Denosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study.

INTRODUCTION: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates. MATERIALS AND METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS). RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good. DISCUSSION: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS. CONCLUSION: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.

Loss of bone mineral density in hemiplegic patients after stroke: Prospective single-center study.

The aim of our prospective single-center study was to assess the loss of bone mineral density (BMD) in the year following stroke with hemiplegia. We evaluated functional disability and bone mineral density (BMD) in 18 patients immediately following and at 1 year of stroke with hemiplegia. The most significant variation in BMD concerns the femoral neck on the hemiplegic side: -0.0551±0.0548g/cm2: -6.85%. This loss is correlated with the functional motor score (Fugl-Meyer Assessment) (r=0.7573; P=0.0004). During follow-up, 11/18 patients fell and 2/18 had a fracture.

Unraveling the nature of charge excitations in La2CuO4 with momentum-resolved Cu K-edge resonant inelastic x-ray scattering.

The results of model calculations using exact diagonalization reveal the orbital character of states associated with different Raman loss peaks in Cu K-edge resonant inelastic x-ray scattering (RIXS) from La2CuO4. The model includes electronic orbitals necessary to highlight the nonlocal Zhang-Rice singlet, charge transfer, and d-d excitations, as well as states with apical oxygen 2p(z) character. The dispersion of these excitations is discussed with prospects for resonant final state wave-function mapping. A good agreement with experiments emphasizes the substantial multiorbital character of RIXS profiles in the energy transfer range 1-6 eV.

Charge-transfer excitations in the model superconductor HgBa(2)CuO(4+delta).

We report a Cu -edge resonant inelastic x-ray scattering (RIXS) study of charge-transfer excitations in the 2-8 eV range in the structurally simple compound HgBa(2)CuO(4+delta) at optimal doping (T(c)=96.5 K). The spectra exhibit a significant dependence on the incident photon energy which we carefully utilize to resolve a multiplet of weakly dispersive (<0.5 eV) electron-hole excitations, including a mode at 2 eV. The observation of this 2 eV excitation suggests the existence of a remnant charge-transfer gap deep in the superconducting phase. Quite generally, our results, which include additional data for the Mott insulator La(2)CuO(4), demonstrate the importance of exploring the incident photon-energy dependence of the RIXS cross section.

Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group.

BACKGROUND: Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. METHODS: We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. RESULTS: Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episode of thrombosis that was associated with a temporary risk factor. Among the 51 women with abnormal laboratory results or a previous episode of idiopathic thrombosis, or both, 3 (5.9 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 1.2 to 16.2 percent). CONCLUSIONS: The risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.

Childhood adversity, parental stress, and depression of negligent mothers.

The objective of this study was to identify major childhood events that were experienced by negligent mothers matched with non-negligent mothers as well as to define the existing link between those events, depression of the mother and parental stress. The sample was composed of 80 French-speaking Canadian families. The measures used were the Parental Stress Index (Abidin, 1983), the Psycho-Social Interview (Ethier et al., 1989) and the Beck Depression Inventory (1961). The results have shown an extreme level of parental stress and a high level a depression for negligent mothers. The negligent mothers had a history of placements, violence and sexual abuse, but they did not differ from control mothers for parental breakups and nonavailability. We have also shown a significant link between childhood events, depression, and parental stress even more so for the control group than for the negligence group. The results are discussed in the perspective of attachment theory.

[Parental communication and support perceived in families of suicidal and non-suicidal adolescents]. / Communication et soutien parental perçus dans des familles d'adolescents suicidaires et non suicidaires.

This study focuses on two family-related variables linked to the issue of teenage suicide, namely communication and parental support. The purpose of the study is to compare the perceptions of suicidal and non-suicidal teenagers with those of their parents in order to better understand the relation between these variables and the issue of teenage suicide. Results confirm that communication and parental support represents a problem in families with suicidal teenagers. These dimensions are perceived more negatively by the latter subjects in comparison to the control group. In addition, the variations in perception between the adolescent and his or her parents are much greater in families with suicidal teens. This data supports the usefulness of family interventions when family problems are identified during detection measures or when counseling is requited by a suicidal teenager.

Primary pulmonary hypertension associated with HIV infection.

A Haitian woman with the human immunodeficiency virus (HIV) presented with dyspnea, cough, fatigue and lower abdominal pain of recent onset. Clinical, radiologic and hemodynamic investigations demonstrated pulmonary hypertension. The patient died a few days later. The pathological findings were compatible with primary pulmonary hypertension. This case is similar to others that have been reported and indicates a possible link between HIV infection and rapidly progressive primary pulmonary hypertension.