tbuckley/cabot-search huggingface dataset:
Patient-defined goals and preferences among older adults with cancer starting chemotherapy (CT).
Authors: Enrique Soto Perez De Celis, Daneng Li, Can-Lan Sun, Heeyoung Kim, Przemyslaw Twardowski, Marwan Fakih, Vincent M. Chung, Mihaela C. Cristea, Dean Lim, Yuan Yuan, William Dale, Leana Chien, Kemeberly Charles, Heidi Tan, Elsa Roberts, Jeanine Moreno, Daisy Rivera, Vani Katheria, Arti Hurria
Journal: Journal of Clinical Oncology (2018)

10009 Background: Older adults with cancer facing decisions with competing health outcomes may favor maintaining quality of life (QOL), independence, or cognition over prolonging survival. The goal of this study was to elicit preferences among outcomes from older adults starting CT. Methods: This is a secondary analysis of an ongoing prospective study aimed at identifying and addressing vulnerabilities in older adults (age ≥65) starting CT (NCT02517034). Patients completed 3 tools assessing preferences in health outcomes: 1) Health Outcomes Tool: rates the relative importance of 4 outcomes (survival, function, freedom from pain, and freedom from symptoms) using a visual analog scale (VAS); 2) Now vs. Later Tool: rates the relative importance of QOL at 3 times: today,1 year (y) in the future , and 5y in the future using a VAS; and 3) Attitude Scale: rates subjects' agreement with statements related to outcomes. We measured the proportion of patients reporting other outcomes being "as important" or "more important" than survival and studied their characteristics. Results: 121 patients (median age 71y, 47% male, 72% Stage IV, 31% gastrointestinal cancer) were included. 52% had poor physical function, 50% needed help with instrumental activities of daily living (e.g. cooking or transportation), and 73% had poor social support. On the Health Outcomes Tool, 44% rated other outcomes as more important than survival. On the Now vs. Later tool, 59% considered current QOL more/as important as QOL at 1y, and 58% considered current QOL more/as important as QOL at 5y. On the Attitude Scale, 58% agreed/strongly agreed with: "I would rather live a shorter life than lose my ability to take care of myself"; and 81% agreed/strongly agreed with: "It is more important to me to maintain my thinking ability than to live as long as possible". Patients with good physical function and/or good social support were more likely to consider survival as the most important outcome, regardless of stage. Conclusions: Half of older patients rated other outcomes (particularly cognitive ability) as being more important than survival. Eliciting which outcomes are the most important for older patients can help define treatment goals and improve shared decision-making.
Quality of life in cutaneous T-cell lymphoma subjects treated with anti-CCR4 monoclonal antibody mogamulizumab versus vorinostat: Results from the phase 3 MAVORIC trial.
Authors: Pierluigi Porcu, Stacie Hudgens, Pietro Quaglino, Richard Cowan, Lysbeth Floden, Mollie Leoni, Stephen Dale, Madeleine Duvic
Journal: Journal of Clinical Oncology (2018)

7577 Background: Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin’s lymphomas that cause significant morbidity and adversely affect quality of life (QoL), most severely in Sezary syndrome (SS) patients (pts). Methods: A multicenter Phase 3 trial compared mogamulizumab (MOGA) vs vorinostat (VOR) in pts with Stage IB-IV CTCL who had failed ≥ 1 systemic therapy. Progression free survival was the primary endpoint. Validated QoL measurements included the Skindex-29 (SDX-29), Functional Assessment of Cancer Therapy-General (FACT-G) and EuroQol-5D. SDX-29 and FACT-G are reported here. Longitudinal modeling of symptoms, function, and QoL subdomains were evaluated using longitudinal mixed models on prespecified covariates. Meaningful change threshold (MCT) was evaluated and categorical change analyzed by group over time. Time to clinically meaningful worsening was defined using distribution-based minimally important difference thresholds. Results: 372 pts were randomized (186 in each arm). MOGA resulted in symptomatic and functional improvement with differences in SDX-29 Symptoms (Cycle, C3, C5, and C7; p < 0.05) and Functional (C3 and 5; p < 0.05) scales. The proportion of pts who improved by at least the MCT from baseline was significantly greater for MOGA vs VOR on SDX-29 Symptoms at C3 (61.1% vs 45.3%), C5 (64.5% vs 42.4%), C7 (67.1% vs 47.5%), and C11 (84.1% vs 50.0%) and SDX-29 Functioning domain at C5 (54.3% vs 28.8%). Significant difference in the FACT-G Physical Well-Being scale (C1, C3, and C5; p < 0.05) were observed in favor of MOGA and a greater proportion of pts declined by at least the MCT in favor of MOGA vs VOR at C1 (19.3% vs 34.7%), C3 (17.4% vs 42.9%), C5 (13.1% vs 43.3%), and C7 (15.9% vs 37.5%). The median time to worsening of symptoms on SDX-29 was 27.4 m for MOGA vs 6.6 m for Vor. In SS pts, the median time to worsening varied in favor of MOGA (p < 0.005) on all SDX-29 domains. In mycosis fungoides pts, time to worsening did not vary between arms. Conclusions: Symptoms, function, and overall QoL of CTCL pts favored MOGA over VOR across study time points. Pts with highest symptom burden and functional impairment derived the most QOL benefit from MOGA. Clinical trial information: NCT01728805.
Abstract 12915: Reduced Fractional Shortening of Right Ventricular Outflow Tract is Associated with Adverse Outcome in Patients with Left Ventricular Dysfunction
Authors: Toshihiro Tsuruda, Masashi Yamaguchi, Kuniko Furukawa, Takeshi Ideguchi, Junji Kawagoe, Hisamitsu Onitsuka, Tetsunori Ishikawa, Kazuo Kitamura
Journal: Circulation (2012)

Background: Recent studies have shown the significance of right ventricular (RV) function on the outcome in patients with left ventricular dysfunction (LVSD). However, global assessment of RV remai...
Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?
Authors: Zainab Ahmadi, Josefin Sundh, Anna B. Hermansson, Magnus Ekström
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?
Abstract 15960: Engineered Vascular Construct via the Ring Stacking Method
Authors: Cameron B Pinnock, Mai T Lam
Journal: Circulation (2015)

Introduction: Treatments for arteriosclerosis such as bypass surgery use vessel grafts that can cause infections in patients, with more than 50% of these grafts failing within 10 years. Discovering different methods to create vascular replacements in vitro has become one of the major focuses of tissue engineering. Material and Methods: Utilizing a novel approach termed the “Ring Stacking Method” we will create tissue resembling that of a blood vessel. With the aid of a 3D-printed PLA tubular scaffold placed in the center of a 35mm plate, we are able to create two cell ring layers. The ring layers are composed of smooth muscle cells and fibroblasts seeded onto fibrin gel, composed of 40μL of 100U/mL thrombin and 160μL of 20mg/mL fibrinogen, which have rolled towards the PLA scaffold. Results and Discussion: To evaluate our proposed technique of the Ring Stacking Method, we began by attempting to fabricate the smooth muscle layer. We used a human aortic smooth muscle cell line for relevance to cardiac bypass surgery application. The contractile properties of smooth muscle cells make them an ideal candidate for our ring formation methods. The SMC rings were subsequently stacked on top of one another using a plastic tube as an internal guide to keep the ring stack initially in place ( Fig. 1A ). The tubular SMC construct contained six ring segments and was about 10 mm in length ( Fig. 1B ). Remarkably, the lumen of the preliminary vascular construct had the ability to hold itself open, displaying structural integrity ( Fig. 1C , white arrow). Conclusion: Creation of engineered vascular replacements could eventually lead to decreased dependence on auto-graft harvesting from other parts of the body. Replacement vessels have potential to integrate into the pre-existing native tissue and promote healing and reestablishment of function of the region. The vascular construct could be applied to other ischemia disease and tissue engineering problems.
Abstract P139: Association of Energy Flux with Change in Cardiovascular Risk Factors in Weight Stable Individuals
Authors: Baqiyyah Conway, Peter Giacobbi, Clemens Drenowatz, Stephen Blair, Gregory Hand
Journal: Circulation (2016)

Background: It is generally accepted that body weight is maintained when there is energy balance between intake and expenditure. Energy balance can be achieved at different rates of expenditure through exercise and caloric intake which has been referred to as energy flux: high flux reflects high expenditure and high intake while low flux describes low energy expenditure and intake. Overweight, obesity, and diabetes are major risk factors for cardiovascular disease and CVD risk factors tend to increase with hyperglycemia and BMI. Exercise is a viable way to achieve weight maintenance, however, there is limited data about the role of energy flux on CVD risk factors when individuals maintain their body weight. We investigated the effect of energy flux and change in energy flux on CVD risk factors in when body weight is maintained. Methods: One hundred and thirteen overweight or obese class I adults ages 21 to 45 were randomized to a control group, moderate exercise (17.5 kcal/kg/week) or high exercise group (35 kcal/kg/week). The exercise groups performed supervised exercise at and intensity of 70-75% of their heart rate maximum. Impaired fasting glucose was defined as a fasting glucose of 100-125 mg/dL. General linear models were used to test the relationship of exercise intensity and impaired fasting glucose on change in energy flux from baseline to six months, as well as the relationship of 6-month change in energy flux with change in CVD risk factors, namely, HDLc, LDLc, vLDLc, total cholesterol, triglycerides, Apolipoprotein B (ApoB), and C-reactive protein. Results: Seventy-two percent of the population was overweight and 22% were obese. Mean change in energy flux from baseline to month six was 128.8 kcal/day. In multivariable analyses including age, sex, BMI, impaired fasting glucose, and energy expenditure group assignment, neither exercise group assignment nor baseline obesity status had any effect on change in energy flux, lipids, or inflammatory markers. Impaired fasting glucose was associated with a significantly greater increase in energy flux from baseline to six months (p=0.03). There was a stepwise change in C-reactive protein from baseline to six months, with a decrease (-2.46 mg/dL) in controls, a moderate increase (+0.32 mg/dL) in the moderate intensity exercise group and a larger increase (+0.82 mg/dL) in the very intensive exercise group, p= 0.03 for moderate intensity and p=0.02 for very intensive exercise groups compared to controls. Finally, increases in energy flux from baseline to six months were associated with increased ApoB (p=0.04), though there were no significant changes in energy flux by group assignment. Conclusion: Intensification of exercise and increases in energy flux while maintaining stable weight is associated with increases in certain cardiovascular risk factors, namely C-reactive protein and ApoB.
Salmonella Aortitis in a Patient with a Hufnagel Valve
Authors: Louisweinstein, Kennethkaplan
Journal: Circulation (1965)

A patient is described in whom Salmonella schwarzengrund bacteremia was associated with infection of the aorta in the area at which a Hufnagel valve had been implanted 4 years earlier. Despite prolonged and repeated therapy with antimicrobial agents to which the organism was sensitive, an abscess developed in the aortic wall and led to a dissecting aneurysm and death. The role of the Hufnagel valve in altering the anatomy and hemodynamics in the lower aorta and predisposing to local and persistent infection is discussed. It is suggested, on the basis of the course of this patient's illness, that the appearance of bacteremia is especially ominous when such a prosthesis is present, and that antimicrobial therapy should be initiated as early as possible, that the doses used be large, and that the treatment be prolonged, without interruption. If manifestations consistent with aortic tear appear, despite apparent control of the infection, the presence of an abscess in the aortic wall must be suspected and the ...
Abstract 19245: Time Trends of Echocardiography Measures of LV Function in a Cohort of Women with Breast Cancer Treated with Anthracyclines, Taxanes and Trastuzumab
Authors: Timothy C Tan, Heloisa Sawaya, Igal A Sebag, Victor Cohen, Randolph P Martin, Michael H Picard, Jonathan J Passeri, Irene Kuter, Marielle Scherrer-Crosbie
Journal: Circulation (2012)

Background: The cardiotoxicity that occurs during treatment by anthracyclines and trastuzumab used for cancer therapy is well recognized. However, the time trend of the decrease in cardiac function is unknown. In particular, the decrease in left ventricular ejection fraction (LVEF) seen with trastuzumab is thought to be transient although there is controversy on this reversibility. Aim: To determine the trends of LVEF, strain and strain rate after treatment by anthracyclines, taxanes and trastuzumab in a cohort of women with breast cancer that had been serially followed during their treatment. Methods: Follow up echocardiograms (TTEs) were performed in 25 women &gt;18 years of age with first time breast cancer treated with anthracyclines and trastuzumab, 26.4±11.1 months after the end of the cancer treatment. These women had undergone serial TTEs before and during the duration of the treatment (15 months). LVEF was calculated using a modified Simpson’s biplane method. Global peak systolic longitudinal strain and strain rate were calculated by averaging the values of peak systolic strain and strain rate in the basal, mid-wall and apical segments of the 4- and 2- chamber views. Results: LVEF, strain and strain rate decreased during the study period (p&lt;0.05 for all 3 parameters) and did not improve after 24 months of treatment completion. Of the three parameters, strain appeared to be most sensitive for the detection of cardiac dysfunction since it demonstrated a significant decrease within the 3 first months of treatment. Conclusion: Impairment in cardiac function from chemotherapy appears to be persistent even at 26.4±11.1 months post treatment suggestive of long term underlying cardiac damage. These results highlight the potential value of echocardiography in detecting sub-acute cardiac pathology and may help guide cardiac treatment in cancer survivors.
Abstract 16759: Active Management During Transfer of Patients with Suspected Acute Aortic Syndrome (AAS): Observations from an Aortic Network
Authors: Bhuvnesh Aggarwal, Chad E Raymond, Damon Kralovic, Kristopher Kormos, Venugopal Menon
Journal: Circulation (2012)

Background: An acute aortic network requires safe transport of patients by a critical care transport team (CCT) to the referral center. Control of BP is a central therapeutic target. We aimed to an...
Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation
Authors: Michelle N. Wray-Dutra, Raghav Chawla, Kerri R. Thomas, Brenda J. Seymour, Tanvi Arkatkar, Karen M. Sommer, Socheath Khim, Cole Trapnell, Richard G. James, David J. Rawlings
Journal: The Journal of Experimental Medicine (2018)

Activating mutations in the adapter protein CARD11 associated with diffuse large B cell lymphomas (DLBCLs) are predicted to arise during germinal center (GC) responses, leading to inappropriate activation of NF-κB signaling. Here, we modeled the B cell–intrinsic impact of the L251P activating mutation in CARD11 (aCARD11) on the GC response. Global B cell aCARD11 expression led to a modest increase in splenic B cells and a severe reduction in B1 B cell numbers, respectively. Following T cell–dependent immunization, aCARD11 cells exhibited increased rates of GC formation, resolution, and differentiation. Restriction of aCARD11 to GC B cells similarly altered the GC response and B cell differentiation. In this model, aCARD11 promoted dark zone skewing along with increased cycling, AID levels, and class switch recombination. Furthermore, aCard11 GC B cells displayed increased biomass and mTORC1 signaling, suggesting a novel strategy for targeting aCARD11-driven DLBCL. While aCARD11 potently impacts GC responses, the rapid GC contraction suggests it requires collaboration with events that limit terminal differentiation to promote lymphoma.
Super-enhancers maintain renin-expressing cell identity and memory to preserve multi-system homeostasis
Authors: Maria Florencia Martinez, Silvia Medrano, Robin Isadora Brown, Turan Tufan, Stephen Shang, Nadia Bertoncello, Omar Guessoum, Mazhar Adli, Brian C. Belyea, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez
Journal: Journal of Clinical Investigation (2018)

Renin cells are crucial for survival — they control fluid-electrolyte and blood pressure homeostasis, vascular development, regeneration, and oxygen delivery to tissues. During embryonic development, renin cells are progenitors for multiple cell types that retain the memory of the renin phenotype. When there is a threat to survival, those descendants are transformed and reenact the renin phenotype to restore homeostasis. We tested the hypothesis that the molecular memory of the renin phenotype resides in unique regions and states of these cells' chromatin. Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. Using the rank ordering of super-enhancers, epigenetic rewriting, and enhancer deletion analysis, we found that renin cells harbor a unique set of super-enhancers that determine their identity. The most prominent renin super-enhancer may act as a chromatin sensor of signals that convey the physiologic status of the organism, and is responsible for the transformation of renin cell descendants to the renin phenotype, a fundamental process to ensure homeostasis.
Caregiver and special education staff perspectives of a commercial brain-computer interface as access technology: a qualitative study
Authors: Sarvnaz Taherian, T. Claire Davies
Journal: Brain-Computer Interfaces (2018)

This study sought to understand the perceptions of special education staff and caregivers (n = 6) who took part in a brain-computer interface (BCI) technology trial for individuals with severe cerebral palsy. Participants were interviewed post-trials regarding the different BCI components. The transcripts were coded and analyzed using thematic analysis. Results showed that BCIs are not suitable for independent use outside of clinical/laboratory settings. The hardware needs to be configurable, comfortable and accommodate physical support needs. The training approach needs to be less cognitively demanding, motivating and support personalized mental tasks. For BCIs to transition into the real world, there should be adequate technological support, improved reliability, and a systemic assessment of how the technology will fit into the lives of end users. Participants emphasized the on-going need to involve users and individuals who support them, to create a system that truly meets the needs of the users.
Moving from the Trial to the Real World: Improving Medication Adherence Using Insights of Implementation Science
Authors: Leah L. Zullig, Mieke Deschodt, Jan Liska, Hayden B. Bosworth, Sabina De Geest
Journal: The Annual Review of Pharmacology and Toxicology (2018)

Medication nonadherence is a serious public health concern. Although there are promising interventions that improve medication adherence, most interventions are developed and tested in tightly controlled research environments that are dissimilar from the real-world settings where the majority of patients receive health care. Implementation science methods have the potential to facilitate and accelerate the translation shift from the trial world to the real world. We demonstrate their potential by reviewing published, high-quality medication adherence studies that could potentially be translated into clinical practice yet lack essential implementation science building blocks. We further illustrate this point by describing an adherence study that demonstrates how implementation science creates a junction between research and real-world settings. This article is a call to action for researchers, clinicians, policy makers, pharmaceutical companies, and others involved in the delivery of care to adopt the implementation science paradigm in the scale-up of adherence (research) programs.
Case-Control Studies
Authors: Telba Z. Irony
Journal: JAMA (2018)

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Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules
Authors: Chun‐Ping Liu, You Hu, Ju‐Chun Lin, Hua‐Lin Fu, Lee Yong Lim, Zhi‐Xiang Yuan
Journal: Medicinal Research Reviews (2018)

Abstract Kidney diseases have become a global public health problem. The application of kidney‐targeted drug‐delivery systems in the management of kidney diseases has profound transformative potential. Kidney‐targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor‐mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.