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Background At present, although cholecalciferol represents the form of vitamin D of choice for the treatment of vitamin D deficiency, there is a growing interest in calcifediol. Aims This study aimed to evaluate the efficacy and the safety of two different daily doses of calcifediol. Methods Fifty osteopenic/osteoporotic women with serum levels of 25-hydroxyvitamin D (25OHD) between 10 and 20 ng/ml were randomized to a 6-month treatment with oral calcifediol 20 µg/day (n = 25) or oral calcifediol 30 µg/day (n = 25). In all, we measured the time course of the levels of 25OHD and other biochemical parameters. Moreover, we evaluated handgrip strength and serum levels of myostatin. Results The peak increase in 25OHD levels was reached after 90 days of treatment in group 1 (59.3 ng/ml) and after only 60 days in group 2 (72.3 ng/ml); thereafter in both groups, the levels of 25OHD showed a tendency towards stabilization. After 30 days, all the patients treated with 30 µg/day had values of 25OHD > 30 ng/ml. Handgrip strength showed a modest but progressive increase which reached the statistical significance in the 30 µg/day group. This latter group also presented a modest and non-significant decrease in serum levels of myostatin. Conclusions Calcifediol is able to rapidly normalize the vitamin D deficiency, and the 30 µg daily dosage could be suggested in those patients who need to rapidly reach optimal 25OHD levels. Moreover, the 6-month treatment with calcifediol at a dose of 30 µg results in a modest but significant increase in upper limb strength.

Background More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects. Methods In 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe. Results As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05). Conclusion This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

Epidemiological and clinical data have suggested the existence of a relationship between cardiovascular diseases and metabolic bone disease. Several studies have demonstrated that heart valve calcification presents substantial similarities with that of bone. Literature data indicate that there are many active processes which promote osteogenesis and loss of mineralization inhibitors that lead to the deposition of extracellular matrix and proteins of bone tissue in cardiac valves. This review aimed to synthesize the available data in order to allow a better understanding of the relationship between osteoporosis or other metabolic bone diseases, such as primary hyperparathyroidism, and valvular calcification in humans. Electronic databases of Pubmed-Medline, Cochrane Library, and SCOPUS from inception to March 31, 2019 were searched. The full set of the articles potentially eligible were carefully assessed and reviewed. Finally, 23 studies were eligible and included in the systematic review. The majority of studies reported that osteoporosis and/or osteopenia were independent risk factors for valvular calcifications, even after adjusting for common cardiovascular risk factors. This suggests that this relationship is not only due to the presence of common cardiovascular risk factors but rather to underlying biological factors that connect them. Instead, regarding the association between primary hyperparathyroidism and valve calcification, conflicting data were found in the literature. To sum up, most of the literature data confirm that cardiac valve calcification processes are strongly influenced by alterations in bone metabolism. In particular, the patients with osteoporosis or primary hyperparathyroidism have an acceleration in the process of valvular calcification. Additional studies are needed to specifically address the mechanisms by which metabolic bone diseases could influence cardiac valve calcification.

IntroductionAnomalies in inferior vena cava represent an uncommon finding with a prevalence of 0. 3 to 0.5% among healthy patients. Specifically, the condition characterized by the agenesis of the inferior vena cava (IVC; AIVC) has been observed among the 0.0005 to 1% of the general population. AIVC is strongly related to deep vein thrombosis (DVT) of the lower limb and pelvic district, especially in young patients. The rarity of the presented condition could relate to an underestimation of its impact on a particular clinical setting leading to a delayed diagnosis and inaccurate early- and long-term management.ReportWe presented a case of this anomaly regarding a 31-year-old man presenting with bilateral symptomatic proximal DVT. Duplex vascular ultrasound and subsequent CT-angiography revealed the complete occlusion of the right external and common iliac vein, as well as partial occlusion of the contralateral external iliac vein, in the patient. The exam also revealed the interruption of IVC in its infrarenal part. At the level of renal veins coalescence, IVC appeared again in its usual position. A dilatated portal system, hepatic veins, and azygos and hemiazygos systems were also highlighted. Anticoagulation was promptly started with the administration of Fondaparinux (7.5 mg/die). In addition, compression stocking was initiated within 24 h from diagnosis. After 3 weeks, the anticoagulation regimen was shifted toward the administration of a direct oral anticoagulant (Apixaban; 5 mg two times a day). At 1-month follow-up, a vascular duplex ultrasound revealed a complete resolution of the iliac veins' thrombosis.ConclusionIt is important to consider the eventuality of IVC anomalies in a young adult presenting with unexplained, extensive, or bilateral DVT. Accurate diagnostic evaluation is necessary to fully identify this condition that could represent a real challenge.

Introduction: Asherson's Syndrome, also defined as Catastrophic Antiphospholipid Syndrome (CAPS), represents the most severe manifestation of Antiphospholipid Antibody Syndrome. Rarely, the first CAPS diagnosis is based on macro-thrombotic event as acute limb ischemia.Case Presentation: We present a case of a 65-year-old woman admitted with an acute lower limb arterial ischemia with a complete occlusion of all the three tibial vessels. Three endovascular recanalization procedures were performed contemporary to 48 h intraarterial thrombolysis administration. The patency of tibial arteries was restored with a near-complete absence of digital arteries and microvessel perfusion of the foot. In the following days, an aggressive foot gangrene was established, leading to a major lower-limb amputation. Due to the general clinical status worsening and aggressiveness of ischemic condition, further investigations were performed leading to the diagnosis of an aggressive Asherson's Syndrome that was also complicated by a severe heparin-induced thrombocytopenia. Medical management with a high dose of intravenous steroids and nine sessions of plasma exchange led to a clinical condition stabilization.Conclusion: In our case, the presence of a “sine causa” acute arterial occlusion of a large vessel represented the first manifestation of an aggressive form of Asherson's Syndrome that could represent a fatal disease. Due to the extreme variety of manifestations, early clinical suspicion, diagnosis, and multidisciplinary management are essential to limit the life-threatening consequences of patients.