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Grand Rapids, Michigan, United States

Luke B.,Michigan State University | Brown M.B.,University of Michigan | Wantman E.,Redshift Technologies | Lederman A.,Redshift Technologies | And 6 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. METHODS: We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. RESULTS: The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. CONCLUSIONS: Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology). Copyright © 2012 Massachusetts Medical Society. Source

Womble P.R.,University of Michigan | Dixon M.W.,University of Michigan | Linsell S.M.,University of Michigan | Ye Z.,University of Michigan | And 4 more authors.
Journal of Urology | Year: 2014

Purpose While transrectal prostate biopsy is the cornerstone of prostate cancer diagnosis, serious post-biopsy infectious complications are reported to be increasing. A better understanding of the true prevalence and microbiology of these events is needed to guide quality improvement in this area and ultimately better early detection practices. Materials and Methods Using data from the MUSIC registry we identified all men who underwent transrectal prostate biopsy at 21 practices in Michigan from March 2012 to June 2013. Trained data abstractors recorded pertinent data including prophylactic antibiotics and all biopsy related hospitalizations. Claims data and followup telephone calls were used for validation. All men admitted to the hospital for an infectious complication were identified and their culture data were obtained. We then compared the frequency of infection related hospitalization rates across practices and according to antibiotic prophylaxis in concordance with AUA best practice recommendations. Results The overall 30-day hospital admission rate after prostate biopsy was 0.97%, ranging from 0% to 4.2% across 21 MUSIC practices. Of these hospital admissions 95% were for infectious complications and the majority of cultures identified fluoroquinolone resistant organisms. AUA concordant antibiotics were administered in 96.3% of biopsies. Patients on noncompliant antibiotic regimens were significantly more likely to be hospitalized for infectious complications (3.8% vs 0.89%, p = 0.0026). Conclusions Infection related hospitalizations occur in approximately 1% of men undergoing prostate biopsy in Michigan. Our findings suggest that many of these events could be avoided by implementing new protocols (eg culture specific or augmented antibiotic prophylaxis) that adhere to AUA best practice recommendations and address fluoroquinolone resistance. © 2014 by American Urological Association Educaton and Research, Inc. Source

Chen Y.,Michigan State University | Wang K.,Michigan State University | Leach R.,Michigan State University | Leach R.,Spectrum Health Medical Group
Biochemical and Biophysical Research Communications | Year: 2013

Placental trophoblast invasion involves a cellular transition from epithelial to mesenchymal phenotype. Cytotrophoblasts undergo epithelial to mesenchymal transition (EMT) when differentiating into extravillous trophoblasts and gaining the capacity of invasion. In this research, we investigated the role of DNA methylation in trophoblasts during this EMT. First, using BeWo and HTR8/SVneo cell lines as models of cytotrophoblasts and extravillous trophoblasts, respectively, we analyzed the gene expression and DNA methylation status of the known epithelial marker genes, E-Cadherin and Cytokeratin7. We found that, in HTR8/SVneo cells, both genes were silenced and their promoters hypermethylated, as compared with the high-level gene expression and promoter hypomethylation observed in BeWo cells. This result suggests that dynamic DNA methylation of epithelial marker genes plays a critical role in the trophoblast EMT process. To verify these results, we treated HTR8/SVneo cells with 5-aza-dC, a known inhibitor of DNA methyltransferase, for three days. Five-Aza-dC treatment significantly increased the expression of epithelial marker genes and slightly decreased the expression of mesenchymal genes, as detected by qRT-PCR, immunocytochemistry and Western blot. Furthermore, 5-aza-dC treated HTR8/SVneo cells changed their morphology from mesenchymal into epithelial phenotype, indicating that 5-aza-dC induced mesenchymal to epithelial transition. Lastly, we examined the effect of 5-aza-dC on trophoblast migration and invasion capacity. We applied 5-aza-dC to HTR8/SVneo cells in trans-well cell migration and invasion assays and found that 5-aza-dC treatment decreased trophoblast migration and invasion capacity. In conclusion, DNA methylation of epithelial marker genes represents a molecular mechanism for the process of trophoblast EMT. © 2013 Elsevier Inc.. Source

Chen Y.,Michigan State University | Wang K.,Michigan State University | Qian C.-N.,Van Andel Research Institute | Leach R.,Michigan State University | Leach R.,Spectrum Health Medical Group
Biochemical and Biophysical Research Communications | Year: 2013

Snail and Slug play critical roles in the epithelial to mesenchymal transition (EMT), the mesenchymal to epithelial transition (MET) and in the maintenance of mesenchymal morphology. In this research, we investigated the correlation of DNA methylation with the transcriptional level of these two genes during the EMT/MET process. First, we used several cell lines associated with EMT/MET processes of induced pluripotent stem cell generation and differentiation, trophoblast invasion, as well as cancer progression to examine the association between DNA methylation and transcription levels of these two genes. We found an inverse correlation between DNA methylation of first intron regions and transcription levels of Snail and Slug genes in these EMT/METs. To further verify the results, we treated two trophoblast cell line BeWo and HTR8/SVneo and one induced pluripotent stem cell line with 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferase, which caused increased expression of these two genes. Lastly, we cloned the promoters of both Snail and Slug into pGL3-Basic vector, after in vitro DNA methylation and transfection into IMR90 and HTR8/SVneo cells; we observed the significant reduction of their promoter activity due to DNA methylation. In summary, based on these results, DNA methylation is one of the molecular mechanisms regulating Snail and Slug genes during EMT/MET process. © 2012 Elsevier Inc. Source

Tobert C.M.,Michigan State University | Riedinger C.B.,Michigan State University | Lane B.R.,Michigan State University | Lane B.R.,Spectrum Health Medical Group
World Journal of Urology | Year: 2014

Purpose: Partial nephrectomy (PN) has become the gold standard for treating small renal masses amenable to such an approach. Surprisingly, the single randomized controlled trial of PN versus radical nephrectomy (RN) indicated an overall survival benefit for RN over PN. Recent studies have shed light on this discordance, and this review will attempt to discern what is known at present. Results: Multiple retrospective observational studies have demonstrated superior outcomes with PN compared with RN. Whether the observed survival benefit with PN is the result of renal functional advantages or the result of selection bias and other unmeasured variables is up for discussion. A meta-analysis of 21 studies including the EORTC 30904 found a 19 % reduction in all-cause mortality (p = 0.0001) and 29 % reduction in cancer-specific mortality (p = 0.0002) with PN versus RN. Recent analysis of SEER-Medicare data revealed that patients undergoing RN had similar survival when compared with non-cancer controls, further supporting concerns about selection biases in prior observational series. Discussion: Although PN is clearly of benefit for those likely to experience end-stage renal disease with RN, a survival benefit with PN in the elective setting is not proven at present. While experts may still believe PN to improve survival for these patients, the only level I evidence in the field would suggest otherwise, and selection bias is undoubtedly responsible for a significant part of the improved survival observed in retrospective studies. Given recent evidence, any further push to limit the role of RN should be tempered until we know PN is indeed superior. © 2014 Springer-Verlag Berlin Heidelberg. Source

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