tbuckley/cabot-search huggingface dataset:
Personalized Risk-Stratified Cancer Follow-Up Care: Its Potential for Healthier Survivors, Happier Clinicians, and Lower Costs
Authors: Deborah K Mayer, Catherine M Alfano
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract The growth in the number of cancer survivors in the face of projected health-care workforce shortages will challenge the US health-care system in delivering follow-up care. New methods of delivering follow-up care are needed that address the ongoing needs of survivors without overwhelming already overflowing oncology clinics or shuttling all follow-up patients to primary care providers. One potential solution, proposed for over a decade, lies in adopting a personalized approach to care in which survivors are triaged or risk-stratified to distinct care pathways based on the complexity of their needs and the types of providers their care requires. Although other approaches may emerge, we advocate for development, testing, and implementation of a risk-stratified approach as a means to address this problem. This commentary reviews what is needed to shift to a risk-stratified approach in delivering survivorship care in the United States.
Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC).
Authors: Gagandeep Brar, Changqing Xie, Charalampos S. Floudas, M. Pia Morelli, Suzanne Fioravanti, Melissa Walker, Donna Mabry-Hrones, Jennifer C Jones, Tim F. Greten
Journal: Journal of Clinical Oncology (2019)

192 Background: Chemotherapy in aPDAC has resulted in only modest improvements in outcome. The effectiveness of ICI monotherapy is also limited in PDAC, suggesting an immunogenic inert tumor microenvironment. SBRT is safe and effective in locally advanced PDAC and exhibits enhanced antitumor immunity. We hypothesize that ICI plus SBRT will improves immunomodulatory effects of ICI in patients with aPDAC resulting in a greater clinical benefit. Methods: Eligible patients with aPDAC were enrolled to four different treatment cohorts. Cohort 1: Durvalumab (Durva) 1500 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 2: SBRT 5 fractions x 5Gy followed by Durva. Cohort 3: Durva + Tremelimumab (Treme) 75 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 4: SBRT 5 fractions x 5Gy followed by Durva + Treme. This was continued until unacceptable toxicity or progression of disease. A biopsy was performed at baseline and pre-cycle 2 of treatment for exploratory correlative analysis. The primary objective was to evaluate the safety and feasibility of combining ICI and SBRT to enhance the efficacy of ICI. Results: 51 patients with aPDAC were enrolled and 31 patients were evaluable for the efficacy. The most commonly TRAEs were lymphopenia. Grade 3-4 AEs were lymphopenia and anemia. No dose limiting toxicities were seen. Out of total 31 evaluable patients, 1 patient achieved a confirmed partial response seen in Cohort 1 and 2 patients in Cohort 4, and 7 stable disease across the 4 treatment arms. Median PFS and OS was 1.7 months (95% CI 0.7-2.8 months) and 3.4 months (95% CI 0.9-11.4 months) in cohort 1; 2.6 months (95% CI 2.1-4.7 months) and 9.1 months (95% CI 3.4-18.7 months)in cohort 2; 1.6 months (95% CI 0.5-4.0 months) and 3.0 months (95% CI 0.7-6.6 months) in cohort 3; and 3.2 months (95% CI 1.5-16.5months) and 6.4 months (95% CI 1.5-17.6 months) in cohort 4. Conclusions: The combination of ICI and SBRT is safe and well tolerated in patients with aPDAC. The overall response rate of 9.6% including 2 patients who achieved a durable partial response lasting over 12 months, suggests meaningful clinical activity. This signifies that ICI and SBRT is a potential new treatment for aPDAC. Clinical trial information: NCT02311361.
Abstract 14073: The Role of Lipoprotein-Associated Phospholipase A2Activity and High Sensitivity C-Reactive Protein in Identifying High Risk Smokers for Incident Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Martin Tibuakuu, Sina Kianoush, Andrew P DeFilippis, William (Bill) McEvoy, Di Zhao, Eliseo Guallar, Christie M Ballantyne, Ron C Hoogeveen, Michael J Blaha, Erin D Michos
Journal: Circulation (2017)

Background: Despite the causal role of cigarette smoking in atherosclerotic cardiovascular disease (ASCVD), the biological mechanisms are not fully understood. This study evaluated the joint relati...
A Randomized Trial of Endometrial Scratching before In Vitro Fertilization
Authors: Sarah Lensen, Diana Osavlyuk, Sarah Armstrong, Caroline Stadelmann, Aurélie Hennes, Emma Napier, Jack Wilkinson, Lynn Sadler, Devashana Gupta, Annika Strandell, Christina Bergh, Kugajeevan Vigneswaran, Wan T. Teh, Haitham Hamoda, Lisa Webber, Sarah A. Wakeman, Leigh Searle, Priya Bhide, Simon McDowell, Karen Peeraer, Yacoub Khalaf, Cynthia Farquhar
Journal: New England Journal of Medicine (2019)

Endometrial scratching (with the use of a pipelle biopsy) is a technique proposed to facilitate embryo implantation and increase the probability of pregnancy in women undergoing in vitro fertilization (IVF).We conducted a pragmatic, multicenter, open-label, randomized, controlled trial. Eligible women were undergoing IVF (fresh-embryo or frozen-embryo transfer), with no recent exposure to disruptive intrauterine instrumentation (e.g., hysteroscopy). Participants were randomly assigned in a 1:1 ratio to either endometrial scratching (by pipelle biopsy between day 3 of the cycle preceding the embryo-transfer cycle and day 3 of the embryo-transfer cycle) or no intervention. The primary outcome was live birth.A total of 1364 women underwent randomization. The frequency of live birth was 180 of 690 women (26.1%) in the endometrial-scratch group and 176 of 674 women (26.1%) in the control group (adjusted odds ratio, 1.00; 95% confidence interval, 0.78 to 1.27). There were no significant between-group differences in the rates of ongoing pregnancy, clinical pregnancy, multiple pregnancy, ectopic pregnancy, or miscarriage. The median score for pain from endometrial scratching (on a scale of 0 to 10, with higher scores indicating worse pain) was 3.5 (interquartile range, 1.9 to 6.0).Endometrial scratching did not result in a higher rate of live birth than no intervention among women undergoing IVF. (Funded by the University of Auckland and others; PIP Australian New Zealand Clinical Trials Registry number, ACTRN12614000626662 .).
Abstract 17513: Strength of Acute Clinical Management and Weakness of Preventive Efforts - Results of Nationwide Myocardial Infarction Registry From Central Eastern Europe With a 3-year Follow-up
Authors: Tomasz Zdrojewski, Marek Gierlotka, Bogdan Wojtyniak, Lech Polonski, Adam Kozierkiewicz, Mariusz Gasior, Krzysztof Chlebus, Lukasz Wierucki, Zbigniew Kalarus, Grzegorz Opolski
Journal: Circulation (2015)

Background and aim. A significant bias of national AMI registries have been described recently. Therefore, to assess a comprehensive picture of AMI in Poland, we performed a study on nationwide data of all Polish AMI patients in 2009-2012 to assess incidence, quality of care, and cardiovascular events up to 3 years following AMI. Methods. The database of the only, public, obligatory, health insurer in Poland (NHF)together with the data from Ministry of the Interior, and Central Statistical Office were used (AMI-PL nationwide registry). The AMI cases were selected based on primary diagnosis coded in ICD-10 as I21 or I22. For years 2009-2012 all hospitalisations (N=311,813) in a given year and death records were analysed. Additionally, for 2009, data on hospitalisations, procedures, and deaths in a 3-year follow-up were obtained. Results. The age-standardized incidence of AMI in Poland in 2009 was 196 cases per 100,000 population (176 per 100,000 were hospitalized) with decreasing trend over time (80-90 thousands AMI patients each year per 38 mln of population). The incidence was 2.5 times higher in men than in women. Proportion of STEMI declined over time from 55% to 47% in 2012. The percentage of patients treated with invasive strategy raised from 72% to 81%. Decrease of in-hospital case fatality was observed, from 9.1% to 8.0% in 2012. Age-standardized fatality was essentially equal in women and men. Data for index hospitalization in 2009 and cardiovascular events up to 3 years following discharge are presented in the table. Total costs of index AMI hospitalizations for NHF insurer in 2009 were 203 mln EUR, and during 3 years following discharge additionally 162 mln EUR. Conclusions. In Poland standards of care and early outcomes in AMI are similar to Western countries. However high incidence of AMI in Polish population, approximately 35 to 50% higher when compared to reported in Denmark or England, indicates a need for intensifying primary prevention programmes.
MYD88 Triggered SYK Activation Promotes BCR Cross-Talk, and Identifies SYK As a Novel Therapeutic Target of Mutated MYD88 Signaling
Authors: Manit Munshi, Jiaji Chen, Xia Liu, Lian Xu, Nickolas Tsakmaklis, Maria Demos, Amanda Kofides, Maria Luisa Guerrera, Gloria G Chan, Christopher Patterson, Kirsten Meid, Joshua Gustine, Jorge J. Castillo, Zachary R Hunter, Jinhua Wang, Sara J Buhrlage, Nathanael S. Gray, Steven P Treon, Guang Yang
Journal: Blood (2018)
Prevalence and Risk Factors of Food Sensitization in Atopic Dermatitis Patients at Songklanagarind Hospital
Authors: Yada Treepaiboon, Pasuree Sangsupawanich, Wipa Jessadapakorn, Vanlaya Koosakulchai, Araya Yuenyongviwat
Journal: Journal of Allergy and Clinical Immunology (2019)
Cancer Outcomes in DCIS Patients Without Locoregional Treatment
Authors: Marc D Ryser, Donald L Weaver, Fengmin Zhao, Mathias Worni, Lars J Grimm, Roman Gulati, Ruth Etzioni, Terry Hyslop, Sandra J Lee, E Shelley Hwang
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract Background The vast majority of women diagnosed with ductal carcinoma in situ (DCIS) undergo treatment. Therefore, the risks of invasive progression and competing death in the absence of locoregional therapy are uncertain. Methods We performed survival analyses of patient-level data from DCIS patients who did not receive definitive surgery or radiation therapy as recorded in the US National Cancer Institute’s Surveillance, Epidemiology, and End Results program (1992–2014). Kaplan-Meier curves were used to estimate the net risk of subsequent ipsilateral invasive cancer. The cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and death were estimated using competing risk methods. Results A total of 1286 DCIS patients who did not undergo locoregional therapy were identified. Median age at diagnosis was 60 years (inter-quartile range = 51–74 years), with median follow-up of 5.5 years (inter-quartile range = 2.3–10.6 years). Among patients with tumor grade I/II (n = 547), the 10-year net risk of ipsilateral invasive breast cancer was 12.2% (95% confidence interval [CI] = 8.6% to 17.1%) compared with 17.6% (95% CI = 12.1% to 25.2%) among patients with tumor grade III (n = 244) and 10.1% (95% CI = 7.4% to 13.8%) among patients with unknown grade (n = 495). Among all patients, the 10-year cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and all-cause mortality were 10.5% (95% CI = 8.5% to 12.4%), 3.9% (95% CI = 2.6% to 5.2%), and 24.1% (95% CI = 21.2% to 26.9%), respectively. Conclusion Despite limited data, our findings suggest that DCIS patients without locoregional treatment have a limited risk of invasive progression. Although the cohort is not representative of the general population of patients diagnosed with DCIS, the findings suggest that there may be overtreatment, especially among older patients and patients with elevated comorbidities.
A phase Ib dose escalation study of vantictumab (VAN) in combination with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients with previously untreated stage IV pancreatic cancer.
Authors: S. Lindsey Davis, Dana Backlund Cardin, Safi Shahda, Heinz-Josef Lenz, Efrat Dotan, Bert O'Neil, Ann M. Kapoun, Robert J. Stagg, Jordan Berlin, Wells A. Messersmith, Steven J. Cohen
Journal: Journal of Clinical Oncology (2019)

249 Background: Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. A phase Ib study of VAN in combination with Nab-P and G was performed in patients with untreated stage IV pancreatic adenocarcinoma. Methods: Patients received VAN at escalating doses (3-7 mg/kg) in combination with standard dosing of Nab-P and G according to a 3+3 design. Due to fragility fractures occurring in this and other related clinical trials, dosing on an every 2 week schedule in cohorts 1 and 2 was transitioned to every 4 week dosing for cohorts 3 through 5. In these later cohorts, a minimum of six patients were treated at each dose level and additional criteria for maximum tolerated dose (MTD) integrating bone safety parameters were added. The bone safety plan was also revised for these cohorts. Sequential dosing of VAN followed by Nab-P and G was explored in cohort 5. Results: Thirty-one patients (52% male, 48% female) were enrolled and treated in 5 dosing cohorts. Median age was 66. Most common study-treatment related adverse events were nausea (68%) and fatigue (52%). One dose limiting toxicity (DLT) event occurred in the study population—grade 3 dehydration in 1 of 9 patients in cohort 4 (5 mg/kg q4w). Fragility fractures attributed to VAN occurred in two patients in cohort 2 (7 mg/kg q2w). Once the dosing schedule was revised to every 4 weeks, the maximum administered VAN dose was 5 mg/kg. No fragility fractures attributed to VAN occurred in these cohorts; pathologic fracture not attributed to VAN was documented in 2 patients. The study was terminated due to lack of an acceptable therapeutic index. Partial response was documented in 13 patients (42%) and stable disease in 11 (36%). Conclusions: The MTD of VAN plus Nab-P and G was not determined, but the maximum administered dose (MAD) of VAN, 7 mg/kg every 2 weeks, was considered unsafe related to bone toxicity, a known effect of WNT inhibition. After the study was revised, the MAD was 5 mg/kg every 4 weeks, with no protocol-specified bone toxicity observed (n = 16). Clinical trial information: NCT02005315.
Impact of Pretransplant HTLV-1 Seropositivity on Hematopoietic Stem Cell Transplantation for the Diseases Other Than ATLL- an Analysis on Behalf of JSHCT Complication Working Group-
Authors: Nobuaki Nakano, Hideki Nakasone, Shigeo Fuji, Akihito Shinohara, Ritsuro Suzuki, Atae Utsunomiya, Tetsuya Eto, Yasushi Sawayama, Sawako Nakachi, Naoyuki Uchida, Takahiro Fukuda, Junya Kanda, Yoshiko Atsuta, Masao Ogata
Journal: Blood (2018)
TCT-812 Ten years follow-up results of left main percutaneous coronary intervention in elderly patients
Authors: Ignacio Sanchez-Perez, Jesus Piqueras-Flores, Fernando Lozano, María Thiscal López Lluva, Natalia Pinilla-Echeverri, Ramón Maseda Uriza, Alfonso Jurado-Román
Journal: Journal of the American College of Cardiology (2017)
Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in <i>DICER1</i>
Authors: Douglas R. Stewart, Ana F. Best, Gretchen M. Williams, Laura A. Harney, Ann G. Carr, Anne K. Harris, Christian P. Kratz, Louis P. Dehner, Yoav H. Messinger, Philip S. Rosenberg, D. Ashley Hill, Kris Ann P. Schultz
Journal: Journal of Clinical Oncology (2019)

Purpose DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks (“cumulative incidence”) of neoplasms (benign and malignant) and standardized incidence ratios for malignant tumors in individuals with DICER1 pathogenic variation. Patients and Methods We combined data from three large cohorts of patients who carry germline pathogenic variation in DICER1. To reduce ascertainment bias, we distinguished probands from nonprobands. Neoplasm diagnoses were confirmed by review of pathology reports and/or central review of surgical pathology materials. Standardized cancer incidence ratios were determined relative to the SEER program, which does not capture all DICER1-associated neoplasms. For all malignancies and benign tumors (“neoplasms,” excluding type Ir pleuropulmonary blastoma and thyroid nodules), we used the Kaplan-Meier method and nonparametric cumulative incidence curves to estimate neoplasm-free survival. Results We calculated the age at first neoplasm diagnosis (systematically ascertained cancers plus DICER1-associated neoplasms pleuropulmonary blastoma, cystic nephroma, and nasal chondromesenchymal hamartoma) in 102 female and male nonproband DICER1 carriers. By age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of nonproband DICER1 carriers had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of nonprobands had developed a neoplasm (females, 26.5%; males, 10.2%). After age 10 years, female risk was elevated compared with male risk. Standardized cancer incidence ratio analysis of 102 nonproband DICER1 carriers, which represented 3,344 person-years of observation, showed significant cancer excesses overall, particularly of gynecologic and thyroid cancers. Conclusion This work provides the first quantitative analysis of site-specific neoplasm risk and excess malignancy risk in 102 systematically characterized nonproband DICER1 carriers. Our findings inform DICER1 syndrome phenotype, natural history, and genetic counseling.
Abstract 14891: Using Immersive Virtual Reality to Observe Differences in Lay Provider Response to an Unannounced Simulated Sudden Cardiac Arrest Based on Demographics
Authors: Marion Leary, Alfredo Almodovar, David G Buckler, Audrey L Blewer, Benjamin S Abella
Journal: Circulation (2017)

Introduction: Sudden cardiac arrest (SCA) is a time-sensitive disease requiring quick action by lay bystanders. Studies have shown that bystander response can vary based on demographic characterist...
Abstract 19491: The Risk Factors for Predicting Ventricular Fibrillation in Asymptomatic Patients Are Different From Those in Symptomatic Patients in Brugada Syndrome
Authors: Hiroshi Morita, Atsuyuki Watanabe, Satoshi Kawada, Yoshimasa Morimoto, Masakazu Miyamoto, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito
Journal: Circulation (2017)

Introduction: The incidence of ventricular fibrillation (VF) in asymptomatic patients with Brugada-type ECG is not high but it cannot be negligible. Risk markers for predicting VF are usually based on results of analysis in symptomatic patients and they have not been determined for asymptomatic patients. Symptomatic patients should have an advanced arrhythmogenetic substrate and risk factors for recurrent VF can be different from risk factors for the first VF episode. Hypothesis: The risk factors for VF in symptomatic high-risk patients will be different from those in asymptomatic patients. Methods: The patients group was consisted of 471 patients with Brugada syndrome and we divided the subjects into two groups; Asymptomatic (n=326) and Symptomatic groups (patients with syncope: n=122 and patients with VF: n=23). We analyzed clinical characteristics (age, gender, family history of sudden death, SCN5A mutation) and ECG markers. ECG markers included PQ, QRS, QT and Tpeak-Tend (Tpe) intervals, ST level, spo...
Essential TNM: a registry tool to reduce gaps in cancer staging information
Authors: Marion Piñeros, D Maxwell Parkin, Kevin Ward, Eric Chokunonga, Morten Ervik, Helen Farrugia, Mary Gospodarowicz, Brian O'Sullivan, Isabelle Soerjomataram, Rajaraman Swaminathan, Ariana Znaor, Freddie Bray, James Brierley
Journal: The Lancet Oncology (2019)
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy
Authors: Peter Hajek, Anna Phillips-Waller, Dunja Przulj, Francesca Pesola, Katie Myers Smith, Natalie Bisal, Jinshuo Li, Steve Parrott, Peter Sasieni, Lynne Dawkins, Louise Ross, Maciej Goniewicz, Qi Wu, Hayden J. McRobbie
Journal: New England Journal of Medicine (2019)

E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments.
Safety and Efficacy of Atezolizumab in Combination with Rituximab Plus CHOP in Previously Untreated Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Primary Analysis of a Phase I/II Study
Authors: Anas Younes, John M Burke, Bruce Cheson, Catherine Diefenbach, Silvia Ferrari, Uwe Hahn, Eliza Hawkes, Cyrus Khan, Izidore S. Lossos, Gerardo Musuraka, Monica Tani, Umberto Vitolo, Sam Yuen, Mikkel Z Oestergaard, Surya Chitra, Michael Wenger, Tina Nielsen, Gila Sellam, Jeff Sharman
Journal: Blood (2018)
Destabilization of AETFC through C/EBPα-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation
Authors: Meng-Meng Zhang, Na Liu, Yuan-Liang Zhang, Bowen Rong, Xiao-Lin Wang, Chun-Hui Xu, Yin-Yin Xie, Shuhong Shen, Jiang Zhu, Stephen D. Nimer, Zhu Chen, Sai-Juan Chen, Robert G. Roeder, Fei Lan, Lan Wang, Qiu-Hua Huang, Xiao-Jian Sun
Journal: Leukemia (2019)
Glycogen Synthase Kinase-3α Promotes Fatty Acid Uptake and Lipotoxic Cardiomyopathy
Authors: Michinari Nakamura, Tong Liu, Seema Husain, Peiyong Zhai, Junco S. Warren, Chiao-Po Hsu, Takahisa Matsuda, Christopher J. Phiel, James E. Cox, Bin Tian, Hong Li, Junichi Sadoshima
Journal: Cell Metabolism (2019)
Mild Hypothermia in Cardiogenic Shock Complicating Myocardial Infarction
Authors: Georg Fuernau, Johannes Beck, Steffen Desch, Ingo Eitel, Christian Jung, Sandra Erbs, Norman Mangner, Philipp Lurz, Karl Fengler, Alexander Jobs, Reinhard Vonthein, Suzanne de Waha-Thiele, Marcus Sandri, Gerhard Schuler, Holger Thiele
Journal: Circulation (2018)

Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction.Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate.No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m2; P=0.50; median difference, -0.025 W/m2; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55).In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction.URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.