tbuckley/cabot-search huggingface dataset:
Treatment of Orbital Rhabdomyosarcoma: Survival and Late Effects of Treatment—Results of an International Workshop
Authors: Odile Oberlin, Annie Rey, James Anderson, Modesto Carli, R. Beverley Raney, Joern Treuner, Michael C.G. Stevens
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS: A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS: At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION: These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.
Coffee intake and death from coronary heart disease
Authors: R. Marchioli, R. Di Mascio, R. M. Marfisi, F. Vitullo, G. Tognoni
Journal: BMJ (1996)

outcome but the one that produces the outcome that the patient favours.When patients are mentally incompetent an advance directive may express their wishes.Having ascertained that the directive was made in the light of knowledge of the medical facts and a clear understanding of
Abstract P051: Longitudinal Decline in Gait Speed is Associated with Hospitalization in the AGES Reykjavik Study
Authors: Kristin Siggeirsdottir, Thor Aspelund, Lenore J Launer, Tamara B Harris, Vilmundur Gudnason
Journal: Circulation (2014)

Background: Functional decline is a characteristic of old age measured by physical performance, such as gait speed and muscle strength. Poorer cardiovascular health may explain much of the functional decline with age. We studied the association of longitudinal change in gait speed and hospitalization, testing whether any association was secondary to baseline subclinical cardiovascular measurements, or physical function. Material and methods: Participants were from two phases of the longitudinal AGES Reykjavik Study. A population study of 3316 men and women (58%), who entered both stages 5 years apart, mean age 75.0 (SD 4.9) at baseline. The time in seconds (s) to walk 6m was measured at both visits. Baseline characteristics were Agatston score of coronary artery calcium (CAC), carotid plaque, carotid intima media thickness (IMT), type 2 diabetes mellitus, physical activity, quadriceps strength and activity of daily living (ADL). The study group was divided into two groups; those who were hospitalized during the follow-up and those who were not. Repeated measures models were used to estimate longitudinal change in gait speed. Results: Mean time to walk 6m was 6.0 (SD=1.2) (s) for men and 6.6 (SD=1.6) (s) for women at baseline and did not differ by hospitalization status. For those hospitalized after the baseline visit (73%) the increase in time to walk 6 m was 0.68 (95%CI: 0.60-0.76) (s) whereas for those not hospitalized the increase in time was significantly smaller (0.39 (95%CI: 0.29 - 0.52) (s), (p&lt;0.0001 for interaction). Those who were not hospitalized had significantly lower levels of CAC, IMT, carotid plaque, ADL, were more physically active, and had greater quadriceps strength (p&lt;0.05 for all measures). After adjustment for these baseline variables, the difference in longitudinal change in gait speed between those who were admitted to hospital and not admitted was still statistically significant. The risk was attenuated only by 7%. Conclusion: Individuals who were hospitalized showed greater decline in health, reflected in slower gait speed. This was not explained by cardiovascular status or other measured variables in this study related to health although those hospitalized had worse profile. This suggests that there are different trajectories influencing the rate of loss of gait speed explained by other factors than cardiovascular indices.
Total therapy 3 (TT3) for multiple myeloma (MM): Contributions to survival outcomes of dosing of maintenance components dexamethasone (D), thalidomide (T) and bortezomib (V).
Authors: F. Van Rhee, B. Barlogie, J. Szymonifka, E. J. Anaissie, B. P. Nair, S. Waheed, Y. Alsayed, N. Petty, J. D. Shaughnessy, A. Hoering, J. Crowley
Journal: Journal of Clinical Oncology (2010)

8121 Background: The role of maintenance therapy in the management of multiple myeloma remains unclear. Methods: TT3 applied 3 years of maintenance therapy with VTD in year 1 and TD in years 2 and 3. The impact was examined on overall survival (OS), event-free survival (EFS) and complete response (CR) incidence and its duration (CRD), and post-relapse survival (PRS) of cumulative doses of V, T and D, employing time-dependence methodology in Cox regression models relevant to induction, peri-transplantation, consolidation and maintenance. Results: Univariately, OS and EFS were longer with higher doses of all agents during induction, consolidation (except T) and maintenance (except V, T); CR rates were higher with V, T and D dosing during most phases; CRD was not affected by VTD dosing; PRS was longer with higher total V dosing and not compromised by T and D dosing prior to relapse. The independent favorable OS/EFS impact of D induction dosing provided the rationale for examining the expression of glucocorticoid receptor NR3C1, top-tertile levels of which significantly prolonged OS and EFS and rendered outcomes independent of D and T dosing, while T and D but not V dosing were critical to outcome improvement in the low-tertile NR3C1 setting. Conclusions: The absence of adverse effects on PRS of any of the VTD components with a benefit from V supports the use up-front of all active agents in a dose- dense and dose-intense fashion, as practiced in TT3, toward maximizing myeloma survival. The observation of NR3C1 top tertile levels being associated with superior and lower tertile levels with inferior survival outcomes support IFM data on the beneficial effect of amp5q31.3 where NR3C1 maps. No significant financial relationships to disclose.
Present Status of Dermabrasion
Authors: Ervin Epstein
Journal: JAMA (1968)

Probably planing is not here to stay. The cosmetic results do not justify its widespread use by dermatologists as a group in patients with scars of all types and causes. It has some applicability in properly selected individuals treated by experienced operators. The procedure is of definite value in externally caused precancerous skin, especially in actinic keratoses. However, this application is limited by the advanced age of many of these patients, the advent of topical chemosurgery, and the comparatively few physicians experienced in the use of dermabrasion in such conditions. At the present time, cutaneous planing may be regarded as a tottering senior citizen stripped of most of the glorious promise of its meteoric youth.
Homocysteine, B Vitamins, and Cognitive Impairment
Authors: A. David Smith, Helga Refsum
Journal: Annual Review of Nutrition (2016)

Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process. Homocysteine may interact with both risk factors and protective factors, thereby identifying people at risk but also providing potential strategies for early intervention. Public health steps to slow cognitive decline should be promoted in individuals who are at risk of dementia, and more trials are needed to see if simple interventions with nutrients can prevent progression to dementia.
Contrast-Enhanced TEE During Thoracic Endovascular Aortic Repair Procedure
Authors: Eustachio Agricola, Massimo Slavich, Luca Bertoglio, Efrem Civilini, Germano Melissano, Enrico Marone, Enrico Rinaldi, Andrea Fisicaro, Claudia Marini, Vincenzo Tufaro, Alberto Margonato, Roberto Chiesa
Journal: JACC. Cardiovascular imaging (2015)
O008 : Efficacy and safety of grazoprevir and elbasvir in hepatitis C genotype 1-infected patients with child–pugh class B cirrhosis (C-salt part A)
Authors: I.M. Jacobson, F. Poordad, R. Firpi-Morell, G.T. Everson, E.C. Verna, S. Bhanja, B. Zhang, L. Caro, J. Wahl, M. Robertson, E. Barr, E.D. Charles
Journal: Journal of Hepatology (2015)
Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University.
Authors: M P Mac Manus, R T Hoppe
Journal: Journal of Clinical Oncology (1996)

To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin's lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994.Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy.The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy.Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.
Cyclostomes Lack Clustered Protocadherins
Authors: Vydianathan Ravi, Wei-Ping Yu, Nisha E. Pillai, Michelle M. Lian, Boon-Hui Tay, Sumanty Tohari, Sydney Brenner, Byrappa Venkatesh
Journal: Molecular Biology and Evolution (2015)

The brain, comprising billions of neurons and intricate neural networks, is arguably the most complex organ in vertebrates. The diversity of individual neurons is fundamental to the neuronal network complexity and the overall function of the vertebrate brain. In jawed vertebrates, clustered protocadherins provide the molecular basis for this neuronal diversity, through stochastic and combinatorial expression of their various isoforms in individual neurons. Based on analyses of transcriptomes from the Japanese lamprey brain and sea lamprey embryos, genome assemblies of the two lampreys, and brain expressed sequence tags of the inshore hagfish, we show that extant jawless vertebrates (cyclostomes) lack the clustered protocadherins. Our findings indicate that the clustered protocadherins originated from a nonclustered protocadherin in the jawed vertebrate ancestor, after the two rounds of whole-genome duplication. In the absence of clustered protocadherins, cyclostomes might have evolved novel molecules or mechanisms for generating neuronal diversity which remains to be discovered.
Incidence and reasons for dose modification of standard-dose vs. high-dose imatinib mesylate (IM) in the Phase III Intergroup Study S0033 of patients (pts) with unresectable or metastatic gastrointestinal stromal tumor (GIST)
Authors: P. Dileo, C. J. Rankin, R. S. Benjamin, M. von Mehren, C. Blanke, V. Bramwell, R. Maki, C. Fletcher, E. C. Borden, G. D. Demetri
Journal: Journal of Clinical Oncology (2005)

9032 Background: IM benefits the majority of patients with metastatic GIST. Study S0033 aims to evaluate differences between two initial dose levels of IM (400 vs. 800 mg/day), with the crossover possible for pts on lower dose to increase dose in case of disease progression. Dose delays and reductions were required for defined toxicities. The present analysis was performed to analyze the incidence and reasons for dose modification in each arm on this multicenter trial. Methods: The dataset of S0033 (746 pts randomized) was analyzed; recorded dose levels of IM were tabulated and reasons for dose modifications assessed. Results: 350 eligible pts enrolled at 400 mg/day with information on dose modifications available on 335 pts. 126 (62%) had at least one dose delay and 34 (10%) had at least one dose reduction, due most commonly to rash, edema, and GI bleeding. 353 eligible pts enrolled at 800 mg/day IM, 337 with full dosing information. 189 (56%) had at least one dose delay and 148 (44%) had at least one dose reduction, due to edema, nausea, and fatigue. Of the subset of 112 eligible pts who eventually crossed over to higher dose IM due to PD, 108 had complete dosing information available prior to crossover: 33 (31%) had at least one dose delay and 6 (6%) had at least one dose reduction while on the lower dose IM, primarily for edema, GI bleeding, or nausea. Following crossover, in 77 pts with complete dosing information, 18 (23%) had at least one dose delay and 12 (16%) had at least one dose reduction, due to edema and rash. Conclusions: IM can be given safely in a multicenter study, although reductions in dose intensity were common. It is possible that management of toxicities could have been accomplished safely without the stringent dose reductions required by the protocol rules. Crossover to high dose IM was feasible with low incidence of required dose modifications. Further analyses of correlations between dose modifications and clinical outcomes (PFS, OS) are in progress. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma
Authors: Bree R. Eaton, Natia Esiashvili, Sungjin Kim, Briana Patterson, Elizabeth A. Weyman, Lauren T. Thornton, Claire Mazewski, Tobey J. MacDonald, David Ebb, Shannon M. MacDonald, Nancy J. Tarbell, Torunn I. Yock
Journal: Neuro-Oncology (2015)

Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) −1.19 (± 1.22) vs −2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.
Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing
Authors: María de Lourdes Moreno, Ángel Cebolla, Alba Muñoz-Suano, Carolina Carrillo-Carrion, Isabel Comino, Ángeles Pizarro, Francisco León, Alfonso Rodríguez-Herrera, Carolina Sousa
Journal: Gut (2015)

Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage.Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines.GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4-6 h after single gluten intake, and remained detectable for 1-2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery.GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development.NCT02344758.
Live attenuated oral vaccine, age and anti-Vi antibody status at baseline significantly affect attack rate in a human Salmonella Typhi challenge model
Authors: Thomas Darton, Claire Jones, Claire Waddington, Christoph Blohmke, Anna Peters, Kathryn Haworth, Christopher Green, Catherine Jeppesen, Maria Moore, Ben Thompson, Tessa John, Robert Kingsley, Ly-mee Yu, Merryn Voysey, Stephen Lockhart, Jeremy Farrar, Marcelo Sztein, Brian Angus, Myron Levine, Andrew Pollard
Journal: Journal of Infection (2015)
Increased diagnosis rates using ultrathin bronchoscopy and thin bronchoscopy with the EBUS-guide sheath method with virtual bronchoscopic navigation assistance
Authors: Masaki Anzai, Yukihiro Umeda, Miwa Morikawa, Chisato Honjo, Yasuyuki Sumida, Maiko Kadowaki, Shingo Ameshima, Takeshi Ishizaki, Tamotsu Ishizuka
Journal: European Respiratory Journal (2013)

Background  At our institution, we generally conduct an ultrathin (UT) (diameter 2.8 mm) bronchoscopy examination followed by a thin (diameter 4.0 mm) bronchoscopy examination using the EBUS-GS method, both with the assistance of virtual bronchoscopic navigation (VBN).  Methods  From May 1, 2011, to December 31, 2012, we examined 53 cases with an abnormal lung shadow less than 30 mm in diameter with UT bronchoscopy using VBN, followed by thin bronchoscopy with the EBUS-GS method and VBN.  Results  With assistance from VBN, we diagnosed 33 cases (62.3%) using UT bronchoscopy and 33 cases (62.3%) by thin bronchoscopy with EBUS-GS. Cases with a positive diagnosis were increased to 37 (69.8%) by the use of both. When limited to cancer cases, 32 (72.7%) were found positive using UT bronchoscopy and 32 (72.7%) were positive using thin bronchoscopy with EBUS-GS. The diagnosis rate was elevated to 81.8% (n=36) by use of both methods.  Conclusion  With the assistance of VBN, the diagnosis rates of UT bronchoscopy and thin bronchoscopy with EBUS-GS were not largely different. However, when both were utilized, the rate increased by 9.1% for cancer and 7.5% for all cases.
Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria
Authors: H Gisslinger, G Jeryczynski, B Gisslinger, A Wölfler, S Burgstaller, V Buxhofer-Ausch, M Schalling, M-T Krauth, A-I Schiefer, C Kornauth, I Simonitsch-Klupp, C Beham-Schmid, L Müllauer, J Thiele
Journal: Leukemia (2015)

Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.