tbuckley/cabot-search huggingface dataset:
Biomarker Tests for Molecularly Targeted Therapies: Laying the Foundation and Fulfilling the Dream
Authors: Gary H. Lyman, Harold L. Moses
Journal: Journal of Clinical Oncology (2016)

Precision medicine focuses on the management of individual patients on the basis of biomarkers and other distinguishing characteristics, with the overarching objective of improving clinical outcomes. The rapid proliferation of biomarker tests and targeted therapies has revolutionized patient care in a variety of serious disorders. Targeted cancer therapies interrupt oncogenic molecular pathways driven by mutations, overexpression, or translocation of specific genes. However, there is concern that the emergence of large-scale genomic data is exceeding our capacity to appropriately analyze and interpret the results.In 2014, the Institute of Medicine convened the Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies. This committee conducted a study to develop recommendations to address diverse and interconnected development, regulatory, clinical practice, and reimbursement issues. The committee conducted an extensive search of the relevant literature and invited testimony from a wide range of experts in the field. The final report of the committee's study and deliberations was released on March 4, 2016, focusing on ways to achieve 10 goals to further advance the development and appropriate clinical use of biomarker tests for molecularly targeted therapies.This article presents an overview of the committee's study and resulting recommendations, which cover establishment of clinical utility, regulatory oversight, coverage and reimbursement, health system data integration, as well as education and access. The committee's recommendations presented and discussed here are fundamentally grounded in the understanding that, when properly validated and appropriately implemented, these assays and corresponding therapies hold considerable promise to enhance the quality of patient care and improve meaningful clinical outcomes.
Sister Joseph's Node in Carcinoma of the Cecum
Authors: S Moll
Journal: New England Journal of Medicine (1996)

Figure 1. A 78-year-old woman who had undergone right hemicolectomy to treat carcinoma of the cecum with involvement of regional lymph nodes noticed a new periumbilical subcutaneous swelling two months after her surgery. Biopsy revealed an adenocarcinoma with the same histologic features as the original cecal tumor. The patient chose not to have any treatment. Two months later, the nodule had enlarged substantially, and abdominal and pelvic computed tomographic (CT) scans were obtained to assess the extent of metastatic disease before further treatment options were discussed.
p53 mutations in HER2 positive and triple negative breast cancer treated with neoadjuvant chemotherapy – A translational subproject of the GeparSixto trial
Authors: S. Darb-Esfahani, W. Weichert, C. Denkert, G. von Minckwitz, V. Nekljudova, J. Lindner, V. Endris, F. Khandan, S. Loibl
Journal: Annals of Oncology (2015)
Cytoplasmic expression of HuR and cyclooxygenase-2 expression in colon cancer
Authors: J. Song, S. Choi, J. Lee, S. Lim
Journal: Journal of Clinical Oncology (2009)

e22161 Background: HuR, human family embryonic-lethal abnormal vision-like protein, can bind to mRNAs and stabilizes them in the cytoplasm, resulting in more efficient translation. HuR is predominantly present in the nucleus and shuttles between the nucleus and cytoplasm. The mRNA of cyclooxygenase-2 (Cox-2) is stabilized by HuR in several cancers, including breast, stomach, lung and brain. Methods: We investigated the expression and its cellular location of HuR, and Cox-2 expression in 79 colorectal cancer patients with immunohistochemistry, and evaluated the biological implications in colorectal carcinoma. Results: Nuclear HuR expression was observed in 59 (74.7%) and cytoplasmic HuR expression was seen in 25 (31.6%). Cox-2 immunoreactivity was noted in 42 (53%). The expression of cytoplasmic HuR was significantly associated with Cox-2 expression (p=0.004). And cytoplasmic expression of HuR showed correlation with lymphatic invasion (p=0.025) and lymph node metastasis (p=0.027). Nuclear HuR showed no correlation with Cox-2 expression or other clinicopathological parameters examined. Conclusions: These results suggest that cytoplasmic translocation of HuR is associated with Cox-2 expression in some colorectal carcinoma. No significant financial relationships to disclose.
Diagnosis of Whipple's Disease by Molecular Analysis of Peripheral Blood
Authors: Robert Lowsky, Gordon L. Archer, Gillian Fyles, Mark Minden, John Curtis, Hans Messner, Harold Atkins, Bruce Patterson, Barbara M. Willey, Allison McGeer
Journal: New England Journal of Medicine (1994)

Whipple's disease is a systemic infection characterized most commonly by fever, weight loss, diarrhea, polyarthritis, and adenopathy1,2. Attempts to culture the causative organism have been unsuccessful, but microscopical examination of infected tissue, usually small-bowel-biopsy specimens or lymph nodes, reveals small gram-positive rods that appear as diastase-resistant intracytoplasmic inclusions on periodic acid-Schiff staining2. Electron microscopy reveals that these organisms possess a trilamellar membrane external to the cell wall, a finding usually associated with gram-negative bacteria3,4. Recent studies have shown that the specific identification of bacterial pathogens does not require culture but can be accomplished by molecular . . .
Abstract 15738: New Left Bundle Branch Block (LBBB) as a Predictor of Coronary Occlusion After Out-of-Hospital Cardiac Arrest (OHCA)
Authors: Lindsey Kowalski, Jacob Jentzer, James Fitzgibbon, Michael Scutella, Clifton Callaway, Cameron Dezfulian
Journal: Circulation (2015)

Introduction: In the setting of recent cardiac arrest, it is controversial whether new LBBB with or without Sgarbossa Criteria is an ST elevation (STE) equivalent for predicting acute coronary occlusions. The 2010 AHA guidelines recommend urgent coronary angiography after OHCA when either STE or new LBBB is present. These guidelines are extrapolated from the non-arrest population with few data from OHCA patients. Hypothesis: New LBBB on EKG early after OHCA will have a weaker association with acute coronary occlusion than STE. Methods: This was a retrospective 2 center study of 284 OHCA subjects who underwent early coronary angiography (within 24 hours of resuscitation). The post-resuscitation EKG was reviewed by a study investigator (LK) with cardiology over reading (JJ). Subjects with either STE or new LBBB were identified. Cardiologists performed percutaneous intervention (PCI) at their discretion when a culprit lesion or acute thrombus was found. We calculated the sensitivity and specificity for STE, LBBB, and STE + LBBB (current standard) for predicting PCI and the odds ratio (OR) and 95% confidence intervals (CI) for the association between these EKG findings and PCI. OR were calculated relative to subjects with no STE or LBBB. Results: Of the 284 patients, 125 presented with STE and 19 presented with new LBBB resulting in 144 patients meeting AHA criteria for angiography. None of the LBBB met Sgarbossa Criteria. PCI was performed in 95/125 (76%) of those with STE, 4/19 (21%) of those with LBBB and 99/144 (69%) with either finding. The sensitivity and specificity of STE for PCI were 62% and 77% and the unadjusted OR was 5.82 (95% CI: 3.45, 9.83; p &lt; 0.001). The sensitivity and specificity of ST elevation or new LBBB for PCI was 65% and 66% (OR =3.72 [95% CI: 2.28, 6.09; p &lt; 0.001]). New LBBB was inversely associated with PCI (OR = 0.21 [95% CI: 0.07, 0.66; p = 0.0075]. Survival was higher in those who underwent PCI with STE (OR 8.23 [95% CI: 3.31, 20.48; p &lt;0.0001]) but not in those with LBBB (OR of 0.60 [95% CI: 0.09, 4.01; p=0.5950]). Conclusions: Our findings confirm STE after OHCA is strongly associated with coronary occlusion amenable to PCI, but cast doubt on using new LBBB as an STE equivalent. These findings mirror recent reports about LBBB in non-OHCA patients.
A Preliminary Study of Diltiazem in the Prevention of Coronary Artery Disease in Heart-Transplant Recipients
Authors: John S. Schroeder, Shao-Zhou Gao, Edwin L. Alderman, Sharon A. Hunt, Iain Johnstone, Derek B. Boothroyd, Voy Wiederhold, Edward B. Stinson
Journal: New England Journal of Medicine (1993)

Accelerated coronary artery disease is a major cause of late morbidity and mortality among heart-transplant recipients. Because calcium-channel blockers can suppress diet-induced atherosclerosis in laboratory animals, we assessed the efficacy of diltiazem in preventing coronary artery disease in transplanted hearts.
P104 Structural and cellular relationships in the peripheral lung: combining micro-CT and immunohistochemistry
Authors: JJ Ramsden, JL Norman, PM Lackie, JA Warner
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> The peripheral lung contains a range of structural elements (small airways, blood vessels and lymphatics) together with infiltrating inflammatory cells. These components exist together in complicated spatial arrangements. Lung disease is frequently accompanied by changes in both lung architecture and the number and distribution of inflammatory cells. Light microscopy has been the conventional technique of choice in understanding these changes and relationships but provides only 2-D representations of a complex 3-D network. We selected to use micro computed tomography (µ-CT) to image structural elements in the peripheral lung. We aimed to reconstruct the 3-D architecture by combining the µ-CT data with immunohistochemistry (IHC) to positively identify the principal structural elements and inflammatory cells. <h3>Methods</h3> Human lung tissue was fixed in formalin, embedded in paraffin wax and subjected to µ-CT scanning. The tissue was then sectioned and immunostained for pancytokeratin (airways), collagen IV (blood vessels), D2–40 (lymphatic vessels) and CD68 (macrophages). The resulting images were used to guide the segmentation of the 3-D µ-CT image stack. IHC, using neurofilament antibodies, was also used on multiple lung samples to attempt to identify nerve fibres in the parenchymal tissue. <h3>Results</h3> The main structural elements of the lung periphery could be identified, segmented out and their 3-D architecture examined. Macrophages were found throughout the tissue in large quantities and were most concentrated around the blood vessels and lymphatics. Lymphatic vessels were especially dense in the pleural region and elsewhere were intertwined with blood vessels. Despite being readily identifiable in bronchial samples, nerve fibres were not identified using IHC in the parenchyma. <h3>Conclusions</h3> Combining µ-CT and IHC provides a robust method to positively identify important structural elements of the peripheral lung and to localise inflammatory cells in 3-D, thus allowing a detailed review of their spatial relationships. Alternative methodologies may however be advantageous regarding identifying parenchymal nerve fibres for reconstruction. µ-CT and IHC together create a highly accurate 3-D reconstruction but this method remains time consuming; advances in automation and improved tools are required to fully exploit the research potential.
The Effects of Cimetidine on the Oxidative Metabolism of Estradiol
Authors: Richard A. Galbraith, Jon J. Michnovicz
Journal: New England Journal of Medicine (1989)

Cimetidine, a histamine H2–receptor antagonist widely used to treat peptic ulceration, is known to cause gynecomastia and sexual dysfunction in some men. Since cimetidine inhibits the cytochrome P-450–dependent biotransformation of numerous drugs, we investigated the possibility that it might also inhibit the cytochrome P-450–dependent metabolism of estradiol. Radiometric analysis of urine and serum samples from nine normal male volunteers showed that the extent of 2-hydroxylation of estradiol was significantly reduced from a mean (±SEM) of 31.7±2.3 percent to 19.7±2.3 percent (P<0.0001) after two weeks of oral treatment with cimetidine (800 mg twice a day); the 16α-hydroxylation of estradiol was unaffected. At the same time, the urinary excretion of 2-hydroxyestrone decreased by approximately 25 percent (P<0.0002), and the serum concentration of estradiol increased by approximately 20 percent (P<0.04). The mean percentage of estradiol 2-hydroxylation was also rapidly reduced, from 36.8±4.4 percent to 24.5±3.4 percent in six men after one week of oral cimetidine at a lower dosage (400 mg twice a day; P<0.0006). In a separate study of seven men, ranitidine, a second-generation H2-receptor antagonist, was found to have no effect on the 2-hydroxylation of estradiol. This study demonstrates that the administration of cimetidine to men decreases the 2-hydroxylation of estradiol and results in an increase in the serum estradiol concentration. This mechanism may help to account for the signs and symptoms of estrogen excess reported with the long-term use of cimetidine. (N Engl J Med 1989; 321:269–74.)
Mortality among Children with Kawasaki Disease in Japan
Authors: Yosikazu Nakamura, Hiroshi Yanagawa, Tomisaku Kawasaki
Journal: New England Journal of Medicine (1992)

It is not certain whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population. We therefore undertook a study to investigate this question. Between July 1982 and December 1988, 53 collaborating treatment centers collected data on all patients who had an unequivocal new diagnosis of Kawasaki disease; patients who had recurrent disease or whose first visit to the treatment center occurred more than 14 days after the onset of symptoms were excluded. Patients were followed from the time of the first visit to the treatment center until December 31, 1989, or until death, whichever occurred first. The expected number of deaths was calculated from Japanese vital-statistics data and compared with the number observed.
Spontaneous Versus Artificial Lung Metastasis: Discrepant Effect of Whole-Body Irradiation in NFSA2ALM and NFSA1SLM Tumor Systems&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: N Suzuki
Journal: JNCI Journal of the National Cancer Institute (1983)

In newly established NFSA2ALM and NFSA1SLM metastases systems, preirradiation of inbred host C3H/HeJ mice with 5 Gy gamma-rays suppressed spontaneous lung metastasis from im inoculated leg tumors while artificial lung metastasis by iv injection was enhanced. The results are unique in two aspects: 1) suppression of spontaneous metastasis by whole-body preirradiation and 2) discrimination of artificial and spontaneous metastasis. This is another example indicating that the results obtained from an artificial metastasis method, which has been widely used, cannot predict the behavior of tumor cells in spontaneous metastasis.
Risk communication as a core public health competence in infectious disease management: Development of the ECDC training curriculum and programme
Authors: Petra Dickmann, Thomas Abraham, Satyajit Sarkar, Piotr Wysocki, Sabrina Cecconi, Franklin Apfel, Ülla-Karin Nurm
Journal: Eurosurveillance (2016)

Risk communication has been identified as a core competence for guiding public health responses to infectious disease threats. The International Health Regulations (2005) call for all countries to build capacity and a comprehensive understanding of health risks before a public health emergency to allow systematic and coherent communication, response and management. Research studies indicate that while outbreak and crisis communication concepts and tools have long been on the agenda of public health officials, there is still a need to clarify and integrate risk communication concepts into more standardised practices and improve risk communication and health, particularly among disadvantaged populations. To address these challenges, the European Centre for Disease Prevention and Control (ECDC) convened a group of risk communication experts to review and integrate existing approaches and emerging concepts in the development of a training curriculum. This curriculum articulates a new approach in risk communication moving beyond information conveyance to knowledge- and relationship-building. In a pilot training this approach was reflected both in the topics addressed and in the methods applied. This article introduces the new conceptual approach to risk communication capacity building that emerged from this process, presents the pilot training approach developed, and shares the results of the course evaluation.
The Use of Intravenous Immune Globulin in Immunodeficiency Diseases
Authors: John A. Oates, Alastair J.J. Wood, Rebecca H. Buckley, Richard I. Schiff
Journal: New England Journal of Medicine (1991)

WITH the discovery of agammaglobulinemia in 1952,1 a pressing need emerged for antibody-replacement therapy to prevent serious bacterial infections. Intramuscularly administered immune serum globulin resulted in a remarkable decrease in the incidence of such infections in patients with this type of immunodeficiency; however, the injections were painful, and the IgG was absorbed slowly and was subject to local proteolysis. Intravenous administration of immune serum globulin resulted in shocklike episodes, chills, and hyperpyrexia, especially in sick and acutely infected children. Beginning in the early 1960s, many attempts were made to modify immune serum globulin so that it could be given safely . . .
Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia
Authors: N Gunnarsson, M Höglund, L Stenke, S Wållberg-Jonsson, F Sandin, M Björkholm, A Dreimane, M Lambe, B Markevärn, U Olsson-Strömberg, H Wadenvik, J Richter, A Själander
Journal: Leukemia (2016)
Epirubicin, Cisplatin, and Fluorouracil in Gastric and Esophageal Cancer: A Step Ahead?
Authors: David H. Ilson
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.8.1962 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11956251 Epirubicin, Cisplatin, and Fluorouracil in Gastric and Esophageal Cancer: A Step Ahead? David H. IlsonxDavid H. IlsonSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2002.20.8.1962 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Case 31-2006
Authors: Alison G. Hoppin, Eliot S. Katz, Lee M. Kaplan, Gregory Y. Lauwers
Journal: New England Journal of Medicine (2006)

A girl had been severely obese since early childhood. She had been adopted in infancy, and her adoptive parents and siblings had normal weights. Numerous programs had failed to produce sustained weight loss. She had problems with snoring, insomnia, somnambulation, daytime sleepiness, and depression. Management options were discussed.
The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone
Authors: A Nademanee, GM Schmidt, P Parker, AC Dagis, A Stein, DS Snyder, M O'Donnell, EP Smith, DE Stepan, A Molina
Journal: Blood (1995)
Regression of Multivalvular Regurgitation after the Cessation of Fenfluramine and Phentermine Treatment
Authors: Lauralyn B. Cannistra, Anthony J. Cannistra
Journal: New England Journal of Medicine (1998)

To the Editor: Treatment with the appetite-suppressant drugs fenfluramine and dexfenfluramine, alone or in combination with phentermine, has been associated with cardiac-valve abnormalities.1–3 Five echocardiologic surveys reviewed by the Food and Drug Administration suggested that the prevalence of cardiac-valve abnormalities is 30 to 38 percent among patients who have taken these drugs2 and led to the withdrawal of fenfluramine and dexfenfluramine from the U.S. market on September 15, 1997. Whether these lesions resolve, progress, or remain unchanged after discontinuation of the drugs is not yet known. We report the possibility of regression of multivalvular regurgitation associated with fenfluramine and . . .
Bilateral Femur Fractures
Authors: G P Conners, D W Ochsenschlager
Journal: New England Journal of Medicine (1994)

Figure 1. Bilateral Femur Fractures. Bilateral femur fractures are visible in a nine-month-old boy who was restrained with only a standard lap belt in the rear seat of an automobile that struck a post at 40 miles (65 km) per hour. The child required hospitalization and a prolonged period in a spica cast. A proper car seat is the only appropriate restraint for a small child.
P200 Domiciliary nocturnal NIV in COPD – still controversial?
Authors: J Barnacle, CME Longley, V Padmanaban, S Elkin, SAA Bloch
Journal: Thorax (2015)

<h3>Introduction</h3> Despite strong evidence for the use of Non-invasive ventilation (NIV) in acute exacerbations of COPD resulting in decompensated type 2 respiratory failure (T2RF), the evidence for the long-term use of nocturnal NIV to prevent readmission or improve survival is controversial and has often been contradictory. Therefore clinicians are faced with the difficult question of what to do with COPD patients who are admitted with severe exacerbations requiring NIV and are considered at high risk of future decompensation. We hypothesised that domiciliary nocturnal NIV, established following an acute admission with decompensated T2RF delayed readmission. <h3>Methods</h3> We performed a retrospective case note analysis of patients started on domiciliary NIV following acute admission to a busy central London acute trust. Indication for NIV and success of treatment were assessed. Time between admissions prior to establishing domiciliary NIV and time to 1<sup>st</sup> readmission were compared. <h3>Results</h3> 18 patients were identified from our database. (2 were excluded: 1 returned their machine immediately, the other never attended for any follow-up at our hospital.) To our knowledge the patients were not admitted to other hospitals in the year pre or post the index admission – the admission at which NIV was initiated. The mean age of the 16 remaining patients was 70 ± 12 years; 9 were female, 8 male. Indication for NIV in 13 patients was COPD with resistant or recurrent T2RF, 1 had COPD plus sarcoidosis and the remaining 2 had COPD plus obesity hypoventilation. NIV was shown to be successful in reducing pCO<sub>2</sub> between discharge and first follow up (mean reduction 0.84 ± 1.17 kPa p = 0.01). There was a trend towards delayed 1<sup>st</sup> readmission following initiation of NIV, when compared to the time between previous admission (Kaplan-meier survival analysis. p = 0.09 Figure 1). <h3>Conclusion</h3> Domiciliary NIV for high risk patients with decompensated T2RF in COPD is often used because of concerns of leaving the condition untreated when objectively NIV improved the patient’s pCO<sub>2 </sub>furthermore there are no consistently ratified guidelines. The data presented here suggest that NIV may help to delay readmission to hospital. The results of ongoing randomised trials are eagerly awaited.
A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection
Authors: Samuel A. Bozzette, Dianne M. Finkelstein, Stephen A. Spector, Peter Frame, William G. Powderly, Weili He, Lucinda Phillips, Donald Craven, Charles van der Horst, Judith Feinberg
Journal: New England Journal of Medicine (1995)

We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV).