tbuckley/cabot-search huggingface dataset:
Abstract 11659: Noninvasive Assessment of Left Ventricular Diastolic Function in Hypertension by Novel One-Beat Real-Time Three-Dimensional Speckle Tracking Echocardiography With High Volume Rates
Authors: Masanori Kawasaki, Michael R Zile, Ryuhei Tanaka, Shingo Minatoguchi, Takatomo Watanabe, Koji Ono, Maki Saeki, Maki Nagaya, Noriaki Sato, Shunichiro Warita, Shintaro Tanihata, Masazumi Arai, Toshiyuki Noda, Sachiro Watanabe, Hidemaro Sato, Helene Houle, Shinya Minatoguchi
Journal: Circulation (2014)

Background:  Left ventricular (LV) pressure overload causes LV hypertrophy (LVH), which leads to reduced relaxation and compliance and may result in heat failure with preserved ejection fraction (HFpEF). LV strain rate (SR) during isovolumic relaxation (SR-IVR) by 2-dimensional speckle tracking echocardiography (2D-STE) was reported as a good index of the time constant of pressure decline. However, heart mechanics in multiple dimensions seem to be best represented by 3D-STE. Thus, we developed novel 3D-STE with high volume rates to measure global myocardial SR and examine diastolic function.   Methods:  HTN patients with preserved EF>50% (age 69±7) were divided into 5 groups (A: normal geometry, n=25; B: concentric remodeling, n=20; C: concentric LVH, n=24; D: eccentric LVH, n=21; and E: HFpEF, n=17). We measured SR-IVR as an index of LV relaxation and strain by novel 3D-STE in HTN patients and control (n=60, age 69±9). Pulmonary capillary wedge pressure (PCWP) was estimated as 10.7 - 12.4 x log [left atrial (LA) active emptying function / minimum LA volume], as we previously reported. LV diastolic stress (DS) was calculated as radius x PCWP / thickness. We estimated LV stiffness as DS / radial strain.   Results:  LV mass increased in HTN with LVH and HFpEF compared with controls. LV radial SR-IVR in HTN decreased even in normal geometry compared with controls (controls: -0.95±0.56; A: -0.66±0.44*; B: -0.65±0.32*; C: -0.52±0.34*; D: -0.47±0.35*; and E: -0.34±0.23S-1*, *p   Conclusions:  LV relaxation assessed by global SR-IVR was impaired even in normal geometry despite no reduction in LVEF and no elevation of E/e’, and further reduced in HFpEF. LV stiffness and PCWP were increased in HTN with LVH and those were further increased in HFpEF. LV diastolic function can be noninvasively evaluated using novel one-beat 3D-STE with high volume rates (66±5 vps).
Efficient modification of <i>CCR5</i> in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template
Authors: Blythe D. Sather, Guillermo S. Romano Ibarra, Karen Sommer, Gabrielle Curinga, Malika Hale, Iram F. Khan, Swati Singh, Yumei Song, Kamila Gwiazda, Jaya Sahni, Jordan Jarjour, Alexander Astrakhan, Thor A. Wagner, Andrew M. Scharenberg, David J. Rawlings
Journal: Science Translational Medicine (2015)

Therapeutic coding sequences can be targeted to the CCR5 locus of primary human T cells with high efficiency by using megaTAL nuclease and an AAV donor template.
Abstract 13544: Differences in the Population of Muscular Dystrophy Patients With Respect to Ventricular Tachycardia, Heart Failure and Use of Implantable Cardioverters Defibrillators
Authors: Ann R Punnoose, Jonathan Kaltman, Christopher Spurney
Journal: Circulation (2014)

Introduction: As the treatment of the respiratory and skeletal muscle complications associated with muscular dystrophy (MD) has improved, males with MD are living longer and are more likely to develop cardiac disease. The impact of sudden cardiac death related to ventricular arrhythmias and heart failure and the indications for ICD implantation are not well established. Hypothesis: We evaluated the hypothesis that VT is a significant contributor to mortality in hospitalized patients with MD and this is improved with ICD implantation. Methods: We searched the Pediatric Health Information System (PHIS) database for males with discharge diagnosis codes of MD and different combinations of heart failure (HF), ventricular arrhythmias (VT) and ICD placement between 2003 and 2013. Results: There were significant differences in the mean length of stay and mean age between MD patients with HF and/or VT versus all hospitalized male MD patients (p&lt;0.05). Out of a total of 76 deaths in MD patients, 32% (n=24) were related to HF. Of those, 30% (n=7) also had a diagnosis of VT. Isolated VT without HF was only 1% (n=42) of admissions and the cause of death in 2 patients. However, ICD’s were implanted in 12% (n=5) of MD/VT patients compared to 5% (n=5) of MD/HF/VT patients. No deaths were seen in patients with ICD’s. Only 1 ICD was placed prior to 2009. Conclusions: VT was a frequent cause of death in hospitalized male patients with MD and HF, however isolated VT without HF was not. No deaths were found in the small number of patients with ICD’s. Further prospective studies are needed to validate the importance of ICD use in MD patients
MAM Domain Containing Glycosylphosphatidylinositol Anchor 2 is a Novel Tumor Suppressor Cooperating With DNA Methyltransferase 1 Associated Protein 1 in Gastric Cancer and is Associated With Disease Outcome
Authors: K. Wang, Q. Liang, X. Li, H. Tsoi, J. Zhang, H. Wang, M. Go, P. Chiu, E. Ng, J. Sung, J. Yu
Journal: Clinical Gastroenterology and Hepatology (2015)
Prediction of Progression of Smouldering into Therapy Requiring Multiple Myeloma By Easily Accessible Clinical Factors [in 527 Patients]
Authors: Roman Hajek, Viera Sandecka, Anja Seckinger, Ivan Spicka, Vlastimil Scudla, Evzen Gregora, Jakub Radocha, Lucie Brozova, Jiri Jarkovsky, Lucie Rihova, Aneta Mikulasova, David Starostka, Lenka Walterova, Dagmar Adamova, Petr Kessler, Martin Brejcha, Ivan Vonke, Jarmila Obernauerova, Kamila Valentova, Zdenek Adam, Jiri Minarik, Jan Straub, Jaromir Gumulec, Anthony D. Ho, Jens Hillengass, Hartmut Goldschmidt, Vladimir Maisnar, Dirk Hose
Journal: Blood (2014)
Clinical Applications of Bronchology.
Journal: Annals of Internal Medicine (1961)

This book is written primarily for the general practitioner and those in other specialties who would desire to understand the use of the bronchoscope and the reports based thereon as well as modern radiologic chest diagnosis. But it is of great value to the otolaryngologist. It involves subtler observations than those usually made in bronchoscopic examinations. It implements a new specialty—bronchology. Here is presented a newer, modified anatomical classification of the bronchi and associated lung structures than that of the London International Nomenclature. This description leads to greater accuracy and facility in localizing any pathology found. The anatomic description is clear and concise. The basic physiology and biochemistry of respiration is well covered. It is closely related to the simple as well as the more complicated clinical problems. For example, the basic rationale of the use of saline and sodium bicarbonate solutions as inhalants is made very clear, and the
Anti-EGFR targeted monoclonal antibody isotype influences anti-tumor immunity in head and neck cancer patients
Authors: Sumita Trivedi, Raghvendra M Srivastava, Fernando Concha-Benavente, Tatiana M Garcia-Bates, Jing Li, Robert L Ferris
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts EGFR is frequently overexpressed on several cancers, and two targeted antibodies are FDA approved but differ by isotype. Cetuximab (IgG1 isotype) has been shown to be effective at both inhibiting downstream signaling of EGFR and activating anti-tumor, cellular immune mechanisms.
Abstract 255: CT Imaging of Pediatric Heart Deformation During Chest Compressions
Authors: George F Glass, Richard Kent, Matthew Maltese, Dale Bass, Mark Sochor
Journal: Circulation (2012)

Background: Adequate chest compression (CC) depth is associated with increased survival to hospital discharge, yet specific data guiding CC depth targets in children are lacking. Current guidelines for pediatric CCs are based on extrapolation from adults, animal models, and expert consensus. Given this lack of data, investigation into the biomechanical effect of CCs on the pediatric thorax is warranted. Methods: Three non-injurious CC simulations were performed on a single 7 year-old post-mortem human subject with intended compression depth of 0%, 15%, and 25% of external thoracic depth. A Phillips CPR Force Deflection Sensor replica was positioned at the inter-nipple line of the subject. Force was statically applied to reach the desired compression depth. Non contrast-enhanced CT imaging was obtained for each compression level. External thoracic depths were measured at the inter-nipple level from the most anterior to most posterior skin surface at midline. Internal depths were measured from the posterior sternal border to the anterior border of the corresponding vertebral body. Left ventricular volumes were calculated using three-dimensional multiplanar reconstruction and a 4-level modified Simpson method. Results: Intended 25% compression resulted in change of 25mm in external chest depth and 20mm of internal depth (a 16.4% and 29.6% change, respectively). Total left ventricular volume (inclusive of myocardium and ventricular cavity) was reduced by 8.8% (62.7cm 3 to 57.2cm 3 ). Right ventricular volumes were not measured due to difficulty in right heart border visualization, but subjective deformation of the right heart was greater than left. Conclusions: This is the first reported CT visualization of thoracic contents during compression of the pediatric chest. Our results indicate a proportionally greater decrease in internal thoracic depth than external depth for a given compression depth. Previous studies extrapolating the desired compression depth from CT-data have assumed internal compression directly proportional to external compression depth. These studies may overestimate the target depth necessary to achieve a given amount of internal thoracic compression.
Capecitabine in combination with docetaxel in the management of metastatic breast cancer
Authors: C. G. Gennatas, V. Michalaki, S. Gennatas, J. Psychogios
Journal: Journal of Clinical Oncology (2008)

12016 Background: We aimed to determine the efficacy of a non-anthracycline-containing regimen, docetaxel/capecitabine as a first -line therapy for patients with advanced breast cancer. Methods: Fifty-two patients have been enrolled in the study. Median age was 56 years (range 35–75). ECOG PS was of 0–2 (PS 0: 14 patients, PS 1: 18 patients, PS 2: 20 patients), All patients were Her-2 neu negative. Patients received Docetaxel 75 mg/m2 on day 1, with routine pre and post-medication with steroids, and Capecitabine 950 mg/m2 p.o. bid on days 1–14, every 3 weeks until disease progression or unacceptable toxicity. Results: Of the 52 evaluable patients, 2 patients (3.8%) achieved complete response, 25 patients (48%) achieved partial response (PR) and 10 patients (19.2%) attained stable disease (SD). The median duration of response was 14 weeks and the median duration of SD was 22 weeks. The median time to progression (TTP) was 30 weeks. The median overall survival was 94 weeks. All patients were evaluable for toxicity. Toxicity was mainly hematological with G3 or 4 neutropenia in 9 patients (17%). Febrile neutropenia was not encountered. There was not significant GI toxicity. Conclusions: The clinical utility of capecitabine in the management of breast cancer is supported by its convenient oral dosing schedule and favorable safety profile, as well as its excellent clinical activity. The combination with docetaxel shows promising efficacy as first- line therapy in advanced breast cancer with an acceptable toxicity profile. No significant financial relationships to disclose.
A multi-factorial analysis of response to warfarin in a UK prospective cohort
Authors: Stephane Bourgeois, Andrea Jorgensen, Eunice J. Zhang, Anita Hanson, Matthew S. Gillman, Suzannah Bumpstead, Cheng Hock Toh, Paula Williamson, Ann K. Daly, Farhad Kamali, Panos Deloukas, Munir Pirmohamed
Journal: Genome Medicine (2016)

Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin.A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R.VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role.Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both VKORC1 and CYP2C9*3 are important determinants of the initial INR response to warfarin. Other novel variants, which did not reach genome-wide significance, were identified for the different outcome measures, but need replication.
Patterns of palliative surgical interventions in patients with metastatic colorectal cancer
Authors: A. Easson, A. Walsh, S. Chadi, M. Ounjian, T. Kandasamy, G. Rodin, C. Zimmerman
Journal: Journal of Clinical Oncology (2008)

15127 Background: Therapeutic invasive procedures including surgery are often required for symptom palliation but frequency and timing are poorly described near the end of life. This study assesses the patterns of invasive palliative intervention (IPI) in patients with advanced colorectal cancer referred to palliative care (PC). Methods: The medical records of 276 patients with metastatic colorectal cancer (141 colon, 136 rectal) referred to PC between Jan 2001 and Dec 2004, were reviewed for IPIs. IPIs were divided into: open, endoscopic, interventional radiology (IR), and bedside. The interval between PC referral and IPI was calculated, and examined with one-way (intervention method) analysis of variance. Results: Mean time to death from PC referral was 4±6 mo, and from first IPI 9±12 mo. Of the 276 patients reviewed, 137 patients (49.6%) received at least one IPI (mean=2.1±1.9, range 1–10). Of the 315 IPIs performed, 25% were for bowel obstruction, 24% ascites drainage, 10% urinary obstruction, 9% biliary obstruction, 9% pleural effusion drainage, 9% bowel obstruction prevention, 7% abscess drainage, 6% for palliative tumor/metastases resection, and 1% for pain management. Sixty percent of IPIs occurred prior to PC referral. Open procedures occurred on average 7.9 mo before referral, endoscopic 1.6 mo before referral, IR procedures 1.6 mo after referral, and bedside procedures 1.8 mo after referral. Endoscopic, IR, and bedside interventions were clustered near the end of life, separately from open interventions. Conclusions: IPIs are commonly performed in patients with metastatic colorectal cancer, and often before PC referral. The pattern and invasiveness change with PC referral and towards the end of life. Understanding these patterns may allow for clearer identification of patients along their disease trajectory, and provides a foundation for further research to explore the indications and timing of IPIs to optimize care for patients near the end of life. No significant financial relationships to disclose.
Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon
Authors: Markus Mueller, Michael E. Gschwandtner, Jutta Gamper, Georgiana-Aura Giurgea, Silvia Charwat-Resl, Hans P. Kiener, Josef S. Smolen, Thomas Perkmann, Renate Koppensteiner, Oliver Schlager
Journal: Circulation (2016)

In incipient Raynaud phenomenon, nailfold capillaroscopy and autoantibody tests are obtained to screen for an emerging connective tissue disease. Whether the presence of abnormal nailfold capillaries and autoantibodies are related to mortality in patients with incipient Raynaud phenomenon is not known.In 2958 consecutive patients (78% women, median age 45 years) with incipient Raynaud phenomenon without previously known connective tissue disease, nailfold capillaroscopy and laboratory tests for antinuclear antibodies (ANA) and ANA subsets were obtained at initial presentation. During a median follow-up period of 9.3 years, 227 women (9.9% of female patients) and 129 men (20% of male patients) with Raynaud phenomenon died. In comparison with a demographically matched standard population, survival was poorer in patients with Raynaud phenomenon (log-rank test P<0.0001). In patients with Raynaud phenomenon, mortality was higher in men than in women (P<0.0001, Cox proportional hazards model). In women, the presence of abnormal nailfold capillaries, ANA, and anti-Scl-70 antibodies were related to an increase in all-cause mortality. The conjoint presence of abnormal nailfold capillaries and autoantibodies was associated with the highest mortality rates. In men, abnormal nailfold capillaries, and ANA and ANA subsets, as well, were not related to survival. In both sexes, patients' age and serum creatinine were associated with mortality.In Raynaud phenomenon, male sex, age, and serum creatinine are related to mortality. Abnormal nailfold capillaries and autoantibodies are associated with an increase in all-cause mortality in female patients, but not in male patients with Raynaud phenomenon.
Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: Systematic review and indirect comparison meta-analysis of randomized trials
Authors: E. Lim, G. Harris, A. Patel, I. Adachi, L. Edmonds, F. Song
Journal: Journal of Clinical Oncology (2008)

7546 Background: A large number of trials evaluated the efficacy of postoperative chemotherapy after resection for lung cancer. A smaller number evaluated preoperative chemotherapy for potentially resectable lung cancer, but no direct comparison has yet been published comparing the two approaches. Methods: We conducted a systematic review of randomized trials, extracted time-to-event data using Parmar methods (when not reported), used random effects meta-analysis to evaluate overall and disease survival treatment effects and performed indirect comparison using surgery (without chemotherapy) as the common comparison. Results: 112 publications were identified and 56 potentially relevant trials retrieved for more detailed evaluation. In total, 17 were excluded for repeat data and data from 8 studies could not be extracted for meta-analysis, leaving 31 randomized trials involving over 10,000 participants, with 21 trials administering postoperative and 10 trials administering preoperative chemotherapy. For overall survival, the hazard ratio in postoperative chemotherapy trials was 0.80 (0.73 to 0.87; P<0.001) and for preoperative chemotherapy trials was 0.81 (0.68 to 0.97; P=0.024). Using indirect comparison meta-analysis, the relative hazards of postoperative compared to preoperative treatment was 0.99 (0.81 to 1.21; P=0.900). For disease-free survival, the hazard ratio in postoperative chemotherapy trials was 0.76 (0.67 to 0.87; P<0.001) and for preoperative chemotherapy trials was 0.79 (0.63 to 1.00; P=0.050). Using indirect comparison meta-analysis, the relative hazards of postoperative compared to preoperative treatment was 0.96 (0.74 to 1.26; P=0.770). Conclusions: In patients with resectable lung cancer, the timing of administration of chemotherapy (postoperative versus preoperative) yielded similar results for overall and disease-free survival. No significant financial relationships to disclose.
Characteristics of women who develop both colorectal and endometrial cancer
Authors: P. T. Soliman, B. M. Slomovitz, C. C. Sun, D. M. Gershenson, K. H. Lu
Journal: Journal of Clinical Oncology (2004)

5052 Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome that confers a 60–80% lifetime risk of developing colorectal cancer and a 40–60% lifetime risk of developing endometrial cancer. Large population-based studies have shown that women with colon cancer who do not meet Amsterdam criteria for HNPCC but have a first-degree relative with colon cancer also have a significant increased relative risk (RR 9.4) for developing endometrial cancer. The purpose of this study was to evaluate the characteristics of patients with both colorectal and endometrial cancer in order to identify subgroups who may benefit from early cancer screening. Methods: Between 1985–2002, 77 patients with both colorectal and endometrial cancer were identified. Clinical and pathologic information was obtained from medical records. Patients were divided into three groups: AC+ (met Amsterdam criteria for HNPCC), AC-R (family history of at least one HNPCC-related cancer), and AC- (no family history of HNPCC-related cancers). Results: Eight patients were assigned to the AC+ group, 27 patients to the AC-R group, and 41 patients to the AC- group. The mean age at diagnosis of the first cancer for each group was 44, 58, and 58 years. The median interval of time between the two cancer diagnoses was 4.7, 3.0, and 8.1 years for each group. Sixteen percent of patients (12/77) developed both colorectal and endometrial cancer within one year. Forty-eight percent of patients (37/77) had colorectal cancer and 36% (28/77) had endometrial cancer as their initial cancer diagnosis. Conclusions: In this cohort of women with both colorectal and endometrial cancer, only 10% met Amsterdam criteria for HNPCC. Thirty-five percent did not meet Amsterdam criteria but had at least one relative with an HNPCC-related cancer. In this group (AC-R), 63% of patients developed their second cancer within 5 years of their initial cancer diagnosis. On-going studies are being performed to identify whether molecular markers in combination with family history can be used to identify women at risk for developing second cancers. No significant financial relationships to disclose.