Fetuin‐A and BMD in Older Persons: The Health Aging and Body Composition (Health ABC) Study

Fetuin‐A is a hepatic secretory protein that promotes bone mineralization in vitro. Whether fetuin‐A levels are associated with BMD in humans is unknown. The Health Aging and Body Composition study enrolled 3075 well‐functioning black and white persons 70–79 yr of age and measured BMD. This cross‐sectional study measured serum fetuin‐A using ELISA among a random sample of 508 participants within sex and race strata. Multivariate linear regression analysis evaluated the associations of fetuin‐A with BMD. Among women (n = 257), higher fetuin‐A levels were significantly associated with higher total hip (p = 0.02), lumbar spine (p = 0.03), and whole body BMD (p = 0.01) in models adjusted for age, race, diabetes, alcohol and tobacco use, physical activity, body mass index, C‐reactive protein levels, calcium supplement, and estrogen use. For example, each SD (0.38 g/liter) higher level of fetuin‐A was associated with 0.016 g/cm² higher total hip areal BMD. The association was of similar magnitude and direction for femoral neck BMD but did not reach statistical significance (p = 0.11). In contrast, among men (n = 251), fetuin‐A had no significant associations with total hip (p = 0.79), lumbar spine (p = 0.35), whole body (p = 0.46), or femoral neck BMD (p = 0.54) in multivariable models. We conclude that higher fetuin‐A levels are independently associated with higher BMD among well‐functioning community‐dwelling older women but not older men. Future studies should evaluate whether fetuin‐A may refine fracture risk assessment in older women.     

The challenge of opportunities: how far can and should we go with targeted treatments and modern diagnostics in gastrointestinal stromal tumors?

The introduction of imatinib has greatly improved the treatment options and quality of life of patients with gastrointestinal stromal tumors. Systemic treatment with imatinib alone most likely, however, does not cure the disease because, despite long-lasting major remissions, the majority of patients eventually relapse. Therefore, complete surgical resection remains the only curative approach in patients with gastrointestinal stromal tumors. Given a strong systemic treatment option at hand, the use of multimodal treatment strategies for patients with locally advanced or metastatic disease seems self-evident as many tumors become resectable after a treatment with imatinib. Few retrospective and no prospective data, however, are yet available on feasibility and the prognostic impact of these strategies, which represents a major challenge on how to decide on these patients in clinical practice. We therefore critically discuss the available evidence and current concepts for multimodal treatment of gastrointestinal stromal tumors and how modern diagnostics, such as KIT genotyping, may influence our clinical decision-making in this context.     

The human CMV-UL86 peptide 981-1003 shares a crossreactive T-cell epitope with the encephalitogenic MOG peptide 34-56, but lacks the capacity to induce EAE in rhesus monkeys

Rhesus monkeys immunized with MOG(34-56), a dominant T-cell epitope from myelin/oligodendrocyte glycoprotein, develop an acute neurological disease resembling acute disseminated encephalomyelitis (ADEM) in humans. The typical large demyelinated lesions and mononuclear infiltrates in the monkey brains are caused by MOG(34-56) T-cells. We show that MOG(34-56)-reactive CD4+ and CD8+ T-cells are induced in monkeys immunized with a peptide from the human CMV major capsid protein (UL86; 981-1003), that shares sequence similarity with MOG(34-56). Monkeys sensitized against the viral peptide and subsequently challenged with MOG(34-56) display histological signs of encephalitis, but do not show overt neurological signs.     

Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of two studies

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N = 722), and one in patients undergoing total knee replacement (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5-9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban 5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5-20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.     

Verbal memory retrieval deficits associated with untreated hypothyroidism

The effects of inadequate thyroid hormone availability to the brain on adult cognitive function are poorly understood. This study assessed the effects of hypothyroidism on cognitive function using a standard neuropsychological battery in 14 patients suffering from untreated hypothyroidism and complaining of subjective cognitive difficulties in comparison with 10 age-matched healthy comparison subjects. Significant differences between groups were limited to verbal memory retrieval as measured by the California Verbal Learning Test (CVLT). On short delay free recall, long delay free recall, and long delay cued recall, significant differences remained between groups despite the limited statistical power of this study. There were no significant results found between groups on attentional or nonverbal tasks. Results suggest that hypothyroid-related memory deficits are not attributable to an attentional deficit but rather to specific retrieval deficits.