Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis.

BACKGROUND: Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. AIM: To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. DISCUSSION: Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. CONCLUSIONS: Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.

A snapshot of geriatric rehabilitation: one year experience.

OBJECTIVE: Frailty is a common condition in older adults, characterized by multimorbidity, physical weakness and nutritional deficit. Frailty can be detected early and a prehabilitation treatment could reduce the incidence of disability. PATIENTS AND METHODS: Two-hundred-fifteen elderly patients were admitted to the Rehabilitation and Physical Medicine Unit of Policlinico Gemelli for one year. Patients were clinically assessed by Charlson Comorbidity Index (CCI) and blood sample values. Numerical Pain Rating Scale (NRS) and Hand Grip Test were assessed before (T0) and after (T1) hospitalization. Number of drugs and number of infections were recorded. RESULTS: Patients were originally hospitalized in orthopaedic, neurology and medical ward. Most patients (68%) after discharge return home. Negative correlations between albumin and CCI and between total protein and CCI were recorded. Positive correlation between CCI cognitive subscore and number of drugs and a negative correlation between that subscore and Vitamin D were detected. An improvement in NRS and in the handgrip strength was recorded. At discharge an increase in the number of drugs and the number of infections was noted. CONCLUSIONS: The handgrip strength improvement increases quality of life. Pain management and NRS indicate a better recovery of activities of daily living. Malnutrition is a real problem; albumin is the principal negative acute-phase reactant and is related to a worse clinical condition and low vitamin D levels are associated with worse cognitive function. The goal of a Rehabilitation Unit is to create an effective multidisciplinary transitional care plan, involving the patient and caregivers, creating a continuity of care after discharge and a sustainable project.

Arterial involvement in Fabry disease: state of the art and future diagnostic purposes.

Anderson-Fabry disease (FD) is a rare genetic, progressive, and multi-systemic condition, with X-linked inheritance. This is caused by pathogenic variants in the GLA gene, coding for the lysosomal enzyme called alpha-galactosidase A (aGLA), responsible for the cleavage of globotriaosylceramide (Gb3). The reduced or absent activity of aGLA causes the intracellular accumulation of Gb3, particularly in smooth and endothelial muscle cells, which causes cellular dysfunction. The main organs involved are the central nervous system, heart, and kidneys. However, being a ubiquitous enzyme, FD disease must be considered a systemic disease involving the peripheral nervous system, ocular and audio-vestibular systems. Also, the vascular district is damaged but the pathophysiology of vasculopathy in FD is not yet entirely understood. In literature, many vascular diagnostic tests were used to evaluate this specific involvement in FD, i.e., carotid intima media thickness (cIMT), arterial stiffness (AS), flow-mediated dilation (FMD) and atherosclerotic plaques; evaluation of vascular calcifications in FD patients is not presently available. In this review, we examined the current available literature on vascular aspects in FD. Moreover, we presented our global vascular evaluation, based on Radio Frequency Duplex Ultrasound (RF-DU), plaques, and vascular calcifications, to apply to FD patients.

Prehabilitation and heart failure: perspective in primary outcomes, a randomized controlled trial.

OBJECTIVE: Prehabilitation, intended as a multidisciplinary approach where physical training is combined with educational and counselling training, in cardiology could optimizing care, and has been shown to be able to reduce morbidity and mortality in several diseases. The present study aims to assess the effectiveness of a prehabilitation program in elderly patients (over 65) with chronic heart failure and to evaluate functional and quality indices of life. PATIENTS AND METHODS: This is randomized, single blind controlled trial. Fourteen older adult patients diagnosed with chronic heart failure were enrolled. Patients were randomly assigned into the study or the control group. Patients in the study group underwent physical training organized into 10 twice-weekly meetings, nutritional and lifestyle counseling. RESULTS: In the Study Group, the quality of life improved significantly (EQoL-5D), and between the two groups there is a statistically significant difference in the motor dimension of SF-36. CONCLUSIONS: Because of our preliminary results, prehabilitation program should be included among the management strategies of in elderly patients with chronic heart failure to better manage their disease and to improve their Quality of Life.

Probiotics: which and when?

There is a natural feeling between our intestinal flora and the gut. These microorganisms, living in the various tracts of human intestine, may affect the host homeostasis. Some of these bacteria can perhaps be a source of infection and sepsis when the bowel barrier is physically or functionally breached. The term 'probiotic' dates from the beginning of the last century and in the last years a market for probiotics worldwide, estimated to be worth billions of pounds, has developed. Although there is persuasive advertising for probiotics and there have been methodological advances in the study of the intestinal microbiota, much remains unproven, e.g. how probiotics work, which strains are effective, what can be expected to be achieved, and what dosage is required for effectiveness. This review of the literature is an evidence-based guide through the developing microbial universe affecting our life.

Subtrochanteric femoral fracture in a 26 year old woman affected by beta-thalassemia major due to minor trauma: analysis of bone modification causing the complication.

Beta-Thalassemia Major (TM), firstly described by Cooley, is and inherited blood disorder that leads to anaemia due to an imbalanced globin chain synthesis effecting erythroid maturation and red cells survival and requests regular life-long blood transfusions and iron-chelating therapy. Among all the complications and organ diseases, osteopenia and osteoporosis, as progressive diseases are getting important cause of morbidity in a population whose longevity is increasing. The authors describe a case of a 26-year-old female with Beta-Thalassemia Major affected by a subtrochanteric fracture of the right femur on minor trauma. Cardiovascular, endocrinologic and thrombotic pattern leading to bone modifications are reported and Literature reviewed. Fracture was surgically treated with anterograde reconstructive intramedullary locked nail (AFN, Synthes) with 2 distal screws inserted in a static mode.

Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease.

Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36-9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD.

Biomarkers of low-grade inflammation in primary varicose veins of the lower limbs.

OBJECTIVE: To analyze serum biomarkers of CVD in selected patients with primary axial reflux of great saphenous vein in one or both lower limbs. PATIENTS AND METHODS: Ninety-six patients affected by uncomplicated varicose veins, were enrolled in the study. A unilateral, primary axial reflux in great saphenous veins was detected in 54 patients (U-CVD group) and a bilateral one in 42 (B-CVD group). Sixty-five age and sex-matched subjects without venous reflux were enrolled as controls. Mean venous pressure of both lower limbs at the distal great saphenous vein (mGSVP) and venous reflux were measured by continuous-wave Doppler ultrasound and echoduplex scanning, respectively. Reactive Oxygen Species (ROS), tissue Plasminogen Activator (t-PA) and its Inhibitor 1 (PAI-1) activities, Hematocrit (HTC), White Blood Cells (WBC), Neutrophyls (NEU), Platelets (PLT), Fibrinogen (FIB) and Blood Viscosity (BV) were assessed in blood samples drawn from the antecubital vein. RESULTS: B-CVD group showed higher fibrinogen values (p < 0.005) and higher mean venous pressure (0 < 0.0001) in comparison to controls, while U-CVD did not. No difference was found between both groups and controls for all the other parameters. CONCLUSIONS: Increased fibrinogen levels in patients with bilateral varicose veins may represent an early warning signal, as it could be associated to the long-term progression of chronic venous disease.

Hemodynamic and functional consequences of radial artery removal for coronary artery bypass grafting.

Five years after surgery the echo-Doppler characteristics of the forearm circulation and the transcutaneous oxygen and carbon dioxide pressures of the operated and control arm were determined at rest and under conditions of hand exercise in 34 patients who received a radial artery graft for myocardial revascularization. Doppler measurements showed the ulnar compensation to radial artery removal, and transcutaneous measurements demonstrated a moderate degree of exercise-induced hand ischemia on the operated site.

Post-traumatic basilar artery thrombosis in a young man with atrial septum aneurysm and prothrombin gene G20210A polymorphism.

Prothrombin gene G20210A polymorphism has been recently identified as a cause of venous thrombosis. However the association between this mutation and arterial thrombosis remains uncertain. Some authors have suggested that the polymorphism in the 3' region of the prothrombin gene may precipitate cerebral arterial thrombosis in young patients with prothrombotic conditions. We report a case of post-traumatic basilar artery thrombosis in a young patient carrier of the prothrombin gene G20210A polymorphism. Thirty-six hours after sustaining a head injury in the occipital region, a young man developed vomiting, headache, dizziness and truncal ataxia, without signs of focal impairment. Magnetic resonance imaging and selective angiography carried out 2 days later showed an obstruction of the basilar artery, with infarction of the right cerebellar region. A transthoracic echocardiogram showed a patent foramen ovale with little left-to-right shunt and an aneurysm of the interatrial septum. Blood examination showed a heterozygous status for prothrombin gene G20210A polymorphism. We conclude that this prothrombin gene mutation and the coexisting particular head injury and interatrial septal aneurysm could have contributed simultaneously to the development of basilar artery occlusion and cerebellar infarction. We suggest that in selected cases of cerebellar ischemia a prothrombin gene G20210A polymorphism should be considered.

Enhanced oxidative stress in workers with a standing occupation.

BACKGROUND: Several epidemiological studies have shown a statistically significant association between standing work and chronic venous insufficiency of lower limbs. This condition has been associated with an enhanced oxidative stress that, according to the literature, could represent a risk factor for cardiovascular and other systemic diseases. AIMS AND METHODS: To evaluate venous pressure of the lower limbs and reactive oxygen species (ROS) before and after work in 62 workers with a standing occupation (surgery room nurses) and 65 outpatient department nurses who can walk during their working time. RESULTS: After work, a statistically significant increase of venous pressure of the lower limbs levels was observed in both the study group and controls. Standing workers showed significantly higher mean levels of ROS after work.

The action of propionyl-L-carnitine on the vasal endothelium: increased t-PA synthesis and a decrease in the activity of PAI-1. A preliminary study.

In this study the authors attempted to restore the coagulative fibrinolytic homeostasis that is compromised in peripheral vascular disease. Eleven patients with arterial disease, eleven with venous disease and seven healthy volunteers underwent oral treatment using 3 g of propionyl-L-carnitine divided into thrice daily doses for a period of 20 days. (1 g t.i.d.). This quaternaria amine is able to correct tissue hypoxia by increasing ATP and energy production and has the capacity to prevent alterations in endothelial membrane permeability. The authors observed a significant increase of t-PA synthesis on the 10th day of therapy in the arterial disease and control groups. All three groups showed a significant increase in t-PA synthesis on the 20th day of therapy. A significant decrease in PAI-1 activity was observed on the 10th and on the 20th day of therapy in both the patient groups, but not in the control group. Although the exact pathological mechanisms of peripheral vascular disease are complex and in many aspects still unknown, it is now absolutely certain that there is a pathogenetic role of functional imbalances. An important part is played by the reduction in t-PA synthesis and the increase in PAI-1 activity, and the authors conclude that it is necessary to use pharmaceutical substances to restore proper equilibrium.

Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial.

The authors evaluated the efficacy of propionyl-l-carnitine, a drug able to reduce peripheral resistance and protect the cells against oxidative stress damage, in patients affected by peripheral arterial obliterative disease at class II of Fontaine. The study was performed on 22 patients according to a double-blind, randomized design in parallel with placebo. The drug was administered at a dosage of 1 g three times a day orally for 90 days. At recruitment and at the end of the study all patients underwent physical examination, treadmill test, doppler C.W. of the lower limbs, ankle/brachial index, dosage of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), hematocrit, hematic filtration, and viscosity. In the group treated with propionyl-l-carnitine a statistically significant increase of claudication distance, blood flow velocity, PAI-1 activity and red blood cell deformity was observed. These data suggest the usefulness of propionyl-l-carnitine in the treatment of patients affected by peripheral arterial obliterative disease.

New prospects for the treatment of Raynaud's phenomenon using a serotoninergic S2 receptor antagonist (ketanserin) and stable derivatives of prostacyclin.

The authors propose a promising new therapy for the treatment of Raynaud's phenomenon, with parenteral prostacyclin (carbaprostacyclin) and a serotonergic S2-receptor antagonist (ketanserin) given orally. They studied 31 patients, 22 treated with ketanserin and carbaprostacyclin, 9 with carbaprostacyclin alone. Both groups demonstrated successful results and a significant improvement in measurements performed by photoplethysmography and transcutaneous pulse oximetry.

[Pulmonary silicosis associated with MacLeod syndrome: a case report]. / Silicosi polmonare associata a sindrome di MacLeod: nota su un caso.

The paper reports a case of silicosis associated with idiopathic unilateral hyperlucent lung--MacLeod's disease (ML)--in a 65-year old miner. ML had not been diagnosed before this clinical observation and the patient had been exposed to silica dust for about 15 years as a truck operator in water supply tunnelling work in central Italy. Impaired ventilatory function due to left pulmonary dystrophy was the favouring or even the causal factor of dust accumulation in the functionally active right lung and of the tissue reaction to the dust, leading to interstitial fibrosis. A radiological diagnosis of p 1/0 pneumoconiosis was made according to the 1980 International Labour Office classification. Clinical, radiological and functional findings indicated the presence of respiratory failure as a result of the sum of silicotic and dystrophic lesions. Two combined pulmonary scintigraphic examinations with Tc99 perfusional and mTc-DPTA inhalatory methods revealed peculiar alterations: absence of ventilation associated with severe vascular impairment in the left lung, inequality of the ventilation/perfusion rate, due to pneumoconiosis, in the right lung. MacLeod's disease is rare, but must be considered as a mandatory contra-indication for work involving dust exposure risk since it is one of the predisposing factors which can cause an occupational disease even if environmental exposure standards are observed.

[t-PA and PAI in patients with Raynaud's syndrome in treatment with a stable prostacyclin analog]. / t-PA y PAI en pacientes afectos de síndrome de Raynaud en tratamiento con un análogo estable de la prostaciclina.

An study was made in order to determinate the relationship between the restoration of the local fibrinolytic activity and the clinical signs in patients with a Raynaud's phenomenon. It is known that local fibrinolytic activity is a system influenced by changes into its components produced by exogenous and endogenous factors. An important role is represented by the t-PA and PAI-1. On the contrary, u-PA doesn't change. Samples were all taken at the same time, approximately at the middle of the morning. In patients with Raynaud's phenomenon treated with a prostacyclin stable analogous, we have perceived a clinical improvement, corresponding with a fibrinolytic activity increase.

Abdominal aortic aneurysm in normotensive patients: association with angiotensin-converting enzyme gene polymorphism.

OBJECTIVE AND DESIGN: to assess if deletion of the angiotensin-converting enzyme (ACE) gene is a risk factor for abdominal aortic aneurysms (AAAs) in normotensive patients. MATERIALS AND METHODS: ACE gene polymorphism was examined by polymerase chain reaction in 124 subjects with AAA and in 112 control subjects. AAA normotensive patients (group A, n=56) were compared to normotensive control subjects (group B, n =112) and to AAA hypertensive patients (group C, n =68). All subjects enrolled in this study were Caucasian and from central and southern Italy. RESULTS: the distribution of ACE genotypes was: normotensive patients with AAAs (group A): 3 II, 14 ID, 39 DD; normotensive control subjects (group B): 36 II, 48 ID, 28 DD; hypertensive patients with AAAs (group C): 14 II, 32 ID, 22 DD. The DD genotype was more common in group A than in control groups (A vs B p<0.001; A vs C p <0.001). The ID genotype was more common in group A as well (A vs B p <0.05; A vs C p <0.005). CONCLUSIONS: our data suggest a role for ACE I/D gene polymorphism in the pathogenesis of AAA in normotensive patients.