Relationship between ectopic calcifications and bone fragility depicted on computed tomography scan in 70 patients with systemic sclerosis.

Background: A higher risk of osteoporotic fracture was described in systemic sclerosis patients than in healthy patients. Objective: To evaluate the relation between osteoporotic fracture risk measured by the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) on computed tomography (CT) scan and the presence of ectopic calcifications: vascular, valvular and spinal. Methods: This monocentric retrospective study was performed on patients followed between 2000 and 2014 at Nancy University Hospital. Systemic sclerosis patients, according to ACR/EULAR 2013 criteria, followed from 2000 to 2014 and who underwent, during their follow-up, a CT including the first lumbar vertebra were included. The SBAC-L1 was measured with a threshold set at 145 Hounsfield units (HU). Vascular and spinal calcifications were studied on CT. For vascular calcifications, the Agatston score was used. Valvular calcifications were studied on echocardiography. Results: A total of 70 patients were included (mean age: 62.3 (±15.6) years, women 88.5%). The mean SBAC-L1 was 157.26 (±52.1) HU, and 35 patients (50%) presented an SBAC-L1 ⩽ 145 HU. The reproducibility of the calcification evaluation was good, with kappa coefficients varying between 0.63 and 1. In univariate analysis, spinal and vascular calcifications were associated with an SBAC-L1 ⩽ 145 HU, with ORs of 13.6 (1.6-113.3) and 8 (95%CI: 2.5-25.5), respectively. In multivariate analysis, the SBAC-L1 was not associated with the presence of any ectopic calcifications. The SBAC-L1 decreased with age (p = 0.0001). Conclusion: Patients with systemic sclerosis with an SBAC-L1 ⩽ 145 HU were older, but they did not have more ectopic calcification. Trial registration: The ethics committee of Nancy Hospital agreed with this study (referral file number 166). This study was designed in accordance with the general ethical principles outlined in the Declaration of Helsinki.

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review.

The presence of calcium deposits in human lesions is largely used as imaging biomarkers of human diseases such as breast cancer. Indeed, the presence of micro- or macrocalcifications is frequently associated with the development of both benign and malignant lesions. Nevertheless, the molecular mechanisms involved in the formation of these calcium deposits, as well as the prognostic significance of their presence in human tissues, have not been completely elucidated. Therefore, a better characterization of the biological process related to the formation of calcifications in different tissues and organs, as well as the understanding of the prognostic significance of the presence of these calcium deposits into human tissues could significantly improve the management of patients characterized by microcalcifications associated lesions. Starting from these considerations, this narrative review highlights the most recent histopathological and molecular data concerning the formation of calcifications in breast, thyroid, lung, and ovarian diseases. Evidence reported here could deeply change the current point of view concerning the role of ectopic calcifications in the progression of human diseases and also in the patients' management. In fact, the presence of calcifications can suggest an unfavorable prognosis due to dysregulation of normal tissues homeostasis.

Primrose syndrome: Characterization of the phenotype in 42 patients.

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.

Raman spectroscopy applications in rheumatology.

Raman spectroscopy is a type of vibrational spectroscopy based on the inelastic scattering of photons, which has attracted much attention due to its potential clinical application in rheumatology. In this review, we discuss the typical spectral features of cartilage, bone, synovial fluid, and pathologic crystal deposits, as well as methods of amplifying the Raman signal of biofluids such as drop-coating deposition Raman spectroscopy. Further, applications of Raman and drop-coating deposition Raman spectroscopy in osteoarthritis are described, highlighting the clinical potential of these methods. We also discuss the role of Raman and related techniques in analyzing pathologic crystals such as monosodium urate, calcium pyrophosphate dihydrate, and hydroxyapatite. The results presented in this review demonstrate that Raman spectroscopy has grown past the stage of proof-of-concept, especially in the case of pathologies involving crystal depositions such as gout and calcium pyrophosphate deposition disease , for which the method has been validated on large number of samples. As the medical community becomes more and more aware of Raman spectroscopy, it is envisioned that it will become a standard technique in the near future.

Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous mutations: what are the therapeutic options for a better control of phosphatemia?

BACKGROUND: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by mutations in genes encoding FGF23 or its regulators, and leading to functional deficiency or resistance to fibroblast growth factor 23 (FGF23). Subsequent biochemical features include hyperphosphatemia due to increased renal phosphate reabsorption, and increased or inappropriately normal 1,25-dihydroxyvitamin D (1,25-D) levels. CASE-DIAGNOSIS/TREATMENT: A 15-year-old girl was referred for a 1.2-kg-calcified mass of the thigh, with hyperphosphatemia (2.8 mmol/L); vascular impairment and soft tissue calcifications were already present. DNA sequencing identified compound heterozygous mutations in the FGF23 gene. Management with phosphate dietary restriction, phosphate binders (sevelamer, aluminum, nicotinamide), and acetazolamide moderately decreased serum phosphate levels; oral ketoconazole was secondary administered, leading to significantly decreased 1,25-D levels albeit only moderate additionally decreased phosphate levels. However, therapeutic compliance was questionable. Serum phosphate levels always remained far above the upper normal limit for age. The patient presented with two relapses of the thigh mass, requiring further surgery. CONCLUSIONS: We suggest that control of phosphate metabolism is crucial to prevent recurrences and vascular complications in HFTC; however, the medical management remains challenging.

Discrimination Between Calcium Hydroxyapatite and Calcium Oxalate Using Multienergy Spectral Photon-Counting CT.

OBJECTIVE: We aimed to determine whether multienergy spectral photon-counting CT could distinguish between clinically relevant calcium crystals at clinical x-ray energy ranges. Energy thresholds of 15, 22, 29, and 36 keV and tube voltages of 50, 80, and 110 kVp were selected. Images were analyzed to assess differences in linear attenuation coefficients between various concentrations of calcium hydroxyapatite (54.3, 211.7, 808.5, and 1169.3 mg/cm3) and calcium oxalate (2000 mg/cm3). CONCLUSION: The two lower concentrations of hydroxyapatite were distinguishable from oxalate at all energy thresholds and tube voltages, whereas discrimination at higher concentrations depended primarily on the energy thresholds used. Multienergy spectral photon-counting CT shows promise for distinguishing these calcium crystals.