Clinical and biological determinants of sclerostin plasma concentration in hemodialysis patients.

BACKGROUND: Sclerostin is a potent inhibitor of bone formation, but the meaning of its serum levels remains undetermined. We evaluated the association between sclerostin levels and clinical or biological data in hemodialyzed patients (HD), notably parathormone (PTH), biomarkers of bone turnover, vascular calcifications and mortality after 2 years. METHODS: 164 HD patients were included in this observational study. The calcification score was assessed with the Kauppila method. Patients were followed for 2 years. RESULTS: Median sclerostin levels were significantly (p < 0.0001) higher in HD versus healthy subjects (n = 94) (1,375 vs. 565 pg/ml, respectively). In univariate analysis a significant association (p < 0.05) was found between sclerostin and age, height, dialysis vintage, albumin, troponin, homocysteine, PTH, C-terminal telopeptide of collagen type I, bone-specific alkaline phosphatase and osteoprotegerin, but not with the calcification score. In a multivariate model, the association remained with age, height, dialysis vintage, troponin, homocysteine, phosphate, PTH, but also with vascular calcifications. Association was positive for all variables, except PTH and vascular calcifications. The baseline sclerostin concentration was not different in survivors and non-survivors. CONCLUSIONS: We confirm a higher concentration of sclerostin in HD patients, a positive association with age and a negative association with PTH. A positive association with phosphate, homocysteine and troponin calls for additional research. The clinical interest of sclerostin to assess vascular calcifications in HD is limited and no association was found between sclerostin and mortality.

Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients.

BACKGROUND: Matrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications. However, in order to be active, MGP must be phosphorylated and carboxylated, with this last process being dependent on vitamin K. The present study focused on the inactive form of MGP (dephosphorylated and uncarboxylated: dp-ucMGP) in a population of hemodialyzed (HD) patients. Results found in subjects being treated or not with vitamin K antagonist (VKA) were compared and the relationship between dp-ucMGP levels and the vascular calcification score were assessed. METHODS: One hundred sixty prevalent HD patients were enrolled into this observational cohort study, including 23 who were receiving VKA treatment. The calcification score was determined (using the Kauppila method) and dp-ucMGP levels were measured using the automated iSYS method. RESULTS: dp-ucMGP levels were much higher in patients being treated with VKA and little overlap was found with those not being treated (5604 [3758; 7836] vs. 1939 [1419; 2841] pmol/L, p < 0.0001). In multivariate analysis, treatment with VKA was the most important variable explaining variation in dp-ucMGP levels even when adjusting for all other significant variables. In the 137 untreated patients, dp-ucMGP levels were significantly (p < 0.05) associated both in the uni- and multivariate analysis with age, body mass index, plasma levels of albumin, C-reactive protein, and FGF-23, and the vascular calcification score. CONCLUSION: We confirmed that the concentration of dp-ucMGP was higher in HD patients being treated with VKA. We observed a significant correlation between dp-ucMGP concentration and the calcification score. Our data support the theoretical role of MGP in the development of vascular calcifications. We confirmed the potential role of the inactive form of MGP in assessing the vitamin K status of the HD patients. TRIAL REGISTRATION: B707201215885.

Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study.

BACKGROUND: The role of cholecalciferol supplementation in end-stage renal disease (ESRD) patients has been questioned. The objective of this randomized double-blinded study is to assess whether cholecalciferol therapy can increase serum 25-hydroxyvitamin D [25(OH)D] levels in haemodialysed patients and the safety implications of this therapy on certain biological parameters and vascular calcifications score. METHODS: Forty-three haemodialysis patients were randomized to receive placebo or cholecalciferol (25,000 IU) therapy every 2 weeks. The biological parameters, serum calcium, phosphorus, 25(OH)D and parathormone (PTH) levels, were monitored monthly for 12 consecutive months. Vascular calcifications were assessed by lateral X-ray radiography. RESULTS: At baseline, the mean serum 25(OH)D levels were low and similar in both groups. Thirty patients (16 treated and 14 placebo) completed the study: 11 patients died (5 placebo and 6 treated), 1 patient dropped out and 1 patient was transplanted (both from the placebo group). After 1 year, the percentage of 25(OH)D deficient patients was significantly lower in the treated group. None of the patients developed hypercalcaemia. The PTH levels tended to increase over the study period under placebo and to decrease in the cholecalciferol group. The median changes in PTH levels from baseline to 1 year were statistically different between the two groups [+80 (-58 to 153) and -115 (-192 to 81) under placebo and cholecalciferol treatment, respectively, P=0.02].The calcification scores increased equivalently in both groups (+2.3 per year). CONCLUSIONS: Cholecalciferol is effective and safe, and does not negatively affect calcium, phosphorus, PTH levels and vascular calcifications. Additional studies are needed to compare the impacts of nutritional and active vitamin D agents on vascular calcification and mortality.

Lemierre Syndrome.

Teaching Point: Lemierre syndrome is a rare complication of bacterial pharyngitis with cervical thrombophlebitis leading to pulmonary abcesses; the radiologist may have a key role.

Two unusual variants of pulmonary intra-lobar sequestration.

A pulmonary sequestration is a congenital malformation characterized by non-functional lung tissue with abnormal arterial systemic supply and abnormal connection to the bronchial tree. This may lead to recurrent infections rendering a surgical intervention more demanding. Because of multiple anatomic variations, it is important to obtain high-quality preoperative radiological clarification to determine the most suitable surgical approach. Although a non-surgical technique, consisting of embolization of the aberrant artery has been described, a surgical technique remains the treatment of choice in operable patients. Preoperative embolization of the aberrant artery may reduce the risk of haemorrhage but could cause technical challenges in a hybrid approach and therefore unforeseen peroperative stress to the surgical team. We report 2 adult patients with unusual intra-lobar sequestration with aberrant vascular rare anatomy. Both were treated by surgery. In the latter patient, we performed a hybrid approach. This was complicated by peroperative coils exposure making it a technical challenge to proceed.

Granulomatous Prostatitis Mimicking Invasive Prostate Cancer.

Teaching Point: Benign granulomatous prostatitis mimics prostate cancer on MRI. Peculiar urological history of a patient undergoing prostate MRI helps sorting out that differential, such as a treatment with topic Bacilli Calmette-Guerin instillations.

Disseminated histoplasmosis: case report and review of the literature.

Case report We report the case of a young Cameroonian woman who presented with cough, hyperthermia, weight loss, pancytopenia, and hepatosplenomegaly. A positive HIV serology was discovered and a chest radiography revealed a 'miliary pattern'. Bone marrow aspiration pointed out yeast inclusions within macrophages. Given the morphological aspect, the clinical presentation and immunosuppression, histoplasmosis was retained as a working hypothesis. Antiretroviral and amphotericin B treatments were promptly initiated. Review Given the immigration wave that Europe is currently experiencing, we think it is important to share experience and knowledge, especially in non-endemic areas such as Europe, where clinicians are not used to face this disease. Histoplasmosis is due to Histoplasma capsulatum var. capsulatum, a dimorphic fungus. Infection occurs by inhaling spores contained in soils contaminated by bat or bird droppings. The clinical presentation depends on the immune status of the host and the importance of inoculum, varying from asymptomatic to disseminated forms. AIDS patients are particularly susceptible to develop a severe disease. Antigen detection, molecular biology techniques, and microscopic examination are used to make a rapid diagnosis. However, antigen detection is not available in Europe and diagnosis needs a strong clinical suspicion in non-endemic areas. Because of suggestive imagery, clinicians might focus on tuberculosis. Our case illustrates the need for clinicians to take histoplasmosis in the differential diagnosis, depending on the context and the patient's past history.