tbuckley/cabot-search huggingface dataset:
Visibility, transphobia, and resilience: addressing transgender women's health in Lebanon
Authors: Rachel L Kaplan, Abhinav Veerina, Cynthia El Khoury
Journal: The Lancet Global Health (2019)

BackgroundWorldwide, transgender women face a disproportionately high risk of HIV/AIDS, violence, and mental health problems, as well as individual and structural discrimination. In Lebanon, health disparities in transgender women have recently been identified. Transgender visibility, a complex concept that involves "outness", gender expression, and context, is associated with risky sexual behaviour among transgender women in Lebanon. This analysis, therefore, aimed to explore associations between visibility, transphobia, and resilience among transgender women in Lebanon.MethodsWe analysed data from 20 semi-structured interviews and 16 surveys that were conducted in Lebanon during a transgender-specific HIV intervention pilot study in 2016 and 2017. Participants were recruited via peer recruiters and included if they were aged 18 years or older and identified as a transgender woman. Mixed-methods analysis of the data assessed relationships between visibility, transphobia, and resilience. Quantitative and qualitative analyses included bivariate tests (Wilcoxon signed rank test and Fisher's exact test) and the constant comparative method, respectively.FindingsWe noted significant associations between "visibility as transgender" and two indicators of resilience: "social cohesion" (p=0·0071) and "community connectedness" (p=0·0380) with other transgender women. Individuals who reported being visible as transgender scored 50·0% and 26·67% lower on these two indicators of resilience, respectively, compared with individuals who reported being not visible as transgender. Qualitative analysis identified three themes: "isolation", "gender identity affirmation", and "resilience". Participants indicated that transgender visibility increased risk of transphobic encounters, resulting in self-isolation as protection from transphobia. Validation of gender identity internally or externally (via physical appearance, gender affirmation procedures, or positive social interactions) was also important. Resilience, for both those self-describing as visibly transgender and those who were not, may be bolstered through positive connections with other transgender women.InterpretationThis analysis supports the importance of understanding visibility as a construct related to transgender women's health. Results indicate that achieving social cohesion and community connectedness with other transgender women could be integral to mitigating the deleterious effects of transphobia in Lebanon, where a hostile environment for transgender women shapes the development of resilience within the continuum of visibilty. Future research should seek to determine whether these associations hold true in larger samples of transgender women in Lebanon and the greater Middle East.FundingUS National Institute of Mental Health.
Patterns of response of organ specific metastasis in patients with metastatic renal cell cancer (mRCC) treated with an immune checkpoint inhibitor (CPI) post tyrosine kinase inhibitor (TKI).
Authors: Sarah Louise Picardo, Marco Adelmo James Iafolla, Srikala S. Sridhar, Adrian G. Sacher, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2019)

605 Background: Both TKIs and the novel immune CPIs targeting PD/PDL1 are now standard treatments for patients with mRCC. Mixed responses in metastatic lesions have been observed. We examined organ specific radiologic responses in a cohort of patients with mRCC who were initially treated with TKI followed by CPI. Methods: We identified patients who were treated with first line TKI followed by CPI from a prospectively maintained database of all mRCC patients treated at our institution from 2010 to 2018. We examined best response to TKI and CPI, as well as organ specific responses to TKI and CPI. Statistical analysis was performed using odds ratios and Fishers exact test. Results: We identified 31 patients with evaluable disease who were treated with a TKI followed by CPI. Best responses to TKI were partial response (PR) (n = 7), stable disease (SD) (n = 17) and progressive disease (PD) (n = 6). Of TKI responders, 4 had lesions in ≥2 organs respond and 3 had a lesion in a single organ respond. Of the 3 patients who responded to CPI, all had lesions in ≥2 organs respond. Patients who had PD to TKI did not respond to CPI. Organ specific metastases at time of initiation of TKI and CPI are described in the table. In lung lesions, the odds of a response to CPI with or without an initial response to TKI were 0.16 and 0.57 respectively (OR 0.29, p = 0.595). In lymph node (LN) metastases, the odds of a response to CPI with or without an initial response to TKI were 0.16 and 0.62 respectively (OR 0.27, p = 0.354). Two patients had a response to TKI in the liver but none had a response to subsequent CPI. Of 3 patients who had a response to TKI in the renal primary, 1 had a response to CPI. Conclusions: In this small series, these data suggest that first line TKI response may dictate subsequent CPI response in an organ specific manner, with higher numbers of CPI responses in lung and LN metastases in patients who did not have TKI response in these organs. This may be due to immune modulation by prior TKI or to tumor heterogeneity. Studies are needed to further elucidate this phenomenon. [Table: see text]
Abstract P149: Ideal Cardiovascular Health is Associated With the Characteristics of and Better Access to Primary Care in a Publicly Funded Healthcare System
Authors: Sarah S Singh, Stephanie J Frisbee
Journal: Circulation (2019)

Background: Cardiovascular health (CVH) and CVD prevention remains a top public health priority across North America. The health of Canadians is largely accredited to the publicly funded healthcare system, which affords “free” healthcare to all its citizens. However, there is little evidence demonstrating whether the characteristics of and access to primary care by Canadians directly impacts their likelihood of ideal CVH. Objective: To examine the association between ideal CVH and the characteristics of and access to primary care in Canadians. Data and Methods: This study is a cross-sectional design using adult data from the Canadian Community Health Survey (CCHS) 2015-2016 database. The CCHS is a nationwide, nationally representative survey that collects information on the health status, health care access and utilization, and health determinants of the Canadian population. CVH, defined using the AHA CVH Index (CVHI), was determined using self-reported responses in CCHS. Weighted logistic regression was performed to examine the association between ideal CVH and the characteristics of and access to primary care, including having regular care, receiving coordinated care, ER use and access to routine care. Models were also adjusted for individual characteristics known to affect CVH. Results: The majority of the population were females (51%), aged 40-60 (37%), with tertiary education (64%) and of the White race (79%). Overall, 19% of the population had ideal CVH (ideal status in 6-7 CVHI factors), representing approximately 6 million individuals nationwide. Individuals reported having a regular primary healthcare provider (82%), insurance for prescription medication (76%), high coordination in their healthcare between health professionals (10%), difficulties in accessing routine care in the past 12 months (3%). The likelihood of ideal CVH were highest in those who reported having: a regular provider (OR 1.11, 95% CI 1.05-1.17), higher coordination of care (OR 1.10, 95% CI 1.01-1.20) and using the ER less frequently (OR 0.90, 95% CI 0.80-0.95). After controlling for age, sex and race, only having a regular provider (OR 1.11, 95% CI 1.02-1.20) and not reporting difficulties in accessing routine care in the past 12 months (OR 1.02, 95% CI 1.01-1.04) were significantly associated with ideal CVH. Conclusion: Findings from this study suggest that individuals experiencing better primary healthcare, including having a regular primary care physician or having less difficulty accessing care, are more likely to have ideal CVH than those experiencing poor primary healthcare. Further studies should investigate policies that promote better primary healthcare as interventions for preventing CVD and improving CVH.
Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature
Authors: Paula Rodríguez-Otero, María Victoria Mateos, Joaquín Martínez-López, Miguel-Teodoro Hernández, Enrique M. Ocio, Laura Rosiñol, Rafael Martínez, Ana-Isabel Teruel, Norma C. Gutiérrez, Joan Bargay, Enrique Bengoechea, Yolanda González, Jaime Pérez de Oteyza, Mercedes Gironella, Jorge M. Nuñez-Córdoba, Cristina Encinas, Jesús Martín, Carmen Cabrera, Luis Palomera, Felipe de Arriba, María Teresa Cedena, Noemí Puig, Albert Oriol, Bruno Paiva, Joan Bladé, Juan José Lahuerta, Jesús F. San Miguel
Journal: Blood Cancer Journal (2019)

Abstract Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) ≥ 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb ≥ 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years.
Inflammatory markers at baseline (C1) and cycle 3 (C3) and their association with clinical outcomes in urothelial cancer patients (pts) treated with immunotherapy (IO).
Authors: Julie M. Shabto, Dylan J Martini, Yuan Liu, Deepak Ravindranathan, Meredith R Kline, Elise Hitron, Greta Russler, Sarah Caulfield, Haydn Kissick, Mehrdad Alemozaffar, Kenneth Ogan, Wayne Harris, Omer Kucuk, Bradley Curtis Carthon, Viraj A. Master, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2019)

390 Background: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been explored as biomarkers for response to IO. We investigated the association between these biomarkers and clinical outcomes in urothelial cancer pts treated with IO. Methods: We conducted a retrospective review of 67 urothelial cancer pts treated with PD-1 or PD-L1 inhibitors at Winship Cancer Institute from 2015-2018. Overall survival (OS) and progression free survival (PFS) were measured from first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. MLR, NLR, and PLR were collected at C1 and C3. The nonlinear relationship between log-transformed biomarkers and OS or PFS was examined by martingale residual plot and optimal cutoff (OC) values were determined. Multivariable analysis (MVA) used Cox proportional hazard model. Results: OC for C1 and C3 NLR, MLR, and PLR were 2.06 and 1.42, -0.331 and -0.153, and 5.7 and 5.6, respectively. Pts with C1 NLR and PLR above OC had worse OS and shorter PFS (all p&lt;0.05) (Table). High C3 MLR portended shorter OS and PFS. NLR, MLR and PLR were highly correlated (Pearson correlation coefficients ≥ 0.67, p&lt;0.0001). Conclusions: High NLR, MLR, and PLR at C1 and at C3 are associated with worse clinical outcomes in this cohort. These values warrant a larger study for validation. MVA† of MLR, NLR, and PLR at C1 and at C3 with OS and PFS. [Table: see text]
Abstract 13976: Optogenetic Monitoring of Endocardial Calcium Transients <i>in vivo</i> Using a Minimally Invasive Fiber Optic Approach
Authors: Laura Menke, Ivar van Asten, Magda S Fontes, Leonie van Stuijvenberg, Toon A van Veen, Marc A Vos, Teun P de Boer
Journal: Circulation (2015)

Rationale: In vivo electrophysiology and contraction can be studied very well using minimally invasive methods. Contrarily, myocardial calcium signaling cannot be studied in vivo, although it is a crucial aspect of cardiac remodeling. Objective: We aimed to establish a method that can be used to study myocardial calcium signaling in vivo. Methods and Results: We employed the optogenetic fluorescent calcium sensor GCaMP3 to record calcium transients from the left ventricular endocardium of closed chest mice (n=8, inducible, cardiomyocyte[[Unsupported Character - Codename &amp;shy;]]specific GCaMP3 transgenic overexpression). Excitation of the sensor and detection of fluorescence emission was done using a thin plastic optical fiber (250 μm) that was introduced via the carotid artery into the left ventricular cavity. Combining optogenetics with fiber optics, we were able to record endocardial calcium transients with good signal to noise ratio (6.9 ± 0.2) for up to 30 minutes at physiological heart rates, without significant bleaching of fluorescence. Conclusions: Our results demonstrate that by employing optogenetics, calcium signaling can be studied in vivo in the presence of physiologically important factors such as hemodynamic load, innervation and interaction with other organs. We expect that this approach is also suitable for other optogenetic sensors, greatly expanding possibilities for in vivo studies.
Computer automated bone scan index (BSI) as an analytically validated imaging biomarker to quantitate change in bone scan of patients with metastatic prostate cancer.
Authors: Aseem Anand, David Minarik, Reza Kaboteh, Sarah Lindgren Belal, Mariana Reza, Andreas Joseffson, Lars Edenbrandt, Anders Bjartell
Journal: Journal of Clinical Oncology (2015)

5044 Background: A consistent imaging biomarker to standardize the evaluation of change in bone scan is an unmet need for patients (pts) with bone metastasis. BSI is quantitative interpretation of bone scan in pts with metastatic prostate cancer (mPCa). Here we have performed analytical and clinical studies to evaluate the change in computer automated BSI as a consistent imaging biomarker in pts with mPCa. Methods: Analytical studies with bone scan simulation using XCAT phantoms and SIMIND-MC program were performed to evaluate the consistency of automated BSI. Specifically, to assess linearity and accuracy, bone scan of 50 phantoms were simulated with tumor burden ranging from low to high disease confluence – from 0.10 to 13.0 BSI. To assess precision, another set of 50 phantoms were divided into 5 subgroups, each containing simulated bone scans of 10 phantoms at 0.5, 1.0, 3.0, 5.0 and 10.0 BSI, respectively. Additionally, to evaluate the clinical utility of automated BSI, two follow-up bone scans of 145 pts with progressing mPCa, irrespective of therapy regiment, were analyzed for change in BSI. The primary objective was to evaluate the association of change in BSI against overall survival (OS). The computer automated BSI was calculated using the software EXINI boneBSI. Cox regression and Kaplan Meier analysis were used to evaluate association between BSI and OS. Results: Pearson correlation to evaluate linearity and accuracy of BSI, in the given range from 0.10 to 13.0, was observed to be 0.995 (N = 50, 95% CI 0.99 – 0.99, p < 0.0001). The mean coefficient of variation indicating precision of BSI at each of the pre-defined tumor burden was observed to be less than 20%. Change in BSI of 145 pts was significantly associated with OS (HR 1.1, p < 0.0001). The median OS for 110 (66%) pts who had a rise in BSI ( > 0.10) was 31 weeks, 35 (34%) pts who had a decline or no change in BSI reached a median 72 weeks (HR 1.9, p 0.0002). Conclusions: Computer automated BSI is a consistent biomarker which can standardize the quantitative analysis of change in bone metastasis of pts with mPCa. The clinical utility of automated BSI, in multivariate biomarker panel, will be validated in subsequent studies.
Fit-Testing Transcatheter Aortic Valve Replacements With 3-D Printing
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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Pulmonary nodules and metastases in non-pulmonary solid tumor bearing patients.
Authors: Pedro Henrique Isaacsson Velho, Milena Perez Mak, Rafael Caparica Bitton, Claudio Lima Rocha, Mauricio Ruettimann Liberato de Moura, Públio C. C. Viana, Marcos Menezes, Olavo Feher
Journal: Journal of Clinical Oncology (2015)

e17762 Background: Pulmonary nodules (PNs) in patients (pts) with non-pulmonary solid tumors present a diagnostic challenge; comprising other possibilities than metastatic disease, such as primary lung cancers, infectious diseases and scar tissue. The precise diagnosis will ultimately impact in treatment decisions and prognosis. Currently, there are no guidelines to help us in the decision process of indicating a PN biopsy. This study aimed to determine variables correlated with finding metastatic disease on a pulmonary biopsy. Methods: In this single-institution retrospective study, we included consecutive pts with non-pulmonary solid malignancies that presented PN and no extra pulmonary metastases. Pts were submitted to a computed tomography (CT) guided biopsy from January 2011 to December 2013. Exclusion criteria are as follows: presence of lung primary, hematologic malignancies, or extra pulmonary metastatic disease. Correlation between imaging and clinical characteristics that yielded higher probability of finding metastatic disease on biopsy was determined by logistic regression analysis. Results: From a total of 487 pts submitted to pulmonary biopsy, 228 were included in the final analysis. Metastatic disease to the lungs was confirmed in 63.1%. Lung primaries were found in 26.3%. Other findings included infectious diseases (7.4%) and benign lesions (2.6%). On multivariate analysis, presence of multiple PNs was associated with higher odds of metastatic disease (OR 4.24; 95% CI 1.97-9.14, p < 0.01), as well as nodule cavitation and/or necrosis on CT scan (OR 4.01; 95% CI 1.24-13.01, p = 0.02). Procedure complications demanding active interventions occurred in 6 patients. No procedure-related death occurred. Conclusions: Presence of multiple PNs and nodule cavitation were associated with higher odds of finding biopsy-proven metastatic disease. However, a high rate of non-metastatic disease was found in this group of pts. Given that procedural complications were low, we conclude that tissue sample is still essential for accurately diagnosing and treating pts with solid tumors presenting with PNs.
Phase II study of sitravatinib in combination with nivolumab in patients with advanced or metastatic urothelial carcinoma (UC) after checkpoint inhibitor therapy (CIT).
Authors: Gurjyot K. Doshi, Nicholas J. Vogelzang, Donald A. Richards, Daniel Chong, David R. Shaffer, Luke T. Nordquist, Joel Picus, Delia Alvarez, Hirak Der-Torossian, James Christensen, Jeffrey Thomas Yorio
Journal: Journal of Clinical Oncology (2019)

TPS498 Background: Combination therapy with agents targeting molecular and cellular mechanisms of CIT resistance is a rational approach to restoring CIT efficacy in patients (pts) with immunotherapy-resistant UC. Sitravatinib is a tyrosine kinase inhibitor (TKI) that targets multiple closely-related receptor tyrosine kinase (RTK) pathways, including the split RTKs VEGFR-2 and KIT, as well as the TAM (TYRO3, AXL, and MER) RTKs. Inhibition of the split RTKs enhances antitumor activity by reduction of immunosuppressive regulatory T cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME). Inhibition of TAM RTKs further restores a more immune-supportive TME by depletion of MDSCs and repolarization of tumor-associated macrophages to the M1 phenotype associated with secretion of pro-inflammatory cytokines. Given these pleiotropic immune-activating effects, the combination of sitravatinib with nivolumab is a rational approach to restoring or enhancing CIT clinical activity in pts with immunotherapy-resistant UC. This combination has been shown to be safe and tolerable in an ongoing Phase 2 study in pts with metastatic non-small cell lung cancer. Methods: This open-label Phase 2 study evaluates tolerability and clinical activity of sitravatinib in combination with nivolumab in pts with advanced or metastatic UC who experienced disease progression on or after CIT as the most recent systemic therapy. Enrollment is stratified by prior receipt of platinum-based chemotherapy. If the initial 2 cohorts are of high interest for efficacy, the protocol allows for addition of new cohorts to include pts previously treated with selected immunotherapies (anti-CTLA-4, anti-OX40 or anti–CD137 therapy) or who are CIT-naïve. The primary objective is Objective Response Rate. A Predictive Probability Design will be applied allowing for expansion to 40 pts per cohort. Sitravatinib is administered orally daily in continuous 28-day cycles at 120 mg; nivolumab intravenously at 240 mg every 2 weeks or 480 mg every 4 weeks. Status: The study is open for enrollment and recruitment is ongoing. Clinical trial information: NCT03606174.