Serum bone specific alkaline phosphatase and urinary deoxypyridinoline in postmenopausal osteoporosis

The objectives of this study were to: (i) evaluate the diagnostic sensitivity and specificity of the biochemical bone markers: serum total alkaline phosphatase (TALP), bone specific alkaline phosphatase (BSALP) and urinary deoxypyridinoline (Dpyr) in postmenopausal osteoporosis, (ii) compare the bone turnover of postmenopausal osteoporotic patients without and with hormone replacement therapy (HRT) against controls and (iii) identify the correlation between these bone markers and bone mineral density (BMD). We examined 42 postmenopausal women with BMD proven osteoporosis and 35 control subjects. Serum TALP, BSALP and urinary Dpyr were measured. All three biochemical bone markers showed comparable moderate diagnostic sensitivity but Dpyr had the highest diagnostic specificity. There were significantly higher serum TALP, BSALP and urinary Dpyr levels in non-HRT treated patients compared to controls (p<0.005, <0.0001 and <0.005 respectively). There were no significant differences in the levels of all three bone markers between HRT treated patients and control subjects. There was no significant correlation between TALP, BSALP or Dpyr and BMD in both controls and patients. In conclusion, the biochemical bone markers are not useful in diagnosis of postmenopausal osteoporosis but may have a role in monitoring progress and response to treatment. HRT treatment reduces bone turnover of postmenopausal osteoporosis.     

Fitness level and body composition indices: cross-sectional study among Malaysian adolescent

Background

The importance of fitness level on the well-being of children and adolescent has long been recognised. The aim of this study was to investigate the fitness level of school-going Malaysian adolescent, and its association with body composition indices.

Methods

1071 healthy secondary school students participated in the fitness assessment for the Malaysian Health and Adolescents Longitudinal Research Team (MyHEART) study. Body composition indices such as body mass index for age, waist circumference and waist height ratio were measured. Fitness level was assessed with Modified Harvard Step Test. Physical Fitness Score was calculated using total time of step test exercise and resting heart rates. Fitness levels were divided into 3 categories - unacceptable, marginally acceptable, and acceptable. Partial correlation analysis was used to determine the association between fitness score and body composition, by controlling age, gender, locality, ethnicity, smoking status and sexual maturation. Multiple regression analysis was conducted to determine which body composition was the strongest predictor for fitness.

Results

43.3% of the participants were categorised into the unacceptable fitness group, 47.1% were considered marginally acceptable, and 9.6% were acceptable. There was a significant moderate inverse association (p < 0.001) between body composition with fitness score (r = -0.360, -0.413 and -0.403 for body mass index for age, waist circumference and waist height ratio, respectively). Waist circumference was the strongest and significant predictor for fitness (ß = -0.318, p = 0.002).

Conclusion

Only 9.6% of the students were fit. There was also an inverse association between body composition and fitness score among apparently healthy adolescents, with waist circumference indicated as the strongest predictor. The low fitness level among the Malaysian adolescent should necessitate the value of healthy lifestyle starting at a young age.

     

Rapid progression of type 2 diabetes and related complications in children and young people—A literature review

Type 2 diabetes (T2D) is suggested to progress faster in children and young people vs type 1 diabetes (T1D) in the same age group and T2D in adults. We reviewed the evidence base for this. A literature search was performed of PubMed‐indexed publications between 2000 and 2018, for the terms “pediatric” and “T2D.” Results were combined and filtered for those relating to “progression.” Searches of abstract books from Latin American and Asian congresses were performed to include these populations. Pediatric populations were defined as <25 completed years of age. Of the articles and congress abstracts found, 30 were deemed relevant. Dividing the studies into categories based on how T2D progresses, we found the following: (a) yearly beta‐cell function deterioration was shown to be 20% to 35% in children with T2D compared with 7% to 11% in adults with T2D, despite similar disease durations; (b) retinopathy progression was likely dependent on diabetes duration rather than diabetes type; however, nephropathy, neuropathy and probably hypertension progressed faster in youth‐onset T2D vs T1D. Nephropathy progression was similar to adults with T2D, allowing for disease duration. Youth with T2D had a worse cardiovascular (CV) risk profile than youth with T1D, and a faster progression to CV death. (c) Progression to treatment failure was faster in youth‐onset T2D vs adult‐onset T2D. Substantial evidence exists for faster progression of T2D in pediatric patients vs T1D or adult‐onset T2D. New treatments targeting the pathology are needed urgently to address this issue.     

Myeloid-derived suppressor cells in non-malignant and non-infectious liver disease

BackgroundMyeloid-derived suppressor cells (MDSC) have been described as potent immunosuppressive cells in malignant and infectious liver disease. However, little is known about their role in non-infectious or non-malignant disease. We sought to characterise MDSC in patients with chronic non-infectious or non-malignant liver disease.MethodsExplants obtained from 12 patients undergoing liver transplantation and blood from 30 patients treated for haemochromatosis at the Queen Elizabeth Hospital, Birmingham, were analysed for the frequency of functional CD14+ HLA-DR– monocytic MDSC. Functional capacity was defined as the capability to suppress proliferation of maximally stimulated, CFSE-labelled CD4 T cells using CD3/CD28-beads (Dynabeads, LifeTechnologies, UK) at a ratio of 1:1. Additionally, MDSC were analysed for their capacity to induce CD4 regulatory T cells (assessed by FoxP3 expression) in cells activated with CD2/CD3/CD28-beads (Miltenyi, Germany). Both MDSC and CD4 cells were isolated by magnet-activated cell-sorting using a combination of depletion steps and positive-selection-steps. Analysis of frequency and immunotyping of MDSC was performed with flow-cytometry.FindingsCD14+ HLA-DR– MDSC obtained both from liver tissue and peripheral blood were able to suppress proliferation of CD4 T cells and to induce FOXP3-expression in CD4 T cells, typical of regulatory T cells. No such findings were observed when using CD14+ HLA-DR+ monocytes. Moreover, MDSC depleted of CD16+ monocytes showed weaker immunosuppressive capacity. In patients with haemochromatosis, the frequency of CD14+ HLA-DR– MDSC in peripheral blood ranged from 0·5% to 79% and in the liver of cirrhotic patients from 9·1% to 75·5%.InterpretationCD14+ HLA-DR– MDSC are fully functional in patients who have non-infectious or non-malignant liver disease. Similar to HLA-DR+ monocytes, CD16 expression may identify subtypes of monocytic MDSC with distinct immunoregulatory properties. Given the varying frequency of MDSC in the patients analysed, the clinical relevance of MDSC in non-malignant and non-infectious liver-disease has to be further analysed since they may influence the course of disease in these patients.FundingDeutsche Forschungsgemeinschaft and Liver Foundation Trust Fund.     

Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

PURPOSE: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, alpha/beta, and the rate of repair of sublethal damage, mu value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. METHODS AND MATERIALS: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for alpha/beta and mu were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, alpha/beta and mu values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of alpha/beta and mu values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. RESULTS: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was obtained for alpha/beta = 1.75 Gy and mu = 0.75 h(-1). When Cox regression analysis was applied for patients who had no steroid treatment after BMT, a maximal chi-square value was obtained for alpha/beta = 1 Gy and mu = 0.6 h(-1). Cox regression analysis was repeated using the data of patients who had not received posttransplant steroid treatment and also no heparin administration; we found alpha/beta = 0.75 Gy and mu= 0.65 h(-1). An increased cataract incidence was observed after steroid treatment of >14 weeks and heparin administration. CONCLUSION: The alpha/beta value of 0.75 Gy and mu value of 0.65 h(-1) found for the eye lens are characteristic for late-responding tissues. The incidence of cataract formation can now be quantified, taking into account the values calculated for alpha/beta and mu, TBI dose, and dose rate. Also, the reduction in cataract incidence as a result of lens dose reduction by eye shielding can be estimated.     

Influence of the time between surgery and radiotherapy on local recurrence in patients with lymph node-positive, early-stage, invasive breast carcinoma undergoing breast-conserving surgery: results of the French Adjuvant Study Group

BACKGROUND: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC. METHODS: Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50 mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of patients. RESULTS: After a median follow-up of 102 months, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02). Patients who received hormone therapy were less likely to develop LR (P = 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors. CONCLUSIONS: In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk.     

Adenocarcinoma at the site of ileo-anal anastomosis in Crohn's disease: report of a case

We reported a case of patient born in 1967 who has been operated on in 1987 on three years after the beginning of ulcerative colitis which became severe and resistant to the medical treatment. A total colectomy with an ileo-rectal anastomosis had been performed. The pathological diagnosis carried of the specimen was Ulcerative colitis Then a proctectomy, followed by ileo-anal anastomosis, was performed in 1993. After several episodes of pochitis and the appearance of intestinal lesions upstream the ileal pocket, the retained diagnosis was Crohn's colitis. Eight years after the ileo-anal anastomosis, the patient developed an adenocarcinoma in the ileal pocket. He has been operated on in 2002 and he had abdominoperineal resection, radiotherapy and chemotherapy. Re died in January 2003. The death was related to the recurrence of malignancy. Endoscopic controls with biopsies are mandatory doing to follow up dysplasia predictive of degeneration.