The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). MT is supported by a project grant from the Stroke Association (TSA 2013/01). HSM is supported by an NIHR Senior Investigator award. HSM and SB are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. VT and RL are supported by grants from FWO Flanders. PR holds NIHR and Wellcome Trust Senior Investigator Awards. PAS is supported by an MRC Fellowship. CML’s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of <it>Emblica officinalis </it>fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.</p> <p>Methods</p> <p>The effects of extracts from <it>Emblica officinalis </it>on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of <it>Emblica officinalis </it>extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, <it>in vitro </it>effects of <it>Emblica officinalis </it>extracts on NF-kB transcription factor activity were determined by gel shift experiments.</p> <p>Results</p> <p>Extracts of <it>Emblica officinalis </it>were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. <it>Emblica officinalis </it>increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that <it>Emblica officinalis </it>extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that <it>Emblica officinalis </it>extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of <it>Emblica officinalis </it>on the expression levels of interleukin-6, a NF-kB specific target gene.</p> <p>Conclusion</p> <p>Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of <it>Emblica officinalis </it>extracts as an alternative tool for therapy applied to bone diseases.</p

Determination and biological relevance of serum cross-linked type I collagen N-telopeptide and bone-specific alkaline phosphatase in breast metastatic cancer

Bone metastasis is a frequent complication of cancer disease. The metastatic spread of cancer to bone is common to many different malignancies, particularly breast (ca. 73%), prostate (ca. 68%) and lung (ca. 36%) cancers. Metastases to bone cause increased bone resorption both from direct effects of the tumor itself and thought osteoclastic activation. The diagnosis and follow-up of bone metastatic cancer patients usually relies on skeletal X-ray and bone scintigraphy. However, the development of biochemical markers, used as indicators of bone metabolism, provides data useful in the clinical practice. The most important markers for bone remodeling process, bone formation and resorption, are bone-specific alkaline phosphatase (BAP) and N-telopeptide of type I collagen (NTx), respectively. In this report, we applied two solid-phase immunoassays used for the determination of BAP and NTx in serum of breast cancer (BC) post-menopausal women with bone metastasis and healthy individuals. BAP level in patients was found to be 45.72±12.92U/l, while the normal range for healthy individuals was 14.2-42.7U/l. The respective level of serum NTx was 19.20±8.87nM bone collagen equivalents (BCE) for patients and 15.9±3.8nM BCE for healthy women. Correlation of the obtained data showed elevated levels for both markers indicating high rate of bone degradation in breast metastatic cancer. © 2003 Elsevier B.V. All rights reserved

Scleral Buckling versus Vitrectomy for Retinal Detachment Repair: Comparison of Visual Fields and Nerve Fiber Layer Thickness

Purpose: To compare visual field loss and retinal nerve fiber layer (RNFL) defects in cases of rhegmatogenous retinal detachment (RRD) treated with scleral buckle (SB) versus pars plana vitrectomy (PPV) and C3F8 injection. Methods: This was a prospective, comparative interventional study of 50 eyes with primary RRD, treated with PPV (25 eyes) or SB (25 eyes). All measurements took place at least 9 months following successful and uncomplicated surgical treatment. The visual field total deviation (TD) values for preoperative attached and detached areas were calculated and compared separately. The optic nerve head morphology was studied with Heidelberg retinal tomography (HRT), and the RNFL using spectral-domain optical coherence tomography. Results: The preoperative detached areas demonstrated more affected TD values (in dB) compared to the preoperative attached areas (-6.9 ± 5.2 vs. -4.3 ± 3.3 for the SB group and -9.6 ± 5.2 vs. -7.8 ± 5.1 for the PPV group; p = 0.001) in both groups. The preoperative attached areas of the SB group showed better TD values (calculated mean values) compared to the preoperative attached areas of the PPV group (-4.3 ± 3.3 vs. -7.8 ± 5.1, p = 0.007). The RNFL and HRT values showed no statistically significant difference between the two groups. Conclusions: It seems that the preoperative detached retina, despite successful reattachment, suffers permanent damage as a result of the detachment, irrespective of the method of treatment. In the PPV group, the postoperative functionality of the preoperative attached areas was detected to be worse compared to the postoperative functionality of the preoperative attached areas of the SB group. We postulate that this fact could be attributed to an additional traumatizing factor (possibly fluid-air exchange or gas injection) in patients with RRD treated with PPV. © 2015 S. Karger AG

Cardiovascular complications in patients with Klinefelter’s syndrome

More than 70 years have passed since the first description of Klinefelter Syndrome (KS), the most frequent chromosome disorder causing male infertility and hypogonadism. KS is associated with increased cardiovascular (CV) mortality due to several comorbidities, including hypogonadism, as well as metabolic syndrome and type 2 diabetes, which are highly prevalent in these patients. Aside from metabolic disturbances, patients with KS suffer from both acquired and congenital CV abnormalities, cerebrovascular thromboembolic dis-ease, subclinical atherosclerosis and endothelial dysfunction, which may all contribute to increased CV mortali-ty. The mechanisms involved in this increased risk of CV morbidity and mortality are not entirely understood. More research is needed to better characterise the CV manifestations, elucidate the pathophysiological mechanisms and define the contribution of testosterone replacement to restoring CV health in KS patients. This review explores the complex association between KS, metabolic syndrome and CV risk in order to plan future studies and improve strategies to reduce mortality in this high-risk population