Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families

BACKGROUND: 25(OH) vitamin D levels may be low in patients with moderately or severely active inflammatory bowel diseases (IBD: Crohn’s disease and Idiopathic Ulcerative Colitis) but this is less clear in patients with mild or inactive IBD. Furthermore there is limited information of any family influence on 25(OH) vitamin D levels in IBD. As a possible risk factor we hypothesize that vitamin D levels may also be low in families of IBD patients. OBJECTIVES: To evaluate 25[OH] vitamin D levels in patients with IBD in remission or with mild activity. A second objective is to evaluate whether there are relationships within IBD family units of 25[OH] vitamin D and what are the influences associated with these levels. METHODS: Participants underwent medical history, physical examination and a 114 item diet questionnaire. Serum 25[OH] vitamin D was measured, using a radioimmunoassay kit, (replete ≥ 75, insufficient 50–74, deficient < 25–50, or severely deficient < 25 nmol/L). Associations between 25[OH] vitamin D and twenty variables were evaluated using univariate regression. Multivariable analysis was also applied and intrafamilial dynamics were assessed. RESULTS: 55 patients and 48 controls with their respective families participated (N206). 25[OH] vitamin D levels between patients and controls were similar (71.2 ± 32.8 vs. 68.3 ±26.2 nmol/L). Vitamin D supplements significantly increased intake but correlation with serum 25[OH] vitamin D was significant only during non sunny months among patients. Within family units, patients’ families had mean replete levels (82.3 ± 34.2 nmol/L) and a modest correlation emerged during sunny months between patients and family (r(2) =0.209 p = 0.032). These relationships were less robust and non significant in controls and their families. CONCLUSIONS: In patients with mild or inactive IBD 25[OH] vitamin D levels are less than ideal but are similar to controls. Taken together collectively, the results of this study suggest that patient family dynamics may be different in IBD units from that in control family units. However contrary to the hypothesis, intra familial vitamin D dynamics do not pose additional risks for development of IBD

Probing the Intermediate-Age Globular Clusters in NGC 5128 from Ultraviolet Observations

We explore the age distribution of the globular cluster (GC) system of the nearby elliptical galaxy NGC 5128 using ultraviolet (UV) photometry from Galaxy Evolution Explorer (GALEX) observations, with UV - optical colors used as the age indicator. Most GCs in NGC 5128 follow the general trends of GCs in M31 and Milky Way in UV - optical color-color diagram, which indicates that the majority of GCs in NGC 5128 are old similar to the age range of old GCs in M31 and Milky Way. A large fraction of spectroscopically identified intermediate-age GC (IAGC) candidates with ~ 3-8 Gyr are not detected in the FUV passband. Considering the nature of intermediate-age populations being faint in the far-UV (FUV) passband, we suggest that many of the spectroscopically identified IAGCs may be truly intermediate in age. This is in contrast to the case of M31 where a large fraction of spectroscopically suggested IAGCs are detected in FUV and therefore may not be genuine IAGCs but rather older GCs with developed blue horizontal branch stars. Our UV photometry strengthens the results previously suggesting the presence of GC and stellar subpopulation with intermediate age in NGC 5128. The existence of IAGCs strongly indicates the occurrence of at least one more major star formation episode after a starburst at high redshift.Comment: 8 pages, 3 figures, accepted for ApJ Lette

Physical activity, weight, and outcomes in patients receiving chemotherapy for metastatic breast cancer (C40502/Alliance)

Background: Obesity and inactivity are associated with increased risk of cancer-related and overall mortality in breast cancer, but there are few data in metastatic disease. Methods: Cancer and Leukemia Group B 40502 was a randomized trial of first-line taxane-based chemotherapy for patients with metastatic breast cancer. Height and weight were collected at enrollment. After 299 patients enrolled, the study was amended to assess recreational physical activity (PA) at enrollment using the Nurses\u27 Health Study Exercise Questionnaire. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using stratified Cox modeling (strata included hormone receptor status, prior taxane, bevacizumab use, and treatment arm). All statistical tests were 2-sided. Results: A total of 799 patients were enrolled, and at the time of data lock, median follow-up was 60 months. At enrollment, median age was 56.7 years, 73.1% of participants had hormone receptor-positive cancers, 42.6% had obesity, and 47.6% engaged in less than 3 metabolic equivalents of task (MET) hours of PA per week (\u3c1 hour of moderate PA). Neither baseline body mass index nor PA was statistically significantly associated with PFS or OS, although there was a marginally statistically significant increase in PFS (hazard ratio = 0.83, 95% confidence interval = 0.79 to 1.02; Conclusions: In a trial of first-line chemotherapy for metastatic breast cancer, rates of obesity and inactivity were high. There was no statistically significant relationship between body mass index and outcomes. More information is needed regarding the relationship between PA and outcomes

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PurposeWomen with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).MethodsPatients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method.ResultsOf the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8).ConclusionLRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy

Serial analysis of circulating tumor cells in metastatic breast cancer receiving first-line chemotherapy

Background: We examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy. Methods: Serial CTC data from 469 patients (2,202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs (bCTC), combined CTC status at baseline to the end of cycle 1 (cCTC), and tCTC. Akaike Information Criterion (AIC) was used to select the model that best predicted PFS and OS. Results: Latent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (tCTCneg, 56.9% ), low (tCTClo, 23.7%), intermediate (tCTCmid, 14.5%), or high (tCTChi, 4.9%). Patients with tCTClo, tCTCmid and tCTChi patterns had statistically significant inferior PFS and OS compared to those with tCTCneg (P&lt;.001). AIC indicated that the tCTC model best predicted PFS and OS when compared to bCTC and cCTC models. Validation studies in an independent cohort of 1,856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model. Conclusions: We identified four novel prognostic groups in MBC based on similarities in CTC trajectory patterns during chemotherapy. Prognostic groups included patients with very poor outcome (tCTCmid+tCTChi, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be utilized for fine-tuning of CTC-based risk-stratification strategies to guide future prospective clinical trials in MBC

Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)

Purpose: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local–regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T). Methods: Patients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan–Meier method. Results: Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4–96.2), and LRR-free survival was 98.6% (95% CI 97.4–99.8). Conclusion: LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy

Improving STD testing behavior among high-risk young adults by offering STD testing at a vocational school

<p>Abstract</p> <p>Background</p> <p>Chlamydia trachomatis infection (CT) is the most prevalent bacterial STD. Sexually active adolescents and young adults are the main risk group for CT. However, STD testing rates in this group are low since exposed individuals may not feel at risk, owing-at least in part-to the infection's largely asymptomatic nature. Designing new testing environments that are more appealing to young people who are most at risk of acquiring chlamydia can be an important strategy to improve overall testing rates. Here we evaluate the effect of a school-based sexual health program conducted among vocational school students, aiming to obtain better access for counseling and enhance students' STD testing behavior.</p> <p>Methods</p> <p>Adolescents (median age 19 years) attending a large vocational school were provided with sexual health education. Students filled in a questionnaire measuring CT risk and were offered STD testing. Using univariate and multivariate analysis, we assessed differences between men and women in STD-related risk behavior, sexual problems, CT testing behavior and determinants of CT testing behavior.</p> <p>Results</p> <p>Of 345 participants, 70% were female. Of the 287 sexually active students, 75% were at high risk for CT; one third of women reported sexual problems. Of sexually active participants, 61% provided a self-administered specimen for STD testing. Independent determinants for testing included STD related symptoms and no condom use. All CT diagnoses were in the high-CT-risk group. In the high-risk group, STD testing showed an increased uptake, from 27% (previous self-reported test) to 65% (current test). CT prevalence was 5.7%.</p> <p>Conclusions</p> <p>Vocational school students are a target population for versatile sexual health prevention. When provided with CT testing facilities and education, self selection mechanisms seemed to increase CT testing rate dramatically in this high-CT-risk population expressing sexual problems. Considering the relative ease of testing and treating large numbers of young adults, offering tests at a vocational school is feasible in reaching adolescents for STD screening. Although cost-effectiveness remains an issue counseling is effective in increasing test rates.</p

Discovery of Molecular Markers to Discriminate Corneal Endothelial Cells in the Human Body

The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro

Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2–positive breast cancer

PURPOSE The Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN). PATIENTS AND METHODS In this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes received paclitaxel (80 mg/m2) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer–specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN. RESULTS A total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%). CONCLUSION With longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors

Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial)

Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50% of all premenopausal recipients [1]