tbuckley/cabot-search huggingface dataset:
Is a negative CTPA good enough to exclude pulmonary embolism
Authors: Rainu Bawa, Stephen Perrio, Vineet Prakash, Paul Murray
Journal: European Respiratory Journal (2014)

Introduction:  National guidelines exist for the investigation of pulmonary embolism (PE). CTPA is the gold standard investigation. Clinical probability should be determined pre-CTPA by using the Wells score and d-dimer testing. Diagnostic yield of CTPA for PE is low (18 -36%). Is a negative CTPA always good enough to safely exclude a PE in everyday clinical practice?  Method:  We conducted a cross-sectional retrospective study on 100 consecutive CTPAs performed within our hospital group looking for PEs from 2013. From these scans, 25 case notes were reviewed (5 +ve PEs, 20 -ve PEs) to correlate request form and findings with recorded Wells score, d-dimer results and possible alternative diagnoses. The opacification of the main PA must be >250 HUs to be considered adequate for scanning and should be achieved in at least 90% of scans.  Results:  Of the 100 CTPAs, 98 were included in the study. 56 scans (57.1%) had adequate opacification (mean 272 HUs, range 76 - 533 HUs). 18 scans confirmed PE (18.4%). 13 (72%) of these had adequate opacification. Of the 80 (81.6%) negative scans only 43 (54%) had adequate opacification. The 20 -ve PE case notes reviewed showed 13 (65%) had a Wells score and d-dimer recorded.  Conclusion:  The review of 20 -ve PE cases revealed that 10 (50%) had inadequate PA opacification. Of these 7 (35%) could be stratified as either high risk (Wells >4, or +ve d-dimer) or having insufficient clinical data and so questioning the need for additional investigation to exclude PE as the -ve CTPA was not conclusive. Our data suggests that a large number of -ve CTPAs are inadequate in excluding PEs in high risk or poorly risk stratified patients and must not be the final investigation when concern for PE remains high.
MicroRNA expression profiles in pancreatic cystic tumors.
Authors: A. E. Frampton, L. Castellano, N. Tsim, N. A. Habib, J. Stebbing, L. R. Jiao
Journal: Journal of Clinical Oncology (2010)

e14579 Background: Short non-coding microRNAs (miRNAs) play a role in post-transcriptional gene regulation and can contribute to cancer development and progression. Expression profiles can distinguish between normal pancreas, chronic pancreatitis and pancreatic adenocarcinoma (PDAC) and may be able to correlate with disease progression from non-invasive precursor lesions to PDAC. We aimed to investigate the global miRNA expression profiles in pancreatic benign-cystic-tumours (BCT) compared with PDAC and carcinoma-ex-IPMN (CEI). Methods: Microarray analysis was conducted on 43 formalin-fixed paraffin-embedded (FFPE) pancreatic tumour surgical resection samples. These included 20 BCT, 9 CEI and 14 PDACs. The total RNA including the miRNA was isolated from the FFPE slides. Samples were analyzed with the Geniom Realtime Analyzer (febit gmbh, Germany) using the Geniom Biochip MPEA Homo sapiens. The probes are specific for all major mature miRNAs and miRNA* sequences in Sanger miRBase (version 13.0). Differential expression analysis was performed. We compared: BCT vs. CEI; BCT vs. PDAC, and CEI vs. PDAC. Certain miRNAs of interest were further investigated using quantitative real-time reverse-transcriptase polymerase chain reaction (RT- PCR). Results: There was a poor correlation in the intensity values between the BCT and PDAC groups. This led us to identify 20 significantly deregulated miRNAs in PDAC when compared to BCT. There were another 54 miRNAs found to be deregulated when we compared BCT to CEI and CEI to PDAC. Benign tumour subgroups were also analysed. Conclusions: There appear to be unique miRNA expression profiles in pancreatic cystic tumours and precursor lesions. In addition, 20 miRNAs have been identified which may be specific to PDAC. We aim to identify miRNAs for use as clinical biomarkers. No significant financial relationships to disclose.
Risk factors in breast-conservation therapy.
Authors: J Borger, H Kemperman, A Hart, H Peterse, J van Dongen, H Bartelink
Journal: Journal of Clinical Oncology (1994)

To identify clinical and pathologic factors associated with an increased risk of local recurrence following breast-conservation therapy (BCT) to assess the safety of this procedure for all subgroups of patients.The study population consisted of 1,026 patients with clinical stage I and II breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute. The BCT regimen consisted of local excision and axillary lymph node dissection (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy.With a median follow-up duration of 66 months, the actuarial breast recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate analysis showed seven factors to be associated with an increased risk of local recurrence; age, residual tumor at reexcision, histologic tumor type, presence of any carcinoma-in-situ component, vascular invasion, microscopic margin involvement, and whole-breast radiation dose. Three factors remained independently significant after proportional hazard regression analysis: age, margin involvement, and the presence of vascular invasion. When the analysis was repeated, but counting only those breast recurrences that occurred before regional or distant failures, only young age and vascular invasion were independent predictive factors. In the third analysis, factors predicting the necessity of local salvage treatment were analyzed. In this analysis, the possible bias in the former analysis caused by censoring actuarial methods was avoided. The results were the same as in the second analysis, showing young age and vascular invasion as the only independent predictive factors. Breast recurrence rates were 6% for patients less than 40 years of age and 8% for patients with tumors showing vascular invasion. In the absence of risk factors, the breast recurrence rate is only 1% at 5 years.Slightly higher recurrence rates were found in patients less than 40 years of age and in patients with tumors showing vascular invasion. The role of margin involvement is uncertain.
Perioperative chemotherapy in operable gastric and lower oesophageal cancer: Final results of a randomised, controlled trial (the MAGIC trial, ISRCTN 93793971)
Authors: D. Cunningham, W. H. Allum, S. P. Stenning, S. Weeden
Journal: Journal of Clinical Oncology (2005)

4001 Background: Epirubicin, Cisplatin and infused 5-FU (ECF) shows significant benefit in advanced oesophagogastric cancer, particularly locally advanced disease. This trial was designed to determine whether this effect translates into a survival advantage in operable disease. Methods: Patients with operable adenocarcinoma of the stomach, oesophagogastric junction or lower oesophagus were randomised to perioperative chemotherapy (CSC arm) or surgery alone (S arm). In the CSC arm, chemotherapy comprised three pre-operative and three post-operative cycles, 3 weeks apart, of E 50mg/m2 IV bolus, C 60mg/m2 infusion and 5-FU 200mg/m2/day continuous infusion. The trial was powered (2α=5%, 1-β=90%) to detect a 15% increase in 5-year survival (∼250 events required), with pre-planned analysis with another European trial of the same design, collectively giving ∼90% power to detect a 10% increase in survival. The latter trial closed early, therefore to increase power to detect a 10% increase from MAGIC alone, the final analysis was deferred until sufficient events had occurred to give at least 70% power (∼320 deaths) to detect a hazard ratio (HR) of 0.75, equivalent to an absolute difference in survival of approximately 10% at 2 and 5 years. Results: Between 1994 and 2002, 503 patients (250 CSC, 253 S) were randomised; 74% gastric, 11% oesophago-gastric junction and 15% lower oesophagus. Initial analysis (ASCO 2003) demonstrated statistically significant differences in favour of CSC with respect to curative resection rate, resected tumour diameter and, for gastric and junctional patients, T stage. As of 12/2004, with median follow-up >3 years and 90% of patients followed to death or >2 years, 319 deaths have occurred, (149 CSC, 170 S). The survival HR is 0.75, 95% CI (0.60, 0.93), p=0.009; 5 year survival rates for CSC and S are 36% (30%, 43%) and 23% (17%, 29%) respectively. Progression-free survival was also significantly prolonged; HR 0.66 (0.53, 0.81), p=0.0001. Conclusions: Perioperative chemotherapy significantly improves resectability, progression-free and overall survival in operable gastric and lower oesophageal cancer. No significant financial relationships to disclose.
Psychosocial Factors and Coronary Calcium in Adults without Clinical Cardiovascular Disease
Authors: Ana V. Diez Roux, Nalini Ranjit, Lynda Powell, Sharon Jackson, Tené T. Lewis, Steven Shea, Colin Wu
Journal: Annals of Internal Medicine (2006)

Psychosocial factors have been linked to coronary events, but the mechanisms underlying these associations have not been established. Evidence is mixed regarding associations of psychosocial factors with subclinical coronary atherosclerosis.To examine associations of 4 psychosocial factors (depressive symptoms, anger, anxiety, and chronic stress) with the presence of subclinical coronary atherosclerosis.Cross-sectional study.The Multiethnic Study of Atherosclerosis, a population-based study of subclinical atherosclerosis.A multiethnic sample of 6789 adults, 45 to 84 years of age, with no history of clinical cardiovascular disease.Coronary calcium was assessed by using chest computed tomography, and psychosocial factors were assessed by using questionnaires with validated scales.There was no evidence that higher levels of the psychosocial measures were associated with greater prevalence of calcification or with greater amounts of calcium among persons with calcium. Age- and risk factor-adjusted relative prevalences of coronary calcification in men for the top fourth category versus the bottom fourth category of anger, anxiety, and depressive symptoms were 0.94 (95% CI, 0.88 to 1.01), 0.97 (CI, 0.90 to 1.04), and 0.97 (CI, 0.90 to 1.05), respectively; these values for women were 1.01 (CI, 0.90 to 1.15), 0.93 (CI, 0.83 to 1.05), and 0.92 (CI, 0.82 to 1.04), respectively. Relative prevalences for the top versus the bottom category of chronic stress burden were 1.02 (CI, 0.94 to 1.11) for men and 0.88 (CI, 0.79 to 0.99) for women.Current measures of psychosocial factors may be a poor proxy for cumulative exposure during development of atherosclerosis.Depressive symptoms, anger, anxiety, and chronic stress burden were not associated with coronary calcification in a multiethnic sample of asymptomatic adults.
Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS-wildtype metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).
Authors: Volker Heinemann, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Juergen Lerchenmueller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Joerg Hielscher, Michael Scholz, Sebastian Mueller, Britta Schaefer, Dominik Paul Modest, Andreas Jung, Sebastian Stintzing
Journal: Journal of Clinical Oncology (2013)

LBA3506 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Abstract 5153: Platelet Activation and Inflammatory Response in Patients With Non-dipper Hypertension
Authors: Mehmet Kaya, Mikail Yarlioglues, Ozgur Gunebakmaz, Ertugrul Gunturk, Tugrul Inanc, Ali Dogan, Nihat Kalay, Ramazan Topsakal
Journal: Circulation (2009)

Objective: We aimed to determine whether MPV and hs-CRP levels are elevated in non-dipper patients compared to dippers and healthy controls. In addition, we tried to find out if MPV and CRP are related to each other or not in non-dipper hypertensives. Method: The total 126 patients study group included 86 patients with hypertension and 40 healthy subjects (16 male, mean age; 51±4) as control. Ambulatory blood pressure monitoring was performed for all patients. Hypertensive patients were divided into two groups; 46 dipper patients (18 male, mean age; 50±9) and 40 non-dipper patients (17 male, mean age; 53±11). Clinical baseline characteristics were similar between groups. We measured mean platelet volume in a blood sample collected in EDTA tubes and high-sensitive CRP was measured by using BN2 model nefelometer. Results: Non-dipper patients demonstrated higher levels of MPV compared to dippers and normotensives (9.72±0.52 vs 9.38±0.33 and 8.92±0.42, p&lt;0.05, respectively). High-sensitive CRP levels were also significantly higher in non-dippers compared to dippers and normotensives (4.9±1.7 vs 3.8±1.5 and 2.7±0.8, p&lt;0.05, respectively). There was significant positive correlation between MPV and CRP levels (p=0.002, r=0.482) in non-dipper hypertensives. Conclusion: Our results suggest that patients with non-dipping tend to have increased platelet activation and inflammatory response. Increased platelet activation and inflammatory response could contribute to increase the atherosclerotic risk in non-dipper patients compared to dippers.
Abstract 5960: Implementation of Noninvasive Subharmonic Pressure Estimation on a Commercial Ultrasound Scanner
Authors: Lauren M Leodore, Corina Leung, Laurent Pelissier, Flemming Forsberg
Journal: Circulation (2008)

This project aims to monitor and quantify intra-cardiac pressures via contrast-enhanced subharmonic imaging. We have proposed subharmonic aided pressure estimation (SHAPE; U.S. Patent 6,302,845) utilizing microbubble-based contrast agent signals for the noninvasive estimation of hydrostatic blood pressures in the heart cavities and in this study implemented real-time SHAPE on a commercial US scanner. An experimental pulse-echo system for SHAPE was constructed based on two single element transducers assembled confocally at a 60° angle to each other. A transducer with a bandwidth of 38% and a center frequency of 2.2 MHz (Staveley, East Hartford, CT) was used as the transmitter and a second transducer with a bandwidth of 86% and a center frequency of 3.6 MHz (Etalon Inc., Lebanon, IN) was the receiver. Changes in first, second, and subharmonic amplitudes of 6 different US contrast agents were measured in vitro at hydrostatic pressures from 0 –186 mmHg, acoustic pressures from 0.35– 0.60 MPa and frequencies of 2.5– 6.6 MHz. The optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Sonix RP scanner (Ultrasonix Medical Corp, Richmond, Canada). The real-time implementation of SHAPE was tested in vitro. Over the pressure range studied the 1st and 2nd harmonic amplitudes reduced ~2 dB for all US contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 10 –14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r 2 &gt;0.98, p &lt; 0.001). The optimal sensitivity for SHAPE was achieved at a transmit frequency of 2.5 MHz (i.e., receiving at 1.25 MHz) at a 0.35 MPa acoustic pressure using Sonazoid (GE Healthcare, Oslo, Norway) which declined ~14.4 dB in vitro. A Sonix RP scanner was modified to implement SHAPE on a phased array transducer PA4 –2 with a frequency range from 1.5– 4.5 MHz. A pulse inversion technique was used and the subharmonic signals are displayed in real-time and can also be stored for off-line analysis. SHAPE offers the possibility of allowing pressure gradients in the heart to be obtained noninvasively. Future studies will include in vivo pressure measurements. Supported by AHA grant no 06554414 and NIH HL081892. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
A Novel Mechanism of Nuclear Factor κB Activation through the Binding between Inhibitor of Nuclear Factor-κBα and the Processed NH2-terminal Region of Mig-6
Authors: Toshiyuki Tsunoda, Junichi Inokuchi, Iwai Baba, Koji Okumura, Seiji Naito, Takehiko Sasazuki, Senji Shirasawa
Journal: Cancer Research (2002)

Mitogene-inducible gene-6 (Mig-6), an adaptor molecule containing the Cdc42/Rac interaction and binding (CRIB) domain, is rapidly induced by mitogenic and stressful stimuli, and sustained mig-6 expression is observed in chronic pathological conditions. The function of this molecule has remained elusive. We find that mig-6 is constitutively expressed in many human cancer cell lines, and Mig-6 is cleaved into the NH(2)-terminal region containing the CRIB domain and the remainder of the COOH-terminal region by limited proteolytic processing. We report here that full-length Mig-6, but not CRIB domain-deleted Mig-6 (DeltaMig-6) or uncleavable mutant of Mig-6 (Mig-6-S38A), induces transcriptional activation of nuclear factor of kappaB (NFkappaB), which is inhibited by inhibitor of kappaBalpha (IkappaBalpha), and that the processed NH(2)-terminal region of Mig-6 but not the full length is bound with IkappaBalpha through its NFkappaB binding region. These findings suggest that the processed CRIB domain of Mig-6 will compete with NFkappaB for IkappaBalpha and result in NFkappaB activation. This novel NFkappaB activation pathway provides new insights regarding tumorigenesis, and the specific inhibition of the cleavage of Mig-6 may be a target for clinical treatment.
Phase III efficacy and safety trial of a new leuprolide acetate 3.75 mg depot formulation in prostate cancer patients
Authors: N. D. Shore, C. Savulsky, R. Mis, G. Karlin, M. Marberger, C. Leuratti, A. Kaisary
Journal: Journal of Clinical Oncology (2009)

e16152 Background: Androgen suppression is the standard palliative treatment for metastatic, localized or locally advanced prostate cancer. This phase III, open-label, international multicenter clinical study was conducted to investigate the efficacy and safety profile of a new formulation of leuprolide acetate (Lutrate 3.75mg Depot) in suppressing testosterone levels in prostate cancer patients. Methods: 160 patients with prostate cancer who could benefit from androgen deprivation therapy received single intramuscular injections of Lutrate 3.75 mg Depot every 28 days for a total of six doses. Plasma testosterone was determined at specific times throughout the study. The primary endpoint was the proportion of successful patients over the total number of evaluable patients. Patients’ success was defined as testosterone suppression (&lt;0.5 ng/ml) at day 28 and continuance of castration until day 168, with no missing data at the monthly assessments. An exact two-sided binomial test (5% significance level) with two-sided 95% confidence interval (CI) estimated with exact method was performed to test the null hypothesis of 86% successful patients versus the alternative hypothesis of 94% . Results: The proportion of successful patients over the total number of evaluable patients was 96.8% (152/157); the exact binomial test was satisfied (p=0.000094, 90% CI: 92.7–99.0 %). The 78.7% (122/157) of evaluable patients achieved testosterone suppression by day 21. At day 28, 96.8% of the patients achieved castrate levels and 73.1% achieved testosterone levels ≤0.2 ng/ml. At conclusion of the trial, all patients (100%)maintained castration and 92.8% had testosterone levels ≤0.2 ng/ml. The most common treatment-related adverse event were hot flashes (45%), associated with testosterone suppression. Fatigue, hyperhydrosis, night sweats and headache occurred in ≤6.3% of patients. The most frequently reported local adverse reaction was pain at the injection site, experienced by 8.1% of patients. Conclusions: The results of this study demonstrate that Lutrate 3.75 mg Depot is as effective as presently marketed one-month leuprolide acetate formulations in establishing and maintaining testosterone concentration below castration levels in prostate cancer patients. [Table: see text]
Lung Cancer Risk and Demographic Characteristics of Current 20–29 Pack-year Smokers: Implications for Screening
Authors: Paul F. Pinsky, Barnett S. Kramer
Journal: JNCI Journal of the National Cancer Institute (2015)

Based on current recommendations, 30+ pack-years of smoking are required for eligibility for low-dose CT (LDCT) lung cancer screening; former smokers must have quit within 15 years. We investigated whether current smokers with 20 to 29 pack-years have similar lung cancer risks as eligible former smokers and also whether they have a different demographic profile. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was a randomly assigned screening trial of subjects age 55 to 74 years with chest radiographs (CXR) used for lung cancer. Subjects completed a baseline questionnaire containing smoking history questions. Cox proportional hazards models, adjusted for age and sex, were utilized to estimate hazard ratios (HRs) for various smoking history groups. Next, we utilized the National Health Interview Survey (NHIS), which inquired about smoking history and race/ethnicity, to analyze the demographic profiles of various high-risk smoking history categories. All statistical tests were two-sided. The PLCO cohort included 18 114 former and 12 243 current LDCT-eligible smokers, plus 2283 20- to 29-pack-year current smokers. The hazard ratio for 20- to 29-pack-year current smokers compared with eligible (30+ pack-year) former smokers was 1.07 (95% confidence interval [CI] = 0.75 to 1.5). Based on the NHIS, 10 million persons in the United States are currently LDCT eligible; an additional 1.6 million (16%, 95% CI = 13.6% to 19.0%) are 20- to 29-pack-year current smokers. The percentage increase in eligibles if 20- to 29-pack-year current smokers were included was substantially greater for women than men (22.2%, 95% CI = 17.9% to 26.7%; vs 12.2%, 95% CI = 9.3% to 15.3%, P < .001) and for minorities than non-Hispanic whites (30.0%, 95% CI = 24.2% to 36.0%; vs 14.1%, 95% CI = 11.1% to 17.0%, P < .001). The potential benefits and harms of recommending LDCT screening for 20 to 29-pack-year current smokers should be assessed.