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Objective To describe clinical characteristics and associated endometrial findings of transgender and gender nonbinary people using gender-affirming testosterone. Design Retrospective case series. Setting Academic medical center and public safety net hospital. Patient(s) Eighty-one patients using gender-affirming testosterone therapy undergoing hysterectomy for the indication of gender affirmation from 2000 to 2018. Intervention(s) None. Main Outcome Measure(s) Preoperative clinical characteristics and endometrium surgical pathology diagnoses. Result(s) Median age was 31 years (interquartile range [IQR] 27–40), and median body mass index 27 kg/m2 (IQR 24–30). Six patients (7%) were parous and 60 (74%) had amenorrhea. Thirty-three patients (40%) had proliferative and 40 (50%) atrophic endometrium. Endometrial polyps were found in nine patients (11%) of the sample. Endometrial findings were similar in the subgroup of 60 patients with preoperative amenorrhea. There were no cases of endometrial hyperplasia or malignancy. In bivariate analysis, those with proliferative endometrium were found to be, on average, 5.6 years younger than those with atrophic endometrium. There were no clinical factors associated with having proliferative versus atrophic endometrium in multivariable models. Conclusion(s) People using gender-affirming testosterone may have either proliferative or atrophic endometrium, including people who present with amenorrhea. Further study is needed to develop evidence-based guidelines for appropriate screening for endometrial hyperplasia or cancer in this population.

SUMMARY This review discusses the current evidence regarding perioperative hormone therapy for transgender individuals, with an emphasis on strategies to reduce the risk of perioperative venous thromboembolism. Historically, surgeons routinely discontinued estrogen therapy in the perioperative period with the goal of reducing the risk of venous thromboembolism. However, abrupt estrogen cessation may also lead to adverse emotional and physiologic effects, including an exacerbation of one's gender dysphoria. The data on the relationship of feminizing hormones and venous thromboembolism in the perioperative setting are largely based on extrapolation of hormone regimens that are no longer in use and may not accurately reflect the actual risk of venous thromboembolism. Future studies will allow surgeons to engage in evidence-based, patient-centered, informed consent while also minimizing the risk of complications, such as venous thromboembolism.

Background Therapeutic drug monitoring measures antiretroviral adherence more accurately than self-report but has not been available at the point-of-care (POC) until now. We compare a novel POC test for urine tenofovir to laboratory-based enzyme-linked immunosorbent assay (ELISA) testing in diverse patient populations urine pre-exposure prophylaxis (PrEP). Setting Urine samples were analyzed using ELISA and the POC lateral flow immunoassay (LFA) test from 2 cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited Kenyan and Ugandan heterosexual men and women, and the IBrEATHe Study, which recruited US transgender women and men using gender-affirming hormone therapy. Methods We calculated the sensitivity, specificity, and accuracy of the POC test compared with ELISA at a cutoff of 1500 ng/mL. Results Overall, 684 urine samples were tested from 324 participants in the 2 cohorts. In Partners PrEP, 454 samples from 278 participants (41% women) were tested with a median age of 33 years. In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested with a median age of 31 years. Comparison of the LFA read-out to ELISA yielded 100% sensitivity [97.5% one-sided confidence interval (CI) = 99.3%], 98.3% specificity (95% CI = 95.2% to 99.7%), and 99.6% accuracy (95% CI = 98.7% to 99.9%). Conclusion The sensitivity, specificity, and accuracy of a novel POC test for urine tenofovir all exceeded 98% when compared with a laboratory-based ELISA method when tested in diverse patient populations. Given the LFA's high accuracy and expected low cost, this POC test is a promising tool to support antiretroviral adherence that could be widely scalable to real-world clinical settings.

The sexual partnerships of transmasculine adults—who were assigned female at birth and identify on the masculine gender continuum—remain understudied. This includes characteristics of transmasculine adults' sexual partnerships associated with engaging in HIV/sexually transmitted infection (STI) sexual risk behavior. This study examined individual- and partnership-level factors of transmasculine adults' sexual partnerships associated with using a protective barrier during sexual activity. Data came from cross-sectional surveys administered to 141 transmasculine adults. Participants provided demographic and sexual health information for up to three sexual partners from the past 12 months (n = 259 partnerships). Generalized estimating equations (GEEs) were used to investigate individual- and partnership-level factors associated with any use of a protective barrier during five sexual behaviors. Transmasculine participants engaged in an array of sexual behaviors with diverse sexual partners. Individual- and partnership-level factors of transmasculine adults' sexual partnerships were associated with their protective barrier use; however, these associations varied in statistical significance across the five sexual behaviors. At the individual level, younger participants had lower odds of protective barrier use during fingering or fisting. At the partnership level, protective barrier use was associated with a sexual partnership's configuration and the gender identity of a sexual partner. Relative to participants with cisgender female partners, those with cisgender male partners generally had lower odds of using a protective barrier. Study findings highlight the importance of studying factors associated with HIV/STI risk behavior located beyond the individual. These findings may have implications for improving measurements of HIV/STI-related risk for transmasculine adults.

The sexual partnerships of transmasculine (TM) adults-those assigned female at birth who identify as transgender men or a masculine spectrum gender identity-and characteristics associated with STI/HIV risk behavior remains understudied. Participants in the current study were TM adults (n = 141) receiving care at a community health center in Boston, Massachusetts between March 2015 and September 2016. Using generalized estimating equations, we examined individual- and partnership-level factors associated with TM adults' odds of engaging in sexual behavior with a sexual partner of unknown STI/HIV status in the past 12 months. TM adults with casual sexual partnerships (vs. monogamous partnerships) and those in partnerships with cisgender men, other TM individuals, or transfeminine partners (vs. cisgender women) had statistically significantly higher odds of engaging in sexual behavior with a partner of unknown STI/HIV status in the past 12 months. Findings may inform future efforts to improve sexual health communication and STI/HIV disclosure between TM adults and their sexual partners.

Background: TRIUMPH (Trans Research–Informed communities United in Mobilization for the Prevention of HIV) was a community-led, transgender-specific pre-exposure prophylaxis (PrEP) demonstration project at 2 community-based clinical sites in California. TRIUMPH used peer health education, community mobilization, and clinical integration of PrEP with hormone therapy to promote PrEP knowledge and acceptability. The goal of this study was to evaluate PrEP uptake, retention, and adherence among TRIUMPH participants and examine site-based differences. Methods: Eligible participants were adult transgender and gender diverse people interested in PrEP. Participants were seen at baseline and at 1, 3, 6, 9, and 12 months for PrEP provision, clinical visits, and HIV testing. PrEP uptake was defined as dispensation of PrEP, PrEP retention was defined as proportion of expected visits completed among those who initiated PrEP, and PrEP adherence was assessed by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models quantified the association of variables with PrEP outcomes. Results: TRIUMPH enrolled 185 participants; the median age was 28 years (interquartile range: 23–35), 7% was Black, and 58% was Latinx. PrEP uptake was as follows: 78% in Oakland and 98% in Sacramento; 91% among trans women, 96% among trans men, and 70% among nonbinary participants. Almost half (47%) rarely/never believed about HIV, and 42% reported condomless sex act in the past 3 months. Participants who reported higher numbers of sex partners were more likely to be retained and adherent; other predictors of adherence included not having a primary partner and not experiencing violence in the past 3 months. Conclusions: This community-led, trans-specific PrEP demonstration project documents high levels of PrEP initiation in a young transgender and gender diverse cohort at risk of HIV acquisition.

Background Sex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood. Methods TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657). Results From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, −6%; 95% confidence interval [CI], −21% to 12%; P = .47), comparable between TGW and CGM (mean difference, −12%; 95% CI, −27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, −23%; 95% CI, −36% to −7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus. Conclusions CGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use. Clinical Trials Registration NCT04050371.

Background Transgender men (TM) have a male, masculine, or nonfemale gender identity, yet were assigned female sex at birth on the basis of their external genitalia. The majority of TM are at risk of infection with one of several high-risk strains of the human papillomavirus (hr-HPV), acquired primarily through sexual contact, that cause 99.7% of cervical cancers. This study aimed to explore the association between sexual behaviors and current cervical hr-HPV infection in TM with a cervix. Methods The primary aim of this analysis was to test for an association between participant self-report of sexual contact with a penis in the past 1 year and current infection with cervical hr-HPV as measured by provider-collected cervical HPV DNA assay. This is a secondary analysis of a bio-behavioral sexual health study conducted at a health center in Boston, MA from 2015 to 2016. Analysis was conducted using logistic regression with significance level set at P less than 0.05; the primary analysis was adjusted for self-reported age, current tobacco use, years of testosterone use, and HPV vaccination status. Results Overall prevalence of hr-HPV was 15.9%. In adjusted analyses, participants reporting receptive penile vaginal sex with any of their most recent 3 sexual partners in the past 12 months had more than 5 times greater odds of current hr-HPV infection than those reporting no penile sex of any kind during this timeframe (odds ratio, 5.23; 95% confidence interval, 1.61-17.02). Conclusions Vaginal-receptive penile sex in the last 12 months was associated with a 5-fold increased odds of cervical high-risk HPV infection among TM. Findings can inform future population level study of associations between sexual behaviors and hr-HPV risk, which could lead to more individualized approaches to screening.

Background Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. Objective The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. Research design This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. Subjects Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. Results We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. Conclusion In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.

Transgender (trans) people, particularly trans women of color, face alarmingly high rates of HIV. HIV pre-exposure prophylaxis (PrEP) with daily coformulated emtricitabine and tenofovir disoproxil fumarate is a promising biomedical HIV prevention modality; however, it has not yet been shown to be efficacious in the transgender population due to data limitations. Initial data suggest that barriers exist to PrEP uptake in the trans community, including lack of access to healthcare and concerns about interactions with hormone therapy. This article discusses these factors and reviews considerations for enhancing PrEP uptake and adherence in trans people at risk for HIV.

Purpose To enhance pediatric trainees' and students' knowledge of the psychosocial and medical issues facing transgender youth through a comprehensive curriculum. Methods During the 2015–2016 academic year, we administered a transgender youth curriculum to fourth-year medical students, pediatric interns, psychiatry interns, and nurse practitioner students on their 1-month adolescent and young adult medicine rotation. The curriculum included six interactive, online modules and an observational experience in a multidisciplinary pediatric gender clinic. The online modules had a primary care focus with topics of general transgender terminology, taking a gender history, taking a psychosocial history, performing a sensitive physical examination, and formulating an assessment, psychosocial plan, and medical plan. At the completion of the curriculum, learners completed an evaluation that assessed change in perceived awareness and knowledge of transgender-related issues and learner satisfaction with the curriculum. Results Twenty learners participated in the curriculum with 100% completing the curriculum evaluations, 100% reporting completing all six online modules, and 90% attending the gender clinic. Learners demonstrated a statistically significant improvement in all pre-post knowledge/awareness measures. On a Likert scale where 5 indicated very satisfied, learners' mean rating of the quality of the curriculum was 4.5 ± .7; quality of the modules was 4.4 ± .7; and satisfaction with the observational experience was 4.5 ± .8. Conclusions A comprehensive curriculum comprised interactive online modules and an observational experience in a pediatric gender clinic was effective at improving pediatric learners' perceived knowledge of the medical and psychosocial issues facing transgender youth. Learners also highly valued the curriculum.

Being transgender is associated with numerous health disparities, and transgender individuals face mistreatment and discrimination in healthcare settings. At the same time, healthcare professionals report inadequate preparation to care for transgender people, and patients often have to teach their own medical providers about transgender care. Our study aimed to evaluate the impact of an elective course for health profession students in transgender health that was implemented to address these gaps in provider knowledge.Students participated in a 10-session, lunch-hour elective course during the spring of 2015. To evaluate impact, course participants completed pre-, immediately post-, and 3-month postcourse questionnaires, including a previously validated nine-item transphobia scale, to determine the course's effect on knowledge, attitudes, and beliefs about transgender health.Forty-six students completed the pre- and immediately postelective questionnaire (74% response rate). Compared with pre-elective surveys, immediately postelective scores demonstrated increased knowledge in most domains and reduced transphobia. Specific knowledge domains with improvements included terminology, best practices for collecting gender identity, awareness of the DSM-V gender dysphoria diagnosis, medications used for gender affirmation, and relevant federal policies. A previously validated transphobia scale was found to have good reliability in the current sample.This elective course led to positive short-term changes in measures of multiple knowledge domains and reduced measures of transphobia among health profession students. Further study is needed to assess the long-term impact. Our methods and findings, including the demonstration of reliability of a previously validated nine-item transphobia scale, serve as formative data for the future development of theory-based transgender medicine curricula and measures.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the treatment of choice for select patients with peritoneal surface malignancies; however, the traditional open approach may be associated with significant morbidity. We evaluated postoperative outcomes with minimally invasive (MI) CRS and HIPEC.Review of our institutional database identified 47 patients who underwent optimal cytoreduction (CC0 or CC1). Those with a PCI ≤ 15 and primary malignancy of gastrointestinal origin were then selected for subgroup analysis. Multivariable regression was performed to identify factors impacting postoperative outcomes.Demographic data did not significantly differ between open (n = 24) and minimally invasive (n = 9) groups. The MI group had a mean age of 57.34 ± 14.92, BMI of 27.03 ± 4.27, Charlson comorbidity score of 1.78 ± 1.72, and PCI of 5.56 ± 5.08. Mean time to flatus (days) was 2.78 in the MI group and 5.04 in the open group (p 0.001), and mean length of IV analgesic use (days) was 3.11 in the MI group compared to 6.00 in the open group (p = 0.006). Mean length of stay (days) was 5.11 in the MI group and 8.67 in the open group (p = 0.033). Surgical approach (p = 0.037) and BMI (p = 0.039) were the only factors impacting length of stay.Minimally invasive CRS and HIPEC is an excellent option for low volume peritoneal disease of gastrointestinal origin. A minimally invasive approach yields faster return of bowel function, reduced postoperative analgesia requirements, and shorter hospital stay.

Objectives This study aims to identify factors associated with the reproductive planning of trans-masculine adults. Study design Between 2015 and 2016, providers enrolled 150 trans-masculine adults in a sexual health study assessing sociodemographics, social support, gender affirmation, sexual partnering, and reproductive history and planning. A brief clinical interview assessed contraceptive use and concerns. Bivariate and multivariable logistic regression analyses examined associations between participant characteristics and three outcomes: current contraceptive use, lifetime pregnancy history and reproductive planning. Results Overall, 37.3% are currently using contraceptives; 5.3% have been pregnant; and 20.0% plan to have biological children (9.3% plan to become pregnant; 12.0% plan to use their oocytes with a surrogate). Participants are less likely to use contraceptives if they are students vs. not, have socially affirmed their gender vs. not and have a partner vs. are single. Greater number of sexual partners is associated with the increased odds of contraceptive use. Further, as social support increases, the odds of having been pregnant decreases. Participants with a nonbinary gender identity are more likely to want to become pregnant than those with a binary gender identity, whereas those who have socially affirmed their gender are less likely to want to become pregnant than those who had not. Finally, participants of color more commonly planned to use their oocytes with a surrogate than white participants. Conclusion Sociodemographic, gender affirmation, social support and sexual partner factors are associated with contraceptive use and reproductive history among trans-masculine patients. Implications Healthcare providers must be aware of the diverse reproductive histories and pregnancy goals of trans-masculine individuals in order to provide comprehensive reproductive healthcare counseling and provision. More research is needed to better understand contraception and reproduction desires in trans-masculine individuals.

Intimate partner violence (IPV) takes on unique dimensions when directed against transgender individuals, with perpetrators leveraging transphobia to assert power and control. Standard IPV measurement tools do not assess this type of IPV. Four questions to assess transgender-related IPV (T-IPV) were developed: (a) being forced to conform to an undesired gender presentation or to stop pursuing gender transition; (b) being pressured to remain in a relationship by being told no one would date a transgender person; (c) being “outed” as a form of blackmail; and (d) having transition-related hormones, prosthetics, or clothing hidden or destroyed. The T-IPV tool was administered to 150 female-to-male transmasculine individuals completing a study of cervical cancer screening in Boston from March 2015-September 2016. Construct validity was assessed by examining correlations between T-IPV and two validated screeners of other forms of IPV (convergent) and employment status and fruit consumption (divergent). The association between T-IPV and negative health outcomes (posttraumatic stress disorder [PTSD], depression, psychological symptoms, binge drinking, number of sexual partners, and sexually transmitted infection [STI] diagnosis) were also calculated. Lifetime T-IPV was reported by 38.9%, and 10.1% reported past-year T-IPV. T-IPV was more prevalent among those who reported lifetime physical (51.7% vs. 31.7%, p = .01) and sexual (58.7% vs. 19.4%, p < .001) IPV than those who did not. Lifetime T-IPV was associated with PTSD (adjusted odds ratio [AOR] = 2.23, 95% confidence interval [CI] = [1.04, 4.80]), depression (AOR = 2.70, 95% CI = [1.22, 5.96]), and psychological distress (AOR = 2.82, 95% CI = [1.10, 7.26]). The T-IPV assessment tool demonstrated adequate reliability and validity and measures a novel type of abuse that is prevalent and associated with significant mental health burden. Future work should further validate the measure and pilot it with male-to-female transfeminine individuals.

Transgender medicine presents a particular challenge for the development of evidence-based guidelines, due to limitations in the available body of evidence as well as the exclusion of gender identity data from most public health surveillance activities. The guidelines that have been published are often based on expert opinion, small studies, and data gathered outside the US. The existence of guidelines, however, helps legitimate the need for gender-affirming medical and surgical interventions. Research conducted on transgender populations should be grounded in gender-affirming methodologies and focus on key areas such as health outcomes after gender-affirming interventions.

Transgender (trans) communities worldwide, particularly those on the trans feminine spectrum, are disproportionately burdened by HIV infection and at risk for HIV acquisition/transmission. Trans individuals represent an underserved, highly stigmatized, and under-resourced population not only in HIV prevention efforts but also in delivery of general primary medical and clinical care that is gender affirming. We offer a model of gender-affirmative integrated clinical care and community research to address and intervene on disparities in HIV infection for transgender people. We define trans terminology, briefly review the social epidemiology of HIV infection among trans individuals, highlight gender affirmation as a key social determinant of health, describe exemplar models of gender-affirmative clinical care in Boston MA, New York, NY, and San Francisco, CA, and offer suggested “best practices” for how to integrate clinical care and research for the field of HIV prevention. Holistic and culturally responsive HIV prevention interventions must be grounded in the lived realities the trans community faces to reduce disparities in HIV infection. HIV prevention interventions will be most effective if they use a structural approach and integrate primary concerns of transgender people (eg, gender-affirmative care and management of gender transition) alongside delivery of HIV-related services (eg, biobehavioral prevention, HIV testing, linkage to care, and treatment).

Research on the health of transgender and gender nonconforming people has been limited with most of the work focusing on transition-related care and HIV. The present review summarizes research to date on the overall development and quality of life of transgender and gender nonconforming adults, and makes recommendations for future research.Pervasive stigma and discrimination attached to gender nonconformity affect the health of transgender people across the lifespan, particularly when it comes to mental health and well-being. Despite the related challenges, transgender and gender nonconforming people may develop resilience over time. Social support and affirmation of gender identity play herein a critical role. Although there is a growing awareness of diversity in gender identity and expression among this population, a comprehensive understanding of biopsychosocial development beyond the gender binary and beyond transition is lacking.Greater visibility of transgender people in society has revealed the need to understand and promote their health and quality of life broadly, including but not limited to gender dysphoria and HIV. This means addressing their needs in context of their families and communities, sexual and reproductive health, and successful aging. Research is needed to better understand what factors are associated with resilience and how it can be effectively promoted.

Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women.The iPrEx trial was a randomised controlled trial of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate compared with placebo in men who have sex with men (MSM) and transgender women, followed by an open-label extension. Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. We did unplanned exploratory analyses to investigate differences in PrEP outcomes among transgender women and between transgender women and MSM.Of the 2499 participants enrolled in the randomised controlled trial, 29 (1%) identified as women, 296 (12%) identified as trans, 14 (1%) identified as men but reported use of feminising hormones, such that 339 (14%) reported one or more characteristics and are classified as transgender women for the purpose of this study. Compared with MSM, transgender women more frequently reported transactional sex, receptive anal intercourse without a condom, or more than five partners in the past 3 months. Among transgender women, there were 11 HIV infections in the PrEP group and ten in the placebo group (hazard ratio 1·1, 95% CI 0·5-2·7). In the PrEP group, drug was detected in none of the transgender women at the seroconversion visit, six (18%) of 33 seronegative transgender women (p=0·31), and 58 (52%) of 111 seronegative MSM (p0·0001). PrEP use was not linked to behavioural indicators of HIV risk among transgender women, whereas MSM at highest risk were more adherent.PrEP seems to be effective in preventing HIV acquisition in transgender women when taken, but there seem to be barriers to adherence, particularly among those at the most risk. Studies of PrEP use in transgender women populations should be designed and tailored specifically for this population, rather than adapted from or subsumed into studies of MSM.US National Institutes of Health and the BillMelinda Gates Foundation.

Long-acting somatostatin analogues (S-LAR) improve recurrence-free survival in patients with metastatic neuroendocrine tumor (NET) from gastrointestinal (GI) primary, but their impact on overall survival when combined with aggressive cytoreductive surgery is unclear.We reviewed our institutional cancer database to identify patients who underwent cytoreductive surgery for metastatic NET from GI primary between December 1997 and June 2013. Additionally, a cohort selected from 3,384 metastatic neuroendocrine cases in the SEER-Medicare database (January 2003 to December 2009) was used to verify and expand on our results.Most of the 49 patients from our institution had primary lesions in the small intestine (22 of 49 [44.9%]) or pancreas (14 of 49 [28.6%]); 37 patients (75.5%) had metastatic disease at initial diagnosis. These patients underwent 1 (32 of 49 [65.3%]), 2 (11 of 49 [22.4%]), or at least 3 (6 of 49 [12.3%]) surgical procedures; 33 patients (67.3%) underwent resection plus ablation, 19 (38.7%) underwent major hepatectomy, and 34 (69.4%) received S-LAR (29.4% administered preoperatively). Median follow-up was 112 months. Rates of 1-, 5-, 10-, and 15-year disease-specific survival (DSS) were 94%, 78%, 64%, and 31%, respectively, in the 34 patients undergoing aggressive cytoreductive surgery plus S-LAR. Of the SEER-Medicare population, 1,741 patients met inclusion criteria. The DSS for the 104 patients treated with combination therapy was 68.3% at 5 years and 60.6% at 10 years, as compared with 54.7% and 51.8%, respectively, for the 202 patients receiving surgery alone, and 50.0% and 36.0%, respectively, for the 342 patients receiving S-LAR alone (p0.0001). The group receiving neither treatment (n = 1,093) had 5-year and 10-year DSS of 34.3% and 26.3%, respectively.Long-acting somatostatin analogues combined with aggressive cytoreductive surgery improves the long-term survival of select patients with metastatic NET from GI primary.

Infiltrating tumors are an under-recognized cause of rapidly progressive dementia (RPD), defined as a 1- to 2-year course from symptom onset to cognitive and functional debilitation (Geschwind, 2010). Many patients with RPD have a fast deterioration of cognition over weeks to months, with death within 2 years. Clinicians evaluating patients with RPD usually consider sporadic Creutzfeldt-Jakob disease (CJD), autoimmune encephalitides, paraneoplastic encephalitis, infectious conditions, and even neurodegenerative disorders before they consider neoplastic dementias. An important potentially treatable neoplastic dementia is primary central nervous system lymphoma (PCNSL); however, there is little information to guide clinicians on the frequency and characteristics of PCNSL presenting as an RPD. Identifying this lymphomatous dementia as soon as possible and distinguishing it from other RPDs is critical because lymphomatous dementia is treatable but untreated PCNSL is rapidly fatal. PCNSL is a type of non-Hodgkin lymphoma that affects only the central nervous system (CNS), without systemic involvement. PCNSL is uncommon, accounting for only 4% of newly diagnosed CNS tumors, with an incidence of 0.47 per 100,000 person-years (Villano et al, 2011). Brain magnetic resonance imaging (MRI) often shows a single contrast-enhancing lesion and/or restricted diffusion on diffusion weighted imaging (DWI), but the disease can instead be multifocal (Degnan and Levy, 2014b; Lai et al, 2002). The most common sites of involvement are the deep periventricular white matter and the corpus callosum, as well as the thalamus and basal ganglia (Eichler and Batchelor, 2006). Homogeneous contrast enhancement, the classic appearance, can help distinguish PCNSL from other conditions, such as glioblastoma (heterogeneous enhancement) (Omuro and DeAngelis, 2013), progressive multifocal leukoencephalopathy (non-enhancing) (Shah et al, 2010), and Creutzfeldt-Jakob disease (CJD) (FLAIR and DWI hyperintensities in the cortical gyri as well as the caudate, putamen, or thalamus) (Degnan and Levy, 2014a; Geschwind et al, 2008). Uncommonly, PCNSL is widespread, with or without contrast enhancement, and may show only nonspecific T2 hyperintense lesions, known as lymphomatosis cerebri (LC) (Bakshi et al, 1999; Vital and Sibon, 2007; Weaver et al, 2007). In patients with LC, diagnosis can be especially challenging, as illustrated by Figure 1. FIGURE 1 Our evaluation for primary central nervous system lymphoma in a 74-year-old right-handed man with 6 months of progressive personality change, confusion, and impaired gait. On a magnetic resonance imaging scan of his brain, axial FLAIR (Panels A–D) ... A finding of neoplastic lymphocytes in cerebrospinal fluid (CSF), by either cytomorphology or immunophenotyping, is sufficient for a diagnosis of PCNSL with meningeal dissemination (Kiewe et al, 2010); however, because these CSF studies are not very sensitive, multiple samples may be needed to confirm the diagnosis. If the CSF is diagnostic, then a brain biopsy can be avoided. In diagnostically challenging cases, patients may be treated empirically with steroids for presumed demyelinating or autoimmune conditions, but the steroids’ lympholytic effects will further delay definitive diagnosis by CSF or biopsy. Neuropsychiatric symptoms account for about 40% of the presenting symptoms in patients with PCNSL (Bataille et al, 2000), but the distinguishing neurocognitive features have not been further characterized, particularly in comparison to other RPDs. Physicians may not suspect PCNSL, particularly if the neuroimaging is nonspecific and does not show a typical contrast-enhancing lesion. We analyzed case reports of patients with PCNSL presenting with dementia so that we could define their cognitive impairment and neurologic features. Then we compared these characteristics to those of CJD and other causes of RPD.

Summary Worldwide, transgender women who engage in sex work have a disproportionate risk for HIV compared with natal male and female sex workers. We reviewed recent epidemiological research on HIV in transgender women and show that transgender women sex workers (TSW) face unique structural, interpersonal, and individual vulnerabilities that contribute to risk for HIV. Only six studies of evidence-based prevention interventions were identified, none of which focused exclusively on TSW. We developed a deterministic model based on findings related to HIV risks and interventions. The model examines HIV prevention approaches in TSW in two settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years. A combination of interventions that achieves small changes in behaviour and low coverage of biomedical interventions was promising in both settings, suggesting that the expansion of prevention services in TSW would be highly effective. However, this expansion needs appropriate sustainable interventions to tackle the upstream drivers of HIV risk and successfully reach this population. Case studies of six countries show context-specific issues that should inform development and implementation of key interventions across heterogeneous settings. We summarise the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose a research agenda to improve HIV services and policies for this population.

Because of a lack of uniform collection of gender identity data, population-level breast cancer statistics in the transgender community are unknown. With recent estimates that at least 0.6% (1 in every 167 people) of the U.S. population is transgender, guidance on breast cancer risk, screening, and management in this population is needed. Such guidance should examine modifications, if any, to recommendations in cisgender populations, taking into consideration any history of hormone therapy exposure or breast surgery. This article describes existing evidence on breast cancer incidence in transgender women and men, and attempts to make rational recommendations regarding the screening for and approach to managing breast cancer in transgender populations. Current data are mostly limited to case reports which are reviewed here. More prospective, population-level research is needed to better understand the risks and predictors of breast cancer in this population, as well as to better inform the most appropriate screening modality, age of starting screening, and interval. Ultimately, a risk score calculator similar to existing risk models such as the Gail score, as well as an approach to shared decision making that involves patient-centered perspectives, is needed to best guide practices in this area.

Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex.To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment.This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy.Overall survival (OS).Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall, patients with gastrointestinal tract metastases undergoing complete, curative resection derived the greatest benefit, with a median OS of 64 months.To our knowledge, this series is the largest single-institution experience with abdominal melanoma metastases, demonstrating that surgical resection remains an important treatment consideration even in the systemic treatment era.

Background/Aims: Prior work in smaller cohorts suggests that traumatic brain injury (TBI) may be a risk factor for frontotemporal degeneration (FTD). We sought to confirm and extend these results using the National Alzheimer's Coordinating Center Uniform Data Set. Methods: We compared the TBI prevalence between FTD subjects and matched normal controls. Indices of cognitive, behavioral, functional, and global dementia severity were compared between FTD subjects with and without prior TBI. Results: Remote TBI with extended loss of consciousness (TBI-ext) was more common in individuals with FTD than in controls (OR: 1.67; 95% CI: 1.004-2.778). With TBI-ext, less functional and global impairment was seen in the behavioral variant of FTD, but more behavioral pathology was seen in the semantic variant. Conclusion: TBI may increase the FTD risk and influence clinical symptomatology and severity in FTD subtypes.

Background The early removal of central intravenous (IV) catheters, as a means of reducing the incidence of central line–associated blood stream infections (CLABSI), remains a major health care initiative. However, attaining IV access in the surgical intensive care unit (SICU) can be quite difficult. We report the success of a novel, resident-driven program for the placement of ultrasound-guided midline catheters in critically ill patients. Materials and methods A prospective pilot study of 31 subjects admitted to the SICU from June to December 2011 was performed. Intermediate-length (20 cm) midline catheters were placed by trained housestaff, under ultrasound guidance, into the basilic or cephalic veins. Procedural details including time to cannulation, complications, and costs were recorded. Results Successful placement was achieved in 96.8% (n = 30), with a mean follow-up of 9.8 ± 5.6 (range 2–21) days. An average of 1.3 ± 0.7 (range 1–4) attempts with a median of 13.0 ± 14.5 (range 0.5–68) minutes was required for successful venous cannulation. The most common site was the basilic vein (n = 23). Only minor complications were encountered; three catheters leaked at the insertion site and one patient developed phlebitis. No CLABSI occurred. The total procedure cost was $87 per catheter for the SICU team compared with $1500 per catheter when performed by an interventional radiologist. During the study period, a total of 283 central line days were avoided with an estimated cost savings of $13,614. Conclusions Ultrasound-guided midline catheters placed by the housestaff are a cost-effective alternative for patients in the SICU with difficult IV access. Successful placement can help facilitate early central line removal and thus may reduce CLABSI rates.

Background Hyperkalemia is a common and life–threatening complication frequently seen in patients with acute kidney injury, end–stage renal disease and chronic heart failure. Cardiac arrest and ventricular fibrillation are possible consequences. Biosensors are currently being developed to measure serum potassium under ambulatory conditions and trigger an alarm if the potassium concentration exceeds normal limits. Only few studies exist on the circadian rhythm of potassium; and its dependence on age and kidney function is less clear. Methods Our observational monocentric exploratory study included 30 subjects of which 15 had impaired renal function (RF) (GFR\60 ml/min/1.73 m2). Subjects were further categorized into three age groups: 18 39 years (N normal RF = 5, N impaired RF = 4), 40 59 years (N normal RF = 5, N impaired RF = 6), 60 80 years (N normal RF = 5, N impaired RF = 5). Serum potassium levels were measured every 2 h during a 24 h period and repeated once after 2, 4, or 6 days." "Results In the 15 subjects with normal RF, the lowest mean potassium level (3.96 ± 0.14 mmol/l) was observed at 9 p.m. and the greatest (4.23 ± 0.23 mmol/l) at 1 p.m. In patients with impaired RF the lowest mean potassium level (4.20 ± 0.32 mmol/l) was observed at 9 p.m. and the highest (4.57 ± 0.46 mmol/l) at 3 p.m. The range between the mean of minimum and maximum was greater in patients with impaired RF (0.71 ± 0.45 mmol/l) than in subjects with normal RF (0.53 ± 0.14 mmol/l) [p\0.001]. No difference in the circadian rhythm was found between the first and second examination." "Conclusion Our results indicate that patients with normal and impaired RF have comparable circadian patterns of serum potassium concentrations, but higher fluctuations in patients with impaired RF. These results have clinical relevance for developing an automatic biosensor to measure the potassium concentration in blood under ambulatory conditions in patients at high risk for potassium fluctuations.

Transgender patients have particular needs with respect to demographic information and health records; specifically, transgender patients may have a chosen name and gender identity that differs from their current legally designated name and sex. Additionally, sex-specific health information, for example, a man with a cervix or a woman with a prostate, requires special attention in electronic health record (EHR) systems. The World Professional Association for Transgender Health (WPATH) is an international multidisciplinary professional association that publishes recognized standards for the care of transgender and gender variant persons. In September 2011, the WPATH Executive Committee convened an Electronic Medical Records Working Group comprised of both expert clinicians and medical information technology specialists, to make recommendations for developers, vendors, and users of EHR systems with respect to transgender patients. These recommendations and supporting rationale are presented here.

Glucocorticoids ameliorate neurologic symptoms in patients with glioblastoma, but their adverse effects limit long-term use. This study sought to identify factors associated with steroid taper success or failure in the early stages of glioblastoma treatment. We retrospectively reviewed steroid prescribing practices from date of surgery until one month following radiotherapy (RT) completion among 85 patients with newly diagnosed glioblastoma who were treated on a prospective clinical trial with RT and temozolomide. Sufficient information on steroid dosing was available in 72 patients included in the final analysis. The mean age was 54 years, and 65 % were men. Thirty-nine percent had a gross-total resection. Fifteen patients (21 %) tolerated steroid taper without requiring dose increase during the study. Men and patients with Karnofsky performance scale 90-100 were more likely to have a successful steroid taper. The most common symptom of taper failure was headache, but the reason for steroid increase differed among the different time intervals examined: worsening neurologic deficit in the early post-operative period, headache and non-focal symptoms during RT, and headache and seizure post-RT. Of the 50 patients in whom steroid use during RT was known, 36 (72 %) underwent dose reduction and of those, 21 (58 %) required an increase. The successful early taper of steroids in glioblastoma was associated with male gender and better functional status. Steroids are often tapered during RT, but there is frequent taper failure with this approach. A prospective trial with standardized steroid dosing regimens would be needed to verify these findings.

Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer's disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social "story" to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency.

Lessons were learned with trans women who participated (as volunteers and investigators) in trials of HIV pre-exposure prophylaxis (PrEP). Trans women are not men. Compared with men who have sex with men, trans women trial participants were more likely to be involved with transactional sex, had more sexual partners, and were less likely to have PrEP medications detected in blood. Trans women define themselves differently in different cultures. One best practice is to ask at least 2 gender questions: sex assigned at birth and current gender. More information is needed to fully situate PrEP efficacy for trans women, including analysis of drug–drug interactions between PrEP medications and feminizing hormones and PrEP drug penetration into neovaginal tissues. Including trans women in studies is helpful only if their participation is specifically reported, as could occur in a table of baseline characteristics of the enrolled cohort. Gender-affirming care is important to foster appropriate uptake and use of PrEP. Such care includes use of preferred pronouns and names, safety to use the bathroom of choice, and access to gender-affirming hormone therapy and surgery. The consistent finding that PrEP works when taken across diverse populations having diverse practices related to gender, sexual intercourse, and hormone use provides a basis for offering PrEP to people at substantial risk of acquiring HIV although some subgroups may not have been fully represented in trials. Nonetheless, specific PrEP implementation science for trans women (and men) is essential to develop best practices for PrEP delivery and use.

An accurate estimate of the number of transgender and gender nonconforming people is essential to inform policy and funding priorities and decisions. Historical reports of population sizes of 1 in 4000 to 1 in 50,000 have been based on clinical populations and likely underestimate the size of the transgender population. More recent population-based studies have found a 10- to 100-fold increase in population size. Studies that estimate population size should be population based, employ the two-step method to allow for collection of both gender identity and sex assigned at birth, and include measures to capture the range of transgender people with nonbinary gender identities.

Transgender individuals experience unique health disparities but are the subject of little focused health research. This manuscript reviews current literature on transgender medical and mental health outcomes and proposes research priorities to address knowledge gaps.Published research in transgender healthcare consists primarily of case reports, retrospective and cross-sectional studies, involving largely European settings. Challenges to US-based transgender health research include a diverse population where no single center has sufficient patient base to conduct clinical research with statistical rigor. Treatment regimens are heterogeneous and warrant study for best practices. Current research suggests increased mortality and depression in transgender individuals not receiving optimal care, and possibly a modest increase in cardiovascular risk related to hormone therapy. Current evidence does not support concerns for hormone-related malignancy risk.The priorities for transgender medical outcomes research should be to determine health disparities and comorbid health conditions over the life span, along with the effects of mental health, medical, and surgical interventions on morbidity and mortality. Specific outcomes of interest based on frequency in the literature, potential severity of outcome, and patient-centered interest, include affective disorders, cardiovascular disease, malignancies, fertility, and time dose-related responses of specific interventions.

Introduction : Globally, transgender (“trans”) women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population. Methods : Available information, including but not limited to existing scientific literature, about trans women and PrEP was reviewed and critiqued based on author expertise, including PrEP clinical trials and rollout. Results : To date, PrEP demonstration projects and clinical trials have largely excluded trans women, or have not included them in a meaningful way. Data collection strategies that fail to identify trans women in clinical trials and research further limit the ability to draw conclusions about trans women’s unique needs and devise strategies to meet them. Gender-affirming providers and clinic environments are essential components of any sexual health programme that aims to serve trans women, as they will largely avoid settings that may result in stigmatizing encounters and threats to their identities. While there is currently no evidence to suggest drug-drug interactions between PrEP and commonly used feminizing hormone regimens, community concerns about potential interactions may limit interest in and uptake of PrEP among trans women. Conclusions : In scaling up PrEP for trans women, it is essential to engage trans communities, utilize trans-inclusive research and marketing strategies and identify and/or train healthcare providers to provide gender-affirming healthcare to trans women, including transition-related care such as hormone provision. PrEP implementation guidelines must consider and address trans women’s unique barriers and facilitators to uptake and adherence. Keywords: transgender women; PrEP; HIV prevention. (Published: 18 October 2016) Citation: Sevelius JM et al. Journal of the International AIDS Society 2016, 19(Suppl 6) :21105 http://www.jiasociety.org/index.php/jias/article/view/21105 | http://dx.doi.org/10.7448/IAS.19.7.21105

This article describes methodological challenges, gaps, and opportunities in US transgender health research.Lack of large prospective observational studies and intervention trials, limited data on risks and benefits of sex affirmation (e.g., hormones and surgical interventions), and inconsistent use of definitions across studies hinder evidence-based care for transgender people. Systematic high-quality observational and intervention-testing studies may be carried out using several approaches, including general population-based, health systems-based, clinic-based, venue-based, and hybrid designs. Each of these approaches has its strength and limitations; however, harmonization of research efforts is needed. Ongoing development of evidence-based clinical recommendations will benefit from a series of observational and intervention studies aimed at identification, recruitment, and follow-up of transgender people of different ages, from different racial, ethnic, and socioeconomic backgrounds and with diverse gender identities.Transgender health research faces challenges that include standardization of lexicon, agreed upon population definitions, study design, sampling, measurement, outcome ascertainment, and sample size. Application of existing and new methods is needed to fill existing gaps, increase the scientific rigor and reach of transgender health research, and inform evidence-based prevention and care for this underserved population.

Transgender people have difficulty accessing gender-affirming hormone therapy (HT), a medically necessary treatment, in part due to a lack of provider knowledge. Patients often seek information on gender-affirming medical care using the Internet. Patients who are better informed about their own care may receive better care. This study evaluated the quantity and quality of online information about HT using several existing and novel measures.Structured Google searches were conducted. Sites were evaluated using previously described Journal of the American Medical Association (JAMA), DISCERN, and Health On the Net (HON) criteria, for citation of the Endocrine Society Guidelines and the World Professional Association for Transgender Health (WPATH) Standards of Care (SOC), and other topic-specific measures.Forty sites were evaluated. The median JAMA score was 3.5/7, and the median DISCERN score was 51/80. No sites held HON certification. Citation of the Endocrine Society Guidelines and the WPATH SOC was inconsistent. Institutional sites had higher DISCERN scores compared with other sites. The presence of a bibliography was most associated with measures of quality.The quality of online information about HT is inconsistent and limited in quantity. Development of reliable online resources on HT for transgender patients is essential. Broadening awareness of key guidelines from the Endocrine Society and WPATH is essential.

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

The standard treatment for primary CNS lymphoma (PCNSL) involves high-dose methotrexate-based chemotherapy (HD-MTX) alone or in combination with whole brain radiotherapy (WBRT). The combined modality regimen carries a substantial risk for cognitive impairment, and HD-MTX alone has been used more often recently in part to reduce neurotoxicity. In this study, we assessed cognitive functioning and quality of life in PCNSL survivors treated with WBRT + HD-MTX or HD-MTX alone. Fifty PCNSL patients in disease remission underwent a posttreatment baseline neuropsychological evaluation, and a subset of patients completed a follow-up evaluation. Quality of life and extent of white matter disease and atrophy on MRI were assessed. Comparisons according to treatment type after controlling for age and time since treatment completion showed that patients treated with HD-MTX alone had significantly higher scores on tests of selective attention and memory than patients treated with the combined modality regimen. Patients treated with WBRT + HD-MTX had impairments across most cognitive domains, and these were of sufficient severity to interfere with quality of life, as over 50% were not working due to their illness. Patients treated with HD-MTX alone did not meet criteria for cognitive impairment but scored within 1 SD below the normative sample on most tests. Patients with more extensive white matter disease had lower scores on tests of set-shifting and memory. Cognitive dysfunction was more prevalent in PCNSL survivors treated with WBRT + HD-MTX compared with patients treated with HD-MTX alone.

Background High-risk human papillomavirus (hrHPV) causes virtually all cervical cancers. Trans masculine (TM) people (those assigned female at birth who identify with a gender other than female) have low uptake of conventional cervical cancer screening. Self-collected hrHPV DNA testing has high levels of acceptability among cisgender (non-transgender) females and may support increased cervical cancer screening uptake in TM individuals. Objective To assess the test performance and acceptability of self-collected vaginal specimens in comparison to provider-collected cervical swabs for hrHPV DNA detection in TM individuals ages 21–64 years. Methods Between March 2015-September 2016, 150 TM participants with a cervix (mean age = 27.5 years; SD = 5.7) completed a one-time study visit comprised of a self-report survey, self-collected vaginal HPV DNA swab, clinician-administered cervical HPV swab, and brief interview on acceptability of clinical procedures. Participants were randomized to complete either self- or provider-collection first to minimize ordering effects. Self- and provider-collected samples were tested for 13 hrHPV DNA types using a DNA Hybridization Assay. The primary outcome variable was the concordance (kappa statistic) and performance (sensitivity, specificity) of self-collected vaginal HPV DNA specimens versus provider-collected cervical HPV swabs as the gold standard. Results Of the 131 participants completing both the self- and provider-collected HPV tests, 21 cases of hrHPV were detected by the provider cervical swab (gold standard; 16.0% hrHPV prevalence); 15 of these cases were accurately detected by the self-collected vaginal swab (71.4% concordance) (Kappa = 0.75, 95% Confidence Interval [CI]: 0.59, 0.92; p

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution’s prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

Survival from gastric cancer in the USA still lags behind Asia. Genetic, environmental, and tumor biology differences, along with extent of surgery have been implicated. Our aim was to evaluate survival outcomes in Asian-American gastric cancer patients undergoing surgical resection by comparing place of birth and clinicopathologic characteristics (including evaluation of 15 lymph nodes).The Surveillance, Epidemiology, and End Results database was queried to identify patients treated surgically for gastric cancer with curative intent in the USA (2000-2010). US-born versus foreign-born Asian-American patients were analyzed for survival. Secondary comparison was made to non-Asian patients. Stage IV and non-surgical patients were excluded. Of 10,089 patients identified, 1467 patients were Asian: 271 were born in the USA, and 1196 were born outside the USA. Median survival was 32 months for non-Asians and 29 months for US-born Asians versus 61 months for Asian immigrants (p

To describe weight, body mass index (BMI), blood pressure (BP), lipids, and hormone levels in transgender women and men presenting for initiation of cross-sex hormone therapy at a community clinic in the United States.Twenty-three transgender women (persons assigned male at birth who identify as female and want to use estrogen to develop female secondary sex characteristics) and 34 transgender men (persons assigned female at birth who identify as male and want to use testosterone to develop male secondary sex characteristics) presenting for initiation of hormone therapy at a community health center were enrolled. Body mass index, BP, lipids, and sex hormone levels were measured at baseline and 6 months. Persistence of menses at 6 months in transgender men was recorded.Sixteen transgender women and 31 transgender men completed the study. Baseline and 6-month median BPs and lipid values were within a normal clinical range. Median systolic BP in transgender women dropped from baseline 130.5 mmHg (interquartile range 11.5) to 120.5 mmHg (interquartile range 15.5) at 6 months (P=.006). Testosterone levels remained elevated in 33% and estradiol (E2) levels were supratherapeutic in 19% of transgender women at 6 months. Median BMI for transgender men was 29.1 kg/m (interquartile range 11.2) at baseline and 30.0 kg/m (interquartile range 11.4) at 6 months (P=.024). Six-month total testosterone levels were subtherapeutic in 32% and E2 levels remained elevated in 71% of transgender men.In transgender women, estrogen therapy, with or without antiandrogen therapy, was associated with lower BP. In transgender men, testosterone therapy was associated with increased BMI. The study had insufficient power to detect other associations. Monitoring of hormone levels to guide therapy appears to be useful.III.

With the first qualifying examination administered September 15, 2014, complex general surgical oncology (CGSO) is now a board-certified specialty. We aimed to assess the attitudes and perceptions of current and future surgical oncology fellows regarding the recently instituted Accreditation Council for Graduate Medical Education (ACGME) accreditation.A 29-question anonymous survey was distributed to fellows in surgical oncology fellowship programs and applicants interviewing at our fellowship program.There were 110 responses (79 fellows and 31 candidates). The response rate for the first- and second-year fellows was 66 %. Ninety-percent of the respondents were aware that completing an ACGME-accredited fellowship leads to board eligibility in CGSO. However, the majority (80 %) of the respondents stated that their decision to specialize in surgical oncology was not influenced by the ACGME accreditation. The fellows in training were concerned about the cost of the exam (90 %) and expressed anxiety in preparing for another board exam (83 %). However, the majority of the respondents believed that CGSO board certification will be helpful (79 %) in obtaining their future career goals. Interestingly, candidate fellows appeared more focused on a career in general complex surgical oncology (p = 0.004), highlighting the impact that fellowship training may have on organ-specific subspecialization.The majority of the surveyed surgical oncology fellows and candidates believe that obtaining board certification in CGSO is important and will help them pursue their career goals. However, the decision to specialize in surgical oncology does not appear to be motivated by ACGME accreditation or the new board certification.

Reproductive traits experience high levels of selection because of their direct ties to fitness, often resulting in rapid adaptive evolution. Much of the work in this area has focused on male reproductive traits. However, a more comprehensive understanding of female reproductive adaptations and their relationship to male characters is crucial to uncover the relative roles of sexual cooperation and conflict in driving co-evolutionary dynamics between the sexes. We focus on the physiology of a complex female reproductive adaptation in butterflies and moths: a stomach-like organ in the female reproductive tract called the bursa copulatrix that digests the male ejaculate (spermatophore). Little is known about how the bursa digests the spermatophore. We characterized bursa proteolytic capacity in relation to female state in the polyandrous butterfly Pieris rapae. We found that the virgin bursa exhibits extremely high levels of proteolytic activity. Furthermore, in virgin females, bursal proteolytic capacity increases with time since eclosion and ambient temperature, but is not sensitive to the pre-mating social environment. Post copulation, bursal proteolytic activity decreases rapidly before rebounding toward the end of a mating cycle, suggesting active female regulation of proteolysis and/or potential quenching of proteolysis by male ejaculate constituents. Using transcriptomic and proteomic approaches, we report identities for nine proteases actively transcribed by bursal tissue and/or expressed in the bursal lumen that may contribute to observed bursal proteolysis. We discuss how these dynamic physiological characteristics may function as female adaptations resulting from sexual conflict over female remating rate in this polyandrous butterfly.

Persistent adaptive challenges are often met with the evolution of novel physiological traits. Although there are specific examples of single genes providing new physiological functions, studies on the origin of complex organ functions are lacking. One such derived set of complex functions is found in the Lepidopteran bursa copulatrix, an organ within the female reproductive tract that digests nutrients from the male ejaculate or spermatophore. Here, we characterized bursa physiology and the evolutionary mechanisms by which it was equipped with digestive and absorptive functionality. By studying the transcriptome of the bursa and eight other tissues, we revealed a suite of highly expressed and secreted gene products providing the bursa with a combination of stomach-like traits for mechanical and enzymatic digestion of the male spermatophore. By subsequently placing these bursa genes in an evolutionary framework, we found that the vast majority of their novel digestive functions were co-opted by borrowing genes that continue to be expressed in nonreproductive tissues. However, a number of bursa-specific genes have also arisen, some of which represent unique gene families restricted to Lepidoptera and may provide novel bursa-specific functions. This pattern of promiscuous gene borrowing and relatively infrequent evolution of tissue-specific duplicates stands in contrast to studies of the evolution of novelty via single gene co-option. Our results suggest that the evolution of complex organ-level phenotypes may often be enabled (and subsequently constrained) by changes in tissue specificity that allow expression of existing genes in novel contexts, such as reproduction. The extent to which the selective pressures encountered in these novel roles require resolution via duplication and sub/neofunctionalization is likely to be determined by the need for specialized reproductive functionality. Thus, complex physiological phenotypes such as that found in the bursa offer important opportunities for understanding the relative role of pleiotropy and specialization in adaptive evolution.