Daytime course of sleepiness in de novo Parkinson's disease patients

Normal subjects show an increase of sleepiness in the morning, early afternoon and before sleep. In the advanced stages of Parkinson's disease (PD) the mean level of sleepiness is quite high, while with respect to healthy subjects it seems to be unchanged in the early stages. The aim of this study was to evaluate the time–course of the sleepiness level during the wakefulness period in untreated patients with early‐stage Parkinson's disease. Eighteen Parkinson's disease patients who had never been treated before with dopaminergic drugs (male = 9, female = 9, age: 68.39 ± 1.89, mean ± standard error) and 18 healthy subjects (male = 9, female = 9, age: 67.22 ± 1.98) were recruited for this study. All subjects underwent continuous actigraphic recording for three consecutive days, during which they also completed the Karolinska Sleepiness Scale (KSS) once an hour throughout wakefulness. Our results showed a higher level of sleepiness in the patients than the controls in the hours following awakening and in the early afternoon, specifically at 08:00 and 14:00 hours (08:00 hours, PD patients, KSS: 3 ± 0.3 versus healthy subjects, KSS: 2 ± 0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 ± 0.5 versus healthy subjects, KSS: 3 ± 0.3, P < 0.05). We suggest that some daytime hours are sensitive windows showing the first increase of sleepiness which will spread later to the whole daytime.     

Beyond the joints,the extra-articular manifestations in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.     

Thalamo-cortical networks in subtypes of migraine with aura patients

BackgroundWe searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom.Methods3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores.ResultsAs compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs.ConclusionsThe present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.     

Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow‐up. The impact of tumor–host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP‐2 and to pro‐survival proteins NFIB and c‐Fos. Kaplan–Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co‐overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12–44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor–host endpoints for new biological treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1205–1211, 2015.     

Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress,arterial oxidation-specific epitopes,and atherogenesis in hypercholesterolemic mice

The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 +/- 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (-5.1 +/- 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages-derived foam cells (F4/80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice.     

Viral load 1 week after liver transplantation, donor age and rejections correlate with the outcome of recurrent hepatitis C.

BACKGROUND: Early identification of patients at a higher risk of rapidly progressive recurrent hepatitis post liver transplantation (LT) could help to tailor antiviral therapy. METHODS: We studied the correlation between early post-LT viral load and the histological and clinical outcomes of 49 consecutive patients (34 males, median age 55 years) in whom viraemia was monitored at days 0, 1, 7, 30, 180 and 365 after LT. RESULTS: Hepatitis C recurred at histology in 38 of 42 (90.5%) patients. Early viral load after LT was higher in patients with rapidly progressive hepatitis C recurrence (day 7 median HCV-RNA levels: 5.84 vs 4.93 Log(10) IU/ml, P=0.003). Day 7 HCV-RNA levels >/=2.5 x 10(5) IU/ml, donor age >60 years and rejection episodes were independently associated with progression to cirrhosis within one year post-LT [P=0.018, odds ratio (OR) 27.59; P=0.043, OR 13.85 and P=0.048, OR 9.95, respectively]. Day 7 viraemia and rejection episodes were independently associated with 5-years survival. Day 7 viraemia, in combination with acute hepatitis and/or donor age, showed 80% sensitivity, 94% specificity and 90.5% diagnostic accuracy to identify severe recurrence. CONCLUSIONS: Early post-LT HCV-RNA correlates with the severity of hepatitis C recurrence and in combination with donor age (>60 years) and rejections, identifies patients with a high risk of severe recurrence and candidates of cost-effective pre-emptive antiviral therapy.     

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.