tbuckley/cabot-search huggingface dataset:
Right ventricular reverse remodeling after balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension
Authors: Shigefumi Fukui, Takeshi Ogo, Yoshiaki Morita, Akihiro Tsuji, Emi Tateishi, Kumi Ozaki, Yoshihiro Sanda, Tetsuya Fukuda, Satoshi Yasuda, Hisao Ogawa, Norifumi Nakanishi
Journal: European Respiratory Journal (2014)

Background: Balloon pulmonary angioplasty (BPA) has been reported to restore hemodynamics and functional capacity, with an acceptable risk, in patients with chronic thromboembolic pulmonary hypertension (CTEPH), who are not candidates for pulmonary endarterectomy. However, right ventricular (RV) function, an important predictor in CTEPH, remains to be examined. We aimed to examine the impact of BPA on RV remodeling and dysfunction relative to hemodynamic improvements in patients with inoperable CTEPH. Methods: We studied 20 consecutive patients with inoperable CTEPH who underwent a series of BPA (3.2±0.9 procedures) with cardiovascular magnetic resonance (CMR) before and at a mean of 4.0±0.8 months after BPA. Results: BPA led to significant amelioration of the mean pulmonary arterial pressure (39±8 to 27±9 mmHg), cardiac index (CI), and pulmonary vascular resistance (PVR, 889±365 to 490±201 dyne sec/cm5) (all P<0.05), without death or major complications including severe reperfusion pulmonary edema. Moreover, BPA significantly improved right-sided heart failure symptoms and signs, and exercise capacity (all P<0.001). CMR revealed a marked improvement in RV end-diastolic volume index (RVEDVI, 130±52 to 92±24 ml/m2) and end-systolic volume index (RVESVI), with concomitant improvements in RV ejection fraction, RV mass, and interventricular septal bowing after BPA (all P<0.001). Changes in RV volumes (RVEDVI and RVESVI) strongly correlated with those in CI and PVR (R=0.62-0.74, all P<0.01). Conclusions: BPA induced RV reverse remodeling and improved systolic dysfunction safely by ameliorating hemodynamics in patients with inoperable CTEPH.
Clinical benefit of INCB7839, a potent and selective ADAM inhibitor, in combination with trastuzumab in patients with metastatic HER2+ breast cancer.
Authors: R. C. Newton, E. C. Bradley, R. S. Levy, D. Doval, S. Bondarde, T. P. Sahoo, D. Lokanatha, P. K. Julka, R. Nagarkar, S. M. Friedman
Journal: Journal of Clinical Oncology (2010)

3025 Background: In HER2+ breast cancer, the HER2 protein is cleaved by the metalloproteinase ADAM10 resulting in release of the HER2 extracellular domain (ECD) into the serum while the truncated HER2 receptor (p95) remains in the membrane as a constitutively active kinase. Studies have shown that the presence of p95 is associated with poor clinical outcome, including resistance to trastuzumab-based therapy. Therefore, inhibition of HER2 cleavage by the ADAM inhibitor INCB7839 may enhance the clinical efficacy of trastuzumab in HER2+ breast cancer patients. Methods: This study was initiated as a single arm modified dose escalation open label trial of INCB7839 + trastuzumab in women with HER2+ metastatic breast cancer, naïve to chemotherapy. Three doses of INCB7839 were studied (100 mg, 200 mg, 300 mg BID) with an expansion arm at the 300 mg dose. Trastuzumab was administered on a Q3 week schedule. Pharmacokinetics, plasma HER2 ECD levels and p95 expression in tumor tissue were assessed in addition to clinical response and safety. The study has been further expanded to evaluate the addition of docetaxel to INCB7839 + trastuzumab. Results: To date, 51 HER2+ patients have been enrolled in the study. INCB7839 administration results in a dose-dependent reduction in plasma HER2 ECD. With the INCB7839 + trastuzumab combination, the currentoverall response rate is 50% (13/26 evaluable patients) with a higher response rate (9/14 or 64%) observed in patients with INCB7839 plasma concentrations above the IC50 for HER2 cleavage. Importantly, INCB7839 increases the clinical response rate and time to progression in p95+ patients, with equivalent responses observed in the p95+ and p95− patients. Thirteen patients have initiated addition of docetaxel and the combination of the three agents has been generally safe and well tolerated. Conclusions: Biomarker and clinical data from this trial demonstrate that INCB7839 can markedly reduce HER2 cleavage in patients with HER2+ breast cancer, and suggest that INCB7839 can improve the response to trastuzumab and render a subpopulation of HER2+ patients, who are p95+ and are predicted to be trastuzumab resistant, responsive to trastuzumab therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Incyte Incyte
Molecular detection of HER2 mRNA-positive cells in the peripheral blood of patients with operable breast cancer
Authors: D. Mavroudis, M. Perraki, G. Kallergi, A. Pallis, P. Kanellou, L. Kalmanti, N. Xenidis, V. Bozionelou, E. Manousakis, V. Georgoulias
Journal: Journal of Clinical Oncology (2005)

668 Background: To evaluate whether the detection of peripheral blood (PB) HER2 mRNA+ positive cells in patients with breast cancer could be another marker of the micrometastatic disease. Methods: The sensitivity and specificity of HER2 mRNA detection by nested RT-PCR were investigated using MCF-7 and ARH-77 cells as well as blood from healthy women and patients with colorectal, early and metastatic breast cancer. PB from 216 patients with operable breast cancer, obtained before initiation of any adjuvant therapy, was tested for the presence of HER2 mRNA+ positive cells. Results: In dilution experiments the nested RT-PCR assay for HER2 mRNA was capable of detecting up to 105 MCF-7 tumor cells in 105 normal peripheral blood mononuclear cells; no signal was detected with the HER2- ARH-77 cells. No HER2 mRNA+ cells could be detected in the peripheral blood of 31 healthy women, as well as the peripheral blood and the bone marrow of 20 patients with colorectal cancer. Detection rates for HER2 mRNA+ cells in the bone marrow/blood of patients with early or metastatic breast cancer were 36.4%/23.8% and 35.5%/18%, respectively. Double immunostaining with a pan-keratin and a HER2 monoclonal antibody and confocal microscopy analysis revealed co-expression on PB cells in 5 (38.5%) of 13 patients. In addition, FISH analysis of PB tumor cells from 5 patients demonstrated HER2 gene amplification in all patients. Finally, aneusomy cells could be detected by LSI 1, CEP 8, CEP 11 and CEP 11 with chromosomal gain or loss in 2 of the patients. Conclusions: The results demonstrate that occult tumor cells expressing HER2 mRNA could be detected in the peripheral blood of patients with operable breast cancer; these cells are not always CK+ indicating that HER2 mRNA detection may represent another marker of the micrometastatic disease. No significant financial relationships to disclose.
A violence clinic: three years' experience
Authors: J R Lion, D J Madden, R L Christopher
Journal: American Journal of Psychiatry (1976)

The authors describe a clinical facility established for the neuropsychiatric treatment of individuals with a variety of psychopathological disorders where the common management problem is one of aggressive behavior. The authors present case vignettes to illustrate the clinic's consultation with mental health workers about the management of violent patients, countertransference problems, ward problems, the role of organic factors, medication, and prediction of violence. They urge that the subject of violence be included in the psychiatrist's training.
US Choosing Wisely campaign has had only modest success, study finds
Authors: Michael McCarthy
Journal: BMJ (2015)

A programme to reduce the use of clinical services that are of little benefit to patients has had only modest success so far, a US study has found. Researchers looked at changes in the frequency of seven services identified in the Choosing Wisely programme as being of minimal benefit.1

Choosing Wisely2 is a physician led initiative to reduce overuse and waste in the US healthcare system. It was launched in 2009 by the National Physicians Alliance and was funded by the American Board of Internal Medicine. Since then, medical and surgical specialty societies have produced more than 70 Choosing Wisely lists with around 400 recommendations aimed at reducing the use of low value services. As much as 30% of US healthcare spending is estimated to go on services that provide little or no clinical benefit to patients. …
Kidney Function and Cerebral Blood Flow
Authors: Sanaz Sedaghat, Meike W. Vernooij, Elizabeth Loehrer, Francesco U.S. Mattace-Raso, Albert Hofman, Aad van der Lugt, Oscar H. Franco, Abbas Dehghan, M. Arfan Ikram
Journal: Journal of the American Society of Nephrology (2015)

CKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population-based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase-contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m(2) and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2-6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, -0.31; 95% confidence interval, -0.58 to -0.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.
Adalimumab drug survival in patients with psoriasis, Crohn's disease, and rheumatoid arthritis: Relevant differences using the same treatment
Authors: Juul M.P.A. van den Reek, Philippe A.R.R. Pijls, Marcia Tummers, Piet C.L.M. van Riel, Wietske Kievit, Frank Hoentjen, Elke M.G.J. de Jong
Journal: Journal of the American Academy of Dermatology (2015)
Complexities in assessing the effectiveness of inactivated influenza vaccines
Authors: H Kelly, I Steffens
Journal: Eurosurveillance (2013)

Preview this article: Complexities in assessing the effectiveness of inactivated influenza vaccines, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/18/7/art20403-en-1.gif
Natural killer cells expanded on membrane-bound IL15 or IL21 activate different miRNA transcriptional profiles with functional consequences
Authors: Anitha Somanchi, Srinivas Somanchi, Dean Lee
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts MicroRNA (miRNA) are non-coding regulatory RNA that are key posttranscriptional regulatory machinery of cells. miRNA play important role in several physiological functions during embryonic development, differentiation, cancer progression as well as hematopoiesis, and regulation of
OP449, a Novel SET Antagonist, Is Cytotoxic To Leukemia Cells and Enhances Efficacy Of Tyrosine Kinase Inhibitors In Drug-Resistant Myeloid Leukemias
Authors: Anupriya Agarwal, Ryan J. Meckenzie, Raffaella Pippa, Christopher A. Eide, Jessica Oddo, Jeffrey W. Tyner, Rosalie Sears, Michael P. Vitek, Maria D. Odero, Dale J. Christensen, Brian J. Druker
Journal: Blood (2013)
Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633).
Authors: P. R. Warde, M. D. Mason, M. R. Sydes, M. K. Gospodarowicz, G. P. Swanson, P. Kirkbride, E. Kostashuk, J. Hetherington, K. Ding, W. Parulekar
Journal: Journal of Clinical Oncology (2010)

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA &gt; 40 μ g/l (119) or T2 PSA &gt; 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.
Abstract 15725: Heart-Type Fatty Acid Binding Protein for Risk Stratification in Patients With Pulmonary Embolism: A Meta-Analysis
Authors: Anurag Bajaj, Parul Rathor, Ankur Sethi, Ajay Shetty, Besher Kabak
Journal: Circulation (2014)

Background:  The role of heart- type fatty acid binding protein(H-FABP) in risk stratification of acute pulmonary embolism is still undefined. We performed a meta-analysis of studies in patients with acute pulmonary embolism to assess the prognostic value of elevated H-FABP levels for short-term adverse outcomes.   Methods:  Two independent reviewers systematically searched “Pubmed”, “ Embase” and “Cochrane” database using the mesh word “heart type fatty acid binding protein” and “pulmonary embolism” through June 2014 . Additionally conference abstracts, review articles and bibliographies were searched. Prospective studies were included if those were done on hemodynamically stable pulmonary embolism patients and they had used H-FABP assay. Primary end point was 30 day adverse outcomes. Adverse outcomes were defined as composite of death, endotracheal intubation, pressors infusion cardiopulmonary resuscitation, or recurrent pulmonary embolism. A random-effects model was used to pool study results and I 2  testing was used to test for heterogeneity.   Results:  Six studies including 1460 patients were included in the analysis. Overall, 66 out of 366 patients with elevated H-FABP levels had adverse 30 day outcomes(19.6%) as compared to 47 out of 1094 in normal H-FABP levels(4.3%). Elevated H-FABP levels were significantly associated with increased adverse outcomes events (odds ratio [OR], 8.37; 95% CI, 3.08 to 22.68, I 2 = 75%). Only 2 out of 6 studies reported separate mortality data. 30 day mortality was significantly increased in elevated H-FABP levels group compared to normal H-FABP levels group(odds ratio[OR], 37.81; 95% CI, 2.21 to 646.77, I 2 =82%). There was significant heterogeneity among studies for both outcomes.   Conclusions:  Elevated H-FABP levels identify patients with hemodynamically stable pulmonary embolism at high risk for short term adverse outcomes and death.
Lung Cancer Prevention
Authors: Christopher Slatore, Marianna Sockrider
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Lung cancer is a common form of cancer.There are things you can do to lower your risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help in quitting, including use of medicines to help with nicotine dependence. discuss with your healthcare provider,what you are taking or doing to decrease your risk for lung cancer
Evaluation Of a Novel 3 Factor Prognostic Score (PS-3) For Patients With Advanced Hodgkin Lymphoma (HL) Treated On US Intergroup E2496
Authors: Catherine S. Diefenbach, Hailun Li, Fangxin Hong, Leo I. Gordon, Richard I Fisher, Nancy L. Bartlett, Michael Crump, Randy D. Gascoyne, Henry Wagner, Patrick J Stiff, Bruce D. Cheson, Douglas A. Stewart, Brad S. Kahl, Jonathan W. Friedberg, Kristie A. Blum, Thomas M. Habermann, Joseph Tuscano, Richard T. Hoppe, Sandra J. Horning, Ranjana H. Advani
Journal: Blood (2013)
Abstract 18782: Regional Action Potential Heterogeneity in the Murine Pitx2c Deficient Left Atrium
Authors: Andrew P Holmes, Ting Yu, Fahima Syeda, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
Journal: Circulation (2014)

Introduction and hypothesis: Genetic abnormalities close to the Pitx2 gene correlate more strongly with atrial fibrillation (AF) than any other genetic modification. It is known that Pitx2c mRNA is expressed in the adult left atrium (LA), but its relevance for the electrical integrity of cardiomyocytes throughout the atria remains unresolved. We therefore compared regional action potential (AP) morphology in PITX2c +/- and wild type (WT) littermate mice. Methods: Transmembrane (T) and optical (O) APs were recorded from superfused intact, isolated LA paced at 100ms. TAPs were recorded from three distinct regions on the LA epicardium: 1) the junction with the interatrial septum (S), 2) the medial muscular dome (M) and 3) the lateral wall (L). OAPs were recorded using a custom murine atrial optical mapping system using the Hamamatsu ORCA flash 4 and Di-4-Anepps. Results: OAPs were shorter in Pitx2c deficient LA (AP duration (APD70); WT 13±2ms, n=4 LA vs Pitx2c +/- 9±1ms, n=4 LA, all data as mean±SEM, p&lt;0.05). Simultaneous recordings of OAPs from multiple LA regions showed an AP gradient with longer OAPs at the septum than at the lateral wall, in both genotypes. In WT LA, TAPs were longer and of greater amplitude at the septum than in the other two regions (APD90; S 26±1ms, M 19±1mV and L 19±1ms, APA; S 81±1mV, M 76±2mV and L 76±2mV, n=6 LA, p&lt;0.05). In Pitx2c +/- , TAPs were shorter than WT in all three regions tested and exhibited the same regional patterning (S 20±1ms, M 15±1ms and L 16±1, n=7 LA, p&lt;0.05). The regional AP amplitude gradient was not apparent, or at least shifted more towards the lateral wall, in PITX2c +/- atria (APA; S 77±2mV, M 76±3mV and L 74±2mV, n=7 LA, ns). Conclusion: Partial depletion in Pitx2c mRNA expression causes a uniform APD shortening throughout the LA and loss of regional changes in AP amplitude. Identification of the targets downstream of Pitx2 accounting for these changes will help to better understand the mechanisms conveying AF due to reduced Pitx2 function.
Prognosis of HPV-positive squamous cell carcinoma of tonsil-expressing high level of p16 and low level of EGFR.
Authors: H. Won, D. Sun, S. Chun, E. Jeon, M. Chang, C. Jung, B. Shim, M. Lee, J. Kang, J. Kim
Journal: Journal of Clinical Oncology (2010)

5546 Background: HPV infection has been known to be one of the important risk factors for carcinogenesis of head and neck squamous cell carcinoma (HNSCC). The over-expression of epidermal growth factor receptor (EGFR) correlates with a poor prognosis in HNSCC. We investigated the relationship between HPV status and EGFR expression and the prognostic impact of these markers in tonsil cancer. Methods: Eligibility criteria was the patients diagnosed as SCC of tonsil and received curative radical resection with available tumor tissue samples. In situ hybridization for HPV and immunohistochemistry for p16, EGFR, and p53 were performed. Results: Among 66 tonsil cancer patients, 24 (36.3%) patients showed HPV positivity. There were no statistically significant differences in clinical characteristics including sex, age, smoking history, TNM stage and treatment modalities between HPV-positive and -negative patients. The over-expression and high intensity of p16 had significant correlation with HPV positivity (p=0.003, 0.017). However, no correlation was found between p53 and HPV infection. There was a trend that the proportion of EGFR over-expression was greater in HPV-negative than in HPV-positive patients (p=0.082), and no or low EGFR intensity was observed in the patients showing p16 over-expression (p=0.015). Among the HPV-positive patients, the frequency of EGFR over-expression was significantly higher in ex- or current smokers (p=0.005). There was meaningful difference of three years disease-free survival between never smokers showing both over-expression of p16 and low expression of EGFR and the others (90.0% and 73.5%, respectively, p=0.082). On univariate analysis, the significant clinicopathologic factors affecting disease-free survival were smoking history and EGFR intensity (p=0.020 and 0.017, respectively). Conclusions: Taken together, p16 was a good surrogate marker for HPV infection. The expression of EGFR was inversely correlated with HPV positivity, but HPV-positive patients with smoking history showed EGFR over-expression. In the HPV-positive tonsil cancers, high p16 and low EGFR expression should be considered as favorable prognostic markers. No significant financial relationships to disclose.
Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism
Authors: Emma Guttman-Yassky, Benjamin Ungar, Shinji Noda, Maria Suprun, Anjali Shroff, Riana Dutt, Saakshi Khattri, Michelle Min, Yasaman Mansouri, Xiuzhong Zheng, Yeriel D. Estrada, Giselle K. Singer, Mayte Suarez-Farinas, James G. Krueger, Mark G. Lebwohl
Journal: Journal of Allergy and Clinical Immunology (2015)