tbuckley/cabot-search huggingface dataset:
Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear
Authors: Raine Sihvonen, Mika Paavola, Antti Malmivaara, Ari Itälä, Antti Joukainen, Heikki Nurmi, Juha Kalske, Teppo L.N. Järvinen
Journal: New England Journal of Medicine (2013)

Arthroscopic partial meniscectomy is one of the most common orthopedic procedures, yet rigorous evidence of its efficacy is lacking.We conducted a multicenter, randomized, double-blind, sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis. Patients were randomly assigned to arthroscopic partial meniscectomy or sham surgery. The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool (WOMET) scores (each ranging from 0 to 100, with lower scores indicating more severe symptoms) and in knee pain after exercise (rated on a scale from 0 to 10, with 0 denoting no pain) at 12 months after the procedure.In the intention-to-treat analysis, there were no significant between-group differences in the change from baseline to 12 months in any primary outcome. The mean changes (improvements) in the primary outcome measures were as follows: Lysholm score, 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group (between-group difference, -1.6 points; 95% confidence interval [CI], -7.2 to 4.0); WOMET score, 24.6 and 27.1 points, respectively (between-group difference, -2.5 points; 95% CI, -9.2 to 4.1); and score for knee pain after exercise, 3.1 and 3.3 points, respectively (between-group difference, -0.1; 95% CI, -0.9 to 0.7). There were no significant differences between groups in the number of patients who required subsequent knee surgery (two in the partial-meniscectomy group and five in the sham-surgery group) or serious adverse events (one and zero, respectively).In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure. (Funded by the Sigrid Juselius Foundation and others; ClinicalTrials.gov number, NCT00549172.).
Changes in Employment Status Associated with Hospitalization for Tuberculosis
Journal: JAMA (1963)

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Post breast therapy pain syndrome - A study of Internet-based patient and healthcare provider education
Authors: R. A. Wascher, E. H. Rosenbaum, A. Andrews, F. Manuel, M. Goldman, R. M. Shapiro, C. M. Dollbaum
Journal: Journal of Clinical Oncology (2004)

8230 Background:Post-breast Therapy Pain Syndrome (PBTPS) is a complex constellation of symptoms with multiple etiologic factors. In this era of breast-conserving therapy, the old term post-mastectomy syndrome is no longer sufficiently descriptive. PBTPS may also result from polyneuropathies caused by chemotherapy (including taxanes, vinca alkaloids, and platinum compounds) and radiation therapy. PBTPS frequently does not become clinically apparent until two to three months following cancer surgery, chemotherapy or radiation. Among patients who develop PBTPS, more than 50% experience significant discomfort that impairs their overall quality of life. The timely diagnosis and treatment of PBTPS requires that both physicians and patients have a clear understanding about this syndrome, and appropriate referrals to experienced pain management specialists be made. Methods:A pilot questionnaire was developed in September 2002 to evaluate the perceived utility of the Post Breast Therapy Pain Syndrome section. In March 2003 a PBTPS handout became available worldwide at CancerSupportiveCare.com. Our website serves on average 2500 pages per month about PBTPS to interested patients, and healthcare providers from over 80 countries, including the USA (the number of website hits is not included because the term hit can be misleading, e.g. 100 graphics + 1 web page = 101 hits). Results:Online Questionnaire September 2002 –November 2003 Of the 186 responses, 156 were from patient and support teams (84%) and 30 were from healthcare professionals (16%). Conclusions: Ease and speed of access to expert opinions, are valuable features of Internet-based forums. These are particularly useful in educating healthcare professionals, patients and support teams about symptoms, diagnostic modalities, and clinical management, in an effort to improve the quality of life of patients with PBTPS. No significant financial relationships to disclose.
The prognostic value of perfusion-weighted magnetic resonance imaging in advanced pancreas carcinoma
Authors: M. Ueno, T. Niwa, S. Ohkawa, T. Masaki, A. Amano, K. Miyakawa, T. Yoshida, K. Tarao
Journal: Journal of Clinical Oncology (2005)

4109 Background: Perfusion-weighted magnetic resonance imaging (MRI) can detect angiogenesis in brain malignant tumors (Cha S et al.2002, Radiology) and the increase of angiogenesis in various carcinomas leads to a poor prognosis. We evaluated the prognostic value of perfusion-weighted MRI in patients with advanced pancreas carcinoma (APC). Methods: Perfusion-weighted MRI was performed in 27 consecutive patients with APC. Imaging acquisition was continually repeated with echoplanar sequence every 2 seconds for 2 minutes with a bolus injection of gadolinium. We made a time intensity curve of perfusion-weighted images of pancreas carcinoma and calculated signal ratio (SR). After perfusion-weighted MRI, patients received chemotherapy (20:gemcitabine, 3:TS-1, 4:TS-1+gemcitabine). We compared SR with overall survival. The curve of overall survival was plotted according to Kaplan and Meier. Difference in overall survival was calculated with the log-rank test. Results: 27 patients (10:locally advanced, 17:with distant metastases) were included. All cases showed transient decreases in pancreatic tumor signal intensity (SR ranged 6.9–55.7%). Overall survival ranged from 38 to 374 days with a median of 192 days. These patients were classified into two groups at the value of mean SR (25.2%) (10: high tumor blood flow (TBF), 17: low TBF) The high TBF group had shorter overall survival than the low TBF group. There was a significant difference in overall survival between these two groups classified in SR (P<.05). Conclusions: Perfusion-weighted MRI may be useful as a prognostic factor in APC patients. No significant financial relationships to disclose.
Cetuximab in combination with cisplatin and docetaxel as first-line treatment in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Italian phase II DOCETUX study)
Authors: C. Pinto, F. Di Fabio, C. Barone, S. Siena, A. Falcone, F. L. Rojas Llimpe, S. Cascinu, S. Giaquinta, G. Schinzari, V. Mutri, A. A. Martoni
Journal: Journal of Clinical Oncology (2008)

4575 Background: The aim of this study was to evaluate the efficacy and safety of cetuximab in combination with cisplatin and docetaxel as first-line treatment for advanced gastric or GEJ cancer. Methods: Eligibility criteria were: histological diagnosis of stomach or GEJ adenocarcinoma, locally advanced/metastatic measurable disease, no prior chemotherapy for advanced/metastatic cancer. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, cisplatin 75 mg/m2 iv and docetaxel 75 mg/m2 iv d1 every 3 weeks, for maximum of 6 cycles; therapy with cetuximab alone was continued in pts with CR/PR/SD. Anti-tumor activity was assessed by CT-scan every 6 weeks. Results: Forty-eight pts were enrolled from December 2006 to December 2007: 34 males (71%), 14 females (29%); median age 64 years (25–74); median KPS 90 (70–100); primary site: stomach 40 (83%), GEJ 8 (17%); prior gastrectomy 21 (44%); stage of disease: locally advanced 1 (2%), metastatic 47 (98%); main metastatic sites: lymphnodes 28 (58%), liver 26 (54%), peritoneal 12 (31%), lung 3 (6.25%). The median number of therapy cycles was 4 (1–6). Median dose intensity was cisplatin 100% (55–100), docetaxel 100% (55–100), cetuximab 100% (65–100). At present, 42 pts are evaluable for response (4 not evaluable and 2 too early), and 48 for toxicity. The objective responses (RECIST) were 1 (2.4%) CR, 16 (38.1%) PR, 40.5% CR + PR (95% CI: 25.7–55.3%), 16 (38.1%) SD, 9 (21.4%) PD. The PFS at 3 months is 80% (95% CI: 64.3–95.7%). Survival data are premature (75% of the pts are still alive). Grade 3–4 toxicity (CTC v3.0) was 45.8% neutropenia (22.9% febrile neutropenia), 6.25% anemia, 2.1% thrombocytopenia, 22.9% asthenia, 8.3% vomiting, 6.3% stomatitis, 4.2% diarrhea, 4.2% hyperbilirubinemia, 20% hyponatremia, 16% hypokalemia, 4% hypomagnesemia. Skin reactions ≥ 2 was 31.3%. Three deaths occurred within 60 days from start of therapy (1 bowel occlusion, 1 gastric bleeding, 1 PD). Conclusions: The combination of cetuximab and cisplatin/docetaxel appears to be active (78.6% of disease control rate), while the greater toxicity appears to be limited to neutropenia. No significant financial relationships to disclose.
Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation.
Authors: R L Wahl, K Zasadny, M Helvie, G D Hutchins, B Weber, R Cody
Journal: Journal of Clinical Oncology (1993)

PURPOSE We assessed the feasibility of noninvasive metabolic monitoring of cancer chemohormonotherapy using sequential quantitative positron emission tomographic (PET) scans of tumor glucose metabolism with the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS Eleven women with newly diagnosed primary breast cancers larger than 3 cm in diameter beginning a chemohormonotherapy program underwent a baseline and four follow-up quantitative PET scans during the first three cycles of treatment (days 0 to 63). Tumor response was sequentially determined clinically, radiographically, and then pathologically after nine treatment cycles. RESULTS Eight patients had partial or complete pathologic responses. Their maximal tumor uptake of FDG assessed by PET decreased promptly with treatment to the following: day 8, 78 +/- 9.2% (P &lt; .03); day 21, 68.1 +/- 7.5% (P &lt; .025); day 42, 60 +/- 5.1% (P &lt; .001); day 63, 52.4 +/- 4.4% (P &lt; .0001) of the basal values. Tumor diameter did not decrease significantly during this period through 63 days. Prompt decreases in the FDG influx rate (K) from basal levels (from .019 to .014 mL/cm3/min) after 8 days of treatment (P &lt; .02) and in the estimated rate of FDG phosphorylation to FDG-6-phosphate (k3) from .055 to .038 min-1 after 8 days of treatment (P &lt; .02) to .029 +/- .004 min-1 at 21 days) (P &lt; .02) were observed. Three nonresponding patients had no significant decrease in tumor uptake of FDG (81 +/- 18% of basal value), influx rate (.015 to .012 mL/cm3/min), or tumor size (81 +/- 12% of basal diameter) comparing basal versus 63-day posttreatment values. CONCLUSION Quantitative FDG PET scans of primary breast cancers showed a rapid and significant decrease in tumor glucose metabolism after effective treatment was initiated, with the reduction in metabolism antedating any decrement in tumor size. No significant decrease in FDG uptake (SUV) after three cycles of treatment was observed in the nonresponding patients. FDG PET scanning has substantial promise as an early noninvasive metabolic marker of the efficacy of cancer treatment.
The Impact of Different DNMT3A Mutations on Outcome in Younger Adults with Acute Myeloid Leukemia
Authors: Rosemary E Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, Alan K. Burnett, Robert K. Hills, David C Linch
Journal: Blood (2014)
Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort
Authors: Johan Pallud, Etienne Audureau, Georges Noel, Robert Corns, Emmanuèle Lechapt-Zalcman, Julien Duntze, Vladislav Pavlov, Jacques Guyotat, Phong Dam Hieu, Pierre-Jean Le Reste, Thierry Faillot, Claude-Fabien Litre, Nicolas Desse, Antoine Petit, Evelyne Emery, Jimmy Voirin, Johann Peltier, François Caire, Jean-Rodolphe Vignes, Jean-Luc Barat, Olivier Langlois, Edouard Dezamis, Eduardo Parraga, Marc Zanello, Edmond Nader, Michel Lefranc, Luc Bauchet, Bertrand Devaux, Philippe Menei, Philippe Metellus
Journal: Neuro-Oncology (2015)

The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. The median progression-free survival was 12.0 months (95% CI: 10.7–12.6) in the implantation group and 10.0 months (9.0–10.0) in the standard group and the median overall survival was 20.4 months (19.0–22.7) and 18.0 months (17.0–19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63–0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60–0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80–1.13], P = .574; HR, 1.06 [0.87–1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44–0.76], P < .0001; HR, 0.54 [0.41–0.70], P < .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40–0.78], P < .0001; HR, 0.46 [95% CI: 0.33–0.64], P < .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit.
Abstract P367: Birth Weight Modifies the Association Between Central Nervous System Gene Variation and Adult Body Mass Index
Authors: Edward A Ruiz-Narvaez, Lynn Rosenberg, Julie R Palmer
Journal: Circulation (2015)

Background: Genome wide association studies (GWAS) have identified 38 genetic loci associated with variation in body mass index (BMI) and weight. At least eleven of the identified BMI loci may be affecting body weight through their effects on the activity of the central nervous system (CNS). Persons with low birth weight have an increased risk of a series of metabolic disorders as adults, including alterations of CNS activity. We postulate that normal CNS-mediated genetic mechanisms of body weight regulation are disrupted in subjects with low birth weight. Methods: We used general linear models to assess interaction between birth weight and CNS-gene variants in relation to BMI at age 18 and in 1995 in the Black Women’s Health Study (BWHS), an ongoing prospective cohort study that began in 1995. Birth weight was categorized as a binary variable (above and below the median, 3,200 g). We calculated a weighted CNS-gene score by summing the number of BMI-increasing alleles in 11 GWAS-identified CNS genes. Each...
A randomized Phase 2a study to assess pharmacodynamics, antitumor activity and safety of intravenous BAL101553, a novel microtubule inhibitor, at two dose levels in adult patients with selected advanced solid tumors.
Authors: Rebecca Sophie Kristeleit, Alan D. Smith, Noor R Md Haris, Ishtiaq Husain Zubairi, Judy W. King, Maria Jose de Miguel Luken, Manolo D'Arcangelo, Julie MacDonald, Nicholas F. Brown, Alan Hilary Calvert, Alison L. Hannah, Stephanie Anderson, Felix Bachmann, Martina Maurer, Anne Schmitt-Hoffmann, Heidi A Lane, Marc Frederick Engelhardt, T.R. Jeffry Evans, Ruth Plummer, L Rhoda Molife
Journal: Journal of Clinical Oncology (2015)

TPS2611 Background: BAL101553 is the pro-drug of BAL27862, a novel small-molecule microtubule-targeting agent with potent activity in drug-refractory tumor models. It exerts antiproliferative effects and dose-dependent vascular disruption, acting as a tumor checkpoint controller by modulating the spindle assembly checkpoint (SAC). In a Phase 1 dose escalation study pharmacodynamic (PD) effects were observed in post-treatment tumor biopsies1. The maximum tolerated dose (MTD) was determined at 60 mg/m2 IV (intravenous), however clinical activity was observed at dose levels of 15-30 mg/m2. A non small cell lung cancer (NSCLC) xenograft mouse model showed similar BAL27862 tumor exposure (AUC) at the MTD and a sub-MTD dose, with 11-fold higher peak intratumoral levels at the lower dose. Thus, enhanced vascular disruption at high BAL101553 doses may be associated with lower intratumoral drug disposition. The goal of this Phase 2a study is to assess the pattern of antivascular and antiproliferative effects and antitumor activity at two BAL101553 dose levels. Methods: This is an ongoing multicenter randomized, open-label Phase 2a study (NCT01397929) to assess PD, antitumor activity and safety of BAL101553. Eligible patients (pts) with advanced colorectal, gastric, pancreatic, ovarian, NSCLC or triple negative breast cancers are randomized to either 60 (MTD) or 30 mg/m2 BAL101553 as a 2-h IV infusion on day(d) 1, 8 and 15 q28d. PD evaluations include serial collection of circulating tumor cells (CTCs), circulating endothelial cells and circulating endothelial progenitor cells. Pts with lesions amenable to biopsy will be asked to undergo pre- and post-dose biopsies. Biomarkers analyzed in CTCs and tumor biopsies include BubR1, a protein kinase involved in the SAC and a potential biomarker for BAL101553 activity. Antivascular effects will be quantified by dynamic-contrast enhanced MRI in a subset of pts. Tumor response will be assessed every 2 cycles using RECIST 1.1. Forty pts will be enrolled into this Phase 2a study, which started in June 2014. 1Molife LR et al. J Clin Oncol 32:5s, 2014 (suppl; abstr 2562) Clinical trial information: NCT01397929.
Why cancer screening has never been shown to “save lives”—and what we can do about it
Authors: Vinay Prasad, Jeanne Lenzer, David H Newman
Journal: BMJ (2016)

The claim that cancer screening saves lives is based on fewer deaths due to the target cancer. <b>Vinay Prasad and colleagues</b> argue that reductions in overall mortality should be the benchmark and call for higher standards of evidence for cancer screening
Amantadine versus trihexyphenidyl in the treatment of neuroleptic- induced parkinsonism
Authors: W E Fann, C R Lake
Journal: American Journal of Psychiatry (1976)

Amantadine is a putative dopaminergic compound known to be therapeutically effective in idiopathic and postencephalitic Parkinson's disease. In a double-blind placebo-controlled crossover study of 39 psychiatric inpatients, amantadine and trihexyphenidyl were equally effective in treating drug-induced parkinsonism, and amantadine produced fewer and less severe side effects. The authors suggest that amantadine is an effective alternative to atropine-like agents, with fewer implications for long-term risk of tardive dyskinesia.
Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions.
Authors: C C Pao, C J Tseng, C Y Lin, F P Yang, J J Hor, D S Yao, S Hsueh
Journal: Journal of Clinical Oncology (1997)

PURPOSE Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.