tbuckley/cabot-search huggingface dataset:
A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213
Authors: S.H. Bernstein, E. Epner, J.M. Unger, M. LeBlanc, E. Cebula, R. Burack, L. Rimsza, T.P. Miller, R.I. Fisher
Journal: Annals of Oncology (2013)
The results of the prevalence screen in Lung SEARCH: A UK based screening trial for lung cancer based on sputum cytology and cytometry, by the Lung SEARCH screening group
Authors: Stephen Spiro
Journal: European Respiratory Journal (2012)

Lung SEARCH is a screening trial in 9 UK centres of 1658 subjects with a >20 pack year smoking history, mild or moderate chronic obstructive pulmonary disease (COPD). Randomisation was to a control group who had no active intervention, but an exit chest X-ray (CXR) at the end of 5 years; or a surveillance group who provide sputum samples annually for 5 years, for cytological and cytometrical analysis, and if normal for the duration of the study, an exit CXR. Samples showing abnormalities would undergo annual low-dose computed tomography (CT) and autofluorescent fibreoptic bronchoscopy (AFB) for the remaining years of the five. Our aim is to identify more early stage cancers in the surveillance arm (>50%) than the control (  We entered 785 subjects into the surveillance, and 783 in the control arms. The two groups were well matched with 52% of men in both groups, 56% and 44% in each group were current or ex-smokers, and their mean ages were 63 years. 75% in each group had moderate COPD and 25% were mild.  Results: Of the 785 subjects in the surveillance arm, 92% provided a sputum sample. Of these only 132 of 742 were inadequate for analysis. 532 (73%) were normal, 128 (17%) were abnormal: 16 were high grade and 112 low grade. All 128 are being followed by CT and AFB.  Conclusions: Sputm cytology/cytometry performed within a high risk population gave a higher than expected yield of abnormal samples. The study may prove a promising and cost effective method to identify those at very high risk of developing early lung cancer.
Thrombopoietic Factors in Chronic Bone Marrow Failure States: The Platelet Problem Revisited
Authors: Razelle Kurzrock
Journal: Clinical Cancer Research (2005)

Abstract Thrombocytopenia is a serious clinical problem in several different clinical settings. In chronic bone marrow failure states, which include aplastic anemia, myelodysplastic syndrome, and graft failure, the prolonged nature of thrombocytopenia often leads to alloimunization after repeated platelet transfusions, the consequence of which is a platelet-refractory state and enhanced risk of bleeding. Despite the introduction of several thrombopoietic factors into clinical trials, an effective way to alleviate thrombocytopenia has been elusive, and the problem in chronic bone marrow failure states has remained poorly addressed by clinical investigations. Even so, several studies by our group and others suggest that a subset of patients suffering from chronic bone marrow failure can respond to appropriate growth factor therapy. The temporal pace of response appears, however, to be much slower than that observed after administering growth factors which act on neutrophils. On the other hand, durable responses can be secured in some patients given thrombopoietic factors for long periods of time. Herein, we provide an overview of the clinical research investigations of thrombopoietic factors in chronic bone marrow failure, and the emerging insights these studies provide for understanding the process of thrombopoiesis and its therapy in this setting.
2-[18F]Fluoro-2-Deoxyglucose Positron Emission Tomography for the Detection of Disease in Patients with Prostate-Specific Antigen Relapse after Radical Prostatectomy
Authors: Heiko Schöder, Ken Herrmann, Mithat Gönen, Hedvig Hricak, Stephen Eberhard, Peter Scardino, Howard I. Scher, Steven M. Larson
Journal: Clinical Cancer Research (2005)

Abstract Experimental Design: Retrospective cohort study in 91 patients with prostate-specific antigen (PSA) relapse following prostatectomy, imaged with 2-[18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in a tertiary care cancer center between February 1997 and March 2003. Comparison was made with magnetic resonance imaging (n = 64), bone scan (n = 56), and computed tomography (n = 37). The standard of reference included biopsy or clinical and imaging follow-up. We calculated sensitivity and specificity of PET and correlated PET findings with PSA values, other clinical parameters, and conventional imaging, when available. Results: PET was true positive in 28 of 91 (31%) patients, showing isolated disease in the prostate bed (n = 3) or metastatic disease with (n = 2) or without (n = 23) simultaneous disease in the prostate bed. In detail, PET identified lesions in the prostate bed (n = 5, all true positives), bones (n = 22; 20 true positives, 2 false positives), lymph nodes (n = 7; 6 true positives, 1 likely false positive), and one liver metastasis. Mean PSA was higher in PET-positive than in PET-negative patients (9.5 ± 2.2 versus 2.1 ± 3.3 ng/mL). PSA of 2.4 ng/mL and PSA velocity of 1.3 ng/mL/y provided the best tradeoff between sensitivity (80%; 71%) and specificity (73%; 77%) of PET in a receiver operating curve analysis. Combination with other clinical parameters in a multivariate analysis did not improve disease prediction. There were only two patients in whom other imaging studies showed isolated local recurrence or metastatic disease. Conclusions: FDG-PET detected local or systemic disease in 31% of patients with PSA relapse referred for this test. There is a link to tumor burden and tumor biology in that the probability for disease detection increased with PSA levels.
Controversies and priorities in amyotrophic lateral sclerosis
Authors: Martin R Turner, Orla Hardiman, Michael Benatar, Benjamin R Brooks, Adriano Chio, Mamede de Carvalho, Paul G Ince, Cindy Lin, Robert G Miller, Hiroshi Mitsumoto, Garth Nicholson, John Ravits, Pamela J Shaw, Michael Swash, Kevin Talbot, Bryan J Traynor, Leonard H Van den Berg, Jan H Veldink, Steve Vucic, Matthew C Kiernan
Journal: The Lancet Neurology (2013)
Vascularity in asthmatic airways: relation to inhaled steroid dose
Authors: J C HOGG
Journal: Thorax (1999)

The physiological consequences of altered airways structure on the function of asthmatic airways has been of interest to clinicians and physiologists since the classic study of Huber and Koessler in 1922.1 These authors provided the first measurements of airway wall thickness in relation to their size and reported that the airway wall of patients who died of asthma was thicker than that of controls. Many have subsequently commented on this finding,2-7 and Freedman provided an excellent review of its functional significance in 1972.8 A systematic analysis of the effect of wall thickening on airway function by Moreno and colleagues showed that a …
IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C
Authors: Thomas J. Urban, Alexander J. Thompson, Shelton S. Bradrick, Jacques Fellay, Detlef Schuppan, Kenneth D. Cronin, Linda Hong, Alexander McKenzie, Keyur Patel, Kevin V. Shianna, John G. McHutchison, David B. Goldstein, Nezam Afdhal
Journal: Hepatology (2010)

Genetic variation in the IL28B (interleukin 28B; interferon lambda 3) region has been associated with sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC) who were treated with peginterferon-α and ribavirin. We hypothesized that IL28B polymorphism is associated with intrahepatic expression of interferon-stimulated genes (ISGs), known to influence treatment outcome. IL28B genotyping (rs12979860) and whole-genome RNA expression were performed using liver biopsies from 61 North American patients with CHC. After correction for multiple testing (false discovery rate < 0.10), 164 transcripts were found to be differentially expressed by IL28B-type. The interferon signaling pathway was the most enriched canonical pathway differentially expressed by IL28B-type (P < 10(-5)), with most genes showing higher expression in livers of individuals carrying the poor-response IL28B-type. In 25 patients for which treatment response data were available, IL28B-type was associated with SVR (P = 0.0054). ISG expression was also associated with SVR; however, this was not independent of IL28B-type. Analysis of miR-122 expression in liver biopsies showed reduced miR-122 levels associated with poorer treatment outcome, independently of IL28B-type. No association was observed between IL28B-type and levels of liver IL28B or IL28A messenger RNA expression. IL28B protein sequence variants associated with rs12979860 were therefore investigated in vitro: no differences in ISG induction or inhibition of HCV replication were observed in Huh7.5 cells.The good response IL28B variant was strongly associated with lower level ISG expression. The results suggest that IL28B genotype may explain the relationship between hepatic ISG expression and HCV treatment outcome, and this is independent of miR-122 expression. IL28B-type was not associated with intrahepatic IL28B messenger RNA expression in vivo. Further investigation of the precise molecular mechanism(s) by which IL28B genetic variation influences HCV outcomes is warranted.
Dependence of correlations between antibody titres and opsonophagocytosis on pneumococcal serotype and patient morbidity in pre- and post-pneumococcal vaccination states
Authors: D. Tarragó, L. Aguilar, W.T.M. Jansen, M.J. Giménez, A. Avellón, J.J. Granizo, J. Casal
Journal: Clinical Microbiology and Infection (2007)
AT-27 * CHALLENGES OF RETROSPECTIVELY DETERMINING THE EQUIVALENCE OF PCV VERSUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED 1p/19q CO-DELETED ANAPLASTIC OLIGODENDROGLIOMAS
Authors: R. Jain, A. Abdelaziz, J. O. Blakeley, X. Ye, S. A. Grossman, M. Holdhoff
Journal: Neuro-Oncology (2014)

BACKGROUND: For many years, patients with anaplastic oligodendrogliomas (AO) have been treated with radiation and temozolomide followed by adjuvant temozolomide (RT/TMZ). Two randomized studies, RTOG 9402 and EORTC 26951 recently showed significantly improved survival in patients with 1p/19q co-deleted AO treated with radiation plus PCV (RT/PCV) versus radiation alone. A randomized controlled study comparing RT/PCV with RT/TMZ is underway, but obtaining definitive answers takes long as AO are rare and survival is long. Our goal was to assess the feasibility of a retrospective analysis to compare RT/TMZ and RT/PCV. METHODS: This was a retrospective, single institution analysis of co-deleted AO treated with RT/TMZ at Johns Hopkins between 2004 and 2012, meeting selection criteria for the subgroup analysis of RTOG 9402 and EORTC 26951: AO or AOA, co-deletion of 1p/19q, age ≥ 18, no prior therapy except surgery. An initial screen of the cancer center database used broad search terms to assure capture of all cases. RESULTS: Of 544 potential patients filtered with the initial screen, only 12 conformed to all eligibility criteria of the subgroup analysis of RTOG 9402 and EORTC 26951. The reasons for exclusion included: Not AO, not co-deleted, 1p/19q co-deletion testing not performed, patients received prior or other therapies or treatment elsewhere. Median age of the 12 patients: 37 (range: 34-73), 50% female. Median follow-up time: 6.2 years for OS (range: 1.5-8.3), 5.3 years for PFS (range: 1.0-7.0). 2 patients progressed, 1 died of disease. Median OS and PFS: Not yet reached. CONCLUSIONS: This exploratory analysis from an active tertiary referral center highlights limitations of a retrospective analysis of patients with co-deleted AO treated with RT/TMZ in an effort to determine how RT/TMZ compares with RT/PCV. Only a prospective randomized controlled trial, such as the CODEL study, will define optimal treatment for these patients.
Chronic kidney disease: A major concern in liver transplantation in the XXI century
Authors: Elsa Solà, Pere Ginès
Journal: Journal of Hepatology (2014)

With an approximate 12,000 transplants performed annually in Europe and the United States during recent years, liver transplantation has become a very common treatment and in fact the only curative method for most advanced chronic liver diseases [1,2]. Survival rates have increased gradually since the first liver transplants were performed in the 1960’s and current survival probability after 10 years of transplantation is above 60% [1,2]. With the steady increase in survival rates after liver transplantation, some complications that were not frequently observed in early years have become progressively apparent. These complications include, among others, cardiovascular events, metabolic diseases, including diabetes mellitus and lipid disorders, extra-hepatic malignancies, and impairment in kidney function. Among them, an important clinical issue is Chronic Kidney Disease (CKD). There is a large body of evidence indicating that patients submitted to a liver transplant have an increased risk of development of chronic and progressive impairment of kidney function, which becomes particularly relevant in long-term survivors [3–16]. The frequency of CKD, as indicated by a marked reduction in glomerular filtration rate (definitions have changed over time) or the need for renal replacement therapy has been estimated to range between 18 and 25% at 10 years of liver transplantation. With the current definition [17], the observed frequency of CKD in liver transplant recipients is even higher [7,10]. Factors associated with an increased risk of development of CKD after liver transplantation include among others, serum creatinine levels at transplant, GFR at one year of transplantation, age, female sex, diabetes mellitus, and arterial hypertension. Non-alcoholic steatohepatitis (NASH) as a cause of transplantation is also associated with an increased risk of CKD after transplant [4–8,10–13,16]. Few studies have provided a histological analysis of kidneys of patients developing severe CKD after liver transplantation. Interestingly, and contrarily to what was expected initially, only a limited proportion of cases of CKD may be attributed to chronic toxicity related to calcineurin
Complete Surgical Resection Is Curative for Children With Hepatoblastoma With Pure Fetal Histology: A Report From the Children's Oncology Group
Authors: Marcio H. Malogolowkin, Howard M. Katzenstein, Rebecka L. Meyers, Mark D. Krailo, Jon M. Rowland, Joel Haas, Milton J. Finegold
Journal: Journal of Clinical Oncology (2011)

Children with pure fetal histology (PFH) hepatoblastoma treated with complete surgical resection and minimal adjuvant therapy have been shown to have excellent outcomes when compared with other patients with hepatoblastoma. We prospectively studied the safety and efficacy of reducing therapy in all children with stage I PFH enrolled onto two consecutive studies.From August 1989 to December 1992, 9 children with stage I PFH were treated on the Intergroup Hepatoblastoma study INT-0098 and were nonrandomly assigned to receive chemotherapy after surgical resection with single-agent bolus doxorubicin for 3 consecutive days. From March 1999 to November 2006, 16 children with stage I PFH enrolled onto Children's Oncology Group Study P9645 were treated with observation after resection. Central confirmation of the histologic diagnosis by a study group pathologist was mandated. The extent of liver disease was assigned retrospectively according to the pretreatment extent of disease (PRETEXT) system and is designated "retro-PRETEXT" to clarify the retrospective group assignment.Five-year event-free and overall survival for the 9 patients treated on INT-0098 were 100%. All 16 patients enrolled onto the P9645 study were alive and free of disease at the time of last contact, with a median follow-up of 4.9 years. Retro-PRETEXT for the 21 patients with available data revealed seven patients with stage I disease, 10 patients with stage II disease, and four patients with stage III disease.Children with completely resected PFH hepatoblastoma can achieve long-term survival without additional chemotherapy. When feasible, surgical resection of hepatoblastoma at diagnosis, without chemotherapy, can identify children for whom no additional therapy is necessary.
Prevalence of myopia between 3 months and 5 years in preterm infants with and without retinopathy of prematurity
Authors: Graham E Quinn, Velma Dobson, Jane Kivlin, Lawrence M Kaufman, Michael X Repka, James D Reynolds, Robert A Gordon, Robert J Hardy, Betty Tung, Richard A Stone
Journal: Ophthalmology (1998)

The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5 1/2 years post-term in preterm children with birth weights of less than 1251 g.A cohort study.There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mild-to-severe ROP. None of the eyes underwent cryotherapy.Refractive error was measured at 3 months, 1 year, and 5 1/2 years term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3 1/2, and 4 1/2 years.Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater.The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4 1/2 years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5 1/2 years of age.The distribution of refractive errors in preterm infants from age 3 months to 5 1/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia.
Medical Management of Angina Pectoris
Authors: R. BRUCE LOGUE, PAUL H. ROBINSON
Journal: Circulation (1972)

The successful medical management of a patient with angina pectoris requires careful attention to many factors including omission of smoking, control of hypertension, and weight reduction for the obese person. Newer knowledge of the importance of the product of the systolic blood pressure and the pulse rate in determining the threshold of angina affords a more meaningful approach to therapy. Each individual must be educated regarding the factors that aggravate and precipitate his distress so that these can be minimized, or prophylactic nitrite therapy can be appropriately applied. Emotional stress is of equal importance to effort in the production of angina. The mainstay stay of treatment is nitroglycerin and sublingual nitrites combined with beta-blocking drugs. Each drug or combination must be properly readjusted for the individual to assure optimum benefit. Digitalis, diuretics, antiarrhythmic drugs, antihypertensive agents, and radioiodine may be useful in selected cases.
Comparison Between Patients With Philadelphia-Positive Chronic Phase Chronic Myeloid Leukemia Who Obtained a Complete Cytogenetic Response Within 1 Year of Imatinib Therapy and Those Who Achieved Such a Response After 12 Months of Treatment
Authors: Ilaria Iacobucci, Gianantonio Rosti, Marilina Amabile, Angela Poerio, Simona Soverini, Daniela Cilloni, Nicoletta Testoni, Elisabetta Abruzzese, Enrico Montefusco, Emanuela Ottaviani, Francesco Iuliano, Domenico Russo, Marco Gobbi, Giuliana Alimena, Bruno Martino, Carolina Terragna, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2006)

Imatinib mesylate is a potent inhibitor of BCR-ABL, the constitutively active tyrosine kinase protein critical for the pathogenesis of chronic myeloid leukemia.We reviewed 284 patients with late chronic-phase Philadelphia chromosome (Ph) -positive chronic myeloid leukemia treated with imatinib 400 mg daily after interferon-alpha failure. In a retrospective study, we evaluated the pattern and rapidity of the response to imatinib, comparing the cytogenetic and molecular responses, progression-free and overall survival rates in patients who obtained a complete cytogenetic response within 1 year of treatment (early responders), and in patients where a complete cytogenetic response was detected after 12 months (late responders).After 3 or 4 years of treatment, the molecular response of the late cytogenetic responders was similar to that of the early cytogenetic responders. At 36 months of treatment the amount of residual disease measured by standardized quantitative reverse-transcriptase polymerase chain reaction was 0.00047 in late responders versus 0.00022 in early responders, and at 48 months it was 0.00019 versus 0.00026 (median values, P value = nonsignificant). The estimated 4-year progression-free survival rate was 88% for early responders and 100% for late responders, while the estimated 4-year overall survival rates were 92% and 100% for early and late responders, respectively.The sensitivity and the response (cytogenic and molecular) to imatinib may require 1 year or more. Long-term follow-up results continue to improve in terms of rates and durability of the complete cytogenetic response, major or complete molecular response, and progression-free and overall survival.
Chronic obstructive pulmonary disease: underdiagnosed, underinvestigated, inappropriately managed?
Authors: C.K. Connolly
Journal: European Respiratory Journal (2003)

To the Editor: 

The article of Rennard et al. 1 and the accompanying editorial by Dekhuijzen 2 proposed that chronic obstructive pulmonary disease (COPD) is not only underdiagnosed and underinvestigated but also that the morbidity is underestimated. The evidence on which they base this hypothesis lacks two essential components. These are independent assessments of exercise tolerance and objective measurement of lung function. If disability is primarily to be attributed to COPD then it must be associated with a commensurate physiological abnormality, which is a reduction in after-bronchodilator forced expiratory volume in one second (FEV1) or at least abnormality of the flow/volume loop. In medico-legal practice, I have been seeing large numbers of subjects managed principally in general practice with COPD or symptoms wrongly attributed to it. Too frequently, limitation of exercise cannot be explained by the objective reduction in pulmonary function. My previous clinical practice leads me to believe that …