Underestimated Fracture Probability in Patients With Unilateral Hip Osteoarthritis as Calculated by FRAX

Osteoporosis (OP) and osteoarthritis (OA) are age-related diseases often considered to be mutually exclusive. We previously found that 25% of women with advanced OA had occult OP and that femoral neck (FN) bone mineral density (BMD) T-scores were significantly higher for osteoarthritic vs contralateral hips. The FRAX calculator incorporates clinical risk factors and FN BMD T-score to estimate 10-yr total fracture probability and hip fracture probability. In 35 women and men aged 41 yr or older with unilateral hip OA scheduled for hip replacement, we tested whether FRAX fracture probability is underestimated when using data for the OA rather than the contralateral hip. There were between-hip differences for FN BMD T-score (p < 0.0001), total fracture probability (p = 0.0004), and hip fracture probability (p = 0.0009). Use of FN BMD T-scores resulted in OP treatment recommendations for 0% and 11% of subjects compared with 11% and 17% for total fracture probability and hip fracture probability, respectively. In 6–11% of subjects in this series, the FRAX calculator underestimated fracture probability with data for the OA hip. With the increased use of FRAX in clinical use, these data suggest that measurement of BMD at the contralateral hip may yield higher calculated FRAX total and hip fracture probabilities.     

Central TNF inhibition results in attenuated neurohumoral excitation in heart failure: a role for superoxide and nitric oxide

This study examined the effect of central tumor necrosis factor-alpha (TNF) blockade on the imbalance between nitric oxide and superoxide production in the paraventricular nucleus (PVN) and ventrolateral medulla (VLM), key autonomic regulators, and their contribution to enhanced sympathetic drive in mice with congestive heart failure (CHF). We also used a TNF gene knockout (KO) mouse model to study the involvement of TNF in body fluid homeostasis and sympathoexcitation in CHF. After implantation of intracerebroventricular (ICV) cannulae, myocardial infarction (MI) was induced in wild-type (WT) and KO mice by coronary artery ligation. Osmotic mini-pumps were implanted into one set of WT + MI/Sham mice for continuous ICV infusion of Etanercept (ETN), a TNF receptor fusion protein, or vehicle (VEH). Gene expressions of neuronal nitric oxide synthase (NOS) and angiotensin receptor-type 2 were reduced, while those of inducible NOS, Nox2 homologs, superoxide, peroxynitrite and angiotensin receptor-type 1 were elevated in the brainstem and hypothalamus of MI + VEH. Plasma norepinephrine levels and the number of Fos-positive neurons were also increased in the PVN and VLM in MI + VEH. MI + ETN and KO + MI mice exhibited reduced oxidative stress, reduced sympathoexcitation and an improved cardiac function. These changes in WT + MI were associated with increased sodium and fluid retention. These results indicate that elevated TNF in these autonomic regulatory regions of the brain alter the production of superoxide and nitric oxide, contributing to fluid imbalance and sympathoexcitation in CHF.     

A model for human leukocyte antigen-matched donor-swap transplantation in India

BACKGROUND: In developing countries such as India, extending donor-swap transplantation (DSTx) to human leukocyte antigen (HLA)-mismatched patient-donor pairs would increase well-matched living donor kidney transplantation rates, resulting in use of less immunosuppression and less expenses, lower infective morbidity, and better survival. A model for DSTx based on HLA matching is presented. METHODS: Consecutive HLA class 1 antigen (A, B) tests of prospective renal allograft recipients and their related donors, performed at a single center in India was analyzed retrospectively using an HLA matching program to determine the proportion of prospective recipients with poorly matched related donors who could have benefited by DSTx based on HLA matching. RESULTS: Over the past 17.5 years, 2,129 prospective renal allograft recipients and 2,890 donors were tested for HLA class I (A and B) antigens. Of the prospective recipients, 33% did not have well-matched donors (defined as blood group compatible and sharing > or =2 of 4 HLA class I antigens). Among such recipients, 19.2% could have found a well-matched donor-swap pair within a year at a single center. This number would increase to 38% if four major national centers were involved with a shared HLA registry. CONCLUSIONS: Nearly 40% of prospective recipients without well-matched donors would find a donor-swap pair based on HLA matching within a year, with coordination among four national centers and a shared HLA registry, increasing the well-matched living donor renal transplant rates and improving transplant outcomes. This finding is relevant in the context of Indian government amending the Transplantation of Human Organs Act to encourage DSTx.