The Role of the Trabecular Bone Score in the Assessment of Osteoarticular Disorders in Patients with HFE-Hemochromatosis: A Single-Center Study from Poland.

Type 1 hereditary hemochromatosis (HH) is an autosomal, recessive genetic entity with systemic iron overload. Iron homeostasis disorders develop as a result of HFE gene mutations, which are associated with hepcidin arthropathy or osteoporosis and may cause permanent disability in HH patients despite a properly conducted treatment with phlebotomies. In this study, selected parameters of calcium and phosphate metabolism were analyzed in combination with the assessment of bone mineral density (BMD) disorders in patients from northern Poland with clinically overt HFE-HH. BMD was determined by a dual-energy X-ray absorptiometry (DXA) test with the use of the trabecular bone score (TBS) function. The study included 29 HH patients (mean age = 53.14 years) who were compared with 20 healthy volunteers. A significantly lower TBS parameter and serum 25-OH-D3 concentration, a higher concentration of intact parathormone and more a frequent occurrence of joint pain were found in HH patients compared with the control group. In HH patients, the diagnosis of liver cirrhosis was associated with lower serum 25-OH-D3 and osteocalcin concentrations. In HH, DXA with the TBS option is a valuable tool in the early assessment of the bone microarchitecture and fracture risk. A supplementation of vitamin D, monitoring its concentration, should be considered especially in HH patients with liver damage and liver cirrhosis.

Dosimetric evaluation of vaginal cuff brachytherapy planning in cervical and endometrial cancer patients.

PURPOSE: The aim of the study was to perform a prospective analysis of dosimetric consequences of rectal enema administration before vaginal cuff brachytherapy (VCB), the dose distribution in organs at risk (OARs), and the presence of air gaps (AGs) in patients with cervical or endometrial cancer. MATERIAL AND METHODS: In total, 75 patients treated in 2019 were randomly divided into two groups including 38 patients with and 37 without an enema before VCB. All patients received post-operative high-dose-rate (HDR). Single-channel vaginal cylinders with active length of 2.75 cm were used. Prescription dose was 7 Gy at 5 mm depth from the applicator surface in all directions. Treatment plans were based on computed tomography (CT). RESULTS: Enema performed before cylinder insertion had no effect on rectosigmoid Dmax or D2cm3. Rectosigmoid median V100 was 0.5 cm3 (range, 0-2.7 cm3). V100 ≥ 1 cm3 in 22 and ≥ 2 cm3 in 6 patients, with Dmax up to 19.7 Gy (282%) were observed. No effect of bladder volume in the range of 27-256 cm3 on Dmax or D2cm3 was found. The median bladder V100 was 0.1 cm3 (range, 0-1.4 cm3). There were 62 (83%) patients with AGs, with 24% at the top of the vagina and 75% on the remaining length of the vagina. Most of the AGs were small (≤ 3 mm), but in 5 (8%) cases, they were bigger than 5 mm. CONCLUSIONS: VCB planning with the use of CT is essential. CT can facilitate the selection of optimal cylinder size to reduce the occurrence of large AGs. A few percent of plans require correction of dose distribution because of hot spots in OARs and the presence of AGs. Enema before cylinder insertion does not influence rectosigmoid Dmax and D2cm3. The analysis revealed no bladder volume effect on bladder doses Dmax and D2cm3.

LDL dinitrosyl iron complex: A new transferrin-independent route for iron delivery in hepatocytes.

In view of the interrelations between NO, Fe, and LDL in the cardiovascular system it appears interesting to find out, if the lipoprotein particles undergo the process of iron-nitrosylation, commonly observed for other proteins and what is the biological fate of iron-nitrosylated LDL particles. Iron-nitrosylated LDL preparation containing Fe(NO)2 motif (DNICLDL) was obtained and characterized for the first time. In order to test its interactions with potential target cells, DNICLDL was administered to the hepatoma HepG2 cells. The effects were referred to those induced by native LDL (nLDL) and oxidized LDL (oxLDL) particles. DNICLDL administration considerably increased total iron content in the studied cell line, but did not influence the level of calcein-chelatable ions. DNICLDL was found to be low toxic to cells. The study suggests that DNICLDL might be a potential transducer of iron. © 2017 BioFactors, 44(2):192-201, 2018.

Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis.

BACKGROUND: The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.