tbuckley/cabot-search huggingface dataset:
The association of metabolic syndrome with triple-negative breast cancer
Authors: B. Maiti, M. N. Kundranda, T. Jin, T. P. Spiro, H. A. Daw
Journal: Journal of Clinical Oncology (2009)

1038 Background: Metabolic syndrome, a conglomerate of obesity, insulin resistance, hypertriglyceridemia, low HDL (high density lipoprotein), and hypertension is associated with an increased risk of breast cancer. However, no clear association has been shown between the highly aggressive triple-negative breast cancer and metabolic syndrome. Methods: In a retrospective review we compared triple-negative and non-triple-negative breast cancer cases for the presence of metabolic syndrome by NCEP (National Cholesterol Education Program) or AACE (American Association of Clinical Endocrinologists) definitions. Data on metabolic syndrome criteria, tumor size, grade, lymph node status, and ductal carcinoma in situ (DCIS) were reviewed. Chi-square test or Student's t-test was used for data analysis. Results: The entire cohort of 176 patients (12.5% African-American) with median age 56.5 years (range 26–91 years) comprised of 86 triple-negative cases and 90 non-triple-negative cases. A statistically significant association of triple-negative breast cancer with metabolic syndrome was observed. According to the NCEP criteria 58.1% of triple negative patients had metabolic syndrome as compared to only 36.7% of non-triple negative patients (p = 0.004). Consistently, by the AACE criteria 52.3% of triple negative patients had metabolic syndrome as compared to 34.4% of non-triple negative patients (p = 0.017). Contrary to blood glucose, triglyceride, or HDL levels, which independently showed significant association with triple-negative breast cancer, hypertension, or BMI showed no independent association. Additionally, triple-negative tumors displayed a significantly higher histologic grade and relative paucity of ductal carcinoma in situ (DCIS) when compared to the non-triple negative tumors (p &lt; 0.001). Conclusions: The data suggests that the metabolic syndrome is significantly more prevalent in triple-negative breast cancer patients when compared to the non-triple-negative patients. Additionally, triple-negative breast cancer showed a significantly higher histologic grade and a relative absence of DCIS. Whether the presence of metabolic syndrome preferentially increases the risk of developing triple-negative-breast cancer needs to be elucidated by future prospective studies. No significant financial relationships to disclose.
Testing, Testing, Testing . . .
Authors: Chaim Putterman, Eldad Ben-Chetrit
Journal: New England Journal of Medicine (1995)

A 55-year-old woman presented with polyarticular arthritis. She had had several attacks of symmetric arthritis during the previous few months, involving particularly the ankles, shoulders, and metacarpophalangeal and proximal interphalangeal joints. She also reported morning stiffness and fatigue, but no other systemic symptoms. No infection or febrile illness preceded the onset of her symptoms. Her medical history was otherwise unremarkable.The patient's age, the onset of symptoms, and the clinical picture support a presumptive diagnosis of rheumatoid arthritis. The absence of fever and the chronic, relapsing course are inconsistent with most infectious arthritides. A reactive arthritis is also . . .
Birth weight, early childhood growth and lung function in middle to early old age: 1946 British birth cohort
Authors: Yutong Cai, Seif O Shaheen, Rebecca Hardy, Diana Kuh, Anna L Hansell
Journal: Thorax (2015)

<h3>Background</h3> Findings from previous studies investigating the relationship between birth weight and adult lung function have been inconsistent, and data on birth weight and adult lung function decline are lacking. Few studies have investigated the relation between early childhood growth and adult lung function. <h3>Methods</h3> FEV<sub>1</sub> and FVC were measured at ages 43 years, 53 years and 60–64 years in the 1946 British birth cohort study. Multiple linear regression models were fitted to study associations with birth weight and weight gain at age 0–2 years. Multilevel models assessed how associations changed with age, with FEV<sub>1</sub> and FVC as repeated outcomes. <h3>Results</h3> 3276 and 3249 participants were included in FEV<sub>1</sub> and FVC analyses, respectively. In women, there was a decreasing association between birth weight and FVC with age. From the multilevel model, for every 1 kg higher birth weight, FVC was higher on average by 66.3 mL (95% CI 0.5 to 132) at 43 years, but significance was lost at 53 years and 60–64 years. Similar associations were seen with FEV<sub>1</sub>, but linear change (decline) from age 43 years lost statistical significance after full adjustment. In men, associations with birth weight were null in multilevel models. Higher early life weight gain was associated with higher FEV<sub>1</sub> at age 43 years in men and women combined but not in each sex. <h3>Conclusions</h3> Birth weight is positively associated with adult lung function in middle age, particularly in women, but the association diminishes with age, potentially due to accumulating environmental influences over the life course.
METRIC: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients (pts) with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC).
Authors: Denise A. Yardley, Michelle E. Melisko, Andres Forero, Brooke R. Daniel, Alberto J. Montero, Troy H. Guthrie, Vikki A. Canfield, Catherine Angela Oakman, Helen K. Chew, Cristiano Ferrario, Gena H. Volas-Redd, Robyn R. Young, Norah Lynn Henry, Lynn Aneiro, Yi He, Christopher D. Turner, Thomas A. Davis, Linda T. Vahdat
Journal: Journal of Clinical Oncology (2015)

TPS1110 Background: The internalizable transmembrane glycoprotein NMB (gpNMB) is overexpressed in 20% of BC, including 40% of TNBC (Yardley JCO, in press), where it is a poor prognostic marker (Rose CCR 2010). gpNMB enhances tumor invasion and metastasis and promotes angiogenesis in preclinical models. GV is a novel antibody drug conjugate targeting the potent cytotoxin monomethylauristatin E (MMAE) to gpNMB+ tumor cells. In a Phase I/II study (Bendell JCO, 2014) and the Phase II "EMERGE" study (Yardley JCO, in press), GV demonstrated promising activity, particularly in pts with TNBC and gpNMB overexpression, and was well-tolerated (treatment related toxicities: rash, neutropenia and neuropathy). In subset analyses, for GV vs. "investigator's choice" (IC) single-agent chemotherapy, objective response rate (ORR) was 30% (7/23) vs. 9% (1/11) in pts with gpNMB overexpression (in ≥ 25% of tumor epithelium); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC, with apparent improvements in progression-free survival (PFS; hazard ratio (HR) = 0.11) and overall survival (OS; HR = 0.14). Methods: The international (US, CA, Aus) "METRIC" study (NCT01997333) is recruiting up to 300 pts with metastatic, gpNMB-overexpressing TNBC. Eligibility criteria include: ≥ 25% of tumor epithelium gpNMB+ by central IHC prescreening of archival tissue; ER and PR < 10% and HER2(-) [0-1+ IHC, or ISH copy number < 4.0 / ratio < 2.0] by local assessment; ECOG 0-1; taxane resistance; anthracycline exposure (if indicated); ≤ 2 chemotherapy regimens for advanced BC; measurable disease; no persistent Grade ≥ 2 toxicity; and capecitabine naive. Pts are randomized (2:1) to GV (1.88 mg/kg IV q 21 days) or capecitabine, a current standard for this population (2500 mg/m2 daily for d1-14, q21 days) until progression or toxicity. Crossover is not permitted. Endpoints are PFS (primary), ORR, duration of response, OS, safety, PK, PD (immune dynamics) and quality of life. Imaging will be centrally assessed per RECIST 1.1. The trial has 85% power to detect a PFS HR of 0.64 with α = 0.05. Clinical trial information: NCT01997333.
Association of BRCA1 mutations with diminished ovarian reserve: A common genetic mechanism for breast/ovarian cancer, and infertility?
Authors: K. Oktay, J. Kim, D. Barad, N. Gleicher, S. Babayev
Journal: Journal of Clinical Oncology (2009)

11039 Background: 25% of all breast cancers (BC) occur prior to menopause and preservation of fertility is an important quality of life issue for these women. We recently reported an ovarian stimulation (OS) protocol utilizing letrozole for women with BC who wish to preserve their fertility by embryo freezing. Because BRCA+ young women are highly represented among those undergoing fertility preservation, and because knock out models showed a relationship between DNA repair genes and germ cell development, we hypothesized that women with BRCA mutations have diminished oocyte reserve (DOR). Methods: We analyzed the letrozole-OS data to assess the association between BRCA mutations and number of oocytes retrieved, which is the most direct non-invasive method of assessing ovarian reserve. Women with infertility history and age&gt;37 were excluded. Results: Of 125 BC patients who underwent OS between 5/03 and 11/08, 82 met the criteria, of which 47 (57%) had BRCA testing. Of those, 14 (30%) were BRCA+; 9 BRCA1+, 4 BRCA2+, and 1 + for both. Mean ages of those untested, BRCA-, and + women were similar (33.0±2.9 vs 32.8±2.9 vs 33.0±2.8; p=0.97)). Age-adjusted poor response (PR) rate (&lt;4 oocytes retrieved) was significantly higher in BRCA+ (28.6%; 4/14) compared to BRCA- (3%;1/33, p=0.009) and untested (2.9%; 1/35, p=0.007). All poor responders were BRCA1+ with one also having a mutation in BRCA2. A BRCA mutation was associated with 17.7 times the relative risk (RR) of PR (95% CI 1.4–214; p=0.024). The mean number of oocytes was significantly lower in BRCA1+ but not BRCA2+ compared to BRCA- and untested (p=0.05). BRCA1 but not BRCA2 mutations were associated with PR with a RR of 24.0 (95% CI 1.9–298; p=0.013). When only mutations of known clinical significance were included, the RR for PR further increased (RR=36, 95% CI 2.5–503; p=0.008) suggesting a common mechanism between BRCA-induced cancer and premature diminishment of oocyte reserve. Conclusions: Because women with BRCA1 mutations may have DOR prematurely, they should be counseled for possible higher risk of ovarian failure and infertility after chemotherapy, and referred for fertility preservation. Diminished ovarian reserve may be a new component of the Hereditary Breast Ovarian Cancer Syndrome. No significant financial relationships to disclose.
Soft-Tissue Necrosis Induced by Extravasated Cancer Chemotherapeutic Agents2, 3
Authors: Ronald D. Barr, Sandra G. Benton, Larry W. Belbeck
Journal: JNCI Journal of the National Cancer Institute (1981)

The inadvertent extravasation of anticancer drugs in clinical use may result in the development of indolent lesions at the site of injection. Investigation of this phenomenon in Hartley guinea pigs showed that the pathogenesis was based on direct tissue toxicity and not on sensitization. The risk of a serious reaction appeared to be related to the localization of the injurious agent within the dermis rather than at the subcutaneous site.
Case 40-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Lot B. Page, Robert E. Scully
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 17-year-old girl was admitted to the hospital because of hypertension.The patient was born of a normal pregnancy and delivery and had an uneventful childhood. Repeated examinations by her pediatrician disclosed no abnormality. She contracted mumps and scarlet fever in childhood. Eighteen months before entry she had a febrile illness of six weeks' duration, without associated back pain or genitourinary-tract symptoms. Six weeks before admission the blood pressure was 180/120 on a routine physical examination. An intravenous pyelographic study was reported to show that the right kidney was small. Chlorthalidone and diazepam were prescribed, and the . . .
The Expanding Spectrum of G Protein Diseases
Authors: Zvi Farfel, Henry R. Bourne, Taroh Iiri
Journal: New England Journal of Medicine (1999)

Disease-causing mutations often reveal key pathways of physiologic regulation and their underlying molecular mechanisms. Mutations in the trimeric guanine nucleotide-binding proteins (G proteins), which relay signals initiated by photons, odorants, and a host of hormones and neurotransmitters, cause many diseases. For the most part, the diseases are confined to a set of fascinating but rare endocrine disorders (Table 1).1 A recent study suggests that mutations in G proteins can also lead to essential hypertension.2 If this study is correct, hypertension may be one of several common disorders caused by defects in this ubiquitous family of signaling molecules.This review focuses . . .
Transfusion Reactions in the Absence of Demonstrable Incompatibility
Authors: Hugh Fudenberg, Fred H. Allen
Journal: New England Journal of Medicine (1957)

HEMOLYTIC transfusion reactions may occur after the administration of donor bloods even when they have apparently been shown compatible by crossmatch tests. Often these have been attributed to laboratory error. This is especially true when, as in many cases, abundant antibody against donor red cells is found in the recipient's post-transfusion serum. In 2 cases of severe hemolytic transfusion reaction we have been able to demonstrate specific antibodies appearing later in the patient's serum, and to confirm that these were absent in the pretransfusion serum.Case 1. A 28-year-old housewife had had 6 transfusions in the previous 9 years, the . . .
Case 7-2010
Authors: Allan H. Ropper, Noopur S. Raje, Tara M. Lawrimore, Sandra Camelo-Piragua, Aliyah R. Sohani
Journal: New England Journal of Medicine (2010)

A 49-year-old man was admitted to this hospital because of ascites. During the past 4 years, paresthesias and weakness of the lower legs and hands had developed, followed by difficulty breathing, peripheral edema, and during the past year, blurred vision, optic-disk edema, and ascites. Imaging studies subsequently revealed retroperitoneal lymphadenopathy and lytic lesions in the tibia and sacrum. A diagnostic procedure was performed.
Effect of Small Doses of Estrogen on Serum Lipids in Female Patients with Myocardial Infarction
Authors: Jessie Marmorston, Oscar Magidson, Jack J. Lewis, John Mehl, Fredrick J. Moore, Jacob Bernstein
Journal: New England Journal of Medicine (1958)

IN 1949 Eilert1 made the original observation that estrogen administration raised the serum phospholipid and lowered the serum cholesterol and cholesterol-phospholipid ratio in female patients. Since these observations and the classic studies in laboratory animals recently summarized by Stamler, Pick and Katz,2 much interest has been directed toward assessing the clinical value of estrogen in atherosclerosis and particularly in myocardial infarction. Although no conclusion is yet possible in that respect, the estrogen lipid observations of Eilert have been confirmed and extended to male subjects by Russ, Eder and Barr,3 Steiner, Payson and Kendall,4 Oliver and Boyd5 and Robinson et al. . . .
TRATAMIENTO ENDOSCÓPICO PRIMARIO DE LA OBESIDAD CON SISTEMA APOLLO. RESULTADOS PRELIMINARES
Authors: J Nebreda Durán, E Espinet Coll, JA Gómez Valero, A Fernández Huélamo, C Vila Lolo, P Díaz Galán, B Lema, K Gunnard, D Bargalló Carulla
Journal: Endoscopy (2015)

En los últimos años se han desarrollado diversas técnicas endoscópicas para el tratamiento de la obesidad, entre ellas se encuentran la Gastroplastia endoscópica en manga o técnica Endosleeve de Apollo.
Lymphoma of Donor Origin Occurring in the Porta Hepatis of a Transplanted Liver
Authors: Ira J. Spiro, David W. Yandell, Chuan Li, Sanjay Saini, Judith Ferry, John Powelson, William N. Katkov, A. Benedict Cosimi
Journal: New England Journal of Medicine (1993)

Non-Hodgkin's lymphoma after organ transplantation is a recognized complication of immunosuppressive therapy. A number of cases of post-transplantation lymphoma arising in allografted tissue have been described1. In addition, leukemia and lymphoma arising from donor cells after allogeneic bone marrow transplantation have been recognized2–8. Two cases of donor-related lymphoma in renal allografts have also been reported9,10. We describe the development of a lymphoma in a hepatic allograft recipient 4.5 months after orthotopic liver transplantation. Using a rapid technique based on the polymerase chain reaction (PCR), which makes use of a DNA sequence polymorphism at the D4S174 . . .
Abstract 3697: Effects of Obesity and Weight Loss on the Functional Properties of Endothelial Progenitor Cells
Authors: Nana-Maria Heida, Marco R Schroeter, I-Fen Cheng, Jan-Peter Mueller, Gerd Hasenfuss, Stavros Konstantinides, Katrin Schaefer
Journal: Circulation (2007)

Studies have shown that cardiovascular risk factors are associated with a reduction of endothelial progenitor cell (EPC) number and functional capacity, but the effects of obesity have not yet been...
Determination of Free Thyroxine in Serum of Patients with Cirrhosis of the Liver
Authors: Daniel Hollander, Joseph C. Meek, Robert T. Manning
Journal: New England Journal of Medicine (1967)

SOME patients with hepatic cirrhosis show values for standard thyroid-function tests consistant with hypothyroidism.1 , 2 Whether these patients are actually myxedematous or whether these laboratory values reflect some biochemical aberration connected with disturbed liver function has not been established. Hypothermia, bizarre behavior and slow or absent deep tendon reflexes3 , 4 are several of the similarities between profound myxedema and hepatic precoma.Since metabolic status appears to be more closely related to the concentration of free serum thyroxine than to the concentration of bound hormone5 this study was undertaken to determine the free serum thyroxine in cirrhotic patients with either normal or abnormally . . .
Immunoglobulins and Measles Antibodies in Optic Neuritis
Authors: Hans Link, Erling Norrby, Jan-Edvin Olsson
Journal: New England Journal of Medicine (1973)

Abstract Patients with optic neuritis have been separated into two groups by the presence or absence of oligoclonal immunoglobulin G (IgG) (demonstrable by agar-gel electrophoresis) in the cerebrospinal fluid. Patients with oligoclonal IgG had mean serum concentration of measles-virus hemolysis-inhibiting antibodies about seven times higher, whereas no difference between the groups was seen in mean serum titers of hemagglutination-inhibiting and of nucleocapsid complement-fixing antibodies. Significantly reduced ratios of serum to cerebrospinal-fluid measles virus antibody were found in 12 of 21 patients with oligoclonal IgG but in only one of 20 without oligoclonal IgG, although either adenovirus hemagglutination enhancement or poliovirus neutralization-enhancement antibody ratios or both were normal. These findings indicate the occurrence of a local measles-virus antibody response within the central nervous system in some patients with optic neuritis and oligoclonal IgG in cerebrospinal fluid. The immun...
Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody
Authors: Ainat Beniaminovitz, Silviu Itescu, Katherine Lietz, Mary Donovan, Elizabeth M. Burke, Barbara D. Groff, Niloo Edwards, Donna M. Mancini
Journal: New England Journal of Medicine (2000)

Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without inducing global immunosuppression.
Exercise Stress Testing
Authors: Donald A. Weiner, Thomas J. Ryan, Carolyn H. McCabe, J. Ward Kennedy, Michael Schloss, Felix Tristani, Bernard R. Chaitman, Lloyd D. Fisher
Journal: New England Journal of Medicine (1979)

To determine to what extent the diagnostic accuracy of stress testing is influenced by the prevalence of coronary-artery disease, we correlated the description of chest pain, the result of stress testing and the results of coronary arteriography in 1465 men and 580 women from a multicentered clinical trial. The pre-test risk (prevalence of coronary-artery disease) varied from 7 to 87 per cent, depending on sex and classification of chest pain. A positive stress test increased the pre-test risk by only 6 to 20 per cent, whereas a negative test decreased the risk by only 2 to 28 per cent. Aothough the percentage of false-positive results differed between men and women (12 +/- 1 per cent versus 53 +/- 3 per cent P less than 0.001), this difference was not seen in a subgroup matched for prevalence of coronary-artery disease. We conclude that the ability of stress testing to predict coronary-artery disease is limited in a heterogeneous population in which the prevalence of disease can be estimated through classification of chest pain and the sex of the patient.
Disputed Indications and Technics for Cesarean Section
Authors: Edward G. Waters
Journal: New England Journal of Medicine (1946)

WITH cesarean section, opinion on indications and choice of operation should certainly approach unanimity. So much has been written and so many formidable analytic compilations have been advanced that one might well doubt that serious divergence of opinion would exist concerning any factor of importance bearing on cesarean section. This happy state can hardly be considered to have arrived, however, if one but scans the more recent publications.Our clinic is somewhat unusual in the interrelations of its three services. Each admits patients for a twenty-four-hour period in rotation, and the conduct of complicated labor is the responsibility of the . . .
Next-generation sequencing (NGS) in metastatic gastrointestinal cancer (mGIC) patients: Translation from sequence data into clinical practice.
Authors: Raphael Brandao Moreira, Matheus Bongers Alessandretti, Carina Mina Abrahao, Aline Da Rocha Lino, Tarcia Tarciane Soares de Sousa, Marcus Paulo Fernandes Amarante, Jessica Ribeiro Gomes, Rodnei Merlrina Martins Junior, Rafael Ferreira de Carvalho, Carolina Kawamura Haddad, Fabio Augusto Barros Schutz, Renata D'Alpino Peixoto, Marcelo Rocha Cruz, Fernando C. Maluf, Antonio C. Buzaid
Journal: Journal of Clinical Oncology (2015)

72 Background: A considerable number of patients with mGIC progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with the use of a NGS platform in refractory mGIC and its clinical utility. Methods: We retrospectively reviewed demographics, NGS results, and the suggested therapies received by patients undergoing NGS (Foundation Medicine, Cambridge, MA, USA): exonic sequencing of 236 genes and selective intronic sequencing from 19 genes for refractory mGIC. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 32 patients were tested. Primary tumors consisted of colorectal adenocarcinoma (37,5%), pancreatic adenocarcinoma (31,2%), gastric adenocarcinoma (12,5%), cholangiocarcinoma (12,5%) and hepatocellular carcinoma (6%). Most patients (87,5%) were found to harbor potentially actionable genetic alterations involving mitogen-activated protein kinase (93,7%), phosphatidylinositol 3-kinase-AKT (18,7%), p53 (50%) and cell-cycle regulation (9%) pathways. Of the 6 patients who received the suggested targeted therapy, 4 achieved an objective response. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations in the majority of advanced gastrointestinal cancer patients. The assay provided clinical benefit in 12% of the patients.
O115 : High antiviral activity of the HBV core inhibitor NVR 3-778 in the humanized uPA/SCID mouse model
Authors: K. Klumpp, T. Shimada, L Allweiss, T. Volz, M. Luetgehetman, O. Flores, G. Hartman, A. Lam, M. Dandri
Journal: Journal of Hepatology (2015)