tbuckley/cabot-search huggingface dataset:
Outcomes of re-treatment with first-line trastuzumab plus taxane in patients (pts) with metastatic breast cancer (mBC) who relapsed after (neo)adjuvant trastuzumab: A prospective multicenter study.
Authors: Binghe Xu, Xi-Chun Hu, Hong Zheng, Xiaojia Wang, Qingyuan Zhang, Shude Cui, Donggeng Liu, Ning Liao, Rongcheng Luo, Qiang Sun, Shiying Yu
Journal: Journal of Clinical Oncology (2016)

e12068 Background: Trastuzumab combined with chemotherapy is the backbone of HER2-positive early breast cancer (eBC) and mBC treatment. In the pivotal phase III study H0648g, all enrolled pts with mBC were trastuzumab-naive. There is limited data about efficacy and safety of trastuzumab retreatment of relapsed pts exposed to trastuzumab-based therapy. Here, we performed a prospective, single arm, multicenter trial to assess efficacy and safety profile of trastuzumab and taxane combination in pts with HER2-positive mBC who relapsed after prior (neo)adjuvant trastuzumab-based therapy. Methods: Pts with HER2-positive mBC who had completed (neo)adjuvant trastuzumab treatment for ≥ 9 weeks, with a relapse-free interval ≥ 6 months after trastuzumab treatment in the (neo)adjuvant setting for eBC were enrolled. 32 eligible pts were assigned to receive trastuzumab (weekly), in combination with paclitaxel (weekly) or docetaxel (every 3 weeks) until disease progression, unacceptable toxicity, death or withdrawal from study. The primary endpoint was progression free survival (PFS). The secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to progression (TTP), overall survival (OS) and safety profile. Results: The median PFS was 9.9 months (95%CI, 6.28-13.63), ORR (CR+PR) was 81.3% (95%CI, 63.6%-92.8%), CBR (CR+PR+SD ≥ 6 months) was 81.3% (95%CI, 63.6%-92.8%), median DOR was 9.8 months (95%CI, 5.82-11.60), median TTP was 9.9 months (95%CI, 6.28-13.63), 5 pts in the enrolled 32 pts (15.6%) had the event of death and median OS has not been reached. The most common adverse events (AEs, all grades) were blood and lymphatic system disorders, 5 subjects (15.6%, 5/32) had occurrence of serious AEs (SAEs). No congestive heart failure or any unexpected trastuzumab-related SAEs were reported. Conclusions: Re-treatment with trastuzumab plus taxane as first-line therapy is an effective regimen for pts with HER2-positive mBC who relapsed after (neo)adjuvant trastuzumab for eBC. The safety profile was good and the adverse reactions were tolerable and manageable. Clinical trial information: NCT01301729.
Improved 123I-Ioflupane Binding After Immunotherapy in Anti–NAE Antibody–Positive Hashimoto Encephalopathy That Clinically Mimicked Multiple System Atrophy
Authors: Juuri Otsuka, Ayumi Hida, Kamiyu Ogyu, Ryogo Minamimoto, Sousuke Takeuchi
Journal: Clinical Nuclear Medicine (2017)

We describe an 84-year-old man with anti-NH2-terminal of α-enolase antibody-positive Hashimoto encephalopathy that clinically mimicked multiple system atrophy who underwent investigation by dopamine transporter SPECT before and after immunotherapy. Before treatment, dopamine transporter SPECT showed reduced striatal I-ioflupane binding, with a mean specific binding ratio of 2.42, even though he had no apparent parkinsonism. After immunotherapy, mean specific binding ratio was improved to 3.22. Dopamine transporter SPECT was useful in this case to detect subclinical striatal dysfunction, and evaluation both before and after immunotherapy helped to distinguish between neurodegenerative disease and neuroimmunological disorder.
The impact of individual surgeons on the likelihood of mastectomy in breast cancer.
Authors: Isabel Boero, Anthony Joseph Paravati, Erin Gillespie, Jiayi Hou, James Don Murphy
Journal: Journal of Clinical Oncology (2016)

1008 Background: Women with localized breast cancer face the difficult personal decision of whether to undergo mastectomy or breast conservation surgery (BCS). Multiple factors impact this decision, though no recent analysis has queried the broader role that the individual surgeon plays in this decision making process. The goal of this study was to evaluate the impact of individual surgeons on the use of mastectomy versus BCS for definitive treatment of breast cancer. Methods: We identified 44,698 Medicare beneficiaries with localized breast cancer diagnosed between 2000 and 2009 who underwent either BCS or mastectomy. Medicare claims were used to determine surgery type and identify the individual surgeon. Multi-level, multivariable logistic models clustered by surgeon and geographic region were used to determine the impact of surgeons on the likelihood of mastectomy while controlling for a patient’s clinical and demographic covariates and a physician’s demographic and practice information. Odds ratios (OR) were used to describe the impact of fixed demographic or clinical covariates, and the median odds ratio (MOR) was used to describe the relative impact of the geographic region and individual surgeon on the likelihood of receiving a mastectomy. Results: Among the entire cohort 10,156 women (22.7%) were treated with mastectomy. Unadjusted rates of mastectomy ranged from 3.2% in the bottom quintile of surgeons to 47.1% in the top quintile. Multivariable analysis found that the individual surgeon (MOR 2.14) had a greater impact on mastectomy use than geographic region (MOR 1.56) or all other clinical and demographic variables except tumor size (OR 3.02) and nodal status (OR 2.86). Male surgeons, those with less experience, and surgeons with a lower volume of breast cancer cases were slightly more likely to perform mastectomy compared to BCS (all p < 0.05). Conclusions: The individual surgeon influences the likelihood of mastectomy for the treatment of localized breast cancer. Further research should focus on specific physician-related beliefs or biases that influence this decision making process.
Cancer Immunotherapy Trials Not Immune from Imprecise Selection of Patients
Authors: Edward B. Garon
Journal: New England Journal of Medicine (2017)

Arguably, no drug class has more radically and rapidly altered the management of non–small-cell lung cancer (NSCLC) than inhibitors of the interaction between programmed death 1 (PD-1) and its ligand PD-L1. By impeding this negative regulatory signal for T-cell response, PD-1 and PD-L1 inhibitors result in longer survival than does chemotherapy among patients with previously treated NSCLC.14 In this issue of the Journal, Carbone and colleagues report on a trial that compared the PD-1 inhibitor nivolumab with chemotherapy as first-line treatment for advanced NSCLC in a population of patients selected on the basis of PD-L1 expression level.5 Progression-free survival . . .
A Pooled Overall Survival Analysis of The COMFORT Studies: 2 Randomized Phase 3 Trials of Ruxolitinib For The Treatment of Myelofibrosis
Authors: Kantarjian Hagop, Jean-Jacques Kiladjian, Jason Gotlib, Francisco Cervantes, Ruben A. Mesa, Giovanni Barosi, Nicholas Sarlis, Wei Peng, Victor A. Sandor, Andres Sirulnik, Abdel Hmissi, Viktoriya Stalbovskaya, Vikas Gupta, Claire N Harrison, Srdan Verstovsek
Journal: Blood (2013)
MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease.
Authors: Maura N. Dickler, Sara M. Tolaney, Hope S. Rugo, Javier Cortes, Véronique Diéras, Debra A. Patt, Hans Wildiers, Martin Frenzel, Andrew Koustenis, Jose Baselga
Journal: Journal of Clinical Oncology (2016)

510 Background: Abemaciclib is an oral, selective inhibitor of CDK4 and CDK6 dosed on a continuous schedule. In a phase 1 trial, abemaciclib demonstrated single-agent activity in refractory HR+ metastatic breast cancer (MBC) with some tumor responses occurring after 8 or more mos of therapy. Methods: MONARCH 1 is a phase 2 single-arm study designed to evaluate safety and efficacy of abemaciclib monotherapy in women with HR+/HER2- MBC whose disease progressed on or after endocrine therapy and chemotherapy. Eligible pts had measurable disease, ECOG PS of 0/1, no CNS metastases, and received at least 1 but no more than 2 lines of chemotherapy in the metastatic setting. Abemaciclib (200 mg) is administered orally on a continuous schedule every 12 hours until disease progression. A sample size of approximately 128 pts was planned to evaluate the primary objective of investigator-assessed objective response rate (ORR) using RECIST v1.1, with interim and final analyses at 8 and 12 mos after the last pt started treatment, respectively. Results: A total of 132 pts have been treated with abemaciclib monotherapy. Pts had a median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy for advanced disease. Median age was 58 (36-89), 44.7% of pts had PS 1, 90.2% had visceral disease, and 85.6% had ≥ 2 metastatic sites. At the 8 mo interim, 35.6% of pts had received ≥ 8 cycles of therapy; the confirmed ORR (per RECIST v1.1) was 17.4%, the clinical benefit rate (CR + PR + SD ≥ 6 mos) was 42.4%, and median PFS was 5.7 mos. Of the 22 pts who remained on treatment at the 8 mo interim, 13 had responded and 9 had SD. The 5 most common TEAEs were diarrhea, fatigue, nausea, decreased appetite, abdominal pain; discontinuations due to AEs were infrequent (6.8%). Conclusions: Abemaciclib induces objective tumor responses as a monotherapy in pts with refractory HR+ HER2- MBC following multiple prior therapies. Treatment was well tolerated, allowing prolonged exposure to therapy. Updated efficacy and tolerability data will be provided at the time of presentation. Clinical trial information: NCT02102490.
Effectiveness of conservative interventions including exercise, manual therapy and medical management in adults with shoulder impingement: a systematic review and meta-analysis of RCTs
Authors: Ruedi Steuri, Martin Sattelmayer, Simone Elsig, Chloé Kolly, Amir Tal, Jan Taeymans, Roger Hilfiker
Journal: British Journal of Sports Medicine (2017)

Objective To investigate the effectiveness of conservative interventions for pain, function and range of motion in adults with shoulder impingement. Design Systematic review and meta-analysis of randomised trials. Data sources Medline, CENTRAL, CINAHL, Embase and PEDro were searched from inception to January 2017. Study selection criteria Randomised controlled trials including participants with shoulder impingement and evaluating at least one conservative intervention against sham or other treatments. Results For pain, exercise was superior to non-exercise control interventions (standardised mean difference (SMD) −0.94, 95% CI −1.69 to −0.19). Specific exercises were superior to generic exercises (SMD −0.65, 95% CI −0.99 to −0.32). Corticosteroid injections were superior to no treatment (SMD −0.65, 95% CI −1.04 to −0.26), and ultrasound guided injections were superior to non-guided injections (SMD −0.51, 95% CI −0.89 to −0.13). Nonsteroidal anti-inflammatory drugs (NSAIDS) had a small to moderate SMD of −0.29 (95% CI −0.53 to −0.05) compared with placebo. Manual therapy was superior to placebo (SMD −0.35, 95% CI −0.69 to −0.01). When combined with exercise, manual therapy was superior to exercise alone, but only at the shortest follow-up (SMD −0.32, 95% CI −0.62 to −0.01). Laser was superior to sham laser (SMD −0.88, 95% CI −1.48 to −0.27). Extracorporeal shockwave therapy (ECSWT) was superior to sham (−0.39, 95% CI −0.78 to –0.01) and tape was superior to sham (−0.64, 95% CI −1.16 to −0.12), with small to moderate SMDs. Conclusion Although there was only very low quality evidence, exercise should be considered for patients with shoulder impingement symptoms and tape, ECSWT, laser or manual therapy might be added. NSAIDS and corticosteroids are superior to placebo, but it is unclear how these treatments compare to exercise.
Mair Eleri Morgan Thomas
Authors: A. E. Livingstone
Journal: BMJ (2015)

“We do not take women at the Royal Dick. Try the medical school down the road,” said the registrar when Mair Eleri Morgan Thomas (Mair Livingstone) tried to transfer to veterinary studies from zoology and botany at Edinburgh University in 1937. So began her medical journey, which took her from medical school to a house officer post in ear, nose, and throat medicine at the Royal Infirmary, where she slept in a side ward, as doctors had banned her from the mess residence as a woman, and nurses from the nurses’ home, as a doctor. With no days off, she even entertained her poet friends in this grim abandoned room, which she painted with cartoons of mice, recognisably representing the foibles of senior surgeons in theatre. It was wartime, and as many male doctors had been called up, she covered several posts as resident medical officer in Aberystwyth General Hospital. She loved eating the plentiful farm sourced food there after Scottish shortages, working among friends, and family, discovering the intrigue in the town and reviving her Welsh. Her own parents had met there at university. She returned to Scotland to embark on a career in bacteriology, and ran the laboratory at Bridge of Earn military hospital, where she distilled elderberry wine into potassium permanganate jars in quiet times between returning troops.

She was born at the end of the first world war in Llanddewi Brefi, Ceredigion, and was fiercely Welsh. Her mother, daughter of the manse, had been a teacher and suffragist and her father, a poor boy from Harlech, became a brilliant industrial chemist who died young. The family moved to Scotland so he could take on management at Scottish Dyes. At age 10 Mair she went to St Trinnean’s School …
Gene-diet interactions in the aetiology of colorectal cancer: results from a population-based case-control study in north-east Scotland
Authors: L Sharp, LF Masson, J Little, NT Brockton, SC Cotton, NE Haites, J Cassidy
Journal: Endoscopy (2006)

Aims: Folate, green vegetables and meat intake have all been linked with colorectal cancer (CRC) risk; variation in genes encoding enzymes involved in metabolising these factors might modify diet-CRC associations. We undertook a case-control study to investigate diet, MTHFR, GSTM1, GSTT1 and CYP1A1 polymorphisms and CRC.
Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3
Authors: Florent Artru, Alexandre Louvet, Isaac Ruiz, Eric Levesque, Julien Labreuche, Jose Ursic-Bedoya, Guillaume Lassailly, Sebastien Dharancy, Emmanuel Boleslawski, Gilles Lebuffe, Eric Kipnis, Philippe Ichai, Audrey Coilly, Eleonora De Martin, Teresa Maria Antonini, Eric Vibert, Samir Jaber, Astrid Herrerro, Didier Samuel, Alain Duhamel, Georges-Philippe Pageaux, Philippe Mathurin, Faouzi Saliba
Journal: Journal of Hepatology (2017)
Clinical and molecular subgroups of ependymoma in adulthood: An analysis of the German Glioma Network.
Authors: Dorothee Gramatzki, Hendrik Witt, Bettina Hentschel, Kristian W. Pajtler, Gabriele Schackert, Manfred Westphal, Ulrich Herrlinger, Torsten Pietsch, Markus Loeffler, Guido Reifenberger, Stefan M. Pfister, Joerg Tonn, Michael Weller
Journal: Journal of Clinical Oncology (2017)

2038 Background: Ependymoma is a subtype of glioma that is rare in adults. Its classification has remained entirely morphological until recently, and surgery and radiotherapy remain the mainstays of treatment. Here we characterized DNA methylation profiles and their clinical correlates in the prospectively assembled cohort of the German Glioma Network. Methods: The GGN cohort was screened for patients diagnosed with myxopapillary ependymoma, subependymoma, classic ependymoma and anaplastic ependymoma for whom clinical data and remaining tumor tissue were available. Tumors were subjected to DNA methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip platform. Molecular data were correlated with morphological tumor and clinical patient characteristics. Results: One hundred and twenty-two ependymoma patients with available tumor tissue were identified. Each adult tumor could be assigned to one of the previously defined methylation classes of ependymoma. Molecular entities of ependymal brain tumors display distinct copy-number variations. PF-EPN-B and ST-EPN-RELA tumors tend to have a worse prognosis than other ependymal subtypes in adults. Conclusions: Molecular classification of adult ependymal methylation subclasses should be implemented in routine diagnostics. Patients with PF-EPN-B and ST-EPN-RELA subtypes might benefit from early treatment beyond surgery.
Multigene hereditary cancer testing in sarcoma patients.
Authors: Sarah A. Jackson, Melanie D. Baxter, Jessica Mester, Lisa Susswein, Megan L. Marshall, Kathleen S. Hruska, Rachel T. Klein
Journal: Journal of Clinical Oncology (2017)

1518 Background: In multi-gene hereditary cancer testing, multiple syndromes may be interrogated simultaneously, increasing the likelihood of detecting an underlying cancer predisposition. We characterized the yield and distribution of pathogenic or likely pathogenic variants (PV/LPV) in patients with a personal history of sarcoma undergoing panel testing through our clinical diagnostic laboratory. Methods: We retrospectively reviewed panel test results, demographic data, and personal/family history information from patients reporting a personal history of sarcoma. Patients included in this study underwent panel testing (NGS and del/dup) of up to 61 genes at this laboratory and concurrent or prior TP53 analysis at this or an outside laboratory. Chi-square and Fisher’s exact tests were used to compare groups. Results: Among 374 sarcoma patients, 53 (14.2%) harbored one or more PV/LPV in 14 genes: TP53, BRCA2, CHEK2, BRCA1, ATM, MSH6, MLH1, NBN, BAP1, BRIP1, FLCN, MSH2, PTEN, and RB1. Thirty-nine (10.4%) individuals reported both a personal and family history of sarcoma; however, PV/LPV were not more likely to be detected among this group than those with personal history alone (p = 1.0). PV/LPV were most often detected in BRCA1/2 (15/374, 4.0%) or TP53 (12/374, 3.2%). Notably, four probands with BRCA1/2 PV/LPV reported a family history of sarcoma, including one kindred in which the variant was present in two brothers, both affected with sarcoma. Additionally, seven patients were found to have PV/LPV (1.9%) in genes causative for Lynch syndrome. Among patients with PV/LPV in genes other than TP53, nearly half (17/41, 41.5%) met National Comprehensive Cancer Network TP53 testing criteria. Conclusions: The majority of PV/LPV were identified in genes for which association with sarcoma risk is not well-established. While several of these genes have been implicated in somatic pathways related to sarcoma development, it is unclear whether these germline findings are causative, play no role, or modify sarcoma risk. Although these data do not inherently associate non- TP53 genes with sarcoma risk, they suggest a potential clinical benefit can be gained from performing hereditary cancer risk assessment and multi-gene panel testing in sarcoma patients.
Support vector machine (SVM) classification of cognitive tasks based on electroencephalography (EEG) engagement index
Authors: J. K. Nuamah, Younho Seong
Journal: Brain-Computer Interfaces (2017)

Human-system interaction may be improved by using proactive systems that detect, measure, and assess a user’s cognitive state in real time via diagnostic neurophysiological sensors and appropriate classification methods. The electroencephalography (EEG) task engagement index (TEI), a ratio of EEG power bands (beta/(alpha + theta)), may be used to track how cognitively engaged a person is in a task. In the present study, we performed statistical tests of significance on task engagement indices computed from EEG recorded from six healthy participants who performed five separate cognitive tasks. For all participants, we found a statistically significant difference in task engagement indices between the five cognitive tasks. Also, we used task engagement indices as inputs to support vector machines (SVMs) to allow identification and offline classification of cognitive engagement. We designed six separate multiclass SVMs to classify five cognitive tasks for the participants. The average classification accuracy across the six participants was 93.33 ± 8.16%. The results show that differences in cognitive task demand do elicit different degrees of cognitive engagement, which can be measured through the use of the TEI.
Clinical Characteristics and Factors of the Impact on the Survival in 133 De Novo FLT3-ITD Acute Myeloid Leukemia with Intermediate Chromosome Karyoptye from a Single Center of China
Authors: Shaowei Qiu, Dong Lin, Hui Wei, Guangji Zhang, Chunlin Zhou, Kaiqi Liu, Shuning Wei, Ying Wang, Bingcheng Liu, Benfa Gong, Xiaoyuan Gong, Yuntao Liu, Yingchang Mi, Jianxiang Wang
Journal: Blood (2016)
Workers’ Memorial Day — April 28, 2018
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Workers' Memorial Day, observed annually on April 28,* recognizes workers who were injured, became ill, or died because of exposures to hazards at work.In 2016, workrelated injuries claimed the lives of 5,190 U.S. workers, and the fatal injury rate (3.6 per 100 full time equivalent workers) † rose for the third consecutive year, to the highest rate since 2010.Although deaths resulting from workrelated injuries are captured through surveillance, most deaths resulting from work-related illness are not.In 2007, an estimated 53,445 persons died from work-related illness (1).In 2016, employers reported approximately 2.9 million nonfatal work-related injuries and illnesses to private industry workers.§ Occupational injuries and illnesses also have economic costs.The societal cost of work-related fatalities, injuries, and illnesses was estimated at $250 billion in 2007, based on methods that focus on medical costs and productivity losses (1).New data on fatal falls overboard in the fishing industry, one of the nation's most hazardous industries, are reported in this issue of MMWR (2).Since 1991, the CDC-NIOSH Western States Division has studied fishing safety and developed interventions to reduce the incidence of injuries and fatalities among the nation's fishermen.More information about commercial fishing safety can be found at https://www.cdc.gov/niosh/topics/fishing/.