The central regulation of bone mass, the first link between bone remodeling and energy metabolism

Evolutionary consideration and clinical observations led us to hypothesize 10 yr ago that there may be a coordinated regulation, endocrine in nature, of bone remodeling and energy metabolism. The existence of this coordinated regulation is motivated by the energetic needs of the skeleton; therefore, this regulation relies on hormones that appear during evolution with the skeleton, not with energy metabolism. Leptin is such a hormone, and it is a critical regulator of bone mass as well as of appetite and energy expenditure. This review goes over the anatomical route and molecular pathways used by leptin to inhibit both bone mass accrual and appetite through its signaling in the brain.     

Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents

Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor-targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progression (TTP) and overall survival (OS). Results. High SFA and VFA values were significantly associated with shorter TTP and OS. By multivariate analysis, high VFA was independently associated with shorter TTP and OS. These results were internally validated using bootstrap analysis. By contrast, VFA was not associated with survival in the cytokine group. In the whole population, interaction between VFA and treatment group was significant for TTP and OS, thereby confirming the results. Conclusion. Our study provides the first evidence that high VFA could be a predictive biomarker from shorter survival in patients given first-line antiangiogenic agents for mRCC.     

Prevalence and clinical impact of endoscopic pseudomembranes in patients with inflammatory bowel disease and Clostridium difficile infection

Background and aimLimited data suggests that pseudomembranes are uncommon in patients with inflammatory bowel disease (IBD) and C. difficile associated disease (CDAD), but the reason for this is unknown.We aimed to evaluate the rate of pseudomembranes in this population, identify predictive factors for pseudomembranes' presence and assess its clinical impact.MethodsThis was a sub-study of a retrospective European Crohn's & Colitis Organization (ECCO) multi-center study on the outcome of hospitalized IBD patients with C. difficile. The present study included only patients who underwent lower endoscopy during hospitalization, and compared demographic and clinical parameters in the group of patients with discernable pseudomembranes versus those without.ResultsOut of 155 patients in the original cohort, 93 patients underwent lower endoscopy and constituted the study population. Endoscopic pseudomembranes were found in 12 (13%) of these patients. Patients with pseudomembranes presented more commonly with fever (p = 0.02) compared to patients without pseudomembranes. No difference between the two groups was found with respect to the use of immunosuppressant drugs, background demographics or disease characteristics. Neither was there a difference between the group with or without pseudomembranes in the frequency of severe adverse clinical outcome or in the duration of hospitalization. On multi-variate analysis the presence of fever remained independently associated with the finding of pseudomembranes (OR 6, 95% CI 1.2–32, p = 0.03).ConclusionsThis study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes.     

Periphilin is a novel interactor of synphilin-1, a protein implicated in Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies. Alpha-synuclein and its interactor synphilin-1 are major components of these inclusions. Rare mutations in the α-synuclein and synphilin-1 genes have been implicated in the pathogenesis of PD; however, the normal function of these proteins is far from being completely elucidated. We, thus, searched for novel synphilin-1-interacting proteins and deciphered periphilin as new interactor. Periphilin isoforms are involved in multiple cellular functions in vivo, and the protein is broadly expressed during embryogenesis and in the adult brain. We show that periphilin displays an overlapping expression pattern with synphilin-1 in cellular and animal models and in Lewy bodies of PD patients. Functional studies demonstrate that periphilin, as previously shown for synphilin-1, displays an antiapoptotic function by reducing caspase-3 activity. Searching for mutations in the periphilin gene, we detected a K69E substitution in two patients of a PD family. Taken together, these findings support for the first time an involvement of periphilin in PD.     

Failed vascularized proximal fibular epiphyseal transfer for hip reconstruction following infection in children

Purpose  Treatment of the sequellae of hip infection with epiphyseal destruction in children has had limited success to date. The aim of this study was to report mid-term results after hip epiphyseal reconstruction using a proximal vascularized fibular graft in three children presenting with massive epiphyseal destruction of the proximal femur following infection. Methods  Three children suffered from hip articular destruction type IVB according to the Choi classification after neonatal septic arthritis. The mean age at reconstruction was 4.3 years (range 3–6 years). The Hunka et al. criteria were used to evaluate the functional results, and the clinical evaluation was based on the Musculo-Skeletal Tumor Society (MSTS) score. Growth and fusion of the graft and hip morphology were evaluated on simple X-rays and by magnetic resonance imaging (MRI). A ratio between cephalic diameter and inter-acetabular gap was defined on the MRI scan as the “acetabular filling index”. Results  No intraoperative complication was reported. With a mean follow-up of 4.8 years (3–6 years), the MSTS score was 22.7/30 (range 20–26), while the average lower limb length discrepancy was 3 cm. Patient 1 required a secondary derotation osteotomy of the femur because of abnormal external rotation and a bad result due to the unexplained occurrence of a painful and stiff hip joint. A secondary distal transfer of the greater trochanter was performed in patient 2, and good results based on Hunka et al.’s criteria were achieved. The X-rays of patients 1 and 2 showed signs of bone growth and a major remodeling process; the MRI filling indices were 83 and 67%, respectively. Patient 3 developed an early slipped capital (fibular) epiphysis 1 month postoperatively, which was treated by percutaneous pinning; this early complication led to a bad result with full resorption of the graft. Conclusions  In contrast to its success in upper limb reconstruction, in this series of three patients with hip articular destruction, articular reconstruction using a vascularized proximal fibula graft was disappointing and led to unsatisfactory results in terms of hip reconstruction. Such a procedure is complex and highly demanding, necessitating extremely intensive post-operative care. An early slipped capital epiphysis can lead to full graft resorption. Consequently, despite important adaptation and remodeling of the graft, the authors do not recommend this procedure at this location.