tbuckley/cabot-search huggingface dataset:
Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma
Authors: Yuri E. Nikiforov, Raja R. Seethala, Giovanni Tallini, Zubair W. Baloch, Fulvio Basolo, Lester D. R. Thompson, Justine A. Barletta, Bruce M. Wenig, Abir Al Ghuzlan, Kennichi Kakudo, Thomas J. Giordano, Venancio A. Alves, Elham Khanafshar, Sylvia L. Asa, Adel K. El-Naggar, William E. Gooding, Steven P. Hodak, Ricardo V. Lloyd, Guy Maytal, Ozgur Mete, Marina N. Nikiforova, Vania Nosé, Mauro Papotti, David N. Poller, Peter M. Sadow, Arthur S. Tischler, R. Michael Tuttle, Kathryn B. Wall, Virginia A. LiVolsi, Gregory W. Randolph, Ronald A. Ghossein
Journal: JAMA Oncology (2016)

Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
Economic Analysis of First-Line Treatment with Erlotinib in an EGFR -Mutated Population with Advanced NSCLC
Authors: Alain Vergnenegre, Bartomeu Massuti, Filippo de Marinis, Enric Carcereny, Enriqueta Felip, Pascal Do, Jose Miguel Sanchez, Luis Paz-Arez, Christos Chouaid, Rafael Rosell
Journal: Journal of Thoracic Oncology (2016)
miR-339-3p Is a Tumor Suppressor in Melanoma
Authors: Claudia E.M. Weber, Chonglin Luo, Agnes Hotz-Wagenblatt, Adriane Gardyan, Theresa Kordaß, Tim Holland-Letz, Wolfram Osen, Stefan B. Eichmüller
Journal: Cancer Research (2016)

Determinants of invasion and metastasis in cancer remain of great interest to define. Here, we report the definition of miR-339-3p as a novel tumor suppressive microRNA that blocks melanoma cell invasion without affecting cell survival. miR-339-3p was identified by a comprehensive functional screen of a human miRNA mimetic library in a cell-based assay for invasion by the melanoma cell line A375. miR-339-3p was determined as a strong inhibitor of invasion differentially expressed in melanoma cells and healthy melanocytes. MCL1 was defined as a target for downregulation by miR-339-3p, functioning through direct interaction with the 3' untranslated region of MCL1 mRNA. Blocking miR-339-3p by an antagomiR was sufficient to increase melanoma cell invasion, an effect that could be phenocopied by RNAi-mediated silencing of MCL1. In vivo studies established that miR-339-3p overexpression was sufficient to decrease lung colonization by A375 melanoma cells in NSG mice, relative to control cells. Overall, our results defined miR-339-3p as a melanoma tumor suppressor, the levels of which contributes to invasive aggressiveness. Cancer Res; 76(12); 3562-71. ©2016 AACR.
Vitamin D–Receptor Gene Polymorphisms and Bone Density in Prepubertal American Girls of Mexican Descent
Authors: Jesus Sainz, Jan M. Van Tornout, M. Luiza Loro, James Sayre, Thomas F. Roe, Vicente Gilsanz
Journal: New England Journal of Medicine (1997)

Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D–receptor genotype to skeletal development and variation in the size, volume, and density of bone in children.
Case 14-2004
Authors: Igor J. Koralnik, Dawid Schellingerhout, Matthew P. Frosch
Journal: New England Journal of Medicine (2004)

A 66-year-old man developed progressive left-sided weakness over a two-month period. He was a renal-transplant recipient and had alcoholic cirrhosis, diabetes, and coronary artery disease. Magnetic resonance imaging studies showed, on T2-weighted images, a hyperintense lesion in the left frontal white matter, which gradually enlarged. New lesions developed in the right frontal area and brain stem. A diagnostic procedure was performed.
An Evaluation of Early or Delayed Adjuvant Chemotherapy in Premenopausal Patients with Advanced Breast Cancer Undergoing Oophorectomy
Authors: David L. Ahmann, Michael J. O'Connell, Richard G. Hahn, Harry F. Bisel, Raymond A. Lee, John H. Edmonson
Journal: New England Journal of Medicine (1977)

We treated randomly 75 premenopausal patients with advanced breast cancer with combination chemotherapy (5-fluorouracil, cyclophosphamide and prednisone), either as an early adjunct to oophorectomy or as a delayed treatment upon appearance of progressive metastatic disease after operation. The group receiving early systemic chemotherapy enjoyed an improved response rate, an improved survival rate and, most importantly, an improved progression-free interval (median of 53 versus 17 weeks). With the exclusion of the group with early (within three weeks after oophorectomy) progression, the progression-free intervals had a median duration of 77 weeks in the early-treatment group versus 33 weeks in the control group. The early-progression group did exceedingly poorly, although systemic chemotherapy was employed at that juncture, having a median survival of 22 weeks as compared to 144 weeks in the immediate-treatment group and 105 weeks in the control group.
Influence of Positive End-Expiratory Pressure on Left Ventricular Performance
Authors: François Jardin, Jean-Christian Farcot, Louis Boisante, Nikita Curien, André Margairaz, Jean-Pierre Bourdarias
Journal: New England Journal of Medicine (1981)

Although left ventricular dysfunction is common during ventilatory support with positive end-expiratory pressure (PEEP), the mechanism of this disorder remains unclear. In 10 patients with the adult respiratory-distress syndrome we studied the effects of a stepwise increase in PEEP from 0 to 30 cm H2O on left ventricular output, intracardiac transmural pressures, and two-dimensional echocardiographic measurements of left ventricular cross-sectional area at end-systole and at end-diastole. Increasing PEEP was associated with progressive declines in cardiac output, mean blood pressure, and left ventricular dimensions and with equalization of right and left ventricular filling pressures. The radius of septal curvature decreased at both end-diastole and end-systole, implying a leftward shift of the interventricular septum. At the highest PEEP, blood-volume expansion did not restore cardiac output, although left ventricular transmural filling pressures had returned to base-line values. We conclude that decreased cardiac output during PEEP is mediated by a leftward displacement of the interventricular septum, which restricts left ventricular filling. (N Engl J Med. 1981; 304:387–92.)
Optic-Nerve Degeneration in Alzheimer's Disease
Authors: David R. Hinton, Alfredo A. Sadun, Janet C. Blanks, Carol A. Miller
Journal: New England Journal of Medicine (1986)

Alzheimer's disease is a dementing disorder of unknown cause in which there is degeneration of neuronal subpopulations in the central nervous system. In postmortem studies, we found widespread axonal degeneration in the optic nerves of 8 of 10 patients with Alzheimer's disease. The retinas of four of the patients were also examined histologically, and three had a reduction in the number of ganglion cells and in the thickness of the nerve-fiber layer. There was no retinal neurofibrillary degeneration or amyloid angiopathy, which are typically seen in the brains of patients with Alzheimer's disease. The changes we observed in the patients with Alzheimer's disease were clearly distinguishable from the findings in 10 age-matched controls and represent a sensory-system degeneration that occurs in Alzheimer's disease. Study of the retina in patients with this disease may be helpful diagnostically, and isolation of the affected ganglion cells may facilitate molecular analysis of the disorder. (N Engl J Med 1986; 315:485–7.)
Abstract IA42: Interpreting the role of acquired gene mutations in defining clinical outcome and treatment response.
Authors: Elli Papaemmanuil
Journal: Clinical Cancer Research (2015)

Abstract Recent sequencing studies in MDS, have identified a diverse range of somatic mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation and cell signalling. Similar to most cancers and other haematological neoplasms the genomic landscape of MDS is composed by a small number of frequently (&amp;gt;10% of the patient population) mutated genes accompanied by a long list of genes that are infrequently mutated (&amp;lt;3%). Importantly the majority of MDS patients have two or more oncogenic mutations (defined by gene mutation or structural variation) with evidence of specific pairwise interactions and intra-clonal heterogeneity. Whilst new gene discoveries improve our understanding of the molecular aetiology of this disease, a detailed evaluation of how the individual genetic contributions as well as the frequently observed genotype interactions and clonal relationships correlate with treatment response is warranted. Next generation sequencing based approaches, deliver quantitative profiles of the composite genomic architecture, support the identification of the key molecular lesions and reconstruction of partial clonal phylogenies from a single sample. Profiling of sequential specimens before and after treatment allows for the first time to track response at a clonal level, providing important new insights into the molecular mechanisms of therapeutic response as well as resistance. Examples of how mutational profiling of samples before, during and after treatment allow for detailed definition of clonal response and the related genetic changes will be presented. The complex genetic architecture, and the large proportion of infrequently mutated genes impose great challenges to the identification of robust and reliable gene-treatment interactions and overall clinical outcome predictions. Importantly, these effects can be modified by comorbidities, performance status and age amongst other demographic variables. Systematic characterisation of well-annotated and large (&amp;gt;1000) clinical trial samples are necessary to accurately define risk contributions and support the development of molecularly guided prognostication and predictive algorithms in the future. Citation Format: Elli Papaemmanuil. Interpreting the role of acquired gene mutations in defining clinical outcome and treatment response. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA42.
Eosinophilia with Aberrant T Cells and Elevated Serum Levels of Interleukin-2 and Interleukin-15
Authors: Melissa Means-Markwell, Timothy Burgess, Dominic deKeratry, Kevin O'Neil, John Mascola, Thomas Fleisher, Daniel Lucey
Journal: New England Journal of Medicine (2000)

The hypereosinophilic syndrome comprises various idiopathic myeloproliferative disorders with sustained eosinophilia and damage to the heart, lungs, skin, and other organs by infiltrating eosinophils.1 A single mechanism for this syndrome has not been identified, and multiple factors are likely to be involved. The serum level of interleukin-5, an eosinophilopoietic cytokine, is increased in some patients with the hypereosinophilic syndrome,2 and a few have been found to have unusual T-cell abnormalities, including CD3–CD4+CD8– T cells3,4 and so-called double-negative CD3+CD4–CD8– T cells.5 CD3, a complex of five proteins associated with the T-cell receptor, is a distinctive feature of all normal T . . .
Ten-Year Survival after Coronary Bypass Surgery for Unstable Angina
Authors: Shahbudin H. Rahimtoola, David Nunley, Gary Grunkemeier, Joseph Tepley, Louis Lambert, Albert Starr
Journal: New England Journal of Medicine (1983)

We have assessed the long-term results of coronary bypass surgery performed for unstable angina in 1282 patients from 1970 to 1982. The operative mortality was 1.8 per cent; in the first 4 years it was 2.5 per cent, and in the last 8 1/2 years it was 1.7 per cent. Using actuarial techniques, we determined that the 5-year and 10-year survival rates (mean +/- S.E.) were 92 +/- 1 per cent and 83 +/- 2 per cent, respectively, for the whole group. For patients with "normal" left ventricular function, they were 92 +/- 2 per cent and 86 +/- 3 per cent, and for patients with "abnormal" left ventricular function 91 +/- 2 per cent and 79 +/- 4 per cent (P = 0.14). No significant differences were observed in the long-term survival for any of the three clinical subgroups of patients with unstable angina--angina at rest, angina after recovery from acute myocardial infarction, and progressive angina of recent onset (P = 0.49). The reoperation rates at 5 and 10 years were 6 +/- per cent and 17 +/- 3 per cent. Currently, 61 per cent of the survivors have no angina; angina occurs on severe exertion in 20 per cent, on ordinary exertion in 14 per cent, and on mild exertion in 5 per cent. We conclude that coronary bypass surgery is an effective form of therapy (for up to 10 years) in patients with unstable angina.
Profound Bleeding after Dental Extractions during Dicumarol Therapy
Authors: Albert M. Ziffer, Irwin W. Scopp, Jan Beck, John Baum, A. R. Berger
Journal: New England Journal of Medicine (1957)

ANTICOAGULANT therapy, often maintained for months or years, is used widely in the management of actual or anticipated thromboembolic states. Drug-induced alteration of the clotting mechanism of the blood not only inhibits or retards beneficially intravascular coagulation but also creates simultaneously the hazard of hemorrhage. The hazard may be increased if the patient on such a regimen should undergo surgical intervention while prothrombic (or other coagulant) activity is reduced markedly. The potentially serious bleeding that occurred in 2 patients when dental extractions were performed during hypoprothrombinemia induced at therapeutic levels is the subject of this report.Case ReportsCase 1. . . .
A Comparison of Bronchodilator Therapy with or without Inhaled Corticosteroid Therapy for Obstructive Airways Disease
Authors: Huib A.M. Kerstjens, Paul L.P. Brand, Michael D. Hughes, N. Jamie Robinson, Dirkje S. Postma, Henk J. Sluiter, Eugene R. Bleecker, P.N. Richard Dekhuijzen, Petra M. de Jong, Hein J.J. Mengelers, Shelley E. Overbeek, Danielle F.M.E. Schoonbrood
Journal: New England Journal of Medicine (1992)

The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group.The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.
Anti-Mullerian hormone (AMH) and ovarian function in young breast cancer (BC) women receiving adjuvant chemoterapy (CT)
Authors: S. Giraudi, P. Marroni, L. Boni, C. Bighin, A. Levaggi, G. Bini, P. Taveggia, M. Venturini, P. Pronzato, L. Del Mastro
Journal: Journal of Clinical Oncology (2009)

e11544 Background: Fertility loss is a main side effect of adjuvant CT in young women with BC. AMH was evaluated as a potential marker of residual ovarian function after CT. Method: AMH (ng/mL), FSH (mIU/mL), E2 (pg/mL) and menstrual activity were evaluated before CT and every 3 months after CT in pre-menopausal BC patients ( pts ) enrolled in a phase III study evaluating the role of triptorelin in the prevention of CT-induced early menopause. Means were compared with Student t test for paired data, anova or ancova. The effect of age, CT regimen, FSH and AMH on time to menstrual resumption was investigated by means of the Cox's proportional hazards model. Results: Among 26 evaluable pts at baseline, mean age was 39 years (range 27-45). Baseline mean values were: FSH 5.67 (SD 4.88), E2 151.81 (SD 134.9), AMH 2.67 (SD 1.85). Levels of AMH were significantly lower (1.26) in old pts ( ≥ 41 yrs) as compared to younger ones (2.97 and 3.63 in 25–36 yrs and 37–40 yrs old women, respectively) (p=0.018). After CT, mean value of AMH significantly decreased from 2.04 ( SD 1.44 ) to 0.59 ( SD 0.59 ) (p=0.0003 ); FSH value increased, from of 8.64 (SD 12.99) to 23.13 (SD 25.80) (p=0.017) and E2 values decreased from 159.71 (SD 147.03) to 73.29 (SD 129.53) (p=0.02). The mean decrease of AMH levels was not affected by the type of CT regimens: -1.50, -1.52 and -1.33 after FEC ⋄ Paclitaxel, FEC ⋄ Taxotere and FEC/CMF, respectively (p=0.97). Among 10 pts with both early (0–5 months) and delayed (6–11 months) post-CT evaluations, no change in AMH values was observed with longer follow up: mean values were 1.49, 0.35 and 0.36, at baseline, after 0–5 months and after 6–11 months, respectively. Menstrual activity resumption occurred in 48% of patients. At multivariate analysis factors significantly associated with the lower probability of menstrual activity resumption after CT were: old age (p=0.05) and chemotherapy with FEC ⋄ docetaxel ( p=0.05 ). In this preliminary analysis baseline and after CT values of AMH were not significantly associated with menstrual resumption. Conclusions: Adjuvant CT significantly affects the levels of AMH in young women with BC. Further studies are needed to assess the role of AMH as a surrogate of ovarian toxicity induced by CT. No significant financial relationships to disclose.
Parathyroid Function in Sarcoidosis
Authors: William G. Cushard, Arthur B. Simon, Janet M. Canterbury, Eric Reiss
Journal: New England Journal of Medicine (1972)

Parathyroid hormone (PTH) concentration was determined by radioimmunoassay in serum specimens in 26 unselected cases of sarcoidosis. Although only six of these patients had hypercalcemia, PTH was unmeasurably low in 19. Of the seven with normal levels, five received steroid therapy at the time of study. PTH levels were low regardless of the apparent activity of the disease and were not correlated with serum calcium concentrations. PTH was unmeasurably low in sarcoidosis even when complicated by moderate renal insufficiency, a condition that ordinarily provokes secondary hyperparathyroidism. Hypercalcemic sarcoid patients with high PTH concentrations were found to have coexistent parathyroid adenomas or hyperplasia. In such cases, hypercalcemia did not respond to steroid therapy, but was corrected by surgery. The data indicate that most patients with sarcoidosis have functional hypoparathyroidism. This fits well with the recognized abnormalities of calcium metabolism in sarcoidosis, since excessive absorption of calcium from the gastrointestinal tract should reduce PTH secretion.