Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes

Objective In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures

Severe Primary Hyperparathyroidism Caused by Parathyroid Carcinoma in a 13‐Year‐Old Child; Novel Findings From HRpQCT

Primary hyperparathyroidism is a condition that occurs infrequently in children. Parathyroid carcinoma, as the underlying cause of hyperparathyroidism in this age group, is extraordinarily rare, with only a few cases reported in the literature. We present a 13-year-old boy with musculoskeletal pain who was found to have brown tumors from primary hyperparathyroidism caused by parafibromin-immunodeficient parathyroid carcinoma. Our patient had no clinical, biochemical, or radiographic evidence of pituitary adenomas, pancreatic tumors, thyroid tumors, pheochromocytoma, jaw tumors, renal abnormalities, or testicular lesions. Germline testing for AP2S1, CASR, CDC73/HRPT2, CDKN1B, GNA11, MEN1, PTH1R, RET, and the GCM2 gene showed no pathological variants, and a microarray of CDC73/HRPT2 did not reveal deletion or duplication. He was managed with i.v. fluids, calcitonin, pamidronate, and denosumab prior to surgery to stabilize hypercalcemia. After removal of a single parathyroid tumor, he developed severe hungry bone syndrome and required 3 weeks of continuous i.v. calcium infusion, in addition to oral calcium and activated vitamin D. Histopathological examination identified an angioinvasive parathyroid carcinoma with global loss of parafibromin (protein encoded by CDC73/HRPT2).HRpQCT and DXA studies were obtained prior to surgery and 18-months postsurgery. HRpQCT showed a resolution of osteolytic lesions combined with structural improvement of cortical porosity and an increase in both cortical thickness and density compared with levels prior to treatment. These findings highlight the added value of HRpQCT in primary hyperparathyroidism. In addition to our case, we have provided a review of the published cases of parathyroid cancer in children

Frequencies and clinical characteristics of common fusion oncogenes in core-binding factor Acute Myeloid Leukemia from Lahore Pakistan

Background: Acute myeloid leukemia (AML) is one of the most common blood cancers among adults. Genetic abnormalities associated with core-binding factor AML (CBF-AML) help in accurate diagnosis and prognostic stratification, and therefore help in clinical management of the disease. No studies have been carried out about frequencies of genetic abnormalities of CBF-AML and their association with clinical parameters in Lahore region of Pakistan. Therefore, objective of this study was to carry out genetic and characterization of CBF-AML.    Methods: The blood samples were collected along with clinical data AML patients from different hospitals of Lahore Pakistan July 2010 to Dec. 2020. RNA was extracted and RT-PCR was employed to detect CBF-AML -associated fusion oncogenes (AML1-ETO and CBFB-MYH11). Data was analyzed using SPSS version 25.Results: Frequencies of AML1-ETO and CBFB-MYH11 were 13.6% and 11.4%, respectively. AML1-ETO had significant association with FAB subtype AML-M2, occupational exposure to chemical solvents and exposure to petrol products. One the other hand, CBFB-MYH11 was significantly associated with splenomegaly, FAB subtype AML-M4 patients and insecticides exposure.Conclusions: Our results show that overall frequencies AML1-ETO and CBFB-MYH11 and hence CBF-AML is comparable to other ethnic groups. Correlation of specific genetic abnormalities with exposures to chemicals indicates a strong interplay between AML genetics and pollutants.   This study will help not only in differential diagnosis and prognostic stratification of AML in Pakistan, but it also opens new windows to better understand biology of AML in correlation with environmental exposure.Keywords: Acute Myeloid Leukemia; Genetic abnormalities; Core-binding factor leukemia, Prognostic stratification; environmental exposure

A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma

We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV and , versus 18F-FDG SUV and , resp., ). In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of and , respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned.Peer Reviewe