Multidimensional frailty and its association with quality of life and disability: A cross-sectional study in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) have a high risk of frailty. We aim to evaluate frailty using the Tilburg frailty indicator (TFI), a multidimensional self-reported questionnaire, and to explore its relationship with autonomy, quality of life (QoL), and disability. METHODS: All the patients with MS enrolled completed TFI (frail when TFI score ≥ 5 points), the Groningen Activities Restriction Scale to evaluate autonomy, and the Multiple Sclerosis Impact Scale-29 to evaluate QoL. We collected the Expanded Disability Status Scale (EDSS) score, age and gender. Data were analysed using descriptive analyses, hierarchical multiple regression, and ANCOVA. RESULTS: A total of 208 pwMS (mean age 44 years, SD=11; 75% women; 89.4% relapsing-remitting) were enrolled. The mean TFI total score was 5.7 points (SD=3.0; range 0-14), with the 62.5% of participants exhibiting frailty. After controlling for age and gender, the EDSS score was associated with the total (ß=0.469; R2=0.255; p<0.001) and the physical (ß=0.571; R2=0.349; p<0.001) frailty score, with an explained variance of 25.5% and 34.9%, respectively. No relationships between the EDSS and psychological and social frailty domains were detected. The proportion of frail patients with EDSS ≥ 6.0, EDSS within 3.5-5.5, and EDSS ≤ 3.0 was 91.7%, 83.3%, and 66.0%, respectively. Frail patients exhibited higher autonomy impairment (p = 0.017) and worse QoL (p<0.001). DISCUSSION: We found a high frequency of frail patients with MS. Frailty is more common in patients with higher disability, but it affects also those with low EDSS. In people with MS frailty could be influenced by factors other than disability.

Efficiency of aseptic open vitrification and hermetical cryostorage of human oocytes.

The present study reports, as far as is known for the first time, the safety of UV sterilization of liquid nitrogen and hermetical cryostorage of human oocytes by comparing the efficiency of fresh and vitrified sibling oocytes of infertile patients. A prospective randomized study on sibling oocytes of 31 patients was carried out. Metaphase-II oocytes were randomized for intracytoplasmic sperm injection and the supernumerary sibling oocytes were vitrified using a novel Cryotop aseptic procedure (UV liquid nitrogen sterilization and hermetical cryostorage). After unsuccessful attempts with fresh oocytes, vitrified sibling oocytes were injected. Mean outcome measures observed were fertilization, cleavage and top-quality embryo rates. No significant differences were observed between the fresh and vitrified-warmed sibling oocytes: oocyte fertilization was 88.3% versus 84.9%; cleavage 72.6% versus 71.0%; top-quality embryos 33.8% versus 26.3% and mean number of transferred embryos 2.6 ± 0.1 versus 2.5 ± 0.1, respectively. Clinical pregnancy rate per cycle with vitrified-warmed oocytes was 35.5% (implantation rate 17.1%) and seven healthy babies were born. This study demonstrated that UV liquid nitrogen sterilization and hermetical cryostorage does not adversely affect the developmental competence of vitrified oocytes, allowing safe aseptic open vitrification applicable under strict directives on tissue manipulation.

Parental history of premature myocardial infarction is a stronger predictor of increased carotid intima-media thickness than parental history of hypertension.

An increased carotid intima-media thickness (IMT) is detectable in young subjects with parental history of premature myocardial infarction (PHPMI) or hypertension (PHH). In this study we evaluated if PHPMI and PHH exert a different influence on carotid IMT and if their conjunction produces additive effects. High-resolution B-mode ultrasonographic evaluation of common carotid artery IMT was acquired from 48 subjects without PHPMI and PHH (22 males, 26 females; mean age 22.1±4.9 years; controls), 24 age- (±1 year) and sex-matched subjects with PHH without PHPMI (PHH-positive/PHPMI-negative subjects), 24 age- and sex-matched subjects with PHPMI without PHH (PHH-negative/PHPMI-positive subjects) and 24 age- and sex-matched subjects with both PHPMI and PHH (PHH/PHPMI-positive subjects). Lipid profile, resting blood pressure, smoking behaviour and body mass index (BMI) were also assessed. Carotid IMT was smaller in controls (0.41±0.07mm) compared to PHH-positive/PHPMI-negative subjects (0.47±0.10, p=0.023), to PHH-negative/PHPMI-positive subjects (0.54±0.11, p<0.001) and to PHH/PHPMI-positive subjects (0.52±0.10mm, p<0.001). Carotid IMT was greater in PHH-negative/PHPMI-positive (p=0.006) and in PHH/PHPMI-positive (p=0.031) than in PHH-positive/PHPMI-negative subjects. No difference in carotid IMT was evident between PHH-negative/PHPMI-positive and PHH/PHPMI-positive subjects (p=0.549). In the comparison among subjects using multiple regression analysis, only PHPMI, age and BMI were independently associated with carotid IMT. In healthy young subjects with PHPMI and/or PHH, carotid IMT is increased. PHPMI is a stronger predictor of increased carotid IMT than PHH. PHH in conjunction with PHPMI does not add any further detrimental effect on carotid IMT.

Use of NaCl saline hydration and N-Acetyl Cysteine to prevent contrast induced nephropathy in different populations of patients at high and low risk undergoing coronary artery angiography.

AIM: Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48-72 h of exposure to intravascular radiographic contrast medium that is not attributable to other causes. In international literature a 25% increase in serum creatinine levels or an increase in absolute values of 0.5 mg/dL from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2% to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis authors evaluated the use of NaCl saline hydration and N-acetyl cysteine (NAC) to prevent CIN in different populations of patients at high and low risk undergoing coronary artery angiography. METHODS: From January 2007 to December 2008, 597 patients underwent coronary artery angiography with a low osmolarity contrast agent. Nephrotoxic drugs such as diuretics, metformin, ACE-I and ARBs were stopped at least 24 h before the procedure. The population was divided into two groups: group A (high risk 342 patients, 57.2%) identified for the presence of at least one risk factor such as diabetes, age >65 years, baseline creatinine >1.4 mg/dL and group B (low risk 255 patients, 42.8%) for the absence of any of the risk mentioned above. Only group A was treated with a saline hydration (1 mL/kg/h) plus NAC 600 mg 12 h before and 12 h after the procedure. RESULTS: The overall incidence of CIN was 6.7% (40 patients). In particular, the incidence of CIN was 4.4% (15 patients) in the group A and 9.8% (25 patients) in the group B respectively (P=0.017). Interestingly, the Contrast Index (volume administrated/theoretical maximum volume) was significantly lower in group B (P<0.005). In the multivariate analysis, including risk factors such as age, diabetes, hypertension, hypercholesterol-mia, current smoke, baseline creatinine level, Contrast Index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (P=0.001). CONCLUSIONS: The hydration with saline and NAC is an effective and low-cost tool in preventing CIN in patients undergoing coronary artery angiography and, according to the current guidelines, should be used in all high-risk patients. Present results show that even in patients at low risk for CIN, hydration could be useful: in fact, despite the Contrast Index was significantly lower in this population, the incidence of CIN was greater, thus suggesting a potential role for hydration also in the low-risk population.

Left atrial myocardial function in either physiological or pathological left ventricular hypertrophy: a two-dimensional speckle strain study.

BACKGROUND: Atrial function is an integral part of cardiac function that is often neglected. The presence of left ventricule hypertrophy (LVH) due to arterial hypertension may impair atrial function. However, it has also been suggested that physical training attenuates the age-associated impairment of diastolic filling. This study investigated whether mechanical dysfunction in the left atrium (LA) is present in patients with either physiological or pathological LVH, using two-dimensional strain rate imaging (2D strain echocardiography; 2DSE). METHODS: Standard echocardiography, exercise stress echo and 2DSE of the left atrium were performed in 40 patients with arterial hypertension, 45 age-matched elite athletes (>40 years) and 25 healthy sedentary controls. Atrial longitudinal strain was performed from the apical views for the basal segments of the LA septum, lateral wall and roof. RESULTS: LV mass index and ejection fraction were comparable between patients with either physiological or pathological LVH. Elite athletes showed increased LV end-diastolic diameter, end-diastolic volume and stroke volume, whereas circumferential end-systolic stress was higher in patients with hypertension. LA diameter and maximum volume were increased but similar between the two groups of patients with LVH. LA active emptying volume and fraction were both higher in patients with hypertension. Conversely, peak systolic myocardial atrial strain was significantly reduced in patients with pathological LVH compared with controls and athletes for all the analysed atrial segments (p<0.0001). Using multivariate analysis, LV end-diastolic volume/body surface area (BSA) (beta coefficient 0.52; p<0.0001) and LV mass (beta = 0.48; p<0.001) in athletes emerged as the only independent determinants of LA lateral wall peak systolic strain. In contrast, in patients with hypertension, an independent negative association of LA lateral wall peak systolic strain with both LV mass (beta = -0.42; p<0.001) and circumferential end-systolic stress (beta = -0.43; p<0.001) was found. In addition, in the overall population of patients with LVH, LA lateral wall systolic strain (beta = 0.49; p<0.0001) was a powerful independent predictor of maximum workload during exercise testing. CONCLUSIONS: 2DSE represents a promising, non-invasive, simple and reproducible technique to assess LA myocardial function in patients with either physiological or pathological LVH. LA myocardial deformation is impaired in patients with hypertension compared with age-matched sedentary controls and elite athletes, and is closely associated with functional capacity during effort.

Prognostic value of intra-left ventricular electromechanical asynchrony in patients with mild hypertrophic cardiomyopathy compared with power athletes.

OBJECTIVES: We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential diagnostic tools and predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM) compared with power athletes. BACKGROUND: the distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function. METHODS: The study population comprised 70 young patients with HCM (mean (SD) age 29.4 (5.9) years) with mild septal hypertrophy (15-19 mm) and 85 age and sex matched athletes with septal thickness >12 mm, followed up for 44.4 (10.8) months. Using pulsed DMI, myocardial peak velocities, systolic time intervals, and myocardial intraventricular and interventricular systolic delays were measured in six different basal myocardial segments. RESULTS: DMI analysis showed in HCM lower myocardial both systolic and early diastolic peak velocities of all the segments. Patients with HCM also showed significant interventricular and intraventricular delay (p<0.0001), whereas athletes showed homogeneous systolic activation of the ventricular walls. During the follow up, seven sudden deaths occurred in the HCM group, while no cardiovascular event was observed in the group of athletes. In patients with HCM, intraventricular delay on DMI was the most powerful independent predictor of sudden cardiac death (p<0.0001). An intraventricular delay >45 ms identified with high sensitivity and specificity patients with HCM at higher risk of ventricular tachycardia and cardiac events (test accuracy 90.6%). CONCLUSIONS: DMI may be a valid supporting tool for the differential diagnosis between HCM and "athlete's heart". In patients with HCM, DMI indexes of intraventricular delay may provide additional information for selecting subgroups of patients with HCM at increased risk of ventricular arrhythmias and sudden cardiac death at follow up. Accordingly, such patients may benefit from early intensive treatment and survey. MINIABSTRACT: Doppler myocardial imaging may represent a valid supporting tool for the differential diagnosis between mild hypertrophic cardiomyopathy (HCM) and "athlete's heart". In patients with HCM, DMI indexes of intraventricular delay may provide additional information for selecting subgroups of patients with HCM at increased risk of ventricular arrhythmias and sudden cardiac death at follow up.

Effects of different dopaminergic antagonists on bromocriptine-induced inhibition of norepinephrine release.

In this study we evaluated the effects of placebo or acute bromocriptine (BC) administration (2.5 mg orally) on plasma catecholamines, systolic and diastolic blood pressure (BP), heart rate, and plasma PRL in six normal subjects [group I, mean age 33.2 +/- 5.4 (SD) yr] in the supine as well as upright position. BC induced a significant decrease in plasma norepinephrine in the supine [167.7 +/- 16.8 (SEM) vs. 101.9 +/- 33.7 pg/ml, P less than 0.005] and upright positions [397.3 +/- 27.7 vs. 211.3 +/- 26.7 pg/ml, P less than 0.005], a decrease in systolic and diastolic BP and a decrease in plasma PRL (P less than 0.01). After standing, epinephrine levels increased significantly (53.6 +/- 11.8 vs. 226.4 +/- 71.0 pg/ml, P less than 0.05). The study was repeated in a second group of seven normal subjects (mean age, 32.3 +/- 12.9 yr) after placebo or metoclopramide (20 mg orally) plus BC. In this group metoclopramide, a central and peripheral antidopaminergic agent, counteracted the BC-induced effects found in group I, both in the basal and stimulated conditions. Plasma PRL increased significantly (P less than 0.025). Finally, to assess the effect of peripheral dopaminergic blockade on BC-induced changes in sympathetic outflow, we repeated the study in seven normal subjects (group III, mean age, 30.1 +/- 5.0 yr) after placebo or domperidone (20 mg orally) plus BC. Domperidone blocked the effects of BC on norepinephrine and BP in the supine position. On standing there was a significant decrease in systolic (P less than 0.05) and diastolic (P less than 0.05) BP and an increase in epinephrine levels (58.9 +/- 12.2 vs. 109.8 +/- 24.6 pg/ml, P less than 0.05) was still observed. Plasma PRL increased significantly (P less than 0.025). The results of this study suggest that the inhibition of sympathetic outflow induced by BC is peripherally mediated. As peripheral dopamine receptor blockade did not counteract all the effects after BC during standing, dopaminergic modulation of central reflex sympathetic activation is suggested.

QT/QS2 ratio as an index of autonomic tone changes.

The effects of changes in sympathetic tone on QT/QS2 ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS2 intervals in each test. In basal conditions, the QT/QS2 ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the QT/QS2 ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the QT/QS2 ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the QT/QS2 ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in QT/QS2 ratio. Therefore, the QT/QS2 ratio might represent a reliable index of sympathetic cardiac tone.

[Media-intima thickness: what is it? how is it measured? what is its clinical significance? what are the pending problems?]. / Lo spessore medio-intimale: che cosa è? Come si misura? Qual è il suo significato clinico? Quali sono i problemi da risolvere?

During the past 20 years, several hundred peer-reviewed publications have documented the critical scientific steps in the determination of the usefulness of B-mode ultrasound measurements of the carotid artery intima-media thickness (IMT) for the detection and monitoring of artery wall atherosclerotic disease. Since the initial validation study of the IMT, carotid ultrasound IMT measurements have been performed in a large number of individuals with "traditional" and "non traditional" cardiovascular risk factors, have been shown to correlate with the severity of atherosclerotic lesions in other vascular territories, and have been used as outcome measures in clinical trials evaluating the various effects of treatment on the progression/regression of atherosclerosis. Furthermore, in longitudinal studies, carotid IMT has been shown to be an independent predictor of stroke and coronary events. However, before this powerful indicator of arterial wall atherosclerotic disease can be used in clinical settings as a routine test for the prediction of an individual's cardiovascular risk, some unresolved issues need to be addressed.

Early increase of carotid intima-media thickness in children with parental history of premature myocardial infarction.

BACKGROUND/OBJECTIVE: Increased carotid intima-media thickness (IMT) is an early manifestation of atherosclerosis. Our group has previously demonstrated that a parental history of premature myocardial infarction (PHPMI) is associated with an increase in carotid IMT in children-adolescents (mean age 13 years) and young adults (mean age 24 years). The aim of the present study was to evaluate if carotid structural changes are detectable in young children with PHPMI. METHODS: 26 healthy children (9 males and 17 females; 5-12 years, mean age 9.1 (2.5) years) with PHPMI and 26 age-matched (plus or minus 1 year), sex-matched and body mass index-matched (BMI; plus or minus 20%) control subjects were enrolled in the study. They underwent high resolution B-mode ultrasonographic evaluation of common carotid artery IMT. Lipid profile, resting blood pressure and BMI were also evaluated. RESULTS: Compared to controls, subjects with PHPMI had increased IMT of common carotid arteries (mean of combined sites: 0.444 (0.076) mm versus 0.382 (0.062) mm in controls, p = 0.001). Offspring of coronary patients showed an unfavourable lipid profile compared to controls; however, the association between a PHPMI and carotid IMT was independent of lipids, apolipoproteins and other traditional risk factors. CONCLUSIONS: Vascular structural changes are detectable in subjects with PHPMI at a young age and occur independently of several traditional cardiovascular risk factors.

Estrogen receptor polymorphism, estrogen content and idiopathic scoliosis in human: a possible genetic linkage.

Idiopathic scoliosis (IS) is a largely diffused disease in human population but its pathogenesis is still unknown. There is a relationship between scoliotic phenotype and the patient age, since in the early stage the pathology shows a ratio of 50% between male and female teenagers. During puberty the sex ratio is 8.4/1 (female/male), suggesting a sex-conditioned manifestation of the disease. Genetic inheritance of idiopathic scoliosis is still unclear although some authors claim for its X-linked dominant inheritance. There is large agreement in considering the IS as a sex-conditioned disease, in terms of steroid content and their receptor activity, although no evidence has been found yet. The blood content of 17beta-estradiol in teenagers with IS shows lower levels than teenagers of the same age without IS. Also testosterone and progesterone content are lower in IS girls with respect to the control girls. Furthermore, we extracted DNA from white blood cells of IS patients and their relatives until the third generation in order to examine estrogen receptor alpha polymorphisms, considering this tool a plausible molecular marker for IS prognosis. In this respect, we identified four polymorphisms in the exons encoding for the steroid binding domain and two other in the trans-activation domain. Our results show a clear relationship with clinical manifestation of IS.

Right bundle branch block, persistent ST-segment elevation in V1-V3 and sudden cardiac death: always a distinct syndrome?

Right bundle branch block, persistent ST segment elevation in right precordial leads and sudden cardiac death, unexplainable by currently known disease, define a new distinct clinical and electrocardiographic syndrome. This report describe a patient with these features, whose physical examination, echocardiography, chest computed tomography and right ventricular angiography were normal. However, despite the negativity of these examinations, cardiac nuclear magnetic resonance allowed the identification of right ventricular dysplasia. Thus, right ventricular dysplasia should be considered in the differential diagnosis of the syndrome characterized by right bundle branch block, persistent ST segment elevation and sudden cardiac death.