Lost opportunities for mismatch repair (MMR) screening among minority women with endometrial cancer.

Lynch Syndrome (LS) prevalence in underrepresented minorities are lacking. The objective of this study was to assess the prevalence of LS in a minority patient population. Secondary objectives included identifying factors associated with successful LS screening and to characterize clinicopathologic features. Women with endometrial cancer treated within a university system from 2014 and 2016 were included. Immunohistochemistry (IHC) results of MLH1, PMS2, MSH2 and MSH6 were obtained from medical records and clinicopathologic factors abstracted. Patients not previously screened for LS were screened. 276 patients were evaluable. More minority women were screened as part of their routine cancer care (p = 0.005). Additionally, women 50 years or younger were more likely to be screened for LS compared to women older than 51(p = 0.009) and uninsured or reliant on Medicaid patients (p = 0.011) were more likely to be screened during routine care. Six patients received confirmatory germline testing for LS (4.3%), and another 8 patients had a staining pattern suggestive of LS. In an underrepresented population, the rate of LS in endometrial cancer is similar to previous reports. LS may be under diagnosed and opportunities missed when universal screening is not applied in minority women.

Vasoactive intestinal peptide infusion reverses existing renal interstitial fibrosis via a blood pressure independent mechanism in the rat.

Dialysis requiring renal failure is a silent epidemic. Despite an annual mortality of 24% the dialysis population has increased by 1-4% per annum. Regardless of the initial injury, tubulointerstitial fibrosis is a feature of the renal pathology and it inversely correlates with declining renal function. Current agents display little efficacy against tubulointerstitial fibrosis. Clearly, therapies effective against tubulointerstitial fibrosis and able to preserve kidney function are needed. Vasoactive intestinal peptide (VIP) has been shown to reverse pre-existing cardiac fibrosis. We sought to determine whether VIP is effective in tubulointerstitial fibrosis. Spontaneous hypertensive rats (SHR) on a 2.2% salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. A fourth group, to match the blood pressure reduction achieved in the VIP infused group was included. Fibrosis was quantitated by computerised histomorphometry, changes in pro-fibrotic mediators were measured by quantitative rt-PCR and macrophage activation assessed by cyclic adenosine monophosphate (c-AMP) response to incubation with VIP. Tubulointerstitial fibrosis in the VIP treated rats was significantly lower than the zero time control (P < 0.0005), the vehicle infused control (P < 0.0005) and the blood pressure matched group (P < 0.01). Although all six profibrotic mediators increased over the 4 week experimental period VIP infusion only decreased tumour necrosis alpha (TNFα) expression significantly (P < 0.001). Incubation of RAW264 macrophages with VIP significantly increased c-AMP (P < 0.01). We conclude that VIP infusion reversed existing tubulointerstitial fibrosis suggesting a possible therapeutic role for a VIP based therapy in chronic kidney disease.

Gynecologic Care for Women With Physical Disabilities: A Qualitative Study of Patients and Providers.

BACKGROUND: Women with physical disabilities have unmet gynecologic care needs, including disparities in cancer screening and contraceptive care, when compared with women without physical disabilities. Our objective was to qualitatively assess provider and patient perspectives regarding barriers to gynecologic health care for women with physical disabilities. METHODS: We used purposive sampling to recruit women with physical disabilities and gynecology providers who had experience caring for this population at two university hospitals. Patient and provider participants completed in-depth, semistructured interviews investigating their experiences with and barriers to receiving or providing gynecologic care. Transcripts were systematically analyzed by reviewing assigned codes and performing thematic analysis. We planned a sample size of at least 20 patient and provider participants to allow for saturation of thematic content. RESULTS: We interviewed 29 women with physical disabilities and 20 providers. Important themes for providers and patients centered around adequate time spent during appointments, challenges with the gynecologic examination, inadequate facilities, clinical space limitations, and lack of formal provider and staff training in caring for this population. CONCLUSIONS: Providers were motivated to provide quality care for women with disabilities, but encountered systems and training barriers. Patients and providers had concordant impressions of barriers that influenced equitable and patient-centered care, with structural barriers, including a lack of accessible space, closely related to perceptions of health care inequity between women with and without physical disabilities.

Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat.

Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) increases and to become undetectable in end stage cardiomyopathy. We sought to determine whether replenishment of myocardial VIP might treat myocardial fibrosis and therefore represent a new therapeutic target. Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR. Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P < 0.01) while fibrosis in the VIP treated rats was significantly lower than in both the zero time control (P < 0.05) and the vehicle infused control (P < 0.0005). Although all six profibrotic mediators which were measured increased over the 4 week experimental period VIP infusion only affected angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a) expression. In both instances VIP caused a significant decrease in messenger rna expression (Agt P < 0.01 and At1a P < 0.01) compared with vehicle infused controls. We conclude that VIP infusion increased myocardial VIP concentration and was able to reverse existing myocardial fibrosis suggesting a possible therapeutic role for a VIP based therapy in cardiac failure.

Impact of molecular testing in clinical practice in gynecologic cancers.

BACKGROUND: With the growing understanding of the molecular and genetic profiles of cancers, targeted treatments are increasingly utilized in personalized cancer care. The objective of this study was to determine how these advances have translated into practice by examining how often molecular profiling of gynecological tumors led to treatment changes. METHODS: We identified women with gynecological cancers at our institution who had molecular tumor testing performed from November 2014 to June 2017. Clinicopathologic data were extracted from medical records. We determined (a) if molecular profiling identified actionable targets for which therapy is available, and (b) whether the patient's treatment course changed as a result of molecular profiling. Chi-square, Wilcoxon rank-sum, and Fisher's exact tests were used with a P < 0.05 considered statistically significant. RESULTS: We identified 152 patients with gynecologic cancers who underwent molecular profiling. Of the 152 patients, 116 (76.3%) had actionable mutations identified, with 41 (35.3%) patients having a treatment change. Stratified by cancer type, molecular profiling most frequently identified an actionable target in patients with endometrial cancer (73.6%). Changes in treatment occurred most frequently in patients with endometrial cancer, 22 (56.4%), and ovarian cancers, 16 (39%), as compared to patients with cervical and vulvar cancer (P = 0.02). Of those patients who received a change in treatment, 39 patients (95.1%) received an FDA-approved therapeutic agent, while two patients (4.8%) were enrolled in a clinical trial. CONCLUSION: Molecular profiling in gynecologic cancers often identified at least one actionable mutation; however, only in a minority of these cases was the course of treatment changed. Further studies are needed to elucidate optimal timing for testing to best utilize actionable information.