Unsuccessful linguistic validation of the Symptom Questionnaire for assessing quality of life in Polish patients with pelvic vein disorders.

Pelvic venous disorder (PeVD) is a prevalent chronic condition characterized by the presence of varicose veins in the pelvis, leading to the development of chronic pelvic pain. Despite the growing interest in assessing quality of life in PeVD, well-designed and validated disease-specific questionnaires are missing. The objective of this study was a linguistic and clinical validation of the Symptom Questionnaire (SQ) in a cohort of Polish females with pelvic vein incompetence. The Polish version of SQ was developed using a standardized validation process that involved a back-and- forth translation protocol. A total of 58 female patients diagnosed with pelvic varicose veins, representing diverse educational back- grounds, participated in the study. Multiple issues were observed during linguistic validation, primarily originating from disparities between the Polish and British healthcare systems, as well as differing levels of sexual health education of those two populations. Cronbach α was calculated separately for each part of the questionnaire with results exceeded 0.6 for each section. Test-retest analysis indicated most Pearson correlation coefficients surpassing 0.70. The absolute agreement consistency between pretest and post-test measures, evaluated using the Intra Class Correlation (ICC), exceeded 0.8 in three sections and 0.7 in the remaining three sections. However, the clinical validation failed due to the lack of standardized score calculation proposed by the authors of the questionnaire and inaccurately assigned values in the answer key for five questions. Consequently, the practical utility of SQ in daily clinical settings remains uncertain, highlighting the urgent need for the development of a new, user-friendly questionnaire specifically tailored to assess the quality of life in individuals with PeVD.

Cellular therapies in no-option critical limb ischemia: present status and future directions.

Critical limb ischemia - an advanced stage of lower extremity arterial disease with presence of rest pain and/or ischemic ulcers - remains an important cause of major amputations and disability in developed societies. Novel treatment strategies are urgently needed to prevent (or delay) amputations in particular for patients in whom effective revascularization is no longer feasible for anatomic and/or technical reasons (no-option critical limb ischemia - N-O CLI). Cellular therapies have been gaining the growing attention of researchers and clinicians in the last two decades. Several cell types have been used in pre-clinical and clinical studies, and a number of mechanisms have been proposed to contribute to vascular reparation and regeneration in N-O CLI. Although early trials suggested clinical improvement with use of cell-based therapies in N-O CLI, meta-analyses that included randomized controlled trials have not provided definitive conclusions. Fundamental limitations have involved poorly defined cell lines/populations, limited numbers of study participants and limited follow-up periods, and enrolling patients "too sick to benefit" (such as those in Rutherford class 6). Recent advances include standardized "unlimited" sources of therapeutic cells and better understanding of mechanisms that may contribute to vascular reparation and regeneration. Furthermore, based on recent pre-clinical and clinical studies, cell-free preparations (such as microvesicle-based) are being increasingly developed along with advanced therapy medical products consisting of engineered cells and pro-angiogenic factors.

Posture commonly and considerably modifies stenosis of left common iliac and left renal veins in women diagnosed with pelvic venous disorder.

OBJECTIVE: Pelvic venous incompetence or pelvic congestion syndrome (commonly referred to as pelvic venous disorder [PVD]) is increasingly diagnosed, especially in multiparous women. This may be either primary or secondary to pelvic venous outflow obstruction-left common iliac vein (LCIV) or left renal vein (LRV) stenosis. Intravascular ultrasound (IVUS) examination performed in the supine position is commonly used for diagnosis of LRV and LCIV stenosis; however, body position may affect the cross-sectional area (CSA) of both of these veins during IVUS. The aim of the study was to test the hypothesis that postural changes may significantly affect the CSA of the LRV and LCIV. METHODS: A single-arm, single-center cohort study of women suffering from PVD was performed at a tertiary hospital in Poland. It comprised consecutive patients with either pelvic vein reflux or suggestion of LCIV or LRV obstruction but no signs of deep venous thrombosis. IVUS examination of the iliac veins, inferior vena cava, and LRV was performed in the supine position. IVUS of the LRV and LCIV was performed also with a Valsalva maneuver and with patients lying on the left side and standing. A 60% CSA reduction was used as a cutoff value between significant and nonsignificant vein stenosis. RESULTS: A total of 41 women were examined. Significant stenosis of the LRV was seen in 22 patients (55%) supine but in only 4 (10%) patients studied when lying on the left side and in 27 (67.5%) patients studied while standing. Significant stenosis of the LCIV was seen in 26 supine patients (63.4%), in 8 lying on the left side (19.5%), and in 10 (24.4%) standing. CONCLUSIONS: Postural changes dramatically affect CSA of the LCIV and LRV and thus the degree of stenosis in women diagnosed with PVD. Stenosis found in patients while supine often disappears when the position is changed to lying on the left side or to standing. Therapeutic decisions based on assessment of CSA reduction in the supine position are likely to be inadequate.

The role of psychopathology in perceiving, reporting and treating intermittent claudication: a systematic review.

INTRODUCTION: The aim of this systematic review is to investigate the association between mental health and intermittent claudication (IC) perception, reporting and treatment in subjects with peripheral artery disease (PAD). EVIDENCE ACQUISITION: Literature searches of experimental and observational studies published until February 1st, 2016 were conducted using the following electronic databases: Medline/PubMed and Embase. The selection criteria for the studies included a population of patients diagnosed with peripheral artery disease who reported symptoms of intermittent claudication and were assessed for any psychopathological states (depression, anxiety, mood and personality disorders), which in turn were analyzed with regard to the following: IC severity, symptom perception and reporting, patients' quality of life, treatment compliance and its effectiveness. The risk of bias was assessed using Cochrane Collaboration's tool and the Newcastle Ottawa Scales. The strength of recommendations was graded according to GRADE system. EVIDENCE SYNTHESIS: The literature search identified 1598 citations, of which 13 studies with varying risk of bias were included in the review. Depression, anxiety, and personality types were described in more than 800 patients with peripheral arterial disease who suffered from intermittent claudication. With regard to IC perception and reporting, individuals with higher levels of depression had lower levels of pain acceptance, were more dissatisfied with their function and control over function and had a poorer quality of life. In the case of the type D personality, the results were not consistent. Studies assessing the influence of psychopathology on IC severity and treatment also showed discrepant results. Some studies indicated no differences between type D and non-type D patients with regard to the Ankle Brachial Index as well as pain free (PFWD) and maximal walking distances (MWD). On the other hand, others revealed that type D and depressed patients terminated 6MWT prematurely due to the onset of symptoms and experienced a greater annual decline in 6-minute walk distance, fast walking velocity and short physical performance battery. With regard to treatment adherence, patients with no mental problems made the best recoveries. Hostility, aggressiveness and affect-liability were the greatest obstacles to compliance. CONCLUSIONS: Mental disorders might influence the way in which the symptoms of the disease are reported, coped with, and treated. However, the results of the review preclude recommending a routine psychological examination as one of basic diagnostic procedures in patients with peripheral artery disease suffering from IC.

Costs of Real-Life Endovascular Treatment of Critical Limb Ischemia: Report from Poland-A European Union Country with a Low-Budget Health Care System.

BACKGROUND: To analyze the costs of inhospital, percutaneous treatment of patients with critical limb ischemia (CLI) carried out in Poland, a European Union country with a low-budget national health system. METHODS: A retrospective analysis of prospectively collected data on all patients admitted to a tertiary care hospital for endovascular treatment of CLI over 1 year. SETTING: A single, large volume, tertiary angiology center located in Southern Poland. PARTICIPANTS: CLI patients due to aortoiliac, femoropopliteal, or infrapopliteal arterial stenoses or occlusions with indications for first-line endovascular therapy or similar patients who refused open surgical procedure despite having primary indications for vascular surgery. INTERVENTIONS: Direct stenting using bare-metal stents was the primary mode of treatment for lesions located within the aortoiliac and femoropopliteal arterial segments. Plain old balloon angioplasty (POBA) was the second most commonly used technique. For below-the-knee arteries, POBA was the mainstay of treatment, which was occasionally supported by drug-eluting stent angioplasty. Directional atherectomy, scoring balloon angioplasty, or local fibrinolysis was used infrequently. Drug-eluting balloon percutaneous transluminal angioplasty was not used. MAIN OUTCOME MEASURES: The main outcome measures were the mean reimbursement of costs provided by the Polish National Health Fund (NHF) for inhospital treatment of patients for whom endovascular procedures were performed as initial treatment for CLI and the inhospital costs of endovascular treatment calculated by the caregiver in the 2 years since the first procedure. The average total number of days spent in hospital, amputation-free survival (AFS), overall survival (OS), and limb salvage rate (LSR) according to a life-table method were also calculated for the 2 years. RESULTS: In the first year, there were 496 endovascular and 15 surgical hospitalizations for revascularization procedures to treat 340 limbs in 327 patients, with a further 53 revascularization procedures in the second year. There were an additional 90 hospitalizations over the first year and 38 over the second year for CLI-associated cardiovascular comorbidities. The mean reimbursement for hospitalizations of patients included into observation, provided by the NHF, was $4901.94 per patient for the first year and $833.57 per patient alive to the second year. The mean cost of hospitalization for percutaneous revascularization treatment was $3804.25 per patient for the first year and $3340.30 per patient requiring revascularization within the second year. All costs were calculated in constant 2011 USD. The average total number of days spent in hospital was 8.4 days for the first year and 1.97 days per patient alive to the second year. At 1 and 2 years, the AFS was 76.8% and 66.6%, the OS was 86.5% and 77.3%, and the LSR was 89.4% and 86%, respectively. CONCLUSIONS: Endovascular therapy using the currently available techniques can be performed in almost all patients suffering from CLI at relatively low costs, and satisfactory results can be obtained. Physicians play a pivotal role in ensuring quality of treatment and the reduction of treatment cost in these patients.

The effect of the renin-angiotensin-aldosterone system inhibition on myocardial function in early and late phases of dilated cardiomyopathy in Tgaq*44 mice.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) determines progression of heart failure (HF) in humans, and RAAS inhibition is a major therapeutic strategy in HF. AIM: To assess the effect of angiotensin-converting enzyme inhibitor (ACE-I) and aldosterone receptor antagonist (ARA) therapy on the development of HF at its early and late stage in a murine model of dilated cardiomyopathy (Tgaq*44 mice). METHODS: Tgaq*44 mice at the early or advanced stage of HF received combined therapy including ACE-I (perindopril 2 mg/kg) and ARA (canrenone 20 mg/kg). Cardiac function was assessed by magnetic resonance imaging before and after 2 months of treatment. RESULTS: Combined therapy with perindopril and canrenone resulted in preserved systolic function at the early stage and reduced chamber dilatation at the advanced stage of HF in Tgaq*44 mice. CONCLUSIONS: Activation of the RAAS is involved in progression of HF in Tgaq*44 mice with dilated cardiomyopathy. Therapeutic efficacy of ACE-I and ARA to inhibit systolic dysfunction and cardiac chamber dilation depends on the stage of HF development.

Application of magnetic resonance imaging in vivo for the assessment of the progression of systolic and diastolic dysfunction in a mouse model of dilated cardiomyopathy.

BACKGROUND: The impairment of cardiac diastolic function is essential for the development and progression of heart failure, regardless of the systolic performance of the heart. Novel methods of diagnosis of diastolic dysfunction in experimental animals are needed in order to validate the effectiveness of novel heart failure treatment. AIM: The in vivo characterisation of diastolic and systolic function of the heart during heart failure progression in Tgalphaq*44 mice using magnetic resonance imaging (MRI) and original image analysis. METHODS: Cardiac function in vivo in both Tgalphaq*44 and FVB mice was analysed using MRI at 4.7 T. Magnetic resonance imaging was performed using an ECG triggered fast gradient echo (cine-like flow compensated FLASH) sequence. For the assessment of left ventricle (LV) dynamics at least 20 images per cardiac cycle were acquired in the midventricular short-axis projection at the level of papillary muscles. End-systolic (ESA) and end-diastolic (EDA) areas were estimated from the minimum and maximum values found in the area-time plot. Fractional area change (FAC) defined as (EDA-ESA)/EDA, ejection (ER) and filling (FR) rates defined as slope of the beginning part of the systolic and diastolic limbs were calculated. In addition, heart failure progression in Tgalphaq*44 mice was assessed by morphometric parameters (ventricular weight to body weight index and wet to dry lung weight index), level of BNP mRNA expression as well as survival. RESULTS: Systolic function assessed by FAC% and ER was stable but slightly impaired up to 10 months of age in Tgalphaq*44 mice as compared to the FVB mice. After 12 months of age of the Tgalphaq*44 mice there was a progressive deterioration of systolic function (ER at 10, 12, 14 months of age were 0.0188 +/- 0.00434, 0.0140 +/- 0.00474, 0.0115 +/- 0.00469 1/ms, respectively). Diastolic function of the Tgalphaq*44 hearts was preserved or even slightly augmented between 4 and 10 months of age, then at the age of 12 months and later profoundly impaired (FR at 10, 12, 14 months of age were 0.0280 +/- 0.01031, 0.0196 +/- 0.01050, 0.0158 +/- 0.00833 1/ms, respectively). CONCLUSIONS: The MRI allows reliable in vivo assessment of the systolic and diastolic function in Tgalphaq*44 mice. In Tgalphaq*44 mice after few months of stable and compensated phase of the heart failure decompensation develops that involves impairment of both systolic and diastolic and leads to the fully symptomatic dilated cardiomyopathy. The precise molecular mechanisms of the systolic and diastolic dysfunction and their relative contribution to the heart failure progression in Tgalphaq*44 mice remain to be established.

Detection of mitochondrial dysfunction by EPR technique in mouse model of dilated cardiomyopathy.

Tgalphaq44 mice with targeted overexpression of activated Galphaq protein in cardiomyocytes mimic many of the phenotypic characteristics of dilated cardiomyopathy in humans. However, it is not known whether the phenotype of Tgalphaq44 mice would also involve dysfunction of cardiac mitochondria. The aim of the present work was to examine changes in EPR signals of semiquinones and iron in Fe-S clusters, as compared to classical biochemical indices of mitochondrial function in hearts from Tgalphaq44 mice in relation to the progression of heart failure. Tgalphaq44 mice at the age of 14 months displayed pulmonary congestion, increased heart/body ratio and impairment of cardiac function as measured in vivo by MRI. However, in hearts from Tgalphaq44 mice already at the age of 10 months EPR signals of semiquinones, as well as cyt c oxidase activity were decreased, suggesting alterations in mitochondrial electron flow. Furthermore, in 14-months old Tgalphaq44 mice loss of iron in Fe-S clusters, impaired citrate synthase activity, and altered mitochondrial ultrastructure were observed, supporting mitochondrial dysfunction in Tgalphaq44 mice. In conclusion, the assessment of semiquinones content and Fe(III) analysis by EPR represents a rational approach to detect dysfunction of cardiac mitochondria. Decreased contents of semiquinones detected by EPR and a parallel decrease in cyt c oxidase activity occurs before hemodynamic decompensation of heart failure in Tgalphaq44 mice suggesting that alterations in function of cardiac mitochondria contribute to the development of the overt heart failure in this model.

NO and PGI(2) in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy.

OBJECTIVE: The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgalphaq*44 mice). METHODS: Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI(2)-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgalphaq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI). RESULTS: In Tgalphaq*44 mice at the age of 2-4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgalphaq*44 mice at the age of 14-16 months cardiac function was significantly impaired and NO, but not PGI(2)-dependent coronary function was altered. Interestingly, the basal level of PGI(2) in coronary circulation increased fourfold as compared to FVB mice. Cardiac O(2) (-) production increased 1.5-fold and 3-fold in Tgalphaq*44 vs. FVB mice at the age of 2-6 and 14-16 months, respectively, and was inhibited by apocynin. Interestingly, inhibition of NADPH oxidase or NOS-3 normalized augmented PGI(2) production in Tgalphaq*44 mice. There was also an increased expression of gp91phox in Tgalphaq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI(2)-synthase. CONCLUSIONS: In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.

Prostacyclin, but not nitric oxide, is the major mediator of acetylcholine-induced vasodilatation in the isolated mouse heart.

In many species, acetylcholine (Ach) induces coronary vasodilatation via endothelium-derived nitric oxide (NO). The aim of the present study was to examine if this rule pertains also to the coronary circulation of the mouse. We examined the involvement of NO and prostacyclin (PGI2) in the coronary flow response to Ach as compared to response to bradykinin (Bk) in hearts isolated from FVB or C57Bl/6 mice and perfused according to the Langendorff technique. In the isolated mouse heart, response to Ach consisted of two distinct phases: immediate, transient vasodilatation/vasoconstriction (less than 1 min) that differed between FVB and C57Bl/6 mice; and delayed sustained vasodilatation (up to 8 min) that was similar in FVB and C57Bl/6 mice. In FVB mice, the immediate phase of the Ach response consisted of a short-lasting vasodilatation followed by a vasoconstriction. In contrast, in C57Bl/6 mice, the immediate phase of the Ach response consisted exclusively of a short-lasting vasoconstriction. However, both in FVB and C57Bl/6 mice, the delayed vasodilatation was a major part of the coronary flow response to Ach and it was associated with an increase in 6-keto-PGF(1 alpha) concentration in the effluent. L-NAME (5 x 10(-4) M) displayed a minor effect on the delayed phase of the Ach response in either mice strain. In turn, indomethacin (10(-6) M), but not rofecoxib (5 x 10(-6)M), completely inhibited the delayed phase of the Ach response and the concomitant PGI2 release. On the other hand, vasodilatation induced by Bk was markedly inhibited by L-NAME, while it was unaffected by indomethacin in FVB as well as in C57Bl/6 mice. In summary, in the isolated mouse heart, Ach-induced coronary flow response displays an unusual biphasic nature and is mediated in major part by PGI2, but not by NO. Thus, in the isolated mouse heart, in parallel to Bk or other agents that are suited for the functional assessment of NO-dependent endothelial function, Ach should be used to assess PGI2-dependent endothelial function.

Radical scavenging and NO-releasing properties of selected beta-adrenoreceptor antagonists.

It is claimed that novel beta-adrenolytic drugs possess superior antioxidant properties as compared to classical selective or non-selective beta-adrenoceptor antagonists. Here we tested this notion by analyzing radical scavenging properties of selected beta-adrenolytic drugs and their ability to release nitric oxide in biological preparations. Selective beta1-adrenolytics such as nebivolol, atenolol, metoprolol and non-selective beta-adrenolytics with alpha1-receptor blocking properties such as carvedilol and labetalol were chosen for analysis. NO-releasing properties of nebivolol and carvedilol distinguished third generation beta-adrenolytics from their older counterparts while the reactivity towards hydroxyl and peroxyl radicals discerns only carvedilol but not nebivolol. Thus, superior clinical efficacy of third generation beta-adrenolytics may be related to their ability to release NO rather then to their direct antioxidant properties.

Compensation of endothelium-dependent responses in coronary circulation of eNOS-deficient mice.

Nitric oxide plays a fundamental role in the regulation of blood flow. Here we analyzed compensatory mechanisms for the genetic eNOS deficiency in aorta and in coronary circulation. Vasodilation induced by acetylcholine, bradykinin, adenosine, and ADP as well as by S-nitroso-penicillamine (SNAP) was assessed in isolated aorta and in isolated mouse hearts from eNOS-/- and age-matched eNOS+/+ mice. In aorta from eNOS+/+ mice acetylcholine-induced vasodilation was entirely dependent on NO, and this response was absent in aorta from eNOS-/- mice. In eNOS+/+ mouse hearts responses induced by bradykinin, adenosine and ADP were partially dependent on NO, but not on PGI2, cytochrome P450-dependent metabolites, or H2O2. On the other hand, vasodilation induced by acetylcholine involved NO, but not PGI2, in its immediate, short-lasting phase, whereas PGI2 and NO mediated delayed, longer-lasting phase of this response. In eNOS-/- mouse hearts coronary vasodilator function was compensated. Responses induced by acetylcholine and adenosine, but not by bradykinin or ADP, were in part compensated by NO, most likely derived from nNOS. However, the major mechanisms compensating for the loss of eNOS in the coronary circulation did not rely on NO, PGI2, cytochrome P450-derived metabolites of arachidonic acid or on H2O2. Deficiency of eNOS is largely compensated in coronary circulation but not in aorta.