Clinical Research Directory

Identifying Individuals at Risk of Glucocorticoid-Induced Impairment of Bone Disease

Previous studies have shown that there is a large inter-individual variability in the degree of bone loss during glucocorticoid treatment, and while some patients experience extensive bone loss other patients\' bone mass remains stable. The aim of the study is to find a biomarker that can be used to identify individuals at risk of glucocorticoid-induced bone loss. The study will include 36 healthy volunteers, that will be randomized to receive either glucocorticoid treatment or placebo. During the study blood samples, bone marrow samples, bone tissue samples, and adipose tissue samples are taken and an oral glucose tolerance test is performed.

Deep Learning for Musculoskeletal Complications in Breast Cancer

Survival after breast cancer has increased due to early diagnosis and advances in treatment methods. Musculoskeletal problems related to cancer and its treatment constitute a significant part of the daily practice of physiatrists and rehabilitation specialists involved in oncological rehabilitation. Lymphedema can occur at any stage of a patient's life following breast cancer. Patients with breast cancer-related lymphedema require lifelong treatment, and as the stage of lymphedema progresses, response to therapy decreases. Advanced stages of lymphedema negatively affect functional status, and patients experience difficulties in performing activities of daily living. Axillary web syndrome (AWS) is characterized by a taut cord extending from the axilla to the volar surface of the wrist, typically appearing within the first 8 weeks postoperatively. AWS can complicate the administration of radiotherapy. Shoulder dysfunction may occur independently or in association with AWS. In particular, scapular dyskinesis developing after mastectomy can lead to secondary shoulder conditions such as rotator cuff syndrome or adhesive capsulitis, which are commonly observed in these patients. Peripheral neuropathy is frequently seen in patients receiving chemotherapy, adversely affecting daily life and sometimes preventing continuation of treatment. Other complications related to chemotherapy and radiotherapy include cardiotoxicity, pulmonary toxicity, fatigue, osteoporosis, and cognitive impairment. There are also specific painful syndromes that may occur after breast cancer, including post-mastectomy pain syndrome, phantom breast pain, and musculoskeletal symptoms associated with aromatase inhibitors. All these conditions can significantly impair daily functioning and even hinder continuation of cancer treatment. Therefore, predicting these complications and implementing or developing preventive interventions is crucial. If it is possible to predict the early development of lymphedema, axillary web syndrome, peripheral neuropathy, and painful syndromes after breast cancer, early intervention may prevent progression. This study is designed to develop and validate a predictive model using deep learning methods to determine the risk of these complications in patients undergoing breast cancer surgery. Among deep learning architectures, ResNet50, AlexNet, GoogleNet, and UNet, which have been widely used in recent studies, are planned to be implemented. Additionally, based on the results of this study, a risk calculation program will be developed, allowing clinicians to input baseline patient data and calculate the individual patient's risk for each complication prior to treatment. No specific risk is expected in the study.

Vitamin k, D-chiro Inositol and α-lactalbumin in Bone Homeostasis

In women with breast cancer undergoing adjuvant hormone therapy, the marked tissue hypoestrogenism induced by therapy with aromatase inhibitors and/or tamoxifen ± GnRH analogues causes a significant acceleration in bone mass loss, with a consequent increased risk of fracture from the first year of therapy. It is therefore essential to start treatment with antiresorptive drugs and calcium and vitamin D supplementation. It has been hypothesized that vitamin K and α-lactalbumin have an effect in improving the absorption of calcium and vitamin D. In addition, vitamin K promotes gamma-carboxylation of osteocalcin, causing its activation and leading to increased incorporation of hydroxyapatite into the bone, resulting in increased calcium uptake from the blood and other tissues. Studies have reported that a combination of alendronate and vitamin K2 can lead to a decrease in the ratio of uncarboxylated osteocalcin to carboxylated osteocalcin, contributing to an increase in BMD, especially in the femoral neck. α-lactalbumin is able to increase the bioaccessibility of calcium due to its ability to prevent its precipitation at the neutral pH present in the absorptive tracts of the small intestine. Furthermore, α- lactalbumin has a binding site for vitamin D3, and the complexes formed by monomers of this protein and vitamin D have shown good stability in the presence of high vitamin concentrations. Inositol is a carbohydrate structurally similar to glucose which, in its isomeric form D-chiro-inositol, acts on bone remodeling by blocking the activation of osteoclasts through inhibition of the binding of RANK-L to its receptor present on pre-osteoclasts. Our hypothesis is that the use of the combination of vitamin K, α- lactalbumin, and D-chiro-inositol should improve the intestinal absorption of calcium and vitamin D, increasing the percentage of patients able to normalize serum levels of vitamin D and urinary calcium excretion (as a parameter of adequate calcium intake). This aspect, together with the direct effect of these components on bone remodeling, could enhance the anti-resorptive effect of standard therapy with bisphosphonates, improving the quantitative and qualitative parameters of bone. Therefore, we design a prospective randomized pilot study to assess efficacy of the combination of vitamin K, α-lactalbumin, and D-chiro-inositol, comparing patients with standard therapy and patients treated with Synostea®