tbuckley/cabot-search huggingface dataset:
Abstract 16737: Maternal Hypertension is More Often Observed Among Hypertensive Patients, and Associates to SNPs of the X Chromosome
Authors: Guido Iaccarino, Federica Uliano, Valentina Trimarco, Raffaele Izzo, Stefano Pagnotta, Rosaria Tremigliozzi, natalia Rivera, Nicola de Luca, marina Marino, Rosa Finelli, Virginia Tagliamonte, Gianluigi Condorelli, Michele Ceccarelli, Bruno Trimarco
Journal: Circulation (2011)

Family history of hypertension (HTN) is present in as many as 70-80% of all patients with primary HTN. It was recently noted that in some selected pedigrees, HTN is transmitted according to a diaginic pattern. However, it is not known whether the general population, differences can be observed between maternal or paternal familiarity in the transmission of HTN. We analyzed the CampaniaSalute database of the Hypertension Clinic of the Federico II University of Naples in Southern Italy, comprising 12.520 (6.868 males and 5.636 females) cases, which were compared with 6.352 non HTN patients present in database. For both groups we calculated the “odd” value for a family history of HTN. Among the HTN group, family history is present in 75% of cases (odds 3.77), whereas in the Non HTN group, occurs in only 26%, (0.94). The odds ratio (OR) indicates that familiarity increases the risk of developing hypertension 2.91 times (2.67-3.17, p &lt;0.001). We found that in mothers HTN (HTN-M) occurs in 32% of cases [OR 3.01 (2.66-3.41, p &lt;0.001)], in fathers (HTN-F) occurs in 18% [2.31 (2.01-2.68, p &lt;0.001)] and in both parents (HTN-Both) in 15% of cases [3.45 (2.87-4.01, p&lt;0.001)]. Such a pattern is similar between male and female patients. Given the higher prevalence of maternal familiarity, we assessed in 375 male HTNs (which bear the same X chromosome of the mother), the presence of polymorphisms on the sexual chromosome that associate with maternal history of HTN, using the Illumina 300K chip technology. In particular, four polymorphisms (ie, rs2182289, rs1317098, rs2346677, and rs2346678) showed a different distribution with a p value &lt;0.0005, being less frequent in male patients with HTN-M compared with male patients with no HTN in the family (respectively 22.1 vs 36.4%, 16.4 vs 30.6%, 9.0 vs 19.4%, 8.6 vs 19.4%). A similar pattern although less significant was observed in female patients, which bear x chromosomes from both parents. These results suggest that polymorphisms on the X chromosome associate with the maternal transmission of HTN.
Therapeutic neovascularization promoted by injectable hydrogels
Authors: Amrita Pal, Brent L. Vernon, Mehdi Nikkhah
Journal: Bioactive Materials (2018)

The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors, stem cells or expansion of pre-existing cells. For efficient neovascularization, controlled release of growth factors is particularly necessary since bolus injection of molecules generally lead to a poor outcome due to inadequate retention within the injured site. In this regard, injectable hydrogels, made of natural, synthetic or hybrid biomaterials, have become a promising solution for efficient delivery of angiogenic factors or stem and progenitor cells for in situ tissue repair, regeneration and neovascularization. This review article will broadly discuss the state-of-the-art in the development of injectable hydrogels from natural and synthetic precursors, and their applications in ischemic tissue repair and wound healing. We will cover a wide range of in vitro and in vivo studies in testing the functionalities of the engineered injectable hydrogels in promoting tissue repair and neovascularization. We will also discuss some of the injectable hydrogels that exhibit self-healing properties by promoting neovascularization without the presence of angiogenic factors.
Abstract 14806: TV Viewing and Incident Venous Thromboembolism: the Atherosclerotic Risk in Communities Study
Authors: Yasuhiko Kubota, Mary Cushman, Neil Zakai, Wayne D Rosamond, Aaron R Folsom
Journal: Circulation (2017)

Introduction: TV viewing is associated with risk of arterial vascular diseases, but has not been evaluated in relation to venous thromboembolism VTE risk in a US. population. Hypothesis: We tested ...
Radioprotection study of topical norepinephrine in postsurgical breast cancer patients.
Authors: James F. Cleary, George M. Cannon, Jens C. Eickhoff, Allen L Thunberg, William E Fahl
Journal: Journal of Clinical Oncology (2012)

TPS9152 Background: This study derives from radiodermatitis studies in a rat model evaluating radioprotection from topical norepinephrine application. In the model, increasing radiation doses induce dermatitis of increasing severity, ranging from mild erythema to wet desquamation. The model was initially designed to identify topical radioprotectants that function as oxygen free radical scavengers. In an experiment designed to test the hypothesis that the co-application of a topical vasoconstrictor and an aminothiol scavenger would limit the systemic uptake of the scavenger, it was observed that the combination was synergistic and that the topical vasoconstrictor was active when administered alone as a control. Subsequent experiments demonstrated that topical a-adrenergic receptor agonists are active in preventing radiodermatitis. The data are consistent with a mechanism based on local and transient vasoconstriction within the skin, which reduces local tissue oxygenation. This subsequently limits the formation of radiation-induced reactive oxygen species and protects skin stem cells from radiation damage. Methods: Two Phase 1 safety studies have been conducted, one in normal volunteers and one in cancer patients receiving palliative radiation therapy for bone metastases. This study is a nonrandomized, open-label safety and exploratory study in post-surgical breast cancer patients treated with 45 to 50 Gy to the whole breast and axilla. A 10-16 Gy boost to the lumpectomy region is permitted. Eligible patients are age 18 years or older with a diagnosis of Stage Ia (T1, N0, M0), Stage Ib (T0 or 1, N1mic, M0) or Stage IIa (T&lt;3cm, N0, M0) infiltrating ductal or lobular carcinoma of the breast or ductal carcinoma in situ (DCIS). The dose is a single daily topical application of 3.0 mL of norepinephrine HCl (82.3 mg/mL in 70% ethanol) applied to the same 50 cm 2 treatment site in the axilla about 20 minutes prior to each radiotherapy fraction. The radiodermatitis severity at the treatment site will be compared to surrounding (untreated) control areas. 5 of planned 12 patients have been enrolled. Clinical trial registry number NCT01263366.
A health system wide approach to the delivery of survivorship care plans.
Authors: Jennifer R. Klemp, Heather Vanbebber, Tanya Folker, Lisa Serig, Tim Metcalf, Audrey Roberts, Meredith Cooper, Debbie Fernandez
Journal: Journal of Clinical Oncology (2018)

42 Background: Survivorship care plans (SCPs) are recognized by organizations including the American Society of Clinical Oncology and the American College of Surgeons Commission on Cancer, as a best practice for improving survivor care. Little evidence supports this and hospitals and cancer centers are scrambling to meet deadlines for SCP development and delivery. The University of Kansas Cancer Center (KUCC) addressed this utilizing electronic health record (EHR) integration, developing a health system wide approach to education and delivery, and building referral workflows to primary care and specialists. We report on this approach to developing and growing a survivorship care program. Methods: KUCC is a NCI designated cancer center within an academic medical center and health system, with 11 outpatient locations across the Kansas City. Under the guidance of a multidisciplinary team: providers, health care informatics, administrators, nursing, tumor registry, quality improvement, and researchers, KUCC developed a step-wise process to deliver comprehensive survivorship care across the health system. This multi-year initiative aligned with institutional accreditation standards and an ongoing focus on expanding evidence based, comprehensive cancer and supportive care. Results: In 2014 a formal survivorship program plan was put into action: Support from leadership, providers, research priority; Staff and patient survivorship education &amp; training; Integrated delivery of survivorship care at all locations with direct interaction and feedback from cancer care teams; Short &amp; long-term programmatic goals; Management and referral of late effects of cancer; EPIC integrated SCP template: auto-populated, customized, personalized; treatment summary uses tools that pull in data stored discreetly in the patient "file"; SCP delivery targeting COC phase-in timeline: 2015: n= 539 (10% projection n= 434); 2016: n= 1,355 (25% projection n=1,253). Conclusions: This step-wise, integrated approach to survivorship care has resulted in a health system wide delivery of SCPs and meeting national accreditation standards. Next steps include the evaluation of cost and clinical/patient reported outcomes.
TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score.
Authors: Joseph A. Sparano, Robert James Gray, William C. Wood, Della F. Makower, Tracy G. Lively, Thomas James Saphner, Maccon M. Keane, Henry Leonidas Gomez, Pavan S. Reddy, Timothy F Goggins, Ingrid A. Mayer, Deborah Toppmeyer, Adam Brufsky, Matthew P. Goetz, Daniel F. Hayes, Elizabeth Claire Dees, Kathleen I. Pritchard, Charles E. Geyer, John A. Olson, George W. Sledge
Journal: Journal of Clinical Oncology (2018)

LBA1 Background: In hormone receptor (HR)-positive, HER2-negative, axillary node (AN)-negative breast cancer, the 21-gene expression assay (Oncotype DX Recurrence Score [RS]) is prognostic for distant recurrence, prognostic for low recurrence with endocrine therapy alone if low (0-10), and predictive of chemotherapy benefit if high (26 or higher). We performed a prospective, randomized trial of endocrine therapy (ET) versus chemoendocrine therapy (CET) in women with a mid-range RS of 11-25. Methods: Eligibility criteria included women 18-75 years of age with HR-positive, HER2-negative, axillary node (AN)-negative breast cancer and tumors 1.1-5.0 cm in size (or 0.6-1.0 cm and int/high grade) and agreed to have chemotherapy assigned or randomized based on the RS. Women with a mid-range RS (11-25) were randomized to receive ET or CET. The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show non-inferiority for ET alone by not rejecting equality (hazard ratio [HR] margin up to 1.322 for omission of chemotherapy, 1-sided type I error rate 10%, type II error rate 5%). The target sample size was adjusted to compensate for non-adherence to randomized treatment, and the protocol-specified final analysis was triggered after 835 iDFS events. Results: Of the 10,253 eligible women enrolled between 4/7/06-10/6/10, 6711 (65.5%) had a RS of 11-25 and adequate information. There were 836 iDFS events at final analysis with a median followup of 90 months. ET was non-inferior to CET for iDFS (HR 1.08, 95% confidence intervals [CI] 0.94, 1.24, p=0.26) in the intention-to-treat (ITT) population. ET was also non-inferior for distant recurrence-free interval (DRFI; HR 1.03, p=0.80), recurrence-free interval (RFI; HR 1.12, p=0.28), and overall survival (OS; HR 0.97, p=0.80). Nine year rates were similar for iDFS (83.3% vs. 84.3%), DRFI (94.5% vs. 95.0%), RFI (92.2% vs. 92.9%), and OS (93.9% vs. 93.8%). Recurrence accounted for 338 (41.6%) the first iDFS event, of which 199 (23.8%) were distant recurrences. Treatment interaction tests were significant for age (iDFS p=0.03; RFI p= 0.02), but not menopause, tumor size, grade, or RS (continuous or RS 11-15, 16-20, 21-25). Conclusions: In women with HR-positive, HER2-negative, AN-negative breast cancer and a RS of 11-25, adjuvant ET was not inferior to CET in the ITT analysis. (Funded by NCI, BCRF, and Komen Foundation.) Clinical trial information: NCT00310180.
Clinical findings and outcomes from MRI staging of breast cancers in women.
Authors: Akshara Raghavendra, Charite Nicolette Ricker, Lingyun Ji, Terry Church, Sujie Tang, Linda Larsen, Pulin Sheth, Debu Tripathy
Journal: Journal of Clinical Oncology (2012)

1124 Background: For patients diagnosed with breast cancer, case series have shown that staging MRI can detect occult breast cancers in 1-10% of cases. Prevalence and risk factors in underserved populations remain unclear. Methods: We performed a retrospective analysis of all patients, newly diagnosed, with breast cancer who had a preoperative staging MRI seen at Norris Comprehensive Cancer Center and LAC +USC, that cares for an underserved and minority population, from 2006 to 2011. Demographic, clinicopathologic and imaging data were obtained through a review of electronic records. Non index lesions were defined as those not known to be malignant, not presenting with clinical, mammographic or ultrasound findings, in a different quadrant and given an MRI BIRADS score of 4 or 5. Results: A total of 718 patients were analyzed and 148 patients (21%) had a total of 187 non index lesions; 63% were ipsilateral, 26% contralateral and 11% bilateral. As initial evaluation of non-index ipsilateral lesions, 71 (38%) had biopsy, 24 (13%) had excision and 34 (18%) had mastectomy. For contralateral non-index lesions, 41 (22%) had contralateral biopsy, 6 (3%) had excision and 11(6%) had mastectomy. Among all non index lesions, 111 (59%) were benign, 14 (7%) DCIS and 62 (33%) invasive cancer. Occult ipsilateral cancer was detected in 50 (6.9%) of patients and contralateral in 10 (1.4%) and bilateral in 6 (0.8%). Conclusions: The occult cancer detection rate with staging MRI was in this 9.2% of this diverse population. No clear risk factors were identified, with detailed factors, including BRCA status to be updated and reanalyzed. [Table: see text]
Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis
Authors: Giuseppina Stifano, Thierry Sornasse, Lisa M. Rice, Leo Na, Haiyin Chen‐Harris, Dinesh Khanna, Angelika Jahreis, Yuqing Zhang, Jeff Siegel, Robert Lafyatis
Journal: Arthritis & Rheumatology (2018)

Objective At present, there are no clinical or laboratory measures that accurately forecast the progression of skin fibrosis and organ involvement in patients with systemic sclerosis ( SS c). The goal of this study was to identify skin biomarkers that could be prognostic for the progression of skin fibrosis in patients with early diffuse cutaneous SS c (dc SS c). Methods We analyzed clinical data and gene expression in skin biopsy samples from 38 placebo‐treated patients, part of the Roche Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis ( FASSCINATE ) phase II study of tocilizumab in SS c. RNA samples were analyzed using nC ounter. A trajectory model based on a modified Rodnan skin thickness score was used to describe 3 skin disease trajectories over time. We examined the association of skin gene expression with skin score trajectory groups, by chi‐square test. Logistic regression was used to examine the prognostic power of each gene identified. Results We found that placebo‐treated patients with high expression of messenger RNA for CD 14, SERPINE 1, IL 13 RA 1, CTGF , and OSMR at baseline were more likely to have progressive skin score trajectories. We also found that those genes were prognostic for the risk of skin progression and that IL 13 RA 1, OSMR , and SERPINE 1 performed the best. Conclusion Skin gene expression of biomarkers associated with macrophages ( CD 14, IL 13 RA 1) and transforming growth factor β activation ( SERPINE 1, CTGF , OSMR ) are prognostic for progressive skin disease in patients with dc SS c. These biomarkers may provide guidance in decision‐making about which patients should be considered for aggressive therapies and/or for clinical trials.
Hemophagocytic Lymphohistiocytosis in Cutaneous T-Cell Lymphoma
Authors: Dylan E. Lee, M. Estela Martinez-Escala, Linda M. Serrano, Xiaolong A. Zhou, Jason B. Kaplan, Barbara Pro, Jaehyuk Choi, Joan Guitart
Journal: JAMA Dermatology (2018)

Hemophagocytic lymphohistiocytosis (HLH) has been reported as a serious complication of cutaneous T-cell lymphoma (CTCL). Despite available diagnostic guidelines, it remains a diagnostic and therapeutic challenge in this patient population.To examine the characteristics of CTCL associated with HLH and analyze the presenting signs and symptoms, therapeutic options, and outcome.In this case series, patients diagnosed with CTCL and HLH who were treated at a single institution from January 1, 2014, through December 31, 2017, were studied.The HLH-2004 trial criteria, HScore, and various clinical and histopathologic variables were applied to and analyzed in the cohort.Subtype of CTCL, treatment administered for HLH, and patient outcome were assessed.Seven patients (4 men and 3 women; median age, 50 years; range, 34-77 years) were identified from the database and included in the study. Cytotoxic subtypes of CTCL that involve the deep dermis and subcutaneous tissue were most commonly associated with HLH. Four patients met 5 or more HLH-2004 trial criteria, and 5 had an HScore probability greater than 85% at presentation. Common presenting HLH symptoms were fever and malaise. Cyclosporine, polychemotherapy, and systemic corticosteroids were the most common treatments. Patients receiving allogeneic stem cell transplants had the best outcomes, with all 3 of these patients alive and in complete remission.Hemophagocytic lymphohistiocytosis is a life-threatening complication of CTCL associated with rare cytotoxic CTCL subtypes that primarily involve the subcutaneous tissue. Because these cases may resemble a granulomatous or infectious condition, the diagnosis and appropriate management are often delayed. The results of this study demonstrate the need for high awareness of HLH in patients with panniculitic lymphomas and indicate that allogeneic stem cell transplantation may be the best option for a sustained remission.
Abstract 15556: Effects of Left Ventricular Assist Device Support on microRNA Levels
Authors: Teresa Wang, Emily O’Brien, Marc Samsky, Joseph Rogers, Adrian Hernandez, Dawn Bowles, G Michael Felker, Chetan Patel, Tariq Ahmad
Journal: Circulation (2014)

Objectives: To examine changes in a broad panel of circulating microRNAs (miRs) following left ventricular assist device (LVAD) support in advanced heart failure (HF). Background: LVAD therapy unloads the failing heart and may result in partial reversal of the end stage HF phenotype; however, molecular changes with support have not been well defined. MicroRNAs are small nucleotide RNAs involved in the pathogenesis of HF and have been postulated to have a potential role as circulating biomarkers or as therapeutic modalities. Human studies of the role of miRs in end stage HF have been limited. Methods: 23 distinct miRs, previously shown to play a role in the pathogenesis of HF, were measured in frozen plasma collected from 40 individuals prior to continuous flow LVAD implantation, and at a median of 96.5 (interquartile range, IQR: 72.25-149.75) days after implantation. Quantitative real-time PCR was performed for miR amplification. Ultimately, 19 miRs (miR-15b, -16, -21, -24, -27a, -29a, -92a, -103, -126, -133a, -146a, -146b, -155, -159a, -195, -221, -222, -320, -423) were expressed in &gt;80% of patient samples. Wilcoxon Rank Sum Tests were used to compare median relative quantification values pre- and post-LVAD placement. Results: The median age of patients was 67 years, and 60% were INTERMACS 1-2 prior to LVAD implantation. Following LVAD implantation, seven miRs (miR-21, -92a, -103, -159a, -195, -320, -423) were downregulated while 12 miRs (miR-15b, -16, -24, -27a, -29a, -126, -133a, -146a, -146b, -155, -221, -222) were up-regulated. After correction for multiple testing, only miR-155 was associated with significant up-modulation in plasma expression levels with LVAD support. Conclusions: While most plasma levels of miRs associated with cardiovascular pathophysiology remained unchanged with LVAD support, miR-155, which has been shown to play a role in cardiac hypertrophy, was up-regulated. The biological relevance of miR-155 in this setting requires further study.
NSABP FB-10: Phase Ib dose-escalation trial evaluating trastuzumab emtansine (T-DM1) with neratinib (N) in women with metastatic HER2+ breast cancer (MBC).
Authors: Jame Abraham, Shannon Puhalla, William M. Sikov, Alberto J. Montero, Mohamad Adham Salkeni, Wajeeha Razaq, Jan Hendrik Beumer, Brian Kiesel, Marc E. Buyse, Laura M Adamson, Ashok Srinivasan, Katherine L. Pogue-Geile, Carmen Joseph Allegra, Samuel A. Jacobs
Journal: Journal of Clinical Oncology (2018)

1027 Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab and the maytansinoid antimicrotubule, DM1. T-DM1 was granted FDA approval in 2nd-line MBC after prior trastuzumab (T) and taxane. Current practice in USA is for pts to receive T and pertuzumab (P) as neoadjuvant or as 1st-line therapy. Retrospective analysis of T-DM1 after T-P suggests a lower response rate (17%) than T-DM1 after T and taxane (EMILIA 43%). This study investigates the safety and efficacy of T-DM1 + N. Methods: Eligible pts had prior T-P as neoadjuvant therapy or in 1st-line, measurable disease, ECOG PS ≤2, adequate hematologic, renal, and liver function. Pts with stable brain metastases (CNS) were eligible. Treatment was T-DM1 at 3.6 mg/kg iv q 3 wk and N at escalating doses of 120, 160, 200, and 240 mg/d using 3+3 design. HER2 + was required on primary tissue but was not reassessed at entry. Blood samples were required upon entry. Pharmacokinetic (PK) studies were performed on a limited number of pts. Primary diarrhea prophylaxis with intensive loperamide was mandated. Results: Twenty-seven T-P resistant pts were enrolled. 26 were evaluable for toxicity, and 20 were evaluable for efficacy. A dose-limiting toxicity occurred in 6 during cycle 1. The RP2D was N 160 mg/d. Treatment-related grade 3 toxicities included diarrhea (5 pts), thrombocytopenia (4), nausea (3), and ALT elevation (1). Of 20 pts evaluable after 2 cycles, 3 had CRs and 9 had PRs (ORR 64%). The duration of response ranged from 42 d to 650+ d. New CNS disease occurred in 1 (8/27 at entry). Nine pts had PK determinations during the first 24h, and 13 had steady-state neratinib level on cycle 2 d1. There was no correlation between N dose and peak or steady-state levels; responses were seen at all doses. Data from blood samples collected on d 1 for HER2 amplification by ctDNA will be presented. Conclusions: Full-dose T-DM1 + N at 160 mg/d was well tolerated with notable activity. Responses were seen at all dose-levels of N. Limited PK analysis did not show that peak or steady-state concentration of N was related to response. Baseline peripheral blood samples are being assessed for HER2 amplification. Support: Puma Biotechnology Clinical trial information: NCT02236000.