Tailoring treatment of salivary duct carcinoma (SDC) by liquid biopsy: ARv7 expression in circulating tumor cells

n/

253puse of red clover in premenopausal breast cancer patients receiving hormonal adjuvant treatment biological and clinical implications from a randomized clinical trial

n/

Clusterin: A potential target for improving response to antiestrogens

Antiestrogens represent the first line of therapy in the treatment of estrogen receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of patients develop resistance associated with progression and frequently die for metastatic breast cancer. The molecular events leading to pharmacological resistance are not completely understood. We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. Treatment with siRNA completely abolished cytoplasmic clusterin expression in all cell lines, but its down-regulation resulted in a significant decrease of cell growth only In the resistant line. We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells. ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) downregulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. Such results support the concept that targeting CLU could represent a promising therapeutic strategy in association with antiestrogen treatment in breast cancer patients

Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary

There has been considerable investigation of the potential for soyfoods to reduce risk of cancer, and in particular cancer of the breast. Most interest in this relationship is because soyfoods are essentially a unique dietary source of isoflavones, compounds which bind to estrogen receptors and exhibit weak estrogen-like effects under certain experimental conditions. In recent years the relationship between soyfoods and breast cancer has become controversial because of concerns – based mostly on in vitro and rodent data – that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. This controversy carries considerable public health significance because of the increasing popularity of soyfoods and the commercial availability of isoflavone supplements. In this analysis and commentary we attempt to outline current concerns regarding the estrogen-like effects of isoflavones in the breast focusing primarily on the clinical trial data and place these concerns in the context of recent evidence regarding estrogen therapy use in postmenopausal women. Overall, there is little clinical evidence to suggest that isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients. Although relatively limited research has been conducted, and the clinical trials often involved small numbers of subjects, there is no evidence that isoflavone intake increases breast tissue density in pre- or postmenopausal women or increases breast cell proliferation in postmenopausal women with or without a history of breast cancer. The epidemiologic data are generally consistent with the clinical data, showing no indication of increased risk. Furthermore, these clinical and epidemiologic data are consistent with what appears to be a low overall breast cancer risk associated with pharmacologic unopposed estrogen exposure in postmenopausal women. While more research is required to definitively allay concerns, the existing data should provide some degree of assurance that isoflavone exposure at levels consistent with historical Asian soyfood intake does not result in adverse stimulatory effects on breast tissue

Use of patient-reported outcome measures (PROMs) in clinical diabetes consultations: study protocol for the DiaPROM randomised controlled trial pilot study

Introduction: Although diabetes distress is found to be associated with decreased glycaemic control among adults with type 1 diabetes, the psychological and emotional impact of living with the condition is often not recognised and often under-reported in diabetes care. Therefore, regular assessment of diabetes distress is recommended. Assessment of diabetes distress using patient-reported outcome measures (PROMs) in clinical practice has the potential to enhance care for people with diabetes by identifying problems and improving patient–clinician communication. In this study protocol, we describe a pilot randomised controlled trial (RCT) aiming to test the feasibility of all components of an empowerment-based intervention using PROMs as dialogue support in clinical diabetes consultations, and to address the uncertainties associated with running a fully powered evaluation study. Methods: and analysis We will undertake a two-arm pilot RCT of an intervention using the Problem Areas In Diabetes (PAID) scale in clinical diabetes consultations in order to conclude whether a fully powered trial is appropriate and/or feasible. The study will also include qualitative indepth interviews with participants and healthcare providers. Our objectives are to (1) evaluate the recruitment procedures and attrition rates; (2) evaluate the performance of the randomisation procedure; (3) evaluate the participants’ mean scores on the outcome measures before and after the intervention; (4) evaluate if the intervention consultations are acceptable and feasible; and (5) explore patients’ and healthcare providers’ experiences with the use of PAID as dialogue support and empowerment-based communication skills in clinical diabetes consultations. The quantitative data analysis includes descriptive statistics (frequencies, percentages, means, SD and CI). For the qualitative data, we will perform thematic analysis. Ethics and dissemination: Ethical approval has been obtained from the Western Norway Regional Committee for Medical and Health Research Ethics (2017/1506/REC west). We will present the findings from the study phases at national and international conferences and submit manuscripts to peer-reviewed journals and popular science journals

No association between osteoporosis and AO classification of distal radius fractures: an observational study of 289 patients

Background: It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures. Methods: In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex). Results: Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture. Conclusions: Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention

Positive IgA against transglutaminase 2 in patients with distal radius and ankle fractures compared to community-based controls

Background: Patients with celiac disease (CD), including adults with subclinical disease, have low bone mineral density (BMD), deteriorated bone microarchitecture and meta-analysis show an increased risk of fracture. Immunoglobulin A (IgA) against transglutaminase 2 (IgA TG2) is a highly reliable marker to detect CD. Main objective: To explore the prevalence of positive IgA TG2 and CD in patients with distal radius and ankle fracture compared to community-based controls. Methods: Four hundred patients aged 40 years or above with distal fractures were included in a case–control study. About 197 controls were identified from the National Population Registry, those included had never suffered a fracture. BMD was measured, and comorbidities, medications, physical activity, smoking habits, body mass index (BMI) and nutritional factors were registered. Blood analysis to detect common causes of secondary osteoporosis was performed. Results: About 2.5% of the fracture patients had positive IgA TG2, compared to 1% in the control group. The odds ratio, adjusted for sex and age, of having positive IgA TG2 was 2.50 (95% CI 0.54–11.56). Conclusions: There were no significantly increased odds of CD in adult patients with fractures compared to controls; however, results imply that positive IgA TG2 is more prevalent in fracture patients than in controls. This study indicates that universal screening for CD in fracture patients is not warranted, but supports current clinical practice in Norway to suspect and investigate for CD in patients with fracture, osteoporosis and other risk factors for CD

No association between osteoporosis and AO classification of distal radius fractures: an observational study of 289 patients

Background It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures. Methods In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex). Results Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture. Conclusions Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention

No association between osteoporosis and AO classification of distal radius fractures: an observational study of 289 patients

Background It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures. Methods In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex). Results Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture. Conclusions Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention