tbuckley/cabot-search huggingface dataset:
A phase 2 multimodality trial of docetaxel/prednisone with sunitinib followed by salvage radiation therapy (RT) in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (RP).
Authors: Andrew J. Armstrong, Susan Halabi, Patrick Healy, Robert Lee, Bridget F. Koontz, Judd W. Moul, Kelly Mundy, Patricia Creel, Sarah Yenser Wood, Kristen Davis, Brooke Reimer, Minh Nguyen, Avery N. Spitz, Ellen Bratt, Sung Kim, Phuoc T. Tran, Mark N. Stein, Michael Anthony Carducci, Daniel J. George
Journal: Journal of Clinical Oncology (2015)

35 Background: In men with high grade PC and rapid PSA progression after RP, failure rates are unacceptably high despite salvage RT. Androgen deprivation therapy (ADT) is not curative in this setting and we thus evaluated a novel multi-modality approach of systemic chemotherapy and anti-angiogenic therapy prior to prostate bed salvage RT in a multicenter trial. Methods: Eligible men had a rising PSA of 0.1-3.0 ng/ml within 4 years of RP, no metastatic disease except resected positive nodes, no prior ADT, and Gleason 7-10. Men received 4 cycles of docetaxel 70 mg/m2 q3w with prednisone 5 mg bid and sunitinib 37.5 mg qd for 14/21 days each cycle. Salvage RT (66Gy/33fx) to the prostate bed started at day 100. The primary endpoint was progression-free survival at 2 years (PFS2), defined as a confirmed PSA rise above the post-RT nadir or baseline if no nadir occurred, clinical/radiographic progression, or death from date of enrollment. Safety and dose-limiting toxicities were evaluated. This was a single arm prospective open-label phase 2 trial. Results: Thirty-four men accrued in this multisite Dept. of Defense Prostate Cancer Clinical Trials Consortium trial (median age 62, 85% Caucasian, 9% African American); 24% were node positive at surgery, 47% had Gleason 8-10. Median PSA at entry was 0.54 (range 0.2-2.8) and median time since RP was 11 months. The trial was terminated prematurely due to excess dose-limiting toxicity (9 DLT events) including grade 3 events of hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1), and vomiting with diarrhea (n=1). PFS at 2 years was 48.9% (95% CI: 32.8%, 67.2%) with a median PFS of 26.2 mo (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. Conclusions: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. However, efficacy data suggests that some men achieved durable long-term disease control with this aggressive approach. Longer-term follow-up and comparative data with salvage XRT and ADT is needed to fully understand the risks/benefits of this combined modality approach in high risk PSA-recurrent PC. Clinical trial information: NCT00734851.
Long-term Results of Side-to-Side Isoperistaltic Strictureplasty for Crohn Disease
Authors: Fabrizio Michelassi
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Ertapenem in the treatment of multidrug-resistant tuberculosis: first clinical experience
Authors: Simon Tiberi, Lia D'Ambrosio, Saverio De Lorenzo, Pietro Viggiani, Rosella Centis, Giovanni Sotgiu, Jan Wilem C. Alffenaar, Giovanni Battista Migliori
Journal: European Respiratory Journal (2015)

Treatment of multidrug-resistant (MDR) tuberculosis (TB) (defined as resistance to at least isoniazid and rifampicin, two core first-line drugs for TB treatment) and extensively drug-resistant (XDR)-TB (defined as resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs amikacin, capreomycin or kanamycin) are a challenge for both clinicians and public health specialists [1–5]. Treatment outcomes of difficult-to-treat MDR-TB cases ( e.g. those with an extensive resistance pattern) are still unsatisfactory, adverse events frequent and severe, and the necessary drugs expensive [6]. Ertapenem may be useful for MDR/XDR-TB to simplify administration of carbapenem when the patient is at home <http://ow.ly/Snx69>
The Value and Significance of Metagenomics of Marine Environments
Authors: Fangqing Zhao, Vladimir B. Bajic
Journal: Genomics Proteomics & Bioinformatics (2015)

Microbes have played a fundamental role in the natural history of our planet, and have done so for billions of years. They have adapted to Earth’s many environments from the mild to the very extreme. Studying their diversity and their way of life is critical for understanding their full impact on the global ecology. Although the field of metagenomics is still young, it has unravelled a wider microbial diversity that had otherwise been completely overlooked by the traditional methods of microbiology. There are three major metagenomic themes: (a) marker metagenomics that surveys microbial community structure by targeting the highly-conserved 16S rRNA gene, (b) functional metagenomics that takes the total environmental DNA, from which it infers the metabolic potential of the microbial community, and (c) identification of novel enzymes.
Carbon Dots with Intrinsic Theranostic Properties for Bioimaging, Red‐Light‐Triggered Photodynamic/Photothermal Simultaneous Therapy In Vitro and In Vivo
Authors: Jiechao Ge, Qingyan Jia, Weimin Liu, Minhuan Lan, Bingjiang Zhou, Liang Guo, Hangyue Zhou, Hongyan Zhang, Ying Wang, Ying Gu, Xiangmin Meng, Pengfei Wang
Journal: Advanced Healthcare Materials (2015)

Cancer nanotheranostics combining therapeutic and imaging functions within a single nanoplatform are extremely important for nanomedicine. In this study, carbon dots (C-dots) with intrinsic theranostic properties are prepared by using polythiophene benzoic acid as carbon source. The obtained C-dots absorb light in the range of 400-700 nm and emit bright fluorescence in the red region (peaking from 640 to 680 nm at different excitations). More importantly, the obtained C-dots exhibit dual photodynamic and photothermal effects under 635 nm laser irradiation with a singlet oxygen ((1)O2) generating efficiency of 27% and high photothermal conversion efficiency of 36.2%. These unique properties enable C-dots to act as a red-light-triggered theranostic agent for imaging-guided photodynamic-photothermal simultaneous therapy in vitro and in vivo within the therapeutic window (600-1000 nm).
A supergene determines highly divergent male reproductive morphs in the ruff
Authors: Clemens Küpper, Michael Stocks, Judith E Risse, Natalie dos Remedios, Lindsay L Farrell, Susan B McRae, Tawna C Morgan, Natalia Karlionova, Pavel Pinchuk, Yvonne I Verkuil, Alexander S Kitaysky, John C Wingfield, Theunis Piersma, Kai Zeng, Jon Slate, Mark Blaxter, David B Lank, Terry Burke
Journal: Nature Genetics (2015)

Terry Burke, Mark Blaxter, David Lank and colleagues report a reference genome sequence of the ruff and analysis of the three distinct male morphs of this bird species. They identify a 'supergene' consisting of a fixed inversion in two of the morphs and identify candidate reproductive trait genes in this region. Three strikingly different alternative male mating morphs (aggressive 'independents', semicooperative 'satellites' and female-mimic 'faeders') coexist as a balanced polymorphism in the ruff, Philomachus pugnax, a lek-breeding wading bird1,2,3. Major differences in body size, ornamentation, and aggressive and mating behaviors are inherited as an autosomal polymorphism4,5. We show that development into satellites and faeders is determined by a supergene6,7,8 consisting of divergent alternative, dominant and non-recombining haplotypes of an inversion on chromosome 11, which contains 125 predicted genes. Independents are homozygous for the ancestral sequence. One breakpoint of the inversion disrupts the essential CENP-N gene (encoding centromere protein N), and pedigree analysis confirms the lethality of homozygosity for the inversion. We describe new differences in behavior, testis size and steroid metabolism among morphs and identify polymorphic genes within the inversion that are likely to contribute to the differences among morphs in reproductive traits.
Reply
Authors: Anthony H. Gershlick, Jamal Nasir Khan, Damian J. Kelly, John P. Greenwood, Thiagarajah Sasikaran, Nick Curzen, Daniel J. Blackman, Miles Dalby, Kathryn L. Fairbrother, Winston Banya, Duolao Wang, Marcus Flather, Simon L. Hetherington, Andrew D. Kelion, Suneel Talwar, Mark Gunning, Roger Hall, Howard Swanton, Gerry P. McCann
Journal: Journal of the American College of Cardiology (2015)
A Randomized Comparison of the Endeavor Zotarolimus-Eluting Stent Versus the TAXUS Paclitaxel-Eluting Stent in De Novo Native Coronary Lesions
Authors: Martin B. Leon, Laura Mauri, Jeffrey J. Popma, Donald E. Cutlip, Eugenia Nikolsky, Charles O'Shaughnessy, Paul A. Overlie, Brent T. McLaurin, Stuart L. Solomon, John S. Douglas, Michael W. Ball, Ronald P. Caputo, Ash Jain, Thaddeus R. Tolleson, Bernard M. Reen, Ajay J. Kirtane, Peter J. Fitzgerald, Kweli Thompson, David E. Kandzari
Journal: Journal of the American College of Cardiology (2010)
Post-earthquake recovery in Nepal
Authors: Maryke J Nielsen, Sally Ferguson, Arun Kumar Joshi, Suman Rimal, Indrawali Shrestha, Sumindra Rama Magar
Journal: The Lancet Global Health (2015)

We are grateful to Buddha Basnyat and colleagues (October, 2015),1Basnyat B Tabin C Nutt C Farmer P Post-earthquake Nepal: the way forward.Lancet Glob Health. 2015; 3: e731-e732Summary Full Text Full Text PDF Scopus (18) Google Scholar for drawing attention to the potential infectious consequences of the devastating April 25 Nepalese earthquake and the subsequent aftershocks. The need to "build back better" is imperative. However, Basnyat and colleagues do not mention the current fuel crisis which is seriously hampering earthquake recovery. A new constitution was passed in Nepal on Sept 20, and since then there have been complex border issues restricting importation of diesel, petrol, and cooking gas from India to Nepal. In Nuwakot District an unparalleled 90% of health institutions were affected by the earthquake. The fuel restrictions have delayed construction of the planned prefabricated hospital, and as the winter cold deepens, inpatients at Trishuli District Hospital are still universally being cared for in tents (figure). Additionally, limitations on petrol supplies have resulted in overloading of public buses. More than 35 people were killed when an overcrowded bus crashed in a neighbouring district on Nov 3, the victims being brought to Trishuli Hospital. The long-term environmental effects of people being forced to use wood for cooking and heating should also be considered. Furthermore, some hospitals are in danger of running out of medication again owing to problems at the border. Inadequate attention has been paid internationally to this issue, which is delaying plans for revitalisation of the health sector in Nuwakot District and indeed the recovery of the rest of Nepal. We call on the international community to demand that the Nepali and Indian governments resolve this problem as a matter of urgency. Opinions express reflect those of the individuals and not of the organisations to which they are affiliated. We declare no competing interests. Nepal: man-made disaster looms7 months ago, Nepal was hit by two major earthquakes, killing more than 8500 people, injuring thousands more, and leaving millions in need of humanitarian assistance. The devastation to the Himalayan nation received worldwide media coverage. But another, less visible crisis is unfolding in the country as it continues to recover from not only natural disaster but also a decade-long civil war. Full-Text PDF
Assessment of a Central Line–Associated Bloodstream Infection Prevention Program in a Burn-Trauma Intensive Care Unit
Authors: Lois Remington, Iris Faraklas, Kristy Gauthier, Colby Carper, J. Bradley Wiggins, Giavonni M. Lewis, Amalia Cochran
Journal: JAMA Surgery (2015)

Although evidence-based strategies have resulted in a sharp decrease in central line-associated bloodstream infection (CLABSI) rates in recent years, including a zero rate in many intensive care unit (ICU) environments, 1,2 burn units continue to have the highest pooled mean rate of CLABSIs (2.9 infections per 1000 central line-days) but only a moderate central line utilization rate (0.47 central line-days per 1000 patient-days). 3 The objective of our study was to evaluate a multimodal, multidisciplinary quality improvement project to reduce the number of CLABSIs in a dedicated burn-trauma ICU (BTICU).Methods | A multidisciplinary committee in our 15-bed BTICU convened to synthesize evidence-based interventions into a multimodal, multidisciplinary CLABSI bundle (Figure).Hospital epidemiology staff monitored and reported CLABSIs as defined by the Centers for Disease Control and Prevention's National Healthcare Safety Network. 4
Selection bias: maintaining less-differentiated T cells for adoptive immunotherapy
Authors: Yang Xu, Gianpietro Dotti
Journal: Journal of Clinical Investigation (2015)

The clinical application of T cell immunotherapy depends on ex vivo modification and expansion of T cells for adoptive transfer. In preclinical models, the use of a purified, naive T cell subset enhances persistence and antitumor immunity; however, the majority of clinical studies rely on modification of mixed populations of T cells that contain only a small subset of highly functional T cells with less-differentiated phenotype. In this month's issue of the JCI, Klebanoff and colleagues uncover a Fas-mediated interaction between naive T cells and antigen-experienced T cells that drives differentiation and impairs adoptive immunotherapy. Further, they show that blockade of Fas signaling enhances antitumor immunity and increases survival in a mouse model of melanoma. Their work supports a growing body of evidence that the use of naive T cells enhances the efficacy of adoptive T cell therapy and suggests a new therapeutic strategy for preserving less-differentiated T cell populations.
Incidence, severity, mortality, and confounding factors for dissecting AAA detection in angiotensin II-infused mice: a meta-analysis
Authors: Bram Trachet, Rodrigo A. Fraga-Silva, Philippe A. Jacquet, Nikolaos Stergiopulos, Patrick Segers
Journal: Cardiovascular Research (2015)

While angiotensin II-infused mice are the most popular model for preclinical aneurysm research, representative data on incidence, severity, and mortality of dissecting abdominal aortic aneurysms (AAAs) have never been established, and the influence of confounding factors is unknown.We performed a meta-analysis including 194 manuscripts representing 1679 saline-infused, 4729 non-treated angiotensin II-infused, and 4057 treated angiotensin II-infused mice. Incidence (60%) and mortality (20%) rates are reported overall as well as for grade I (22%), grade II (26%), grade III (29%), and grade IV (24%) aneurysms. Dissecting AAA incidence was significantly (P < 0.05) influenced by sex, age, genetic background, infusion time, and dose of angiotensin II. Mortality was influenced by sex, genetic background, and dose, but not by age or infusion time. Surprisingly, both incidence and mortality were significantly different (P < 0.05) when comparing angiotensin II-infused mice in descriptive studies (56% incidence and 19% mortality) with angiotensin II-infused mice that served as control animals in treatment studies designed to either enhance (35% incidence and 13% mortality) or reduce (73% incidence and 25% mortality) dissecting AAA formation. After stratification to account for confounding factors (selection bias), the observed effect was still present for incidence, but not for mortality. Possible underlying causes are detection bias (non-uniform definition for detection and quantification of dissecting AAA in mice) or publication bias (studies with negative results, related to incidence in the control group, not being published).Our data provide a new meta-analysis-based reference for incidence and mortality of dissecting AAA in angiotensin II-infused mice, and indicate that treatment studies using this mouse model should be interpreted with caution.
Efficacy and safety findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5- FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC)
Authors: M. Ducreux, J. Bennouna, M. Hebbar, M. Ychou, G. Lledo, T. Conroy, A. Adenis, R. Faroux, C. Rebischung, J. Douillard
Journal: Journal of Clinical Oncology (2007)

4029 Background: X has comparable efficacy, safety and convenience benefits over 5-FU/LV (Mayo clinic) in adjuvant colon cancer and first-line MCRC. A recent phase III trial in first line MCRC showed that XELOX is well tolerated and non inferior to FOLFOX-4 for progression-free survival (PFS) [Cassidy ESMO 2006]. Methods: We initiated a phase III trial to demonstrate non inferiority in terms of best response rates (RR, RECIST) of XELOX versus FOLFOX-6 as first-line therapy in patients (pts) with MCRC. Between 16 May 03 and 31 Aug 04, 306 patients (intention to treat), were randomized to receive either XELOX (n=156: × 1,000mg/m 2 bid d1–14, O 130mg/m 2 d1, q3w) or FOLFOX-6 (n=150: O 100mg/m 2 d1 LV 400mg/m 2 2h infusion then 5-FU 400mg/m 2 i.v. bolus then 2,400–3,000mg/m 2 46h infusion, q2w) for 6 months. Efficacy results are presented in the per protocol population (PP) (n=284:144 pts XELOX; 140 pts FOLFOX-6). Results: Baseline characteristics were well balanced. Pts received a median of 8 and 11 cycles of XELOX (range 0–8) and FOLFOX-6 (range 0–12), respectively. Dose intensity (median) for oxaliplatin was 99.6% and 95.4% with XELOX and FOLFOX-6, respectively. Best RR (independent review, PP) was 42% and 46% with XELOX and FOLFOX-6, respectively. Difference between groups for RR was 4.7%; upper limit of 95% unilateral CI (14.4%) was below non-inferiority margin of 15%. RR by investigators (PP) was 46% for each arm. With a median follow up of 16.5 months (range 0.4–38.3), median PFS and overall survival (PP) were 9.3/19.9 vs. 9.7/18.4 months with XELOX and FOLFOX-6, respectively. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 0%, p=0.21), thrombocytopenia (12 vs. 5% p=0.052), and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001), neuropathy (8 vs. 19% p=0.003), than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% in XELOX and FOLFOX-6 arms, respectively. Conclusions: The primary endpoint has been met: XELOX is non inferior to FOLFOX-6, with a good safety profile in first-line MCRC. No significant financial relationships to disclose.
College has found strong demand for training programmes
Authors: R. Peyton
Journal: BMJ (1996)

EDITOR,—As Chris Bulstrode and Gareth Holsgrove emphasise, consultant surgeons need to be educated in the principles and methods of teaching while undertaking clinical work.1 Indeed, it is important that they are educated in these principles and methods so that they can apply them to any educational opportunity and thereby maximise the efficiency of their teaching.

At the Royal College of Surgeons of England we have been running a …
Abstract P032: Adiponectin is Significantly Associated with NT-pro BNP Levels: The Multi-Ethnic Study of Atherosclerosis
Authors: Matthew A Allison, Michael Criqui, Lori Daniels, Alan Maisel, Joseph Polak, Mary Cushman
Journal: Circulation (2014)

Background: Increasing adiposity results in an increase in intravascular volume, while natriuretic peptides increase in response to pressure and volume overload. Adiponectin and leptin are cytokines released from adipose tissue (adipokines) that have purportedly opposite associations with CVD and measures of left ventricular structure and function. Methods: Subjects were 1970 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis who were without clinical CVD at baseline and evaluated by extensive survey information, relevant physical measurements and fasting venous blood that was analyzed for NT-pro BNP (proBNP) and the adipokines adiponectin and leptin. proBNP was assayed from two different study visits about 4 years apart. Results: At baseline, the mean age was 64.8 years and 48% were female. Forty-two percent were White, 26% Hispanic American, 18% African American and 14% Chinese American. Median values for adiponectin, leptin and proBNP were 17.3 μg/ml, 13.1 ng/ml and 66.7 pg/ml, respectively, while the median change in proBNP was 11.6 pg/ml. With adjustment for traditional CVD risk factors, adiposity, renin, aldosterone and LV mass and volume, a 1-SD increment in adiponectin was associated with a 13.7 pg/ml higher proBNP level (p &lt; 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles were associated with 28, 45 and 67% higher proBNP levels (p &lt; 0.01 for all). For changes in proBNP over the follow-up period, and after multivariable adjustment including baseline proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml increase in proBNP (p &lt; 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and &lt; 0.01, respectively). There were no significant multiplicative interactions by race or obesity status. However, there was a significant interaction between adiponectin and gender for proBNP, such that the associations detailed above were significantly stronger in men. Leptin was not associated with proBNP (data now shown). Conclusions: Higher adiponectin, but not leptin, is significantly associated with higher levels of proBNP, as well as significant longitudinal increases in proBNP. The findings appear to be stronger in men.