tbuckley/cabot-search huggingface dataset:
Real-world practice patterns of providers managing older patients with non-small cell lung cancer.
Authors: Devika Govind Das, Avnish K Bhatia, Debra Wujcik, Susie Owenby, Wanda D. Hall, Tasha Smith, Ralph Zinner
Journal: Journal of Clinical Oncology (2019)

17 Background: Most patients with non-small cell lung cancer (NSCLC) have advanced disease at diagnosis and are older with median age 72 years. Evidence-based treatment (EBT) selection requires availability of molecular testing (MT) results at time of treatment decision and geriatric assessment (GA) helps determine a patient’s ability to tolerate therapy. This study describes practice patterns and evidence based treatment selections of providers managing older patients with NSCLC. Methods: After provider education and using care planning software (CPS), 50 patients with advanced NSCLC from two academic centers completed surveys regarding treatment goals and decision-making preferences, and patients ≥ 65 completed a modified GA that included activities of daily living and comorbidity assessment. Once treatment was selected, a personalized care plan was generated. Comparison treatment data from 17 community patients was obtained. Results: Participants were mean age 65, 52% female, and 78% white. Of 28 stage IV patients, 79% had MT and results available at time of treatment decision, and 100% met EBT guidelines. The community cohort had 47% testing, 29% results available, and 65% met guidelines. GA results in 24 patients were 46% frail, 29% intermediate fit, and 25% fit. Two patients (8%) were frail and had a plan change due to GA results. Conclusions: Obtaining timely MT results remains challenging. Continued strategies to ensure MT and timely results should be explored, including quality assurance monitoring given the increasing importance of MT in treatment selection. GA was less impactful in this setting, likely due to later stage patients, presumed frailty, and treatment goal being palliation. We believe GA would have greater impact in early stage NSCLC where aggressive treatments are offered with curative intent.
Adeno-Associated Viral Vector Mediated Gene Transfer for Hemophilia B
Authors: Amit C Nathwani, Edward GD Tuddenham, Savita Rangarajan, Cecilia Rosales, Jenny H McIntosh, David C Linch, Pratima Chowdary, Anja Griffioen, Anne Riddell, Jun Pie, Chris Harrington, James O’Beirne, Keith Smith, John Pasi, Bertil Glader, Pradip Rustagi, Catherine Ng, Mark Kay, Junfang Zhou, Yunyu Spence, Christopher Morton, James Allay, John Coleman, Susan Sleep, John M Cunningham, Etiena Basner-Tschakarjan, Federico Mingozzi, Katherine A. High, John T. Gray, Ulrike M. Reiss, Arthur W. Nienhuis, Andrew Davidoff
Journal: Blood (2011)
Wirelessly Heating Stents via Radiofrequency Resonance toward Enabling Endovascular Hyperthermia
Authors: Ying Yi, Jiaxu Chen, York Hsiang, Kenichi Takahata
Journal: Advanced Healthcare Materials (2019)

Abstract Thermal therapy known as hyperthermia has served as an effective method for cancer treatment. This therapeutic approach has also been attracting attention for treatment of in‐stent restenosis, the most common complication of stenting. Mild heating of stents has been shown to be a possible path to addressing this problem. Despite various studies on stent‐based thermotherapy, this area still lacks a clinically viable method and technology. Here, a radiofrequency‐powered “hot” stent prototype is reported in vitro and in vivo. An implantable stent device based on medical‐grade stainless steel acts as an electrical resonator, or an efficient wireless heater operating only when resonated using tuned external electromagnetic fields. The system architecture uses a custom‐developed power transmitter for wireless resonant powering/heating of the stent. An eight‐shaped antenna is shown to be highly effective for near‐field power transfer to the device and potentially to other smart implants, revealing stent heating efficiencies of up to 120 °C W −1 , 206% of the level provided by a conventional loop antenna. Testing with swine models, the prototyped system achieves stent heating in blood flow by powering through air and skin tissue in vivo in a fully controlled manner. The results advance stent hyperthermia technology toward possible future clinical application.
循環器病の診断と治療に関するガイドライン (2006-2007年度合同研究班報告) : ペースメーカ, ICD, CRTを受けた患者の社会復帰 就学 就労に関するガイドライン
Authors: 謙 奥村, 治彦 安部, 聡 小川, 宏 笠貫, 史郎 鎌倉, 直方 住友, 隆 新田, 俊雄 野島, 正知 堀江, 益徳 松崎, 巖 山口, 浩一郎 江島, 浩 金丸, 重人 菅野, 真吾 佐々木, 健 豊島, 博 中島, 敏寿 長友, 崇 野田, 京子 副島, 和也 村田, 重行 渡辺, 透 大江, 貴雄 加藤, 晃久 田邉, 誠太郎 土肥, 稔 堀江
Journal: Circulation (2008)
Re: Hutnik et al.: Selective laser trabeculoplasty versus argon laser trabeculoplasty in glaucoma patients treated previously with 360° selective laser trabeculoplasty: a randomized, single-blind, equivalence clinical trial (Ophthalmology. 2019;126:223–232)
Authors: Shyam Sundar Das Mohapatra, Prafulla Sarma, Chengchira A. Sangma, Shahinur Tayab, Susmita Paul, Mayuri Borgohain
Journal: Ophthalmology (2019)
Appropriateness of Heparin-Induced Thrombocytopenia (HIT) Testing and the Reliability of 4-Ts Scoring in Critically Ill Patients
Authors: Phyo Thazin Myint, Amani Erra, Taha Alrifai, Salman Syed, Bibek Singh Pannu, Shyam Chalise, Kelley E. Kozma
Journal: Blood (2018)
Activation of the Mineralocorticoid Receptor Stimulates Protein Disulfide Isomerase: Role in Sickle Cell Disease
Authors: Alexandra Lozano, Christopher Vega, Yaritza Inostroza-Nieves, Lorena Rivera González, Pablo J. López, Jamie Rosado Alicea, Gregory N. Prado, Alicia Rivera, Jose R. Romero
Journal: Blood (2016)
Genomic Profiling Identifies Association of <i>IDH1/IDH2</i> Mutation with Longer Relapse-Free and Metastasis-Free Survival in High-Grade Chondrosarcoma
Authors: Guo Gord Zhu, Khedoudja Nafa, Narasimhan Agaram, Ahmet Zehir, Ryma Benayed, Justyna Sadowska, Laetitia Borsu, Ciara Kelly, William D. Tap, Nicola Fabbri, Edward Athanasian, Patrick J. Boland, John H. Healey, Michael F. Berger, Marc Ladanyi, Meera Hameed
Journal: Clinical Cancer Research (2019)

Chondrosarcomas are the second most common primary malignant bone tumors. Although histologic grade is the most important factor predicting the clinical outcome of chondrosarcoma, it is subject to interobserver variability. Isocitrate dehydrogenase 1 (IDH1) and IDH2 hotspot mutations were recently found to be frequently mutated in central chondrosarcomas. However, a few published articles have been controversial regarding the association between IDH1/IDH2 mutation status and clinical outcomes in chondrosarcomas.We performed hotspot sequencing of IDH1 and IDH2 genes in 89 central chondrosarcomas and targeted next-generation sequencing in 54 of them, and then correlated the IDH1/IDH2 mutation status with the patient's clinical outcome.Although no association was discovered between IDH mutation status and the patient's overall survival, IDH1/IDH2 mutation was found to be associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas. Genomic profiling reveals TERT gene amplification and ATRX mutation, for the first time, in addition to TERT promoter mutation in a subset (6/30, 20%) of high-grade and dedifferentiated chondrosarcomas. These abnormalities in telomere genes are concurrent with IDH1/IDH2 mutation and with CDKN2A/2B deletion or TP53 mutation, suggesting a possible association and synergy among these genes in chondrosarcoma progression. We found 21% of patients with chondrosarcoma also had histories of second malignancies unrelated to cartilaginous tumors, suggesting possible unknown genetic susceptibility to chondrosarcoma.IDH1/IDH2 mutations are associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas, and they tend to co-occur with TERT mutations and with CDKN2A/2B and TP53 alterations in a subset of high-grade chondrosarcomas.
Detecting Complex Mutations in Myeloid Leukemia Using the GeneReader NGS System and QIAact Myeloid DNA UMI Panel
Authors: Veronique Laloux, Olivier Biglia, Alexandre Bona, Sarah Lafi, Ferose Charifi, Jan Larsen, Dietrich Lueerssen, Vikas Gupta, Juergen Lauber, Simon Hughes
Journal: Blood (2018)
Study of the Clinical Significance of the Length of FLT3-ITD in Acute Myeloid Leukemia Patients
Authors: Tamara Castaño, Rosa Ayala, Maria Pilar Llamas Sillero, Joaquin Martinez Lopez, Rocio N Salgado, Mireia Atance, Jose Luiz Lopez Lorenzo, Jose F. Tomas, Carlos Blas, Juan Manuel Alonso Dominguez
Journal: Blood (2018)
Abstract 106: Cardiac Fibroblast as a Critical Constituent of the Cellular Niche Driving Cardiac Maturation
Authors: Fang Yao
Journal: Circulation Research (2019)

Rationale: Cardiac maturation lays the foundation of postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. Objective: To identify non-cardiomyocyte cell types and important signaling pathways central to cardiomyocyte maturation. Methods and Results: Through building cell-cell interactomes and signaling regulatory networks from single-cell RNA-sequencing data of mouse hearts at various postnatal stages, we identified switching of fibroblast subclusters state as a key driving force behind cardiac maturation. Molecular and functional maturation of immature (neonatal) mouse cardiomyocytes or human embryonic stem cell-derived cardiomyocytes were considerably enhanced when co-cultured with their corresponding adult cardiac fibroblasts in vitro . Further, single-cell analysis of the cardiac maturation trajectory revealed highly conserved signaling pathways and ligands in fibroblast-induced cardiomyocyte maturation in vivo and in vitro . Targeting these signaling pathways using inhibitors significantly delayed cardiac maturation in postnatal hearts, and markedly induced cardiomyocyte proliferation in infarcted hearts. Conclusions: Our study unveiled cardiac fibroblasts as a major constituent in the microenvironment driving cardiac maturation. Targeting signaling pathways and ligand-receptor interactions involved in their crosstalk with cardiomyocytes may yield useful strategies to modulate cardiomyocyte maturation state in cardiac diseases and for regeneration purposes. Keywords: Cardiac Maturation, Fibroblast, Single-Cell RNA-Sequencing
Normalizing the use of patient-provider agreement for opioid treatment within a cancer institute.
Authors: Katie Cherenzia, Megan Begnoche, Mary Anne Fenton
Journal: Journal of Clinical Oncology (2019)

251 Background: Addressing the opioid epidemic can be challenging in a large academic cancer program and necessitates the need for a multidisciplinary approach for implementation of a successful program. The oncologist has a challenging role caring for patients with preexisting pain conditions, acute cancer-related pain, pain at the end of life and cancer survivors who live with cancer as a chronic condition after treatment. Methods: A structured program was developed to address the mounting pressure from many fronts related to the opioid epidemic including insurance companies, pharmacies, and the Department of Health. In April 2018, the Lifespan Cancer Institute implemented a system wide opioid program including patient education, an electronic patient-provider treatment agreement, and an electronic template for provider documentation. The intent of the program is to implement safe processes to safe guard the patient and their family along with the providers. The patient-provider treatment agreement clearly describes the roles and responsibilities of both groups with a goal of reducing risks by improving education. Our responsibility is to provide optimal management while addressing patient concerns and maintaining patient safety. Results: The opioid program has been well received by both caregivers, patients and families. All are engaged in the embedded education process and fully appreciate the need to use opioids safely. The program has been helpful in managing patient expectations and focusing difficult conversations in cases of potential abuse. In April 2018, only 13% of patients prescribed an opioid had a signed patient-provider treatment agreement. As of April 2019, 75% of patients have a signed agreement. Conclusions: The transitioning of care for the patient with chronic pain after completion of active cancer treatment continues to be a focus of future initiatives. Patient satisfaction remains a top priority as the patient-provider agreement becomes a standard of care for all patients receiving opioids. As oncology healthcare providers, our responsibility is to screen and educate patients on the risk of opioid addiction and diversion while providing compassionate palliative care.
Poor Outcome of CRLF2 Rearranged Philadelphia Negative Acute Lymphoblastic Leukemia Adults Patients
Authors: Yasser H Elnahass, Omar A Fahmy, Mohamed Abdel Mooti Samra, Fatma A Elrefaey, Mahmoud T Bokhary, Haitham Elsherif, Hazem H Afifi, Abdallah S Elkomy, Mona Hola, Hossam K Mahmoud
Journal: Blood (2018)
Abstract 905: Length Dependent Activation in Porcine Cardiac Myofilaments is Modulated by Mavacamten
Authors: Marcus Henze, Weikang Ma, Fiona Wong, Henry Gong, Robert Anderson, Carlos del Rio, Thomas C Irving
Journal: Circulation Research (2019)

Length dependent activation (LDA) is a property of muscle where increased sarcomere length (SL) leads to increased force of contraction. Despite its key role in both normal and pathological states, the molecular mechanisms underlying LDA are not understood. Previous studies suggest that increased titin-based passive tension at longer SL triggers structural changes in the troponin complex leading to increased Ca 2+ sensitivity. Stretch also appears to release myosin heads from the OFF or super-relaxed state (SRX) increasing the number of available heads for cross-bridge formation, and, hence, maximum force. The small molecule inhibitor of myosin, mavacamten (mava) has been shown to stabilize the SRX state. Here, we used both stretch and mava on permeabilized porcine myocardium for force/pCa measurements coupled with x-ray diffraction to interrogate the mechanisms underlying LDA. Increasing SL from 2.0 to 2.3 um increases Ca 2+ sensitivity and elevates both diastolic and maximal tension (i.e. LDA). Mava abolished LDA while blunting the passive stiffness/tension relationship, suggesting increased compliance. The equatorial x-ray reflection intensity ratio, I 1,1 /I 1,0 , increases with stretch, indicating increased myosin head displacement towards actin. Stretch also decreases the intensities of both the m3 meridional and the MyBPC reflections, suggesting stretch-induced disordering of the thick-filament. Surprisingly, these findings in pig skinned muscle are opposite to those previously reported in intact rat muscle despite robust LDA in both preparations. Consistent with previous studies, stretch increases thick filament strain (indicated by changes in the m6 meridional spacing) and changes in the structure of the troponin complex (indicated by increased intensity of the third order troponin reflection), suggesting that the mechanism for increased Ca 2+ sensitivity are similar in both muscle systems. Interestingly, all diffraction pattern changes that occurred with stretch moved in the opposite direction in the presence of mava. Together, these data indicate that mava is not only capable of stabilizing the SRX state of myosin, but can modulate inter-filament interactions responsible for increasing Ca 2+ sensitivity and force.
Abstract 752: A Novel Senolytic Drug, Seno-7284 Ameliorates Aging and Age-related Cardiometabolic Disorders
Authors: Goro Katsuumi, Ippei Shimizu, Yohko Yoshida, Masayoshi Suda, Yuka Hayashi, Ryutaro Ikegami, Takayuki Wakasugi, Masaaki Nakao, Ryo Furuuchi, Ayako Nagasawa, Ryota Mikawa, Masataka Sugimoto, Tohru Minamino
Journal: Circulation Research (2019)

Accumulation of senescent cells is promoted in various organs as aging, and it also contributes to the progression of age-related disorders. Recent reports have demonstrated the elimination of senescent cells, so-called "senolysis" ameliorated various age-related disorders including cardiovascular diseases. However, there is currently no senolytic drug available in clinical settings. Here, we found a novel senolytic drug (termed “seno-7284”) from those already used in clinical setting and it exhibited senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid aging. Conducting senescence-associated beta-galactosidase staining(SA-beta gal), we found that administrating seno-7284 for one week significantly reduced the accumulation of senescent cells in viscerala dipose tissue of diabetic mice induced by fed high-fat diet(Figure). This drug also ameliorated systemic glucose metabolism and adipose tissue inflammation without a reduction of body weight. Further analysis including RNA-seq analysis suggested seno-7284 stimulates the endogenous senolytic function of NK cells and CD8+ T cells via the Cxcl9-Cxcr3 axis. We also found administrating seno-7284 for two weeks also reduced the accumulation of senescent cells and atherosclerotic lesions in the aorta of western-diet-fed ApoE knock out mice. Surprisingly, this drug significantly improved the lifespan of Zmpste24 KO progeroid aging mice. Correctively, our results indicate that seno-7284 mediates its senolytic effect through the recruitment of lymphocytes. Senolytics would become a promising therapy for aging and age-related cardiometabolic disorders.
A Retrospective Study of 108 Cases of Relapsed or Refractory Classical Hodgkin Lymphoma: Second Line Therapies and Autologous Hematopoietic Stem Cell Transplantation
Authors: Mingzi Yang, Meng Wu, Reyizha Nuersulitan, Yanfei Liu, Liya A, Lingyan Ping, Yuqin Song, Jun Zhu
Journal: Blood (2018)
A Phase II Study of the MEK 1/2 Inhibitor AZD6244 (Selumetinib, ARRY-142866) in Relapsed or Refractory Multiple Myeloma
Authors: Beata Holkova, Ashraf Z. Badros, Robert Geller, Peter M. Voorhees, Adriana Zingone, Neha Korde, Hui-Yi Lin, Mary Beth Tombes, Ellen Shrader, Heidi Sankala, Maciej Kmieciak, John D. Roberts, Daniel Sullivan, Ola Landgren, Steven Grant
Journal: Blood (2011)
Abstract 192: Sex Dependent Differences in Cardiac Myocyte Excitation-Contraction Coupling After Chronic Stimulation of the Delta or Kappa Opioid Receptors During Normoxic and Hypoxic Conditions
Authors: Matthew Klos, Ramiz Ahmad, Isabella Pua, Kayla Hicks, Shreyas Suresh, Sherry Morgenstern, Eric Devaney
Journal: Circulation Research (2019)

Introduction: In 2016 the US government declared opioid misuse a public emergency. While most opioid related deaths can be attributed to overdose, recent data suggest a link between opioid use and cardiovascular disease. Further, epidemiological data suggest it may be sex dependent, with females (♀) being at a somewhat higher risk than males (♂). This is paradoxical because until menopause, ♀ have a lower risk of heart disease when compared to ♂. Healthy adult hearts express the δ and κ ORs, but not the μOR. Therefore, the overall goals of this study using a reductionist model were to: 1). To determine if there are sex specific differences in cardiac myocyte excitation-contraction coupling between ♂ and ♀ myocytes exposed to δ or κ OR agonists during normoxia/hypoxia. 2). Examine if 17β-Estradiol enhances or augments the effects of δ or κ OR stimulation. Methods: Myocytes were isolated from adult ♂ and ♀ Sprague-Dawley rats and cultured overnight in M199 HEPES media, or M199 HEPES media containing either 1 μM DADLE (δ agonist), 20 μM U50-488 (κ agonist), 100 nm 17β-Estradiol, 1μM DADLE + 100 nm 17β-Estradiol, or 20 μM U50-488 + 100 nm 17β-Estradiol. To simulate an infarct, a subset of the myocytes was incubated at 1%O 2 , 5% CO 2 for 4 hours + 10 nM isoproterenol followed by 60 min normoxia (21%O 2 , 5% CO 2 ) before recordings. Excitation-Contraction was measured using an IonOptix rig (IonOptix LLC, Milton MA) at 36±1° at 1 Hz pacing. Results: During normoxia, ♂ myocytes compared to ♀ myocytes had an increased peak contraction and peak Ca 2+ transient. The addition of 100 nM 17β-Estradiol did not affect peak contraction in either sex but decreased the Ca 2+ transient in ♂ myocytes while increasing it in ♀ myocytes. DADLE and U50-488 had no effect on ♀ myocyte contractility but decreased ♂ myocyte contractility by a minimum of 13% and a maximum of 26% with/without 100 nM 17β-Estradiol. ♀ myocytes were immune to the effects of hypoxia, even exhibiting a slight increase in their peak calcium compared to control conditions, arguably because of the addition of isoproterenol. ♂ myocytes on the other hand, had an overall decrease in excitation-contraction coupling during hypoxia which was made worse by OR stimulation. Conclusion: ♀ myocytes are immune to the detrimental effects of δ and κ OR stimulation.
WHO drafted in to help control severe dengue outbreak in Pakistan
Authors: Ashfaq Yusufzai
Journal: BMJ (2019)

The World Health Organization is supporting officials in Pakistan amid an escalating outbreak of dengue fever.

More than 40 000 people have been infected by the mosquito-borne disease in Pakistan this year, surpassing previous records. There have been over 50 deaths so far this year, and 370 since 2011.

The severe outbreak prompted the government to enlist WHO’s support to improve surveillance and monitoring systems.

Palitha Mahipala, WHO’s chief in Pakistan, told The BMJ that it was supporting a comprehensive response plan. He said, “We have donated equipment and investigation kits, as well as building the capacity of health …
Cancer-related suicide in the United States, 1999-2015.
Authors: Xuesong Han, Jingxuan Zhao, Jiemin Ma, K Robin Yabroff, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2019)

148 Background: Cancer patients have an elevated risk of suicide given the prevalent psychological distress, treatment side effects, and uncontrolled pain. This study aims to examine temporal trends in cancer-related suicide in the US during the past two decades in view of progress in psycho-oncology care and symptom control for cancer patients in the country. Methods: Cancer-related suicide was defined as deaths with suicide as the underlying cause and cancer as a contributing cause in the US Multiple Cause of Death Data. We first calculated annual age-standardized cancer-related suicide rates and overall suicide rates from 1999 to 2015. Then, we fitted the log-transformed age-standardized rates to Joinpoint regression models to calculate the annual percentage change (APC) by demographic factors and overall. Results: Among 599,786 suicides in the US from 1999 to 2015, 5,559 were cancer-related. Seventy-three percent of the cancer-related suicides were committed by firearm and 14% were by poisoning. The age-standardized cancer-related suicide rate per 100,000 persons decreased from 0.17 in 1999 to 0.12 in 2015, with an APC of -2.5% (95% CI: -3.3%, -1.7%). In contrast, the age-standardized overall suicide rate per 10,000 persons increased from 13.22 in 1999 to 16.73 in 2015, with APC of 0.9% (95% CI: 0.4%, 1.3%) from 1999 to 2006 and 2.0% (95% CI: 1.7%, 2.2%) from 2006 to 2015. The decline in cancer-related suicide rate was largest among male (APC = -3.1%, 95% CI: -3.9%, -2.3%), 65-74-year-olds (APC = -3.1%, 95% CI: -4.2%, -2.0%), in the South (APC = -4.0%, 95% CI: -5.8%, -2.3%), and in urban area (APC = -3.0%, 95% CI: -4.2%, -1.7%). Conclusions: Despite the continuous increasing overall suicide rates in the US during the past two decades, cancer-related suicide has been decreasing, suggesting an evolving role of psycho-oncology care and symptom control during this period. Well-designed prospective studies are warranted to identify cancer patients at high-risk of suicide and to develop effective care intervention.