tbuckley/cabot-search huggingface dataset:
Antibiotics for Community-Acquired Pneumonia in Adults
Authors: John Kinsella, Rachel J Kearns
Journal: New England Journal of Medicine (2015)

note that 38.7% of patients in this group received an additional agent during their hospital stay that provided atypical coverage for an average of 4.5 days.The addition of a macrolide, a fluoroquinolone, or doxycycline was accepted as strategycompliant if the agent was added for medical reasons.Since the study assessed empirical antibiotics only, atypical coverage could be added after the first day of the hospital stay without deviating from the protocol, even in the subgroup referred to as "antibiotic-adherent." The benefit of beta-lactam monotherapy versus other guideline-recommended regimens has historically centered on the question of whether atypical coverage is beneficial. 1 It would therefore be useful to know the difference in mortality between those in the beta-lactam monotherapy group who did not receive additional antibiotics against atypical pathogens and those who received betalactam-macrolide or fluoroquinolone.
Abstract 20170: Plasma Apolipoprotein C-III Levels Correlate With Malignant HDL-Lipid Composition Associated With Coronary Artery Disease in Primary Dyslipidemia
Authors: Atsushi Nohara, Akihiro Inazu, Masa-aki Kawashiri, Hayato Tada, Mie Yoshida, Mika Mori, Chiaki Nakanishi, Kunimasa Yagi, Takeshi Kobayashi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2015)

APOC3 has been focused as an emerging therapeutic target beyond LDL. ApoC-III circulates in blood on TG-rich lipoprotein and also on HDL. ApoC-III inhibits LPL activity that is essential for HDL maturation. We investigated the roles of plasma apoC-III on HDL-lipid composition beyond simple HDL-C. Methods: Fasting lipid profiles without lipid drugs were analyzed by ultracentrifugation, and free cholesterol (FC), cholesterol ester (CE), triglycerides (TG) and phospholipids (PL) levels in each fraction were determined. 500 patients (285 males, age 56±18 ys, TC 225±51, TG 168±146, HDL-C 50±15 mg/dL) with primary dyslipidemia (Dyslipidemia Group), and also 171 patients (96 males, age 39±19, TC 338±60, TG 126±98, HDL-C 49±15) with genetically confirmed heterozygous familial hypercholesterolemia (FH Group) were analyzed. Coronary stenosis index (CSI) was estimated with angiography in 195 patients (125 males, age 62±11) in Dyslipidemia and 54 patients (29 males, age 53±14) in FH Group. Results: ApoC-III correlated with TG, LDL-C, fasting glucose, and BMI in both groups as previously reported. Plasma apoC-III levels were slightly higher in Dyslipidemia Group (12±7 vs. 11±4 mg/dL, p &lt;0.01). ApoC-III did not correlate with HDL-C, but negatively correlated with apoAI/AII ratio in Dyslipidemia Group (R 2 15%, p &lt;0.0001). In HDL composition, apoC-III strongly correlated with HDL-TG/HDL-PL ratio (R 2 30%, p &lt;0.0001) rather than HDL-TG (R 2 25%, p &lt;0.0001). ApoC-III did not correlated with HDL-FC, HDL-CE, or HDL-PL, but negatively correlated with HDL-FC/HDL-PL (R 2 9%, p &lt;0.0001) in Dyslipidemia Group. These data may suggest the participant of apoC-III in disturbance of HDL maturation. Intriguingly, apoC-III did not correlate with HDL-TG/HDL-PL or HDL-FC/HDL-PL in FH Group. In angiographic analysis, HDL-TG/HDL-PL ratio strongly correlated with CSI (R 2 10%, p &lt;0.0001) rather than TG (R 2 3%, p &lt;0.05) or HDL-TG (R 2 3%, p &lt;0.05). Highest quartile of apoC-III showed significantly higher CSI compared with other quartiles ( p &lt;0.05) in Dyslipidemia Group. No such tendency was observed in FH Group. Conclusion: Plasma apoC-III strongly correlated with malignant HDL-lipid composition strongly associated with coronary artery disease in patients with primary dyslipidemia.
CT7 (MAGE-C1) is a widely expressed Cancer-Testis antigen in multiple myeloma
Authors: H. J. Cho, A. A. Jungbluth, B. Williamson, D. Kolb, S. Ely, Y.-T. Cheng, N. Bhardwaj, M. Coleman, R. Niesvizky, L. Old
Journal: Journal of Clinical Oncology (2004)

6554 Background: CT7 (MAGE-C1) is a member of the Cancer-Testis (CT) family of tumor-associated antigens. CT antigen-based vaccines are currently under investigation in clinical trials. It has previously been demonstrated that myeloma cells lines and primary myeloma cells express CT antigens. Therefore, CT antigens may be suitable targets for multiple myeloma vaccine immunotherapy. To characterize CT antigen expression in primary myeloma cells, a comprehensive survey of patient specimens was undertaken to identify optimal target candidates. Methods: Bone marrow biopsy and aspirate samples were obtained from 27 patients with multiple myeloma or monoclonal gammopathy of uncertain significance (MGUS). Plasma cells were purified from bone marrow aspirates by anti-CD138 magnetic bead selection. RT-PCR analysis was performed for MAGE-A1, -A3, -A4, -A10, LAGE-1, NY-ESO-1 and CT7. Protein expression was studied by immunohistochemistry (IHC) for the following antigens (using the following mAbs): MAGE-A1 (mAb MA454), MAGE-A3 (mAb M3H67), MAGE-A4 (mAb 57B), CT7 (mAb CT733), NY-ESO-1 (mAb E978 & ES121). Results: CT7, MAGE-A3, and NY-ESO-1 were the most frequently detected CT antigens in multiple myeloma, as shown in the table below. Surprisingly, CT7 mRNA and protein were detected in all stage III multiple myeloma patients. Of note, 13/18 samples demonstrated positive IHC for CT7 in more than 25% of malignant cells. CT7 was also detected in a subset of earlier stage and MGUS samples. Conclusions: CT antigens are variably expressed in primary myeloma cells. CT7 appears to be the most widely expressed CT antigen in the malignant plasma cells of multiple myeloma and is a potential universal target for vaccine immunotherapy. There is good correlation between CT7 mRNA and protein expression. The common expression of CT7 in multiple myeloma also suggests the possibility that it plays a pathogenic role in this disease. No significant financial relationships to disclose.
Needed: clinical trials for older patients.
Authors: B J Kennedy
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.5.718 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2016614 Needed: clinical trials for older patients. B J KennedyxB J KennedySearch for articles by this author https://doi.org/10.1200/JCO.1991.9.5.718 First Page PDF © 1991 by American Society of Clinical Oncology
The Biologic Spectrum of Thymic Epithelial Neoplasms: Current Status and Future Prospects
Authors: Richard T. Cheney
Journal: Journal of the National Comprehensive Cancer Network (2010)

Thymoma is the most common anterior mediastinal tumor in adults and is frequently associated with autoimmune disorders such as myasthenia gravis. Thymomas are a diverse group of epithelial neoplasms with a behavioral spectrum that spans the complete clinical gamut from entirely benign to highly aggressive, lethal thymic carcinomas. The biologic behavior seems to depend primarily on the clinical stage at presentation and histologic subtype. This article discusses thymic organogenesis, Masaoka staging, WHO histologic classification of thymoma and thymic carcinoma, and selected molecular characteristics that highlight this diversity. This discussion will further underscore both the similarities and differences between categories of thymic epithelial neoplasms and offer support for the notion that tumor heterogeneity and/or tumor progression may explain the observed clinical variation in behavior. Recommendations are offered for future investigational approaches to further the understanding of the complexity of these tumors.
Impact of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) on outcomes of postoperative patients with gastric cancer
Authors: J. Matsubara, Y. Yamada, T. Shimoda, T. Eguchi, T. Hamaguchi, Y. Shimada, Y. Okayama, Y. Sugimoto, T. Oka, K. Shirao
Journal: Journal of Clinical Oncology (2006)

4053 Background: The clinical significance of biomarkers in resected gastric cancer (GC) remains unclear. Detailed exploratory evaluations are required to better understand the clinical implications of biomarkers. Methods: The study group comprised 87 patients who received chemotherapy for recurrent or residual GC after resection of their primary tumors at National Cancer Center Hospital. The patients received 1 to 5 regimens of chemotherapy (median: 2). Total RNA was isolated from laser-captured tumor cells of the resected cancer specimens, and the gene expressions of TS, DPD, DHFR, ERCC1, MRP1, and 22 other biomarkers related to anticancer drug sensitivity were quantitatively evaluated by a real-time RT-PCR assay. Results: The gene expressions of TS, DHFR, MTHFD, RRM1, and ERCC1 were significantly related to survival ( Table ). Multivariate analysis revealed that high DHFR (p &lt; 0.001, RR = 1.70 [95% CI, 1.28–2.29]) and high TS (p = 0.004, RR = 1.53 [1.15–2.06]) gene expressions were independently related to poor survival. As compared with intestinal type tumors, diffuse type tumors had higher DPD (p &lt; 0.001) and lower Her2 (p &lt; 0.001) gene expressions. As for first line chemotherapy, an analysis of 29 patients treated with S-1, an oral DPD inhibitory fluoropyrimidine, showed that patients with diffuse type tumors tended to respond better (p = 0.13) than those with intestinal type tumors. An analysis of 29 patients treated with cisplatin plus irinotecan as first line therapy showed that low ERCC1 gene expression was slightly but not significantly related to a better response (p = 0.087). Analyses of patients treated with other first line regimens revealed no significant correlation of any biomarker with response. Conclusions: Increased gene expressions of DHFR and TS in surgical specimens are significantly predictors of poor outcomes in postoperative patients with GC. [Table: see text] [Table: see text]
PO81A LACK OF CONSENT TO DONATE BRAIN TUMOUR TISSUE FOR RESEARCH HAMPERS PROGRESS
Authors: C. Mitchell, N.E. Bailey, H. Bulbeck, K. Hopkins, S. Price, W. Stewart, D. Hilton, J.A.R. Nicoll, K.M. Kurian
Journal: Neuro-Oncology (2015)

INTRODUCTION: Brain tumour tissue can be difficult for researchers to access. BRAIN UK is a collaborative virtual brain bank, facilitating access to under-utilised neuropathology archives for research. A review of National Health Service CNS biopsy archives revealed around 400,000 stored samples, accruing a further 18,500 annually. We aimed to determine how many of these samples were consented to use for research. Without obtaining this consent, it may not be possible to carry out testing on brain tissue samples using emerging diagnostic, prognostic or predictive tests which could improve disease management and access to new treatments. METHOD: 24 UK neuropathology centres were surveyed, by email, on their consent processes, recording and rates of consent. RESULTS: 23/24 centres participated in the audit, 16/23 (70%) obtained prospective informed consent but 6/23 (26%) did not. Of the 16 centres obtaining consent, 9/16 (56%) provided details of consent rates, 6 (37%) estimated their consent rates to be 95-100% of samples, 3 (19%) estimated rates around 10%. CONCLUSION: We estimated that only 30% of neurosurgical tissue samples had been consented to use for research. Robust systems for recording consent accurately were not consistent across the NHS and not all centres had ‘consent to research' procedures in place. Archived residual tissue could be a valuable research resource but could go unused due to lack of consent. This is despite research to suggest that patients are largely supportive of the use of their tissues in research.
Erratum. Consequences of Comorbidity of Elevated Stress and/or Depressive Symptoms and Incident Cardiovascular Outcomes in Diabetes: Results From the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Diabetes Care 2016;39:101–109
Authors: Doyle M. Cummings, Kari Kirian, George Howard, Virginia Howard, Ya Yuan, Paul Muntner, Brett Kissela, Nicole Redmond, Suzanne E. Judd, Monika M. Safford
Journal: Diabetes Care (2016)
Abstract 14865: Epicardial Catheter Ablation of Ventricular Tachycardia in Patients at Time of Ventricular Assist Device Implant
Authors: Farshad Raissi Shabari, Jamil Yousef, Wiliam Cohn, Igor Gregoric, O.h. Frazier, Jie Cheng, Nilesh Mathuria
Journal: Circulation (2012)
A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK)
Authors: T. Powles, J. Brown, J. Larkin, R. Jones, C. Ralph, R. Hawkins, S. Chowdhury, E. Boleti, A. Bhal, K. Fife, A. Webb, S. Crabb, T. Geldart, R. Hill, J. Dunlop, P.E. Hall, D. McLaren, C. Ackerman, L. Beltran, P. Nathan
Journal: Annals of Oncology (2016)
Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.
Authors: D S Thompson, J D Hainsworth, K R Hande, M C Holzmer, F A Greco
Journal: Journal of Clinical Oncology (1993)

PURPOSE This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms. PATIENTS AND METHODS Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion. RESULTS Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL. CONCLUSION Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.
A randomized, double‐blind, phase <scp>III</scp> , multicentre study to evaluate the safety and efficacy of <scp>BF</scp> ‐200 <scp>ALA</scp> (Ameluz <sup>®</sup> ) vs. placebo in the field‐directed treatment of mild‐to‐moderate actinic keratosis with photodynamic therapy (PDT) when using the <scp>BF</scp> ‐Rhodo <scp>LED</scp> <sup>®</sup> lamp
Authors: U. Reinhold, T. Dirschka, R. Ostendorf, R. Aschoff, C. Berking, W.G. Philipp‐Dormston, S. Hahn, K. Lau, A. Jäger, B. Schmitz, H. Lübbert, R.‐M. Szeimies
Journal: British Journal of Dermatology (2016)

Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun‐damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. To evaluate the efficacy, safety and cosmetic outcome of BF‐200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF‐RhodoLED® lamp for the field‐directed treatment of mild‐to‐moderate AK with PDT. The study was performed as a randomized, multicentre, double‐blind, placebo‐controlled, parallel‐group, phase III trial with BF‐200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF‐200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF‐RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm−2 was achieved. BF‐200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority” should not be skipped since this is an important result. Treatment‐emergent adverse events (TEAEs) were experienced by 100% of the BF‐200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF‐200 ALA group compared with placebo. Field‐directed therapy with BF‐200 ALA and BF‐RhodoLED lamp is highly effective and well tolerated for multiple mild‐to‐moderate AK lesions, providing greatly improved skin quality.
The concerted evolution of 5S ribosomal genes linked to the repeat units of other multigene families.
Authors: G Drouin, M M de Sá
Journal: Molecular Biology and Evolution (1995)

We review all instances in which the nuclear 5S rRNA genes of fungi, protist, nematode, and arthropod species have been reported to be linked to the tandemly repeated units of the rDNA, trans-spliced leader, and histone multigene families. The evolution of these gene arrangements is analyzed by mapping them to independently derived phylogenies. These analyses show that 5S rRNA genes have repeatedly become linked to diverse tandemly repeated gene families and that such linkages have also been subsequently inverted or lost in some species. These variable gene linkages are probably the result of stochastic gains and losses of variant repeat units, where functional 5S rRNA had transposed, by the mechanisms which are responsible for the concerted evolution of tandemly repeated multigene families. We discuss the possible mechanisms of 5S rRNA gene transposition and suggest that the characteristics of their promoter elements, transcription, and termination signals may allow functional copies of these genes to be fortuitously transposed through an RNA intermediate. We also review the evidence which shows that the linked 5S rRNA gene copies are transcribed. We conclude that the observed patterns of 5S rRNA gene linkages to the repeat units of other tandemly repeated multigene families have likely arisen due to fortuitous recombination events and are unlikely to represent the remnants of an eubacterial-like arrangement of rDNA operons or to have been established due to selective pressures.
The Royal Marsden Hospital experience of trabectedin in patients with advanced soft tissue sarcoma (STS): Toxicity and efficacy in a nonselected group.
Authors: S. N. Banerjee, S. Mitchell, O. Al-Muderis, K. Pennert, A. Dunlop, C. Propert-Lewis, I. R. Judson, M. R. Scurr
Journal: Journal of Clinical Oncology (2011)

e20507 Background: Trabectedin (T) is approved in Europe for advanced soft tissue sarcoma (STS). The Royal Marsden Hospital (RMH) has treated 133 STS pts with this agent, the majority outside of clinical trial. This affords the opportunity to determine the toxicity profile and clinical benefit of T in the largest, non-selected cohort published to date. Methods: Patients who started T as a 24 hr infusion for advanced STS between May 1999 and August 2010 were analysed for clinical outcome and toxicity. Results: 133 patients were identified: 60% female; median age 50yrs (18-77yrs) and median prior treatments =1 (0-4). The histological subtypes included leiomyosarcoma (43%), myxoid liposarcoma (13%) and synovial sarcoma (12%); metastatic sites: lung (57%), liver (27%), retroperitoneal (20%). Median number of cycles was 3 (1-24); 32% ≥6 cycles, and 19% only 1 cycle (65% due to PD). Median overall PFS and OS were 67 and 153 days respectively and 28% were progression-free at 6 months. Myxoid liposarcomas were associated with significantly better PFS (median 221 vs 52 days; p=0.003), with synovial sarcomas showing a trend towards an improved PFS. Clinical benefit (PR +SD) was seen in 52% (PR=10%). Dose reductions, delays and change to q4wk schedule due to toxicity were necessary in 25%, 28% and 11% respectively. 22% required hospitalisation and 9% died within 3 weeks of therapy (3.5% toxicity-related). Overall 55% of patients experienced grade 3/4 toxicity (predominantly myelotoxicity, transaminitis, and fatigue), toxicity-related dose modification (25%), and there were 5 toxicity related deaths. Elevations in creatinine kinase occurred in 18% of cycles. Conclusions: This analysis of this largely non-selected STS cohort confirms the clinical activity of trabectedin, particularly in myxoid liposarcomas and synovial sarcomas, with approximately a third of patients experiencing prolonged disease control. Whilst it is generally well tolerated, significant toxicity was observed, with 25% of cases requiring dose reduction. Further analysis of the data is ongoing to better define those factors that may better define those not likely to benefit from T.
A Case of Acute Massive Pulmonary Thromboembolism Treated by Mechanical Clot Fragmentation Using a Percutaneous Transluminal Angioplasty Balloon
Authors: Kikuo Isoda, Kmio Satomura, Akira Hamabe, Kohsuke Hagisawa, Yasuhiro Kamezawa, Yasunori Sugiyabu, Akira Kurita, Haruo Nakamura
Journal: Circulation (1997)

Large, bilateral central pulmonary thromboemboli (PTE) led to cor pulmonale and severe hypoxemia in a patient who had undergone Hardy's operation. After several unsuccessful efforts (thrombolysis using a percutaneous catheter and aspiration of the emboli), mechanical clot fragmentation using a percutaneous transluminal angioplasty (PTA) balloon was attempted. This procedure was successful, resulting in a decrease in pulmonary artery pressure from 58/22 (mean 34) mmHg to 20/10 (mean 13) mmHg together with an increase in aortic pressure from 64/36 (mean 45) mmHg to 112/60 (mean 77) mmHg. Thus, mechanical clot fragmentation using a PTA balloon is a promising method for reducing pulmonary artery pressure and increasing aortic pressure in patients with acute PTE. (Jpn Circ J 1997; 61: 531 - 535)
Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer.
Authors: Emilio Bajetta, Irene Floriani, Maria Di Bartolomeo, Roberto Labianca, Lorenza Landi, Armando Santoro, Rossanna Casaretti, Enzo Pasquini, Francesca Di Fabio, Ermanno Rondini, Graziella Pinotti, Paolo Bidoli, Gerado Rosati, Andrea Mambrini, Andrea Ciarlo, Stefano Sergio Cordio, Sergio Ricci, Luca Frassineti, Francesco Di Costanzo, Anna Maria Bochicchio
Journal: Journal of Clinical Oncology (2012)

LBA4001 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.