whether lowering the calcium-phosphate product and increasing dialysis efficiency can reduce cardiovascular calcifications in dialysis patients remains to be determined.

Screening of vascular calcifications in patients with end-stage renal diseases.

Vascular calcifications (VC) are a major contributor to the massively increased mortality in hemodialysis (HD) patients. The present study aimed to detect arterial media and intima calcifications in HD patients and to evaluate potential risk factors. 214 patients aged 59.0 +/- 11.0 years on HD for 6.39 +/- 4.59 years were studied. VC were scored based on to plain radiographs. Potential risk factors were assessed. Out of the 214 patients studied, only 14% did not display any detectable VC. Using plain radiographs calcifications could be detected in 136 (63.6%) patients. Calcified plaques on carotid arteries were detected in 168 (78.4%) patients. There was the highest frequency of patients with the most pronounced calcifications. Calcifications of heart valves were detected in 89 (44.1%) patients. Univariante analysis indicate that risk to develop VC is present in older patients, patients with longer dialysis vintage, thicker intima media, higher lumen diameter and mitral valve calcifications. Multivariate multinomial logistic regression analysis revealed these factors as independent predictors of VC in dialysis patients. Our data confirm a high prevalence of VC in HD patients, their association with older ages, longer dialysis vintage, and presence of valvular calcifications and early markers of atherosclerosis.

The influence of various morphologic and hemodynamic carotid plaque characteristics on neurological events onset and deaths.

A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age 65.42 +/- 9.21, and a group of 36 patients with 58 symptomatic carotid stenoses (SCS), mean age 67.63 +/- 8.79, were analyzed prospectively during a 3-year follow-up period. All patients underwent color duplex scan sonography (CDS), carotid arteriography, computed tomography (CT) scan, and neurological examination. The aim of the study was to analyze the correlation between echo plaque morphology (degree and plaque quality), local hemodynamic plaque characteristics, ischemic CT findings, and onset of new neurological events and deaths. The results analysis showed significantly more ACS in the group of 30-49% stenosis (p < 0.001), but significantly more SCS in the group of 70-89% (p < 0.0001) and > or = 90% stenosis (p < 0.05). Fibrous plaque was more frequent in the ACS group (p < 0.001), while ulcerated and mixed plaques were more frequent in the SCS group (both p < 0.0001). In the SCS group, a significantly higher frequency of increased peak systolic and end diastolic velocities was noted at the beginning and end of the study (both p < 0.01), as well as for contralateral common (CCA) or internal carotid artery (ICA) occlusion (p < 0.05 and p < 0.01, respectively), but reduced carotid blood flow volume (p < 0.05) only at the end of the study. In the ACS group, the best correlation with new neurological events and deaths was shown with positive CT findings, peak systolic flow velocity over 210 cm/sec, end diastolic flow velocity over 110 cm/sec, plaque stenosis > or = 70%, plaque ulceration, mixed plaque (all p < 0.0001); stenosis > or = 50% (p < 0.001); and reduced carotid blood flow volume (p < 0.05).

Vascular access calcification predicts mortality in hemodialysis patients.

Vascular calcification is a recognized risk factor for cardiovascular mortality in patients with end-stage renal disease. The aim of this study was to identify risk factors for vascular access calcification and to determine if patients with this disorder are at increased risk of death. Vascular access calcification was found in 49 of 212 hemodialysis patients as measured by plain X-ray (arteriovenous fistula or synthetic graft) in two dimensions. Male gender, diabetes mellitus, and length of time on dialysis were independent predictors for access calcification determined by logistic regression multivariate analysis. Serum parameters were not independently related to access calcification. Kaplan-Meier analysis showed an increased mortality risk, and Cox regression analysis confirmed that vascular access calcification was an independent mortality predictor. Our study suggests that detection of vascular access calcification is a cost-effective method to identify patients at increased mortality risk.

Prognostic value of cardiovascular calcifications in hemodialysis patients: a longitudinal study.

PURPOSE: Cardiovascular calcifications (CVC) are present in up to 70% of non-diabetic dialysis patients. Sparse data are available on predictors of very long-term outcomes of such patients. The Belgrade Aachen Study on Calcification in Hemodialysis patients (BASCH study) aimed to study this using a comprehensive CVC assessment. METHODS: We prospectively analyzed 220 hemodialysis patients followed for a mean of 76 months (median 73 months, range 6-160 months). We compared patients deceased from cardiovascular diseases (CVD) and survivors. Analyses included composite calcification scores (determined by combining ultrasound and X-ray analyses), demographic, clinical and laboratory data and pulse wave velocity (PWV). For survival analysis, patients were divided into group according to quartiles (Q). RESULTS: Compared to survivors, deceased patients from CVD were significantly older, more frequently hypertensive, had shorter dialysis times per week and lower Kt/V values, and they exhibited lower serum fetuin A, osteoprotegerin and hemoglobin as well as higher CRP levels. Composite calcification and Adragao scores were significantly higher in deceased patients from CVD as was PWV. Mean survival was 101 ± 47 months (Q1), 87 ± 51 month (Q2), 66 ± 48 (Q3) and 54 ± 45 months (Q4), p = 0.000. Cox multivariate regression analysis showed that independent predictors for cardiovascular mortality were composite calcification score in the range of third and fourth quartiles. CONCLUSION: Composite calcification score emerged as significant predictors of long-term survival in our group of largely non-diabetic dialysis patient population, finding that should be confirmed by intervention studies.

Relationship between RANKL and neuroendocrine activation in elderly males with heart failure.

The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.

[Rare cardiomyopathy in haemodialysis patients: noncompaction of the ventricular myocardium].

INTRODUCTION: Isolated noncompaction of the ventricular myocardium is a rare, unclassified cardiomyopathy characterized by the presence of numerous prominent trabeculations and deep intratrabecular recesses which communicate with the left ventricular cavity. CASE REPORT: We describe a case of noncompaction of the ventricular myocardium in a 67 years old, asymptomatic patient on regular hemodialysis. The male patient, on haemodilaysis for three and a half yrs (mesangioproliferative glomerulonephritis was a cause of end-stage renal disease), with no previous signs or symptoms of congestive heart failure or ventricular tachycardia or systemic embolisation, had a routine echocardiography assessment. We found enlarged left (60 mm) and right ventricle (32 mm) with small ejection fraction (EF 48%), but the left ventricle wall was thickened (septum 13 mm and posterior wall 13 mm) with many small lacunes and chanells with blood flow in it. Spongious muscle made more than two thirds of the ventricle wall of both chambers. No thrombus was seen. Diastolic dysfunction was also present (EA). DISCUSSION: The most frequent symptoms in these patients are: heart failure, ventricular tachycardia, sudden cardiac death, cardioembolic events and syncopa. Because of that, all patients need oral anticoagulant therapy, and regular Holter ECG--to identify patients with ventricular tachycardia for whom implantabile cardioverter--defbrilator is indicated. CONCLUSION: Although non-compaction left ventricle is a very type of cardiomyopathy, it is important to be aware of its presence and criteria for diagnosis (left ventricle wall thickened with many trabeculations and deep intertrabecular recessess with blood flow in it), and the need for adequate therapy and follow-up.

[Correlation between the inferior vena cava collapsibility and asymptomatic pericardial effusion in hemodialysis patients].

INTRODUCTION: The inferior vena cava collapsibility index is a sign of hypervolemia in hemodialysis patients. Asymptomatic pericardial effusion in these patients can be either a sign of hypervolemia or bad systolic function of the left ventricle, or both. The aim of this study was to assess the incidence of asymptomatic pericardial effusion and its correlation to collapsibility index in haemodialysis patients during 2-year follow-up. RESULTS: Of 115 consecutive hemodialysis patients, at the beginning of the study and on every 6 months we performed: clinical, ECG, echocardiography, laboratory assessment. There was 29 patients with asymptomatic pericardial effusion (25.21%) vs. 86 (74.79%) without asymptomatic pericardial effusion. There was no significant difference considering gender, age, vintage of HD between the groups. Colapsibillity index was statistically significantly lower among the patients with asymptomatic pericardial effusion: 0.39+/-0.09 vs. 0.69+/-0.21 in those without it; p<0.001. Asymptomatic pericardial effusion correlated inversely with colapsibillity index (r=-0.577; p<0.0001) and ejection fraction of left ventricle (r=-0.282; p<0.030) and positively with the dimension of left ventricle in diastole. The colapsibillity index had inverse correlation with asymptomatic pericardial effusion (r=-0.668; p<0.0001), end-diastolic dimension of the left ventricle (r=-0.464; p<0.0001), and only one positive correlation with Kt/V (r=0.294, p<0.002). During the follow-up, 16 pts (13.91%) died: 7 of them had a symptomatic pericardial effusion (43.75%). Factors with greatest relative risk for death were: persistent asymptomatic pericardial effusion (3.48); systolic dysfunction at the second examination (2.95): heart failure (2.88) at the third. CONCLUSION: Colapsibillity index and asymptomatic pericardial effusion are the closely correlated in inverse manner and both are the sign of hypervolemia. Asymptomatic pericardial effusion is also a sign of a bad systolic function and a very bad prognosis.

[Autoimmune thyroid disease--clinical symptoms of associated autoimmunity].

Autoimmune diseases are manifested in a broad spectrum. Classic examples of organ-specific autoimmune disease include Addison's disease, insulin-dependent type-1 Diabetes mellitus, Grave's disease (MGB), and Hashimoto thyroiditis (HT). The initial report of this autoimmune thyroid disease (AITD) dates back to Hakira Hashimoto (1912). In HT, as an organ-specific autoimmune disease, massive infiltration of lymphoid cells and parenchyma destruction are a consistent feature. The infiltration appears to be immune-mediated, primarily lymphocytic (T helper, T suppressor cells), NK cells and B cells. The pathological characteristics of AITD include development of the goitre (atrophic form is not so frequent), impaired thyroid gland function (from hyperthyroidism to subclinical and manifested hypothyroidism) and the formation of antithyroidal antibodies against thyroglobulin (AbTg) and the microsomal antigen (Ab TPO). There is a very good correlation between the antibodies against TPO and the histological findings. Morbus Graves Basedow is characterized by autoimmune hyperthyroidism with goitre, and infiltrative orbitopathy. Autoantibodies against the TSH-receptor molecule on the plasma membrane of the thyroid gland follicles cause a nonphysiological activation and an increase of the cellular function. Besides this hyperthyroidal condition, an autoimmune attack against the retrobulbar tissue leading to endocrine orbitopathy, can be noted in about 40% of patients suffering from MGB.

[Autoimmune haemopoietic disturbances simultaneous with autoimmune thyroid diseases].

Out of 362 patients with diagnosis of autoimmune haemopathy treated in eight-year period at the Hematology centre, concomitant autoimmune thyreoideopathy was confirmed in 22 (5.52%). The most frequent was simultaneous manifestation of pernicious anemia and autoimmune thyreoiditis-Phenomenon was less frequently observed in patients with immune thrombocytopenic purpura and Graves disease. In the subgroup of patients with autoimmune hemolytic anemia, there was no evidence of simultaneous autoimmune thyreoideopathy. General opinion is that etiopathogenesis of these immunological disorders does not include unique mechanism of humoral and cellular immune response; more probable, it is the question of normal immune response regulation impairment, based on the paerticular genetic predisposition.

[Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

[Dilated cardiomyopathy associated with autoimmune disease of thyroid gland].

Congestive heart failure is the main cause of cardiovascular morbidity and mortality with more than one million hospitalizations per year. Dilated cardiomyopathy is one of the main causes of congestive heart failure characterized by diminished function of the left, right or both ventricles and ejection fraction less than 40%. Numerous studies reported that the diseases of thyroid gland among the patients with dilated cardiomiopathy were very frequent: with prevalence from 18% to 49%. The impaired thyroid gland function was found as primary cause of cardiomyopathy in 1% of patients. At the same time, among patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very frequent with low values of T3. According to our results, 29.4% of patients with dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with present antithyroglobin and antimicrosomal antibodies. These patients had lower ejection fraction and worse prognosis. In American College of Cardiology/American Heart Association guidelines for the evaluation and treatment of the congestive heart failure, evaluation of thyroid gland function was recommended; but the evaluation of antitireoglobulin antibodies and free T3 and free T4 was also essential, as was calculation of their ratio. This is the way to discover the autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In patients with dilated cardiomyopathy and low-T3 syndrome, short-term administration of thyroid hormones resulted in improvement of ejection fraction, diminishing of symptoms and better survival.