Faculty Bibliography

OBJECTIVE:This study aimed to determine the progression-free interval (PFI) for patients with platinum-resistant ovarian cancer on antiestrogen therapy (AET), and to correlate PFI with tumor estrogen receptor (ER) expression status. MATERIALS AND METHODS/METHODS:This single-institution retrospective cohort study investigated platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers treated with tamoxifen or an aromatase inhibitor from January 1999 to January 2012. Median PFI was calculated and a 95% confidence interval was constructed by bootstrapping. Relationships of PFI with disease characteristics were examined using 1-way analysis of variance or Pearson correlation. Estrogen receptor status of tumor specimens was assessed by immunohistochemistry. Progression-free interval was compared between ER groups with the Mann-Whitney test. Kaplan-Meier estimate was used to determine overall survival. RESULTS:Ninety-nine patients met inclusion criteria: 77 (78%) received tamoxifen and 22 (22%) an aromatase inhibitor. Patients had a mean of 4 prior chemotherapy regimens (range, 1-14). Median PFI for any AET was 4.0 months (range, 1-49; 95% confidence interval, 3.0-5.0). Progression-free interval was independent of the number of prior treatments and type of AET, but longer with earlier stage at diagnosis. Estrogen receptor status was obtained for 63 patients, 44 were positive and 19 were negative. Progression-free interval was not statistically significant between ER-positive (median, 4.0 months) and ER-negative (median, 2.0 months) tumor status (P = 0.36). CONCLUSIONS:This is the largest study to date investigating AET in heavily pretreated, platinum-resistant ovarian cancer patients. The median PFI of 4.0 months is comparable to standard cytotoxic therapies, and some patients with PFI greater than this median interval had ER-negative tumors. Given the limited adverse effects of AET, as well as low cost including oral administration, this treatment should be considered in all patients with platinum-resistant ovarian cancer.

OBJECTIVE:The objective of the study was to evaluate the efficacy of an educational intervention at increasing the rates of postpartum (PP) follow-up for women with gestational diabetes mellitus (GDM). STUDY DESIGN/METHODS:A retrospective cohort study of all patients with GDM delivering during 2002-2009 was conducted. The primary outcome was obtaining PP diabetes testing. The 2002-2006 cohort was advised to obtain PP testing by their providers. The 2007-2009 cohort received educational counseling at the 37-38 week visit by a nurse educator. Univariate and multivariable statistical tests were utilized. RESULTS:The PP testing frequency was 53% for the 2007-2009 cohort, compared with 33% for the 2002-2006 cohort (P < .001). When stratified by race/ethnicity, increased rates of testing were seen in whites (28% to 53%, P < .001), Latinas (15% to 50%, P < .001), and Asians (43% to 59%, P = .005). There was a nonsignificant decrease in the African American follow-up, 28% to 17% (P = .414). CONCLUSION/CONCLUSIONS:GDM precedes the development of type 2 diabetes. Antepartum education counseling increases postpartum diabetes testing. More efforts are needed to obtain universal screening.

We sought to determine the frequency of postpartum follow-up for women diagnosed with gestational diabetes mellitus. A retrospective cohort study of women with gestational diabetes mellitus from 2002 to 2008 ( N = 745) at an academic center was conducted. The primary outcome was either fasting blood glucose or 2-hour oral glucose tolerance, both measured at ≤6 months postpartum. Chi-square test and multivariable logistic regression analysis were used for statistical comparisons, and statistical significance was indicated by P < 0.05 and 95% confidence intervals. The frequency of follow-up for the study cohort was 33.7%. Of these women, 28.3% had values consistent with impaired glucose tolerance and 2.0% were diagnosed with type 2 diabetes mellitus. Asian women were the most likely to follow up (43%), and Latinas had the lowest follow-up frequency (18%; P < 0.001). Compared with their counterparts, women ≥35 years old, nulliparas, and women with GDM subtype A2 were more likely to return for postpartum glucose testing (odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.2 to 2.5; OR = 1.9, 95% CI 1.3 to 2.7; OR = 2.28, 95% CI 1.4 to 3.6, respectively). The frequency of postpartum follow-up for women diagnosed with gestational diabetes mellitus is exceedingly low. More effective strategies are needed to increase the postpartum and longitudinal follow-up for all women with gestational diabetes mellitus.

Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network by cross-linking actin, linking cell membrane to the cytoskeleton and regulating intracellular signaling pathways responsible for skeletal development (Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. and Shapiro, S.S. (2001) Filamins as integrators of cell mechanics and signalling. Nat. Rev. Mol. Cell Biol., 2, 138-145). Mutations in FLNB cause human skeletal disorders [boomerang dysplasia, spondylocarpotarsal (SCT), Larsen, and atelosteogenesis I/III syndromes], which are characterized by disrupted vertebral segmentation, joint formation and endochondral ossification [Krakow, D., Robertson, S.P., King, L.M., Morgan, T., Sebald, E.T., Bertolotto, C., Wachsmann-Hogiu, S., Acuna, D., Shapiro, S.S., Takafuta, T. et al. (2004) Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat. Genet., 36, 405-410; Bicknell, L.S., Morgan, T., Bonafe, L., Wessels, M.W., Bialer, M.G., Willems, P.J., Cohn, D.H., Krakow, D. and Robertson, S.P. (2005) Mutations in FLNB cause boomerang dysplasia. J. Med. Genet., 42, e43]. Here we show that Flnb deficient mice have shortened distal limbs with small body size, and develop fusion of the ribs and vertebrae, abnormal spinal curvatures, and dysmorphic facial/calvarial bones, similar to the human phenotype. Characterization of the mutant mice demonstrated increased apoptosis along the bone periphery of the distal appendages, consistent with reduced bone width. No changes in the initial proliferative rate of chondrocytes were observed, but the progressive differentiation of chondrocyte precursors was impaired, consistent with reduced bone length. The extracellular matrix appeared disrupted and phosphorylated beta1-integrin (a collagen receptor and Flnb binding partner) expression was diminished in the mutant growth plate. Like integrin-deficient chondrocytes, adhesion to the ECM was decreased in Flnb(-/-) chondrocytes, and inhibition of beta1-integrin in these cells led to further impairments in cell spreading. These data suggest that disruption of the ECM-beta1-integrin-Flnb pathway contributes to defects in vertebral and distal limb development, similar to those seen in the human autosomal recessive SCT due to Flnb mutations.