tbuckley/cabot-search huggingface dataset:
Abstract 2022: Feasibility of Dynamic Substrate Mapping: Insights from an Animal Infarction Model and Comparison with Bipolar Voltage Mapping in Patients
Authors: Tilko Reents, Johann Cristoph Geller, Jörg Mittag, Ralf Schneider, Isabell Deisenhofer, Bernhard Zrenner, H.U. Klein, Sven Reek
Journal: Circulation (2007)

Background: Different substrate based ablation strategies have been developed for ablation of ventricular tachycardia (VT) after myocardial infarction (MI). We investigated the “Dynamic Substrate Mapping (DSM)”, a tool integrated into the noncontact mapping (NCM) system. Methods: An electrophysiologic study (EPS) was performed 96 ± 10 days after experimental anteroseptal MI in 19 female sheep. Scar was defined by NCM during sinus rhythm. The area of scar was determined using the DSM tool with a cut-off of 50 %, 40%, 30% and 20% of the largest deflection of the unipolar electrogram. The scar was determined by either magnetic resonance imaging (MRI, n=9) or pathology (n=10). Areas determined by MRI or pathology and by DSM were compared. In 11 patients referred for ablation of VT simultaneous electroanatomical mapping and NCM was performed. The location of the low voltage area in the bipolar voltage map and the DSM were compared. Results: For all 19 animals a low voltage area was delineated with a cut off of 50% of the largest unipolar deflection. The low voltage area determined with DSM was greater then the scar determined by pathology or MRI (29,32 ± 28,83 cm 2 vs 8,52 ± 3,48 cm 2 . p &lt; 0,05). Infarct scar determined by MRI or pathology was always located within the low voltage area determined by DSM. There was no correlation between the sizes of the low voltage area determined by pathology/MRI and DSM. Delineation of a low voltage area was not possible in all animals with a cut off of 40%, 30%, and 20%. In 11 patients, locations of the low voltage areas determined by bipolar voltage maps and DSM corresponded well. The area defined by DSM was larger then the area defined by bipolar voltage map. there was a good correlation between the size of the low voltage areas determined by bipolar voltage map and DSM for cut off values of 50% and 40% (r 2 = 0,66 and r 2 = 0,61; p&lt;0,05). With a cut off of 30% and 20% of the largest unipolar deflection a low voltage area could not be defined for all patients. Conclusion: Sizes of abnormal myocardium defined by DSM do not correlate with scar areas determined by pathology or MRI. Areas of abnormal myocardium delineated by DSM are greater then areas defined with bipolar voltage map. A detailed description of the scar border zone with DSM during sinus rhythm alone is not feasible.
A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma
Authors: Marjorie G. Zauderer, Anne S. Tsao, Tao Dao, Katherine Panageas, W. Victoria Lai, Andreas Rimner, Valerie W. Rusch, Prasad S. Adusumilli, Michelle S. Ginsberg, Daniel Gomez, David Rice, Reza Mehran, David A. Scheinberg, Lee M. Krug
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Determine the 1-year progression-free survival (PFS) rate among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy versus those receiving control adjuvants. Experimental Design: This double-blind, controlled, two center phase II trial randomized MPM patients after surgery and another treatment modality to galinpepimut-S with GM-CSF and Montanide or GM-CSF and Montanide alone. An improvement in 1-year PFS from 50% to 70% was the predefined efficacy threshold, and 78 patients total were planned. The study was not powered for comparison between the two arms. Results: Forty-one patients were randomized. Treatment-related adverse events were mild, self-limited, and not clinically significant. On the basis of a stringent prespecified futility analysis (futility = ≥10 of 20 patients on one arm experiencing progression &amp;lt; 1 year), the control arm closed early. The treatment arm was subsequently closed because of the resultant unblinding. The PFS rate at 1 year from beginning study treatment was 33% and 45% in the control and vaccine arms, respectively. Median PFS was 7.4 months versus 10.1 months and median OS was 18.3 months versus 22.8 months in the control and vaccine arms, respectively. Conclusions: The favorable safety profile was confirmed. PFS and OS were greater in those who received vaccine, but the trial was neither designed nor powered for comparison between the arms. On the basis of these promising results, the investigators are planning a larger randomized trial with greater statistical power to define the optimal use and benefit of galinpepimut-S in the treatment of MPM. Clin Cancer Res; 23(24); 7483–9. ©2017 AACR.
Minimal Residual Disease Assessment in Lymphoma: Methods and Applications
Authors: Alex F. Herrera, Philippe Armand
Journal: Journal of Clinical Oncology (2017)

Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction–based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.
Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe
Authors: Miranda M. Fidler, Raoul C. Reulen, David L. Winter, Rodrigue S. Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Chloe J. Bright, Julianne Byrne, Elizabeth A. M. Feijen, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Momcilo Jankovic, Peter Kaatsch, Melanie Kaiser, Rahel Kuonen, Helena Linge, Milena Maule, Franco Merletti, Hilde Øfstaas, Cecile M. Ronckers, Roderick Skinner, Jop Teepen, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Zsuzsanna Jakab, Riccardo Haupt, Päivi Lähteenmäki, Lorna Zadravec Zaletel, Claudia E. Kuehni, Jeanette F. Winther, Florent de Vathaire, Leontien C. Kremer, Lars Hjorth, Michael M. Hawkins
Journal: JNCI Journal of the National Cancer Institute (2017)

We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors. This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided. Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk. For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.
Anti-VEGFR, PDGFR, and CSF1R tyrosine kinase inhibitor CM082 (X-82) in combination with everolimus for treatment of metastatic renal cell carcinoma: a phase 1 clinical trial
Authors: Xieqiao Yan, Xinan Sheng, Bixia Tang, Zhihong Chi, Chuanliang Cui, Lu Si, Li Li Mao, Bin Lian, Siming Li, Li Zhou, Xuan Wang, Xue Bai, Yan Kong, Jie Dai, Jun Guo
Journal: The Lancet Oncology (2017)
Acute Abdominal Pain in a Man in His 50s
Authors: Qiang Tang, Shuai-Tao Shi, Tao Qin
Journal: JAMA Surgery (2017)

A man in his 50s with a history of smoking and chronic hypertension is admitted with sudden-onset upper abdominal pain, nausea, vomiting, moderate epigastric tenderness with rebound and guarding but no history of previous surgery or trauma, and hemodynamic instability. What is your diagnosis?
Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope
Authors: Gonzalo Baron-Esquivias, Carlos A. Morillo, Angel Moya-Mitjans, Jesus Martinez-Alday, Ricardo Ruiz-Granell, Javier Lacunza-Ruiz, Roberto Garcia-Civera, Encarnacion Gutierrez-Carretero, Rafael Romero-Garrido
Journal: Journal of the American College of Cardiology (2017)

Pacing in vasovagal syncope remains controversial.The authors evaluated dual-chamber pacing with closed loop stimulation (DDD-CLS) in patients with cardioinhibitory vasovagal syncope.This randomized, double-blind, controlled study included Canadian and Spanish patients age ≥40 years, with high burden syncope (≥5 episodes, ≥2 episodes in the past year), and a cardioinhibitory head-up tilt test (bradycardia <40 beats/min for 10 s or asystole >3 s). Patients were randomized to either DDD-CLS pacing for 12 months followed by sham DDI mode pacing at 30 pulses/min for 12 months (group A), or sham DDI mode for 12 months followed by DDD-CLS pacing for 12 months (group B). Patients in both arms crossed-over after 12 months of follow-up or when a maximum of 3 syncopal episodes occurred within 1 month.A total of 46 patients completed the protocol; 22 were men (47.8%), and mean age was 56.30 ± 10.63 years. The mean number of previous syncopal episodes was 12 (range 9 to 20). The proportion of patients with ≥50% reduction in the number of syncopal episodes was 72% (95% confidence interval [CI]: 47% to 90%) with DDD-CLS compared with 28% (95% CI: 9.7% to 53.5%) with sham DDI mode (p = 0.017). A total of 4 patients (8.7%) had events during DDD-CLS and 21 (45.7%) during sham DDI (hazard ratio: 6.7; 95% CI: 2.3 to 19.8). Kaplan-Meier curve was significantly different between groups in time to first syncope: 29.2 months (95% CI: 15.3 to 29.2 months) versus 9.3 months (95% CI: 6.21 months, NA; p < 0.016); odds ratio: 0.11 (95% CI: 0.03 to 0.37; p < 0.0001).DDD-CLS pacing significantly reduced syncope burden and time to first recurrence by 7-fold, prolonging time to first syncope recurrence in patients age ≥40 years with head-up tilt test-induced vasovagal syncope compared with sham pacing. (Closed Loop Stimulation for Neuromediated Syncope [SPAIN Study]; NCT01621464).
Association of Multiorgan Computed Tomographic Phenomap With Adverse Cardiovascular Health Outcomes
Authors: Ravi V. Shah, Ashish S. Yeri, Venkatesh L. Murthy, Joe M. Massaro, Ralph D’Agostino, Jane E. Freedman, Michelle T. Long, Caroline S. Fox, Saumya Das, Emelia J. Benjamin, Ramachandran S. Vasan, Christopher J. O’Donnell, Udo Hoffmann
Journal: JAMA Cardiology (2017)

Increased ability to quantify anatomical phenotypes across multiple organs provides the opportunity to assess their cumulative ability to identify individuals at greatest susceptibility for adverse outcomes.To apply unsupervised machine learning to define the distribution and prognostic importance of computed tomography-based multiorgan phenotypes associated with adverse health outcomes.This asymptomatic community-based cohort study included 2924 Framingham Heart Study participants between July 2002 and April 2005 undergoing computed tomographic imaging of the chest and abdomen. Participants are from the offspring and third-generation cohorts.Eleven computed tomography-based measures of valvular/vascular calcification, adiposity, and muscle attenuation.All-cause mortality and cardiovascular disease (myocardial infarction, stroke, or cardiovascular death).The median age of the participants was 50 years (interquartile range, 43-60 years), and 1422 (48.6%) were men. Principal component analysis identified 3 major anatomic axes: (1) global calcification (defined by aortic, thoracic, coronary, and valvular calcification); (2) adiposity (defined by pericardial, visceral, hepatic, and intrathoracic fat); and (3) muscle attenuation that explained 65.7% of the population variation. Principal components showed different evolution with age (continuous increase in global calcification, decrease in muscle attenuation, and U-shaped association with adiposity) but similar patterns in men and women. Using unsupervised clustering approaches in the offspring cohort (n = 1150), we identified a cohort (n = 232; 20.2%) with an unfavorable multiorgan phenotype across all 3 anatomic axes as compared with a favorable multiorgan phenotype. Membership in the unfavorable phenotypic cluster was associated with a greater prevalence of cardiovascular disease risk factors and with increased all-cause mortality (hazard ratio, 2.61; 95% CI, 1.74-3.92; P < .001), independent of coronary artery calcium score, visceral adipose tissue, and 10-year global cardiovascular disease Framingham risk, and it provided improvement in metrics of discrimination and reclassification.This proof-of-concept analysis demonstrates that unsupervised machine learning, in an asymptomatic community cohort, identifies an unfavorable multiorgan phenotype associated with adverse health outcomes, especially in elderly American adults. Future investigations in larger populations are required not only to validate the present results, but also to harness clinical, biochemical, imaging, and genetic markers to increase our understanding of healthy cardiovascular aging.
Preterm birth prevention—Time to PROGRESS beyond progesterone
Authors: Jane E. Norman, Phillip Bennett
Journal: PLoS Medicine (2017)

In this week's PLOS Medicine, Crowther and colleagues publish the results of the PROGRESS Study, which examined the effect of maternal vaginal progesterone on the risk of respiratory distress syndrome in the baby [1].Women at high risk of preterm birth because of a previous spontaneous preterm birth were recruited to this study, which involved self-administering 100 mg progesterone or a placebo vaginally from 20 to 34 weeks of pregnancy.No differences were found in the rate of the primary outcome (incidence of respiratory distress syndrome and severity of respiratory disease) between the progesterone and the placebo groups (incidence of respiratory distress syndrome in 42/402 [10.5%] and 41/388 [10.6%], respectively [RR 0.98, 95% CI 0.64-1.49]),nor were there differences in any of the other secondary outcomes.The study, a double-masked randomised placebo-controlled trial, was well conducted.About 40% of women who were approached agreed to participate.The primary outcome was available for all participating women, and around 65% of women were still taking study treatment by 34 weeks gestation.Rates of preterm birth were 36% and 17% before 37 and 34 weeks, respectively; hence, the recruitment strategy effectively identified a group at high risk.Although the study was terminated earlier than planned (after recruitment of 787 women rather than the 984 initially intended), and the incidence of the primary outcome was lower than anticipated in the placebo group (10.6% rather than 15%), it is unlikely that these issues have materially affected the conclusions of the study.Although vaginal progesterone is not licensed for prevention of preterm birth, it has been widely adopted by clinicians around the world for this purpose.Progesterone for preterm birth prevention in high-risk women is endorsed by expert guideline groups [2], including the National Institute for Clinical Excellence (UK) [3] and the FIGO Working Group on Best Practice in .The PROGRESS Study is the third large randomized trial (the others being our own OPPTIMUM study [5] and the study of O'Brien et al. [6]) to show a lack of efficacy of vaginal progesterone.Specifically, the PROGRESS trial showed no difference between the 2 groups in gestation of delivery, preterm birth before 37 weeks, or preterm birth before 34 weeks.We believe it is now time for a comprehensive review of the data on progesterone to identify risks and benefits in women at risk of preterm birth for different reasons.Ostensibly, there is biological plausibility behind the administration of progesterone for prevention of preterm birth.Progesterone can inhibit contractions of the myometrium in vitro [7], and antiprogestogens are used as abortifacients.However, progesterone levels are high during pregnancy, far above receptor saturation.There is no evidence that women delivering preterm have lower progesterone levels and administration of progesterone vaginally
Response to: ’A response to Singh. “Lesinurad combination therapy with allopurinol in gout: do CLEAR studies make the treatment of gout clearer?”' by Valiyil and Schechter
Authors: Jasvinder A Singh
Journal: Annals of the Rheumatic Diseases (2017)

I thank Valiyil and Schechter for their letter1 to the editorial related to clinical studies of lesinurad.2 The letter correctly states that the 200 mg lesinurad dose is the only (initial and maximum) dose that should be prescribed to patients, always in combination with a xanthine oxidase inhibitor. The letter provides an important clarification regarding the dose of lesinurad that was approved by the regulatory agencies. Based on higher toxicity, the sponsor did not pursue regulatory approval (Food and Drug Administration (FDA) and European Medicines Agency (EMEA)) for …
A Large‐scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma
Authors: Ping Luo, Peiyuan Yin, Rui Hua, Yexiong Tan, Zaifang Li, Gaokun Qiu, Zhenyu Yin, Xingwang Xie, Xiaomei Wang, Wenbin Chen, Lina Zhou, Xiaolin Wang, Yanli Li, Hongsong Chen, Ling Gao, Xin Lu, Tangchun Wu, Hongyang Wang, Junqi Niu, Guowang Xu
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. The lack of effective biomarkers for the early detection of HCC results in unsatisfactory curative treatments. Here, metabolite biomarkers were identified and validated for HCC diagnosis. A total of 1,448 subjects, including healthy controls and patients with chronic hepatitis B virus infection, liver cirrhosis, and HCC, were recruited from multiple centers in China. Liquid chromatography–mass spectrometry–based metabolomics methods were used to characterize the subjects' serum metabolic profiles and to screen and validate the HCC biomarkers. A serum metabolite biomarker panel including phenylalanyl‐tryptophan and glycocholate was defined. This panel had a higher diagnostic performance than did α‐fetoprotein (AFP) in differentiating HCC from a high‐risk population of cirrhosis, such as an area under the receiver‐operating characteristic curve of 0.930, 0.892, and 0.807 for the panel versus 0.657, 0.725, and 0.650 for AFP in the discovery set, test set, and cohort 1 of the validation set, respectively. In the nested case–control study, this panel had high sensitivity (range 80.0%‐70.3%) to detect preclinical HCC, and its combination with AFP provided better risk prediction of preclinical HCC before clinical diagnosis. Besides, this panel showed a larger area under the receiver‐operating characteristic curve than did AFP (0.866 versus 0.682) to distinguish small HCC, and 80.6% of the AFP false‐negative patients with HCC were correctly diagnosed using this panel in the test set, which was corroborated by the validation set. The specificity and biological relevance of the identified biomarkers were further evaluated using sera from another two cancers and HCC tissue specimens, respectively. Conclusion: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of HCC from at‐risk populations. (H epatology 2018;67:662‐675).
Prognostic implication of GATA3 gene mutation on survival in invasive ductal carcinoma of the breast.
Authors: Karthik Kailasam, Mohammad Omaira, Hardik Satish Chhatrala, Marie Ravichandar
Journal: Journal of Clinical Oncology (2017)

e13114 Background: GATA3 encodes a transcription factor, which is involved in activation and suppression of genes involved in cell maturation. GATA3 is necessary in the adult mammary gland to maintain the integrity and function of the luminal epithelium. Methods: METABRIC project funded by cancer research UK, the British Columbia cancer foundation and the Canadian breast cancer foundation mapped 173 gene mutations and amplifications in 2,433 primary breast tumors. Retrospective analysis was done for patients with invasive ductal carcinoma of the breast in the age group 30-60; to study the effect of GATA3 mutation on survival. Median survival was obtained from Kaplan-Meier plot, and mortality between groups was compared by Odds ratio (OR). Results: A total of 1500 patients across all age groups had invasive ductal carcinoma. 650 were within the age group 30-60; of which 234 died due to the disease, 360 were alive and 55 died due to other causes. 398 patients (61.2%) tested positive for estrogen receptor (ER) and 521 patients (80.2%) were negative for HER2 (human epidermal growth factor receptor 2). TP53 (50%) and PIK3CA (36%) mutations were more prevalent. GATA3 mutation was found in 79 patients (12.34%); among which, all 79 patients tested positive for ER (100%) and 74 patients (94.9%) negative for HER2. 10 patients (12.7%) died due to the disease, 62 patients (78.5%) were alive and 7 patients (8.9%) died due to other causes. Hence, patients with GATA3 mutations were more likely to survive (OR 4.66; CI 2.33-9.29 p &lt; 0.0001) than patients without the mutation. The median survival for patients with GATA3 mutation (300 months) was also greater than patients without the mutation (219 months). In addition, patients with GATA3 mutation were more likely to be ER positive and HER2 negative. Conclusions: In the mammary gland, GATA3 is required for luminal epithelial cell differentiation. Loss of GATA3 results in de-differentiation to stem cell phenotype. It is found that GATA3 mutation correlates with a better prognosis compared to more common TP53 and PIK3CA gene mutations.
Pirfenidone photosensitization in patients with idiopathic pulmonary fibrosis: a case series
Authors: C. Droitcourt, H. Adamski, A. Polat, E. Polard, M. Kerjouan, B. Arnouat, M. Le Garrec, E. Oger, A. Dupuy, S. Jouneau
Journal: British Journal of Dermatology (2017)

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