tbuckley/cabot-search huggingface dataset:
Pleuro-pulmonary synovial sarcoma: clinico-pathologic and molecular characteristics from a multi-institutional series of 48 cases
Authors: A. Spallanzani, F. Bertolini, F. Barbieri, L. Longo, C. Tomasello, S. Noventa, A. Cavazza, G. Pelosi, R. Carella, P. Graziano, S. Ascani, S. Asioli, B. Murer, G. Rossi
Journal: Annals of Oncology (2015)
Emergence of community-associated methicillin-resistant Staphylococcus aureus strains in the neonatal intensive care unit: an infection prevention and patient safety challenge
Authors: P.J. Reich, M.G. Boyle, P.G. Hogan, A.J. Johnson, M.A. Wallace, A.M. Elward, B.B. Warner, C.-A.D. Burnham, S.A. Fritz
Journal: Clinical Microbiology and Infection (2016)
HCP-16POPULATION-BASED SURVIVAL RATES FROM HIGH GRADE GLIOMA (HGG) ARE NOT IMPROVED BY INCREASED CHEMOTHERAPY USE
Authors: Yang Liu, Christine Pittman, Margie Richardson, Nimish Mohile, Michael Milano, Kenneth Usuki, Kevin Walter
Journal: Neuro-Oncology (2015)

BACKGROUND: Clinical trials favor aggressive therapy for glioblastoma. Maximally safe surgical resection, radiotherapy, and temozolomide chemotherapy are considered standards of care. However, it is unclear if these treatments improve population-based overall survival, as the selection criteria used in clinical trials are often relatively narrow. METHODS: We prospectively collected patients registered in a population-based database for primary HGGs (n = 363) treated in Rochester, NY from 2000 to 2014. We sought to track survival trends and evaluate treatment efficacies. RESULTS: The median age at diagnosis was 61 years. The majority of patients were white (94.5%) with glioblastoma (77.7%). Most (84.3%) had died (all causes) during the follow-up interval. Overall, patients who received combination treatment of surgery, radiation and chemotherapy have better survival (median 490.0 days) than those who received combination of surgery and radiation therapy (median 239.0 days, p < 0.001) or surgery alone (median 95.0 days, p < 0.001). We further grouped patients into three time periods for comparison: 2000 to 2004, 2005 to 2009, and 2010 to 2014. We found no appreciable differences in the median, 6-month, and 2-year survivals between each time interval (median survival time: 368.0 vs. 360.0 vs. 358.0 days, respectively). Notably, the rate of combination of surgery, radiation and chemotherapy significantly increased over the time (32.5% vs. 64.0% vs. 67.6%, respectively). We also observed that patients who received surgery and radiation therapy had a better survival time during 2000 to 2004 (median 275.5 days) compared to those in 2005 to 2009 (median 89.0 days, p < 0.05). CONCLUSIONS: Our data indicate that while temozolomide chemotherapy clearly improves survival with HGG, its benefit is limited to a subset of patients. Expanding its use to all HGG as is now common practice does not improve overall patient population survival. A more personalized usage strategy for temozolomide is needed.
Effect of Detecting and Isolating<i>Clostridium difficile</i>Carriers at Hospital Admission on the Incidence of<i>C difficile</i>Infections
Authors: Yves Longtin, Bianka Paquet-Bolduc, Rodica Gilca, Christophe Garenc, Elise Fortin, Jean Longtin, Sylvie Trottier, Philippe Gervais, Jean-François Roussy, Simon Lévesque, Debby Ben-David, Isabelle Cloutier, Vivian G. Loo
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> <i>Clostridium difficile</i>infection (CDI) is a major cause of health care–associated infection worldwide, and new preventive strategies are urgently needed. Current control measures do not target asymptomatic carriers, despite evidence that they can contaminate the hospital environment and health care workers' hands and potentially transmit<i>C difficile</i>to other patients. <h3>Objective</h3> To investigate the effect of detecting and isolating<i>C difficile</i>asymptomatic carriers at hospital admission on the incidence of health care–associated CDI (HA-CDI). <h3>Design, Setting, and Participants</h3> We performed a controlled quasi-experimental study between November 19, 2013, and March 7, 2015, in a Canadian acute care facility. Admission screening was conducted by detecting the<i>tcdB</i>gene by polymerase chain reaction on a rectal swab. Carriers were placed under contact isolation precautions during their hospitalization. <h3>Main Outcomes and Measures</h3> Changes in HA-CDI incidence level and trend during the intervention period (17 periods of 4 weeks each) were compared with the preintervention control period (120 periods of 4 weeks each) by segmented regression analysis and autoregressive integrated moving average (ARIMA) modeling. Concomitant changes in the aggregated HA-CDI incidence at other institutions in Québec City, Québec (n = 6) and the province of Québec (n = 94) were also examined. <h3>Results</h3> Overall, 7599 of 8218 (92.5%) eligible patients were screened, among whom 368 (4.8%) were identified as<i>C difficile</i>carriers. During the intervention, 38 patients (3.0 per 10 000 patient-days) developed an HA-CDI compared with 416 patients (6.9 per 10 000 patient-days) during the preintervention control period (<i>P</i> &lt; .001). There was no immediate change in the level of HA-CDIs on implementation (<i>P</i> = .92), but there was a significant decrease in trend over time of 7% per 4-week period (rate ratio, 0.93; 95% CI, 0.87-0.99 per period;<i>P</i> = .02). ARIMA modeling also detected a significant effect of the intervention, represented by a gradual progressive decrease in the HA-CDI time series by an overall magnitude of 7.2 HA-CDIs per 10 000 patient-days. We estimated that the intervention had prevented 63 of the 101 (62.4%) expected cases. By contrast, no significant decrease in HA-CDI rates occurred in the control groups. <h3>Conclusions and Relevance</h3> Detecting and isolating<i>C difficile</i>carriers was associated with a significant decrease in the incidence of HA-CDI. If confirmed in subsequent studies, this strategy could help prevent HA-CDI.
The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin
Authors: Yifan Wang, Andrea J. Bernhardy, Cristina Cruz, John J. Krais, Joseph Nacson, Emmanuelle Nicolas, Suraj Peri, Hanneke van der Gulden, Ingrid van der Heijden, Shane W. O'Brien, Yong Zhang, Maribel I. Harrell, Shawn F. Johnson, Francisco J. Candido Dos Reis, Paul D. P. Pharoah, Beth Karlan, Charlie Gourley, Diether Lambrechts, Georgia Chenevix-Trench, Håkan Olsson, Javier J. Benitez, Mark H. Greene, Martin Gore, Robert Nussbaum, Siegal Sadetzki, Simon A. Gayther, Susanne K. Kjaer, Alan D. D'Andrea, Geoffrey I. Shapiro, David L. Wiest, Denise C. Connolly, Mary B. Daly, Elizabeth M. Swisher, Peter Bouwman, Jos Jonkers, Judith Balmaña, Violeta Serra, Neil Johnson
Journal: Cancer Research (2016)

Abstract Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo. Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778–90. ©2016 AACR.
A Recent Whole-Genome Duplication Divides Populations of a Globally Distributed Microsporidian
Authors: Tom A. Williams, Sirintra Nakjang, Scott E. Campbell, Mark A. Freeman, Matthías Eydal, Karen Moore, Robert P. Hirt, T. Martin Embley, Bryony A. P. Williams
Journal: Molecular Biology and Evolution (2016)

The Microsporidia are a major group of intracellular fungi and important parasites of animals including insects, fish, and immunocompromised humans. Microsporidian genomes have undergone extreme reductive evolution but there are major differences in genome size and structure within the group: some are prokaryote-like in size and organisation (<3 Mb of gene-dense sequence) while others have more typically eukaryotic genome architectures. To gain fine-scale, population-level insight into the evolutionary dynamics of these tiny eukaryotic genomes, we performed the broadest microsporidian population genomic study to date, sequencing geographically isolated strains of Spraguea, a marine microsporidian infecting goosefish worldwide. Our analysis revealed that population structure across the Atlantic Ocean is associated with a conserved difference in ploidy, with American and Canadian isolates sharing an ancestral whole genome duplication that was followed by widespread pseudogenisation and sorting-out of paralogue pairs. While past analyses have suggested de novo gene formation of microsporidian-specific genes, we found evidence for the origin of new genes from noncoding sequence since the divergence of these populations. Some of these genes experience selective constraint, suggesting the evolution of new functions and local host adaptation. Combining our data with published microsporidian genomes, we show that nucleotide composition across the phylum is shaped by a mutational bias favoring A and T nucleotides, which is opposed by an evolutionary force favoring an increase in genomic GC content. This study reveals ongoing dramatic reorganization of genome structure and the evolution of new gene functions in modern microsporidians despite extensive genomic streamlining in their common ancestor.
Efficiency of Prostate Cancer Diagnosis by MR/Ultrasound Fusion-Guided Biopsy vs Standard Extended-Sextant Biopsy for MR-Visible Lesions
Authors: M. Minhaj Siddiqui, Arvin K. George, Rachel Rubin, Soroush Rais-Bahrami, Howard L. Parnes, Maria J. Merino, Richard M. Simon, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Use of magnetic resonance (MR) imaging to improve prostate biopsy efficiency is rapidly gaining in popularity. The aim of this study was to assess the biopsy efficiency of MR/ultrasound (MR/US) fusion-guided ("targeted") biopsies vs extended-sextant 12-core ("standard") biopsies for overall and high-grade prostate cancer detection.
TCTAP A-058 Randomized, Prospective, Double-Blinded, Placebo Controlled Trial to Assess the Effects of BM-Derived Immunoselected CD133+ Cells on LV Perfusion and Function in Patients with Inducible Ischemia and Refractory Angina. Insights from Endomyocardial Mapping
Authors: Wojciech Wojakowski
Journal: Journal of the American College of Cardiology (2016)
TCTAP C-105 Successful Recanalizing Two Segments of Chronic Total Occlusion Lesions over Left Anterior Descending Artery with Bridgepoint Reentry Device Following IVUS-guided Puncture into Unidentifiable Entrance
Authors: Cheng-Jui Lin, Chiung-Jen Wu, Wen-Jung Chung, Mostafa Mohammad Omran
Journal: Journal of the American College of Cardiology (2016)
Will it play in Peoria?
Authors: S M Grunberg
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.1991.9.5.713 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1826738 Will it play in Peoria? S M GrunbergxS M GrunbergSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.5.713 First Page PDF © 1991 by American Society of Clinical Oncology
A Microfluidic Paper‐Based Origami Nanobiosensor for Label‐Free, Ultrasensitive Immunoassays
Authors: Xiao Li, Xinyu Liu
Journal: Advanced Healthcare Materials (2016)

Microfluidic paper‐based analytical devices (μPADs) represent a promising platform technology for point‐of‐care diagnosis. Highly sensitive, rapid, and easy‐to‐perform immunoassays implemented on μPADs are desirable to fulfill the promise of the μPAD technology. This article reports the first microfluidic paper‐based origami nanobiosensor (origami μPAD), which integrates zinc oxide nanowires (ZnO NWs) and electrochemical impedance spectroscopy (EIS) biosensing mechanism, for label‐free, ultrasensitive immunoassays. The EIS mechanism features simple and label‐free assay operations which take less than 25 min to be finished, while the ZnO NWs allow covalent bonding for immobilizing probe proteins and improve the biosensing performance with such features as high surface‐area‐to‐volume ratios and high sensitivity to surface binding. The calibration of the device reveals an ultralow limit of detection (LOD) of 60 fg mL −1 (&gt;100 times lower than those of existing μPADs) for rabbit immunoglobulin G in phosphate‐buffered saline. The detection of human immunodeficiency virus p24 antigen in human serum with a low LOD of 300 fg mL −1 (&gt;33 times lower than that of a commercial p24 antigen test kit) is also demonstrated. This novel μPAD design offers ultrahigh sensitivity, short assay time, and ease of operation, and thus possesses significant potential for low‐cost, rapid molecular diagnosis of early‐stage diseases.
Book: Fundamentals of Anaesthesia
Authors: Robert Stephens
Journal: BMJ (2000)

Eds Colin Pinnock, Ted Lin, Tim Smith


Greenwich Medical Media, £55, pp 750 




ISBN 1 900151 618

———————

Rating: ★★★

Anaesthesia has seen several changes recently, including a change to its examination system—the primary and final FRCA having replaced the old parts one, two, and three. The primary exam combines the basic anaesthesia content of the old part one with the basic sciences component of the old part two. It used to be said that the point of the old part one was to assess whether you had a good grounding in day to day anaesthesia and could practise it safely. Most trainees (including me) found that much revision could be done “on the job,” by giving anaesthetics under supervision and by asking their consultant-teachers how they would manage certain situations.

When it came to the old part two, however, we were required to have an in depth knowledge of pharmacology and physiology not necessarily used on a regular basis. A different approach was needed: the consultants didn't have all the answers. Not surprisingly, the details of receptors or drug pharmacokinetics had long been forgotten. Frustratingly, these weren't always available in text- books, resulting in behaviour familiar to anyone who has ever sat a medical exam—reading and re-reading those things that they know best while delaying revision of the unknown aspects until the day before the exam.

In Fundamentals of Anaesthesia the editors have obviously tried to rethink the traditional format and have deliberately avoided the usual “big names” as authors. The book is divided into four parts: clinical anaesthesia, physiology, pharmacology, and measurement. As well as the standard subjects, there are some useful chapters on areas not often covered in textbooks, such as information on pacemaker codes, electrical safety, sterilisation of instruments, intravenous fluids, and antimicrobial treatment. Information boxes provide summaries ideal for quick revision or for viva-style answers. Especially welcome were chapters on “The Surgical Insult” and basic statistics, and I'm sure it won't be long before we see chapters on preoptimisation, clinical governance, and management!

While no book could cater for all shades of opinion, Fundamentals of Anaesthesia manages to combine common sense with concise information to be an all in one anaesthetic textbook. Although it is aimed at trainees sitting the primary FRCA, I suspect it will be useful for the final fellowship, for anaesthetists returning to clinical work after time out, and for consultants wanting a brief overview for teaching purposes.
Preventing injuries in professional football: thinking bigger and working together
Authors: Jan Ekstrand
Journal: British Journal of Sports Medicine (2016)

Avoiding injuries ensures high player availability and allows coaches to have the most complete squad possible available for training and to select their best squad for matches. In the UEFA Champions League (UCL), the unavailability of players to compete in matches due to injury averages 14% but varies between 5% and 20%.1 Lower injury rates have been linked with team success in national and international matches.2

Top players are expensive to sign (transfer fees) and they have large salaries. It has been estimated that an injured player in the starting 11 of a UCL team will cost the club around €500 000 to €600 000 a month or around between €17 000 and €20 000 a day.3 Since the average number of absence days in a UCL team with a squad of 25–28 players is around 1100 days a season, the average cost to the club due to injuries is around €20 …
Case 21-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Sylvan E. Stool, Max L. Goodman
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 13-year-old boy was admitted to the hospital because of chronic otitis media, episodic dizziness, fluctuating left-sided hearing loss, and a destructive process in the left mastoid bone.There was a long history of otitis media. The insertion of bilateral pressure-equalization tubes six years before entry was followed by improvement in the bouts of otitis media. Repeated audiometric examinations performed at school and in his pediatrician's office showed no evidence of hearing loss. Five years before admission the right pressure-equalization tube was extruded. One year before entry left-sided otorrhea occurred and was treated with topical antibiotic drops. . . .
Externally Validated Predictive Clinical Model For Untreated Del(17p13.1) Chronic Lymphocytic Leukemia Patients
Authors: Deborah M Stephens, Amy Stark, William G. Wierda, Jeffrey A. Jones, Jennifer A. Woyach, Kami Maddocks, Samantha M. Jaglowski, Leslie A Andritsos, Joseph M. M. Flynn, Michael R. Grever, Gerard Lozanski, Constantine S Tam, Susan O'Brien, Michael J. Keating, Natarajan Muthusamy, Lynne V. Abruzzo, Nyla A. Heerema, John C. Byrd
Journal: Blood (2013)
CYP3A5*3 genotypes and advanced non-small cell lung cancer development
Authors: A. Nogal, A. Coelho, A. Araújo, I. Azevedo, A. Faria, M. Soares, R. Catarino, R. Medeiros
Journal: Journal of Clinical Oncology (2007)

21030 Background: Lung cancer is the most common cancer in Europe (381.500 new cases in 2004) and the third in the U.S.A (172.570 new cases in 2005). Smoking is one of the major causes of lung cancer: there are many procarcinogens present in tobacco smoke that, when activated, contribute to the development of this disease. The CYP3A subfamily represents a group of enzymes responsible for the metabolism of many currently used drugs, exogenous carcinogens and endogenous molecules such as steroids. Two of the major enzymes in this family, CYP3A4 and CYP3A5, activate polycyclic aromatic hydrocarbons such as benzo[a]pyrene and other procarcinogens present in tobacco smoke. Functional polymorphisms, such as CYP3A5*3 (associated with the lack of the CYP3A5 protein), could alter individual susceptibility to lung cancer. The aim of our study was to evaluate the influence of this polymorphism in the development of lung cancer. Methods: DNA samples were extracted from peripheral blood cells of 203 patients with non small cell lung cancer, including 42 non- smokers and 156 smokers or former smokers (no data available for the other 5 patients) and 162 blood donors. The CYP3A5*3 polymorphism was analysed through PCR-RFLP (SspI). Analysis of data was performed using the computer software SPSS for windows. The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between CYP3A5*3 genotypes and NSCLC progression. Results: We found significant statistical differences between the control group and the patients with advanced stages (III and IV) of epidermoid and undifferentiated NSCLC (p=0.04; OR = 0.48; 95% CI = 0.232–0.977). Conclusions: Individual differences in the metabolism of carcinogens may influence the susceptibility to cancer development and behaviour. Our preliminary results suggest that the carriers CYP3A5*3 polymorphism are at lower risk of developing advanced lung cancer. This is probably due to a decreased activation of procarcinogens present in tobacco smoke in result of the lack of CYP3A5 caused by the CYP3A5*3 polymorphism. This is consistent with the hypothesis of a cumulative effect of carcinogens on the aggressive behaviour of the disease. No significant financial relationships to disclose.
Docetaxel-based chemotherapy in elderly patients (≥ 75 years) with castration resistant prostate cancer (CRPC): A French National study of 175 patients
Authors: E. Bompas, A. Italiano, C. Ortholan, S. Oudard, D. Pouessel, G. Gravis, P. Beuzeboc, A. Flechon, F. Joly, J. Ferrero, K. Fizazi
Journal: Journal of Clinical Oncology (2008)

5145 Background: Although docetaxel-based chemotherapy is a standard in CRPC, only limited data is available in elderly patients (pts) with CRPC treated with chemotherapy. Methods: Data from 175 pts older than 75 years with metastatic CRPC treated with first-line docetaxel in 9 French cancer centers from 2000 to 2007 were analyzed. Results: Median age was 78 years. 95 pts (54%) received a “standard” docetaxel regimen (SR) (70–75 mg/m² d1, q3w) and 80 pts (46%) an “adapted” regimen (AR) (30–35 mg/m² weekly). Pts treated with an AR were older (≥ 80 years: 41.2% vs 25.3%, p=0.04), had a poorer performance status (PS≥ 2: 28% vs 14%; p=0.04) and had pain more often (63% vs 42%, p=0.01) than pts treated with a SR. Grade 3–4 adverse events occurred in 46% and were correlated with a poor PS and the presence of visceral metastases, but not with the regimen (SR vs AR). More pts in the SR group had febrile neutropenia (9.5% vs 1%, p=0.02) whereas more pts in the AR group had severe fatigue (20% vs 6%, p=0.01). Early discontinuation of chemotherapy due to toxicity occurred more frequently in the AR group (30% vs 8%, p=0.0005). Four deaths (2.3%) were related to treatment. The PSA response rate was 71% and 68% in the SR and in the AR groups, respectively. Median progression-free survival was 7.4 months (95% confidence interval (CI): 6.5–8.4). Median overall survival was 15 months (95%CI: 12.8–17.1). In multivariate analysis, PS and presence of visceral metastases, but not age, predicted for overall survival. Conclusions: Pts over 75 years considered fit for the SR had a similar safety and efficacy profile than younger pts. In contrast, frail pts treated with an AR experienced a poor tolerance. The optimal schedule of docetaxel in frail pts remains to be elucidated. Geriatric tools should be used to detect more accurately elderly CRPC pts unfit for chemotherapy. No significant financial relationships to disclose.
Breast Cancer Screening Using Tomosynthesis and Digital Mammography in Dense and Nondense Breasts
Authors: Elizabeth A. Rafferty, Melissa A. Durand, Emily F. Conant, Debra Somers Copit, Sarah M. Friedewald, Donna M. Plecha, Dave P. Miller
Journal: JAMA (2016)

Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection in Women With Dense Breasts
Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children’s Oncology Group
Authors: M A Kutny, T A Alonzo, E R Gamazon, R B Gerbing, D Geraghty, B Lange, N A Heerema, L Sung, R Aplenc, J Franklin, S C Raimondi, B A Hirsch, A Konkashbaev, N J Cox, K Onel, A S Gamis, S Meshinchi
Journal: Leukemia (2015)