tbuckley/cabot-search huggingface dataset:
Prospective Study of Alcohol Consumption and Cancer
Authors: Earl S. Pollack, Abraham M. Y. Nomura, Lance K. Heilbrun, Grant N. Stemmermann, Sylvan B. Green
Journal: New England Journal of Medicine (1984)

The relation between alcohol consumption and the subsequent occurrence of the five most frequent cancers in Japanese men in Hawaii (cancer of the stomach, colon, rectum, lung, and prostate) was analyzed in a prospective study of 8006 subjects. Information on alcohol consumption was obtained through interviews in the mid-1960s, and the cohort has been followed since then. The analysis, which was adjusted for the effects of age and cigarette smoking, revealed a positive association between consumption of alcohol and rectal cancer, accounted for primarily by an increased risk in men whose usual monthly consumption of beer was 500 oz (15 liters) or more (relative risk, 3.05; P<0.01, as compared with those who did not drink beer). A significant positive relation between alcohol consumption and lung-cancer incidence was also found, accounted for primarily by an increased risk among subjects who consumed larger amounts of wine or whiskey, as compared with the risks among nonconsumers of these beverages (relative risk, 2.19, [P = 0.03] and 2.62 [P<0.01], respectively). No significant relation between alcohol consumption and the incidence of the other three cancers was found. (N Engl J Med 1984; 310:617–21.)
S75 A Clinical Model to Estimate the Probability of Pulmonary Nodule Malignancy in a Population of Oncology Follow-up Patients
Authors: A Talwar, LC Pickup, JMY Willaime, M Gooding, T Kadir, NM Rahman, F Gleeson
Journal: Thorax (2015)

<h3>Introduction</h3> The new BTS Pulmonary Nodule Guidelines 2015 recommend the use of composite prediction models to assess the pre-test probability of malignancy in patients presenting with pulmonary nodules (PNs). These models were not developed for use in patients with a history of malignancy within five years of presentation with a PN. In order to assist in the diagnosis of PNs, CT texture analysis has been proposed as a potential biomarker in tumour characterisation.<sup>1</sup> Image texture refers to the statistical analysis of spatial intensity variations of the pixels within an image to produce a CT texture score.<sup>2</sup> <h3>Aims and objectives</h3> To evaluate four existing models for the probability of malignancy in the target population. To create and validate prediction models for probability of malignancy for patients undergoing oncology follow-up for an indeterminate PN. <h3>Methods</h3> Retrospective data on clinical and radiological characteristics were collected from the medical records of 61 patients with a PN (mean diameter 7 mm, SD 4 mm) that had an active or previous history (within 5 years) of primary lung or extra-thoracic malignancy. The gold standard diagnosis of the nodules was established by histology or 2-year stable follow-up. Three multivariable logistic regression models were evaluated using a leave-one-out cross-validation strategy: Model 1: Age, Sex, Smoking status, Emphysema, Nodule diameter. Model 2: Age, Sex, Smoking status, Emphysema, CT Texture score. Model 3: CT Texture score only. The models’ performance, measured using the area under the ROC curve (AUC), were reported and further compared to existing clinical models. <h3>Results</h3> The highest AUC, 0.86, was obtained from Model 3 (texture score only). Utilising clinical parameters (Model 2) did not improve performance. In comparison, AUCs for previously published clinical models were 0.76(Mayo), 0.84(Herder), 0.66(VA) and 0.70(McWilliams) (Figure.1). <h3>Conclusion</h3> This texture feature model is successful at discriminating benign from malignant nodules in a population of patients undergoing oncology follow-up. While not significantly better than the Herder model (which incorporates PET avidity), this model offers improved risk stratification for PNs in the absence of PET in this patient group. <h3>References</h3> 1 RSNA 2014, SSC03-05 2 IEEE International Conference doi: 10.1109/SMC.2013.663
Case 28-2010
Authors: Marc S. Sabatine, Farouc A. Jaffer, Paul N. Staats, James R. Stone
Journal: New England Journal of Medicine (2010)

A 32-year-old woman, 3 weeks post partum, was seen in the emergency department because of intermittent substernal chest pain. The pain had developed suddenly during normal activity, resolved after 20 minutes, and then recurred. Diagnostic procedures were performed.
Variability of Thrombosis among Homozygous Siblings with Resistance to Activated Protein C Due to an Arg-to-Gln Mutation in the Gene for Factor V
Authors: Judith S. Greengard, Sabine Eichinger, John H. Griffin, Kenneth A. Bauer
Journal: New England Journal of Medicine (1994)

The most frequent laboratory abnormality in patients with idiopathic deep-vein thrombosis is resistance to activated protein C1. Depending on the selection criteria, in vitro resistance to activated protein C can be identified in 20 to 50 percent of patients2–6. Protein C, a key element in the regulation of coagulation, circulates in plasma as an inactive precursor. On contact with thrombin bound to the thrombomodulin receptors on vascular endothelial cells, protein C rapidly becomes activated. Activated protein C enzymatically lyses two cofactors of the coagulation cascade, factor VIIIa and factor Va. It is thus a natural anticoagulant that . . .
A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors
Authors: Anthony W. Tolcher, Johanna C. Bendell, Kyriakos P. Papadopoulos, Howard A. Burris, Amita Patnaik, Wayne J. Fairbrother, Harvey Wong, Nageshwar Budha, Walter C. Darbonne, Franklin Peale, Michael Mamounas, Stephanie Royer-Joo, Ron Yu, Chia C. Portera, Jeffrey R. Infante
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To determine the dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetics, and preliminary evidence of antitumor activity of CUDC-427 (formerly GDC-0917), a selective antagonist of inhibitor of apoptosis (IAP) proteins. Experimental Design: Patients with advanced solid malignancies were treated with escalating doses of CUDC-427 orally on a daily 14-day on/7-day off schedule in 21-day cycles using a modified continuous reassessment method design. Blood samples were assayed to determine the pharmacokinetic properties, pharmacodynamic alterations of cellular IAP levels in peripheral blood mononuclear cells (PBMC), and monocyte chemoattractant protein-1 (MCP-1) levels. Results: Forty-two patients received 119 cycles of CUDC-427. Overall, the most common treatment-related toxicities were fatigue, nausea, vomiting, and rash. One DLT (grade 3 fatigue) occurred in a patient at 450 mg dose level during cycle 1, and 5 patients experienced AEs related to CUDC-427 that led to discontinuation and included grade 3 pruritus, and fatigue, and grade 2 drug hypersensitivity, pneumonitis, rash, and QT prolongation. The maximum planned dose of 600 mg orally daily for 2 weeks was reached, which allometrically scaled to exceed the IC90 in preclinical xenograft studies. Significant decreases in cIAP-1 levels in PBMCs were observed in all patients 6 hours after initial dosing. Responses included durable complete responses in one patient with ovarian cancer and one patient with MALT lymphoma. Conclusions: CUDC-427 can be administered safely at doses up to 600 mg daily for 14 days every 3 weeks. The absence of severe toxicities, inhibition of cIAP-1 in PBMC, and antitumor activity warrant further studies. Clin Cancer Res; 22(18); 4567–73. ©2016 AACR.
Failure of Cytarabine in Progressive Multifocal Leukoencephalopathy Associated with Human Immunodeficiency Virus Infection
Authors: Colin D. Hall, Urania Dafni, David Simpson, David Clifford, Patricia E. Wetherill, Bruce Cohen, Justin McArthur, Harry Hollander, Constantin Yainnoutsos, Eugene Major, Linda Millar, Joseph Timpone
Journal: New England Journal of Medicine (1998)

Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine.
Prevalence of Total Coronary Occlusion during the Early Hours of Transmural Myocardial Infarction
Authors: Marcus A. DeWood, Julie Spores, Robert Notske, Lowell T. Mouser, Robert Burroughs, Michael S. Golden, Henry T. Lang
Journal: New England Journal of Medicine (1980)

To define the prevalence of total coronary occlusion in the hours after transmural myocardial infarction, we used coronary arteriography to study the degree of coronary obstruction in 322 patients admitted within 24 hours of infarction. Total coronary occlusion was observed in 110 of 126 patients (87 per cent) who were evaluated within four hours of the onset of symptoms; this proportion decreased significantly, to 37 of 57 (65 per cent), when patients were studied 12 to 24 hours after the onset of symptoms. Among 59 patients with angiographic features of coronary thrombosis, the thrombus was retrieved by Fogarty catheter in 52 (88 per cent) but was absent in seven (12 per cent false positive). Among an additional 20 patients without angiographic features of thrombosis, a thrombus was discovered in five (25 per cent false negative). Thus, total coronary occlusion is frequent during the early hours of transmural infarction and decreases in frequency during the initial 24 hours, suggesting that coronary spasm or thrombus formation with subsequent recanalization or both may be important in the evolution of infarction.
A Comparison of Salmeterol with Albuterol in the Treatment of Mild-to-Moderate Asthma
Authors: David S. Pearlman, Paul Chervinsky, Craig LaForce, James M. Seltzer, D. Loren Southern, James P. Kemp, Robert J. Dockhorn, Jay Grossman, Roger F. Liddle, Steven W. Yancey, David M. Cocchetto, W. James Alexander, Andre van As
Journal: New England Journal of Medicine (1992)

An effective, long-acting bronchodilator could benefit patients with asthma who have symptoms not controlled by antiinflammatory drugs. We compared a new long-acting, inhaled β2-adrenoceptor agonist, salmeterol, with a short-acting β2-agonist, albuterol, in the treatment of mild-to-moderate asthma.
Evaluation of a New Concentrate for the Treatment of Factor IX Deficiency
Authors: Gerald S. Gilchrist, Henry Ekert, Edward Shanbrom, Denman Hammond
Journal: New England Journal of Medicine (1969)

A commercially prepared plasma concentrate was administered in six infusions to four patients with factor IX deficiency. All showed a distinct rise in the factor IX level. On the basis of the preliminary data a dose of 2 factor IX units per kilogram of body weight could be expected to produce a 1 percent rise in the factor IX level. Larger doses may be necessary in the actively bleeding patient. No serious side effects were observed. The increased factor IX concentration and the relatively low protein content of the material greatly reduces the possibility of precipitating circulatory overload while still achieving hemostatic factor IX levels.
Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell Disease
Authors: Ernest Beutler, Cage Johnson, Darleen Powars, Carol West
Journal: New England Journal of Medicine (1974)

Glucose-6-phosphate dehydrogenase genotypes were determined in 24 male patients with sickle-cell disease from 21 families and from 24 male sibs, including at least one from each family. The frequency of A- genotype of glucose-6-phosphate dehydrogenase was somewhat higher in the patients with sickle-cell disease than has been reported in the general Afro-American population; however, the prevalence of that genotype in brothers of patients with sickle-cell disease was even higher. These findings are not consistent with the proposal that glucose-6-phosphate dehydrogenase deficiency confers protection upon patients with sickle-cell disease. They can be explained by the fact that the frequency of the deficiency will parallel the frequency of the sickle-cell gene as genes of African origin are diluted by other gene pools. (N Engl J Med 290:826–828, 1974)
Clinical factors contributing to the differential diagnosis of primary insomnia and insomnia related to mental disorders
Authors: P D Nowell, D J Buysse, C F Reynolds, P J Hauri, T Roth, E J Stepanski, M J Thorpy, E Bixler, A Kales, R L Manfredi, A N Vgontzas, D M Stapf, P R Houck, D J Kupfer
Journal: American Journal of Psychiatry (1997)

Primary insomnia and insomnia related to mental disorders are the two most common DSM-IV insomnia diagnoses, but distinguishing between them is difficult in clinical practice. This analysis was performed to identify clinical factors used by sleep specialists to distinguish primary insomnia from insomnia related to mental disorders.Clinicians evaluated 216 patients referred for insomnia at five clinical sites, rated a list of clinical factors judged to contribute to each patient's presentation, and assigned diagnoses. Analysis of variance was performed, with contributing factors as the dependent variable and diagnostic group and clinic location as independent variables.Sleep specialists rated a psychiatric disorder as a stronger factor for insomnia related to mental disorders and rated negative conditioning and sleep hygiene as stronger factors for primary insomnia. However, a psychiatric disorder was rated as a contributing factor for 77% of patients who received a first diagnosis of primary insomnia.While neither sleep hygiene nor negative conditioning is a diagnostic criterion in DSM-IV, these results support the face validity of these clinical factors distinguishing between primary insomnia and insomnia related to mental disorders. The use of a psychiatric disorder as an inclusion criterion for insomnia related to mental disorders and an exclusion criterion for primary insomnia reinforces a categorical distinction between the two diagnoses, but the contribution of psychiatric symptoms in primary insomnia appears to be a clinically relevant one. These findings suggest the need for studies on the validity of negative conditioning and sleep hygiene in the etiology of primary insomnia, as well as on the significance of psychiatric disorders, especially depression, in primary insomnia.
P188 Survey of use of safety checklists and standardisation of practice in thoracoscopy centres in the UK
Authors: T Duncan, S Clarke, J Hoyle
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Safety checklists have been part of routine surgical practice for some time with evidence for reduction in morbidity and mortality. The use of such checklists in physician led interventions is more of a novelty. Several recent papers have been published outlining the introduction of safety checklists in the field of cardiology and gastroenterology. The 2013 BTS bronchoscopy guidelines include an adapted WHO surgical checklist, but there are no such recommendations in the BTS pleural disease guidelines. A literature search did not reveal any evidence of use of safety checklists within the area of local anaesthetic thoracoscopy. Our department set out to adapt and introduce a safety checklist for use on our thoracoscopy list, and to ascertain whether such practice is common place on UK thoracoscopy lists. Additionally, we looked to assess whether other aspects of thoracoscopy practice were standard across the UK. <h3>Method</h3> A checklist for use in thoracoscopy was adapted from the WHO surgical checklist. Additions specific to thoracoscopy included assessment of drain function post procedure. A brief survey was sent out electronically to 23 medical thoracoscopy practitioners throughout the UK. Questions assessed whether a safety checklist was in use, whether significant complications had occurred and whether MRSA screening and antibiotics prophylaxis were common practice. <h3>Results</h3> A 35% response rate was achieved. 75% of participants were using pre procedure checklists. 63% of respondents had experienced issues with equipment malfunction or sterility. 75% of respondents had experienced significant clinical complications; death (12.5%), pleural space infection (50%), bleeding (25%), other (25%). MRSA screening was carried out in 50% of centres whilst prophylactic antibiotics were used in 25%. <h3>Conclusions</h3> Amongst the responders there was a high rate of use of pre-procedure checklists. This may not be representative of practice throughout the UK due to the relatively low response rate. A significant proportion of respondents had experienced equipment related complications, something that is likely to be picked up during routine safety checks prompted by a checklist. The survey results suggest a lack of consistency in practice across the UK and more prescriptive guidelines may be beneficial.
Emerging Research Directions in Adult Congenital Heart Disease
Authors: Michelle Gurvitz, Kristin M. Burns, Ralph Brindis, Craig S. Broberg, Curt J. Daniels, Stephanie M.P.N. Fuller, Margaret A. Honein, Paul Khairy, Karen S. Kuehl, Michael J. Landzberg, William T. Mahle, Douglas L. Mann, Ariane Marelli, Jane W. Newburger, Gail D. Pearson, Randall C. Starling, Glenn R. Tringali, Anne Marie Valente, Joseph C. Wu, Robert M. Califf
Journal: Journal of the American College of Cardiology (2016)
Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?
Authors: Marius E. Mayerhoefer, Chiara Giraudo, Daniela Senn, Markus Hartenbach, Michael Weber, Ivo Rausch, Barbara Kiesewetter, Christian J. Herold, Marcus Hacker, Matthias Pones, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Werner Dolak, Julius Lukas, Markus Raderer
Journal: Clinical Nuclear Medicine (2015)

To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed-time-point 2-F-fluoro-2-deoxy-d-glucose-positron emission tomography (F-FDG-PET) performs better than standard-time-point F-FDG-PET.Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic F-FDG-PET/computed tomography (CT) and consecutive F-FDG-PET/magnetic resonance imaging (MRI), using a single F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective F-FDG-PET scans at time points 1 (45-60 minutes after tracer injection, TP1) and 2 (100-150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed.F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%-84.67%) and 100% (CI, 100%-100%) for F-FDG-PET at TP1; and 87.0% (CI, 73.26%-100%) and 100% (CI, 100%-100%) for F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%-80.9%) for F-FDG-PET at TP1, and 76.9% (CI, 54.0%-99.8%) for F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001).Delayed-time-point imaging may improve F-FDG-PET in MALT lymphoma.
Abstract 441: IL-17 and IL-17-producing cells associated with advanced stage or poor prognosis in oral cancers, through enhancing tumor progression
Authors: Meng Hua Lee
Journal: Cancer Research (2015)

Abstract Introduction: Interleukin 17 (IL-17) majorly produced by Th17 and Tc17 cells, contributes greatly in inflammatory associated diseases. However, its presence was reported to suppress tumor growth by enhancing cytotoxic T cell responses. On the contrary, through inducing angiogenesis, IL-17 appeared to promote tumor progression. Here we demonstrated IL-17 and their producing cells directly correlating with advanced stage or poor prognosis of oral cancer patients. Methods: Peripheral blood samples were obtained from the oral patients in Chang Gung Memorial Hospital, and the multi-color flow cytometric analysis and enzyme conjugated immunoassays were utilized to identify the IL-17 producing T cell subsets and to quantify the production of inflammation-associated cytokines. The effects of IL-17 on the growth and invasion of oral cancer cells were determined with the supplement with recombinant IL-17 (γhIL-17) and cell culture supernatant. Results: The significantly increased prevalence of IL-17-producing T cells was correlated with clinical stage and the patients’ peripheral blood mononuclear cells secreted higher amount of IL-17 and other related factors. Such responses also appeared to be associated with poor prognosis. Moreover, the stimulation of γhIL-17 apparently induced cell proliferation, migration and invasion in oral cancer cells, indicating that IL-17 directly contribute to tumor progression. Conclusion: These findings suggest IL-17 and its related factors are crucial to tumor development, and such responses may therefore lead to the clinical impact of advanced stage or poor prognosis in oral cancer. Citation Format: Meng Hua Lee. IL-17 and IL-17-producing cells associated with advanced stage or poor prognosis in oral cancers, through enhancing tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 441. doi:10.1158/1538-7445.AM2015-441