tbuckley/cabot-search huggingface dataset:
Abstract POSTER-CTRL-1213: Whole exome and targeted resequencing, of population based ovarian cancer cases and controls, identifies susceptibility genes for ovarian cancer
Authors: Susan J. Ramus, Honglin Song, Ed Dicks, Maria Intermaggio, Jane Hayward, Jonathan P. Tyrer, Jacek Gronwald, Susanne Krüger Kjær, Alice Wittemore, Beth Karlan, Kunle Odunsi, Usha Menon, David D. Bowtell, Ellen L. Goode, Paul D.P. Pharoah, Simon A. Gayther
Journal: Clinical Cancer Research (2015)

Abstract The known genetic variance for epithelial ovarian cancer (EOC) accounts for less than half the familial risks of the disease. BRCA1 and BRCA2 are the major high-penetrance EOC susceptibility genes. More recently genes that interact with BRCA1 and BRCA2 in the same biological pathways, but conferring more moderate penetrance (e.g. RAD51C, RAD51D) have also been identified. Mutations in these genes result in defects in homologous recombination and double strand break repair (HR/DSB). We hypothesized that other genes operating in these and other DNA repair pathways may also confer EOC susceptibility. Whole exome sequencing data, available from more than 400 high-grade serous ovarian cancers, were used to identify 24 candidate genes harboring germline truncating mutations in at least 2 cases, followed by replication analysis using targeted resequencing in ~3,000 cases and 3,000 controls. Subjects were also sequenced for the known susceptibility genes listed above. The data confirmed the previously reported contributions of BRCA1, BRCA2, RAD51C and RAD51D to EOC. In addition, we identified BRIP1, and FANCM as candidate EOC susceptibility genes. Surprisingly, for several genes we found truncating mutations were equally prevalent in cases as they were in controls. These mutations may still represent rare low-penetrance susceptibility alleles for EOC, which we are too limited in sample size and power to confirm; or more likely, it indicates that cells can tolerate heterozygous loss-of-function mutations in apparently critical DNA repair genes without any impact on neoplastic development. These findings may have implications for risk prediction and prevention strategies for EOC and possibly for the identification of novel therapeutic targets. Citation Format: Susan J. Ramus, Honglin Song, Ed Dicks, Maria Intermaggio, Jane Hayward, Jonathan P. Tyrer, Jacek Gronwald, Susanne Krüger Kjær, Alice Wittemore, Beth Karlan, Kunle Odunsi, Usha Menon, David D. Bowtell, Ellen L. Goode, Paul D.P. Pharoah, Simon A. Gayther. Whole exome and targeted resequencing, of population based ovarian cancer cases and controls, identifies susceptibility genes for ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1213.
S106 Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS® trials in IPF
Authors: G Raghu, A Wells, AG Nicholson, L Richeldi, KR Flaherty, F Le Maulf, S Stowasser, R Schlenker-Herceg, DM Hansell
Journal: Thorax (2015)

<h3>Introduction</h3> The two replicate, randomised, placebo-controlled, 52-week INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with IPF. The primary endpoint was met in both trials; nintedanib significantly reduced the annual rate of decline in FVC compared with placebo, consistent with a slowing of disease progression. <h3>Methods</h3> To qualify for the INPULSIS® trials if a surgical lung biopsy was unavailable, patients needed to have a high-resolution computed tomography (HRCT) scan showing honeycombing and/or a combination of reticular abnormality and traction bronchiectasis, without features suggestive of alternative causes. Surgical lung biopsies, if available, were used to confirm eligibility. A <i>post-hoc</i> subgroup analysis of patients with diagnosis based on honeycombing and/or confirmation of usual interstitial pneumonia (UIP) by biopsy versus patients with no honeycombing and no biopsy was undertaken using pooled data from both trials. <h3>Results</h3> 723 patients (425 nintedanib, 298 placebo) had honeycombing and/or confirmation by biopsy and 338 (213 nintedanib, 125 placebo) had no honeycombing or biopsy for diagnosis of IPF. Demographics and baseline characteristics were similar between these subgroups. In patients with honeycombing and/or biopsy, the adjusted annual rate of decline in FVC was -108.7 mL/year with nintedanib and -225.7 mL/year with placebo (difference: 117.0 mL/year [95% CI: 76.3, 157.8]); in patients with no honeycombing or biopsy, it was -122.0 mL/year with nintedanib and -221.0 mL/year with placebo (difference: 98.9 mL/year [95% CI: 36.4, 161.5]). The treatment by subgroup interaction p-value was not significant for the primary endpoint (p = 0.81) or for the key secondary endpoints of time to first acute exacerbation (p = 0.37) or change from baseline in St George’s Respiratory Questionnaire total score (p = 0.67), indicating that the treatment effect of nintedanib was not statistically significantly different between the subgroups. <h3>Conclusion</h3> Decline in FVC in placebo arms was virtually identical in patients with A) the presence of honeycombing and/or biopsy confirmation of UIP; and B) the absence of both, but features of “possible UIP” on HRCT. Nintedanib slowed FVC decline equally in both sub-groups. These findings have major implications for diagnosis and clinical trial design.
"Artificial Wrist"
Authors: A. M. Sallam
Journal: BMJ (1954)

The "Artificial Wrist"I (Intentional Pseudoarthrosis in Colles's Fracture)Non-union very rarely occurs in Colles's fracture.Watson-Jones (1941) and Hamada (1944) each reported a case.In both cases non-union presented a problem for which a suit- able answer had to be sought.In the first case non-union occurred after a simple comminuted fracture which could not be properly immobilized; the second case was an old septic compound fracture.In managing both these cases the aim was naturally to establish union (Nation'al Research Council, 1943).The following case is presented to show that non-union is not always an evil, but may, on the contrary, be very desirable. CASE REPORTIn 1947 a 28-year-old man, while trying to start a car, held the handle with both hands.After a few turns the engine started, but he could not take the handle away quickly I li(, I(,
Théophraste Renaudot (1586–1653)
Authors: Robert M. Goldwyn
Journal: New England Journal of Medicine (1958)

THE remarkable accomplishments of the very versatile physician Théophraste Renaudot stirred the seventeenth century; yet the founder of France's first unemployment agency, its first free medical clinic, its first pawnshop and its first newspaper has been peculiarly, and ungratefully, ignored.In 1586 Renaudot was born into a rich Protestant family of Loudun, France. He journeyed to Paris in his teens and served as an apprentice to a surgeon barber. Unwelcomed as a Protestant by the Paris Medical Faculty, he left Paris and went to the more tolerant University of Montpellier, where he obtained his medical degree in three months — . . .
Risks Associated with Exchange Transfusion
Authors: William J. Jablonski
Journal: New England Journal of Medicine (1962)

ALTHOUGH most medical centers perform exchange transfusions on newborn infants if the bilirubin reaches levels of 18 to 20 mg. per 100 ml. in the first few days of life1 2 3 4 there are many who doubt its necessity as a routine procedure at these levels.5 6 7 8 Since the decision to perform an exchange transfusion is based essentially on the risks inherent in the procedure itself versus those associated with the concentration of serum bilirubin, more precise knowledge of these hazards would enable the operator to make his decision on a more rational basis. Moreover, there is still wide variation in the literature . . .
RTRB-24SYMBIOSIS BETWEEN GBM CELL SUBPOPULATIONS, WITH OR WITHOUT EGFR AMPLIFICATION, IS A NEW MECHANISM OF TUMOR RESISTANCE TO RADIATION THERAPY
Authors: Yi-Hong Zhou, Yumay Chen, Katherine Tran, Liping Yu, Mark Linskey, Ping Wang, Charles Limoli
Journal: Neuro-Oncology (2015)

BACKGROUND: EGFR amplification in a tumor cell subpopulation was frequently found of GBMs, through multiple copies of chromosome 7 fragment known as EGFR double minute. Intra-tumoral heterogeneity is thought to confer a survival advantage to tumor, and may be the basis for the observed resistance to therapeutic interventions such as irradiation - a frontline therapy for malignant gliomas. However, direct evidence supporting this hypothesis is currently limited. We have established two syngeneic primary cultures (51A and 51B) of a recurrent GBM with high level of EGFR amplification, under neural sphere (NS) and serum adherent (SA) and culture conditions for more than three months or eight passages, respectively. EGFR-FISH analysis showed 77% cells in 51A carrying EGFR double minute, while absence of such cell subpopulation in 51B. In comparison to 51B, 51A showed higher levels of invasiveness and cell doubling time. METHODS: To study symbiosis between GBM cell subpopulations with or without EGFR amplification in response to radiation, we firstly compared their differential response to radiation on growth/survival, cellular bioenergetics and redox, and cell invasiveness. Then using matrigel invasion assay, we analyzed the effect of radiated 51A to un-radiated 51B cells on their invasiveness, after 1-week culture with serum-supplied conditioned medium of 51A (0 or 0.5GyX10d). RESULTS: Both mitochondrial and glycolytic respirations were increased in 51A but decreased in 51B, 1 week post a 2-Gy dose of irradiation. Reactive oxygen species (ROS) level was increased in 51A, which was not shown in 51B, even after a 5-Gy dose of radiation. Consistently, 51A was more radio-resistance compared to 51B. Interestingly, 51B cells cultured for 1 week in conditioned medium of radiated 51A cells doubled their invasion activity. CONCLUSIONS: There exists a symbiotic relationship between GBM cell subpopulations, with or without EGFR amplification, which supports overall tumor growth/expansion under radiation therapy.
Donor-Derived Acute Promyelocytic Leukemia in a Liver-Transplant Recipient
Authors: Imre Bodó, Marion Peters, Jerald P. Radich, Jay Hess, Morey Blinder, Michael S. Watson, Richard Van Rheeden, Shanti Natarajan, Jeffrey A. Lowell, Randy Brown, John DiPersio, Douglas Adkins
Journal: New England Journal of Medicine (1999)

The long-term survival of donor lymphoid cells in recipients of solid-organ transplants or of fetal lymphocytes that cross the placenta and enter the maternal circulation has been established,1–3 but the fate of other hematopoietic progenitors in organ allografts, especially those of the myeloid lineage, is not known. We describe a case in which acute promyelocytic leukemia developed in a recipient of a liver transplant two years after transplantation. The leukemic clone had genetic and phenotypic markers of the donor, a previously healthy 16-year-old boy who died of a head injury. Our findings indicate that leukemic transformation of donor myeloid . . .
Case 13-2008
Authors: Nikhil C. Munshi, Subba Digumarthy, Aliyah Rahemtullah
Journal: New England Journal of Medicine (2008)

A 46-year-old man with rheumatoid arthritis was seen in the hematology–oncology clinic because of anorexia and generalized lymphadenopathy. One month earlier, diffuse lymphadenopathy developed in his neck, axillae, and groin, associated with sore throat and loss of appetite but not with weight loss. Serum protein electrophoresis disclosed a monoclonal spike in the gamma region. A diagnostic procedure was performed.
Adoption of Gene Expression Profiling for Breast Cancer in US Oncology Practice for Women Younger Than 65 Years
Authors: Suzanne C. O'Neill, Claudine Isaacs, Calvin Chao, Huei-Ting Tsai, Chunfu Liu, Bola F. Ekezue, Nandini Selvam, Larry G. Kessler, Marc D. Schwartz, Tania Lobo, Arnold L. Potosky
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: A number of practice guidelines incorporate the use of gene expression profiling (GEP) tests for early-stage, hormone receptor–positive, HER2-negative breast tumors. Few studies describe factors associated with GEP testing in US oncology practice. We assessed the relationship between clinical, demographic, and group-level socioeconomic variables and test use in women younger than 65 years. Patients and Methods: Data from 5 state cancer registries were linked with insurance claims data and GEP test results. We assessed rates of testing and variables associated with test use in an incident cohort of 9,444 commercially insured women younger than 65 years, newly diagnosed with stage I or II hormone receptor–positive breast cancer from 2006 through 2012. Results: Rates of testing for women with N0 disease increased from 20.4% in 2006 to 35.2% in 2011. Variables associated with higher rates of testing, beyond clinical factors such as nodal status (P<.001), included being diagnosed from 2008 through 2012 versus 2006 through 2007 (adjusted odds ratio [OR], 1.67; 95% CI, 1.47–1.90), having preexisting comorbidities (adjusted OR, 1.35; 95% CI, 1.14–1.59), and higher out-of-pocket pharmacy costs (adjusted OR, 1.66; 95% CI, 1.40–1.97). Women younger than 50 years were more likely to be tested if they had stage I versus stage II disease (P<.0001). Conclusions: In an insured population of women younger than 65 years, GEP testing increased after its inclusion in clinical practice guidelines and mounting evidence. Additional research is needed to better understand oncologists' decision not to order GEP testing for their patients who are otherwise eligible.
Updated analysis of the NCIC CTG MA.17 randomized placebo (P) controlled trial of letrozole (L) after five years of tamoxifen in postmenopausal women with early stage breast cancer
Authors: P. E. Goss, J. N. Ingle, S. Martino, N. J. Robert, H. B. Muss, M. J. Piccart, M. M. Castiglione, D. Tu, L. E. Shepherd, J. L. Pater
Journal: Journal of Clinical Oncology (2004)

847 Background: Over half of recurrences and two thirds of deaths from hormone dependent breast cancer occur after completion of 5 years of adjuvant tamoxifen. We previously reported an improvement in disease free survival in women receiving extended adjuvant treatment with L after tamoxifen. Toxicities reported up until February 2003, 8 months prior to unblinding of the study medication, were low grade and included vasomotor symptoms, arthritis, joint and muscle pain. Hypercholesterolemia and cardiovascular events were similar in both arms and while new patient-reported diagnoses of osteoporosis were slightly more common (5.8% vs 4.5% L vs P), clinical fracture rate was unchanged by L. Methods: The study database was locked as of August 2003 for analysis of events in disease free survival (DFS) which were local or distant recurrence or new contralateral breast cancer. A subset analysis of outcome according to nodal status was performed. A full and updated analysis of all study endpoints, including safety and quality of life, as of the date of unblinding the trial (October 9 2003) will be conducted in mid-January 2004. Results: 5187 patients were randomized. Demonstration of an improvement in DFS was achieved earlier than anticipated (P = 0.00008 at the first interim analysis) with a hazard rate of 0.57, indicating a 43% reduction in risk. L decreased the risk of events by 53% and 40% for node negative and node positive patients respectively. This translated into an absolute improvement in 3-year disease free survival of 3% and 7% in node negative and node positive patients, respectively. Conclusions: Letrozole is indicated as extended adjuvant therapy for the majority of breast cancer patients completing about 5 years of tamoxifen regardless of nodal status. Further data from the updated analysis will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis; Pfizer Novartis; Pfizer AstraZeneca; Novartis
Case 4-1995
Authors: S. Levitsky, V. Nickeleit
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 26-year-old woman was readmitted to the hospital 81/2 weeks after a triple coronary-artery bypass procedure because of unstable angina.First AdmissionThe patient had been well until five months before admission, when she began to have substernal “tightness” during brisk walks, with relief after several minutes of rest. Two months before admission she had two bouts of pain while driving a car. An electrocardiographic stress test showed inferior and lateral ischemia; atenolol and nitroglycerin were prescribed. One day before admission a coronary angiographic examination, performed at another hospital, revealed severe ostial narrowing of the left . . .
Employment status and work-related difficulties in family caregivers of terminal cancer patients compared with the general population
Authors: S. Kim, J. Lee, Y. Yun, S. Kim, S. Kim, Y. Do, J. Ro, S. Park, H. Jeong, J. Kang
Journal: Journal of Clinical Oncology (2009)

9580 Background: This study was aimed to investigate the employment status and work-related difficulties among family caregiver of terminal cancer patients compared with the general population. Methods: A survey was administered to 381 family caregivers of terminal cancer patients at 11hospitals and 994 general populations aged more than 18 years. Results: Family caregivers of terminal cancer patients were female (66.7%) and the patient's spouse (50.9%), with mean age of 46.8years (SD, 13.5). 212(56.1%) were working before cancer diagnosis, however, only 133(36.3%) continued working currently. Compared with the general population, 233(63.7%)family caregivers of terminal cancer patients were more likely to be not working (adjusted odds ratio [aOR] =2.39; 95% confidence interval [95%CI] = 1.73 to 3.29).Those who continued working reported more easy fatigability (40.6% vs 22.4%) and reduced working hours (20.3% vs 2.1%) than general population. For those doing housework, caregiving itself (56.4%) were identified to be the most common difficulties, followed by easy fatigability (32.3%). Major reasons for not working were providing care to the terminal cancer patients (24.0%). Older age (aOR=10.37; 95%CI=2.80 to 38.41), female sex (aOR=4.28; 95%CI=2.25 to 8.13), lower household income (aOR=2.19; 95%CI=1.19 to 4.06), bearing medical cost by other than spouse (aOR=2.10; 95%CI=1.05 to 4.19), and low performance status of the patients (aOR=2.00; 95%CI=1.01 to 3.95) were significantly associated with not working. Conclusions: When compared to the general population, family caregivers of terminal cancer patients were at risk job loss from their caregiving burden, and caregiving and easy fatigability were the major work-related difficulties. Our study might help make a strategy to reduce job loss for family caregivers' caregiving burden. No significant financial relationships to disclose.
Case 51-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Thomas M. Walshe, Wanda Szyfelbein
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 92-year-old woman was admitted to the hospital because of diplopia and weakness of the right facial nerve and left leg.There was a history of hypothyroidism, managed with levothyroxine. She was otherwise in good health until about two years earlier, when her family began to notice intermittent mild confusion. Ten months before admission the patient felt slightly fatigued and unsteady. A physician found that she had discontinued the levothyroxine and advised her to resume it. During the next year the patient was well except for occasional dizziness. Three months before entry there was an exacerbation of . . .
The Effect of Antenatal Phenobarbital Therapy on Neonatal Intracranial Hemorrhage in Preterm Infants
Authors: Seetha Shankaran, Lu-Ann Papile, Linda L. Wright, Richard A. Ehrenkranz, Lisa Mele, James A. Lemons, Sheldon B. Korones, David K. Stevenson, Edward F. Donovan, Barbara J. Stoll, Avroy A. Fanaroff, William Oh, Joel Verter, George A. Taylor, JoAnna Seibert, Michael DiPietro
Journal: New England Journal of Medicine (1997)

The administration of phenobarbital to pregnant women before delivery has been thought to decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this potential neuroprotective therapy further, we determined the effect of antenatal administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and early death.We studied 610 women who were 24 to 33 weeks pregnant and who were expected to deliver their infants within 24 hours. The women were randomly assigned to receive either phenobarbital (10 mg per kilogram of body weight) or placebo intravenously, followed by maintenance doses until delivery or 34 weeks of gestation. The infants born to these women underwent cranial ultrasonography to detect the presence of intracranial hemorrhage.There were 309 women in the phenobarbital group and 301 in the placebo group. A total of 247 women (80 percent) in the phenobarbital group and 235 (78 percent) in the placebo group delivered within 24 hours after infusion of the study drug or administration of the last maintenance dose. Intracranial hemorrhage or early death occurred in 83 of the 344 infants born to the women in the phenobarbital group (24 percent) and in 74 of the 324 born to the women in the placebo group (23 percent; risk ratio for the infants in the phenobarbital group, 1.1; 95 percent confidence interval, 0.8 to 1.4). Among infants born before 34 weeks' gestation in whom ultrasonographic studies were performed, intracranial hemorrhage was diagnosed in 70 of 311 infants in the phenobarbital group (23 percent) and 64 of 279 in the placebo group (23 percent; risk ratio, 1.0; 95 percent confidence interval, 0.8 to 1.4).Antenatal administration of phenobarbital does not decrease the risk of intracranial hemorrhage or early death in preterm infants.
Case 5-1999
Authors: Paul R. Skolnik, Eugene J. Mark
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 37-year-old man was admitted to the hospital because of fever, chills, and diffuse lymphadenopathy.Eight weeks before this admission, the patient entered a rehabilitation hospital for alcohol detoxification. He had a two-week history of fever, chills, myalgia, and a sore throat. The white-cell count was 2100 per cubic millimeter. He had a seizure disorder for which he took carbamazepine; at the rehabilitation hospital, phenobarbital was substituted for the carbamazepine. Treatment with human granulocyte colony-stimulating factor was begun. Five blood-culture specimens were negative. Treatment with oxacillin and gentamicin was ineffective, and the patient was transferred to this . . .
Gastric Acid Secretion after Parenterally and Intragastrically Administered Histamine in Patients with Portacaval Shunt
Authors: Rodman J. Bendett, Harvey L. Fritz, R. M. Donaldson
Journal: New England Journal of Medicine (1963)

SEVERAL recent reports1 2 3 4 5 have suggested that peptic ulceration may be a complication of portal–systemic shunt surgery. It has been firmly established in dogs that gastric acid secretion is enhanced when portal blood is diverted around the liver by a variety of technics.6 7 8 This augmentation occurs in dogs not only in the fasting state9 , 10 and after test meals6 , 7 , 9 10 11 but also after the intrajejunal12 or parenteral7 , 9 , 10 , 12 administration of histamine. It has also been reported that the experimental production of ulcer can be facilitated by alteration of the portal circulation.1 , 8 , 13 It is not clear whether these studies of gastric function in dogs are . . .