tbuckley/cabot-search huggingface dataset:
Better patient flow in cardiac and thoracic surgery could save £45m a year in England
Authors: Nigel Hawkes
Journal: BMJ (2018)

The greatest potential gains in cardiac and thoracic surgery in England would come from improvements in the patient pathway, a report has found.1

Operating on the day of admission and reducing cancellations, length of stay, and nights in critical care could save as much as £45m (€52m; $64m) a year, the lion’s share of a potential £52m that could be saved if all units operated as economically as the top quartile do.

The figures come from a report by David Richens, a cardiac surgeon, as part of the Get It Right First Time (GIRFT) programme created by Tim Briggs, who is now director of clinical quality and efficiency at NHS England. The programme aims to reduce unwarranted variation in service and practice and will ultimately cover 35 specialities.

Richens does not find much to complain about in surgical competence at the …
182P Real world anti-PD-L1 treatment (tx) outcomes in a multinational European non-small cell lung cancer (NSCLC) cohort with focus on toxicity (tox) and brain metastases (BM): Preliminary data from an EORTC young investigators lung cancer group collaborative analysis
Authors: R. Tassi, F. Taylor, S. Canova, L. Low, O. Abdel-Rahman, B. Hasan, E. De Maio, A. Levy, B. Besse, L. Hendriks
Journal: Journal of Thoracic Oncology (2018)
Assessment of community-level effects of intermittent preventive treatment for malaria in schoolchildren in Jinja, Uganda (START-IPT trial): a cluster-randomised trial
Authors: Sarah G Staedke, Catherine Maiteki-Sebuguzi, Andrea M Rehman, Simon P Kigozi, Samuel Gonahasa, Jaffer Okiring, Steve W Lindsay, Moses R Kamya, Clare I R Chandler, Grant Dorsey, Chris Drakeley
Journal: The Lancet Global Health (2018)

Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda.We included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215.Among 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5-20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73-1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36-1·80, p=0·59).IPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed.UK Medical Research Council, UK Department for International Development, and Wellcome Trust.
170P A phase II trial of nab-paclitaxel and gemcitabine in patients with non-small cell lung cancer previously treated with platinum based chemotherapy
Authors: Y. Hatakeyama, M. Tachihara, T. Kiriu, A. Hata, T. Nagano, M. Yamamoto, K. Kobayashi, H. Ohnishi, N. Katakami, Y. Nishimura
Journal: Journal of Thoracic Oncology (2018)
Should we try to manage non-financial interests?
Authors: Miriam Wiersma, Ian Kerridge, Wendy Lipworth, Marc Rodwin
Journal: BMJ (2018)

Ideological biases influence medical research and practice and should be disclosed and managed, say <b>Miriam Wiersma and colleagues</b>. But <b>Marc Rodwin</b> argues that many of these interests are widespread and inherent to life and cannot be avoided or eliminated
69P The diabetes drug canagliflozin sensitizes non-small cell lung cancer (NSCLC) to radiotherapy and chemotherapy
Authors: T. Tsakiridis, L. Villani, L. Broadfield, K. Marcinko, E. Tsakiridis, P. Ellis, P. Muti, G. Steinberg
Journal: Journal of Thoracic Oncology (2018)
Bronchoalveolar lavage in children
Authors: None Ers Task Force on bronchoalveolar lavage in children, None Members of the Task Force: J. de Blic and F. Midulla (co-chairmen), A. Barbato, A. Clement, I. Dab, E. Eber, C. Green, J. Grigg, S. Kotecha, G. Kurland, P. Pohunek, F. Ratjen and G. Rossi.
Journal: European Respiratory Journal (2000)

Bronchoalveolar lavage (BAL) is routinely performed in adults for sampling cellular and biochemical components.Many studies have been performed that have enabled the proposal of recommendations for BAL, methodology and processing, as well as reference values in different clinical settings.In contrast, despite a world-wide increase in the use of BAL in children, including neonates, there are, at the present time, no clear recommendations on the methodology, the clinical applications and the research areas for BAL.A Task Force on BAL in children has been approved by the European Respiratory Society (ERS) Task Force committee 1996.The objectives of this task force were: 1) to provide recommendations and guidelines on how to perform BAL and how to process the return fluid in children; 2) to collect and discuss available reference values; 3) to list indications and results in both immunocompetent and immunocompromised children; 4) to define areas for future research.This task force included paediatric respiratory physicians involved in bronchoscopy and BAL and was run as a collaboration between the Paediatric Bronchology Group
Lessons learned from the blockade of immune checkpoints in cancer immunotherapy
Authors: Xiaolei Li, Changshun Shao, Yufang Shi, Weidong Han
Journal: Journal of Hematology & Oncology (2018)

The advent of immunotherapy, especially checkpoint inhibitor-based immunotherapy, has provided novel and powerful weapons against cancer. Because only a subset of cancer patients exhibit durable responses, further exploration of the mechanisms underlying the resistance to immunotherapy in the bulk of cancer patients is merited. Such efforts may help to identify which patients could benefit from immune checkpoint blockade. Given the existence of a great number of pathways by which cancer can escape immune surveillance, and the complexity of tumor-immune system interaction, development of various combination therapies, including those that combine with conventional therapies, would be necessary. In this review, we summarize the current understanding of the mechanisms by which resistance to checkpoint blockade immunotherapy occurs, and outline how actionable combination strategies may be derived to improve clinical outcomes for patients.
Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations
Authors: Qiuying Chen, Kathryne Kirk, Yevgeniya I. Shurubor, Dazhi Zhao, Andrea J. Arreguin, Ifrah Shahi, Federica Valsecchi, Guido Primiano, Elizabeth L. Calder, Valerio Carelli, Travis T. Denton, M. Flint Beal, Steven S. Gross, Giovanni Manfredi, Marilena D'Aurelio
Journal: Cell Metabolism (2018)
Abstract 19205: Prognostic Value of Overnight Holter Monitor Post Pulmonary Vein Isolation
Authors: Alejandra Gutierrez, Mohamed Bassiouny, Jacob Jessen, Ayman Hussein, John Rickard, Mina K Chung, Thomas Dresing, Patrick J Tchou, Mohamed H Kanj, Bruce Lindsay, Oussama Wazni
Journal: Circulation (2016)

Introduction:  Pulmonary vein isolation (PVI) is effective for management of atrial fibrillation (AF). However, early prediction of its outcome is not feasible as a blanking period of up to 3 months post ablation is typically recommended.   Purpose:  Our aim is to evaluate the value of overnight holter monitor for early prediction of long-term success of PVI.   Methods:  We reviewed data of consecutive patients who underwent PVI between Dec 2010 and July 2012. The procedure included isolation of all pulmonary veins and left atrial substrate modification as needed. The overnight post ablation holter monitor results was analyzed as a predictor of long-term success defined as freedom from any atrial arrhythmia lasting more than 30 seconds after a 3 month blanking period.   Results:  Our study included 958 consecutive patients: mean age 61.2 ± 10.4, 256 (27%) females, median AF duration of 4 years (Q1-Q3: 2,8), 422 (44%) persistent AF, CHA2DS2VASC score 2 (Q1-Q3: 1,3), mean ejection fraction (EF) of 54.5% ± 9.4. mean left atrium diameter of 4.26 ± 0.9 cm.  The results of the overnight holter monitor were available for 951 patients. The mean heart rate post ablation was 72.5 ± 12 bpm. 56 (6%) patients had recurrent arrhythmia overnight (34 paroxysmal AF, 12 persistent AF). On long-term follow of 490 days (Q1-Q3: 202, 809). 454 (47%) patients had recurrent atrial arrhythmia (41% in patients with paroxysmal AF and 55% in those with persistent AF). 46 (82%) of the 56 patients who had recurrent arrhythmia on holter monitor within 24 hours of PVI had late recurrence on long-term follow up.   Conclusion:  Recurrent arrhythmia within 24 hours of atrial fibrillation ablation is uncommon. However, it is strongly associated with recurrent arrhythmia on long-term follow up. Closer monitoring and early management of recurrent arrhythmia should be considered those patients.
Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma
Authors: Roland Schmitz, George W. Wright, Da Wei Huang, Calvin A. Johnson, James D. Phelan, James Q. Wang, Sandrine Roulland, Monica Kasbekar, Ryan M. Young, Arthur L. Shaffer, Daniel J. Hodson, Wenming Xiao, Xin Yu, Yandan Yang, Hong Zhao, Weihong Xu, Xuelu Liu, Bin Zhou, Wei Du, Wing C. Chan, Elaine S. Jaffe, Randy D. Gascoyne, Joseph M. Connors, Elias Campo, Armando Lopez-Guillermo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M. Rimsza, Kevin Tay Kuang Wei, Andrew D. Zelenetz, John P. Leonard, Nancy L. Bartlett, Bao Tran, Jyoti Shetty, Yongmei Zhao, Dan R. Soppet, Stefania Pittaluga, Wyndham H. Wilson, Louis M. Staudt
Journal: New England Journal of Medicine (2018)

Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics.
GP trainee facing deportation must be allowed to stay, says BMA
Authors: Abi Rimmer
Journal: BMJ (2018)

The BMA has criticised the government for threatening a GP trainee who qualified in the UK with deportation.

Chaand Nagpaul, BMA council chair, said that the government’s decision to deport Luke Ong, who is from Singapore, because of a delay in his visa process was “utterly incomprehensible.”

“This situation, in which a doctor—who has committed the past ten years of his life to studying, …
159P Clinical activity of afatinib in a cohort of patients with lung adenocarcinoma harbouring uncommon EGFR mutations: A Spanish retrospective multicentre study
Authors: M.T. Moran Bueno, C. Aguado, M. Dómine, A. Gomez Rueda, A. Calles, S.M. Cedres, N. Viñolas, D. Isla, R. Palmero, M. Sereno Moyano
Journal: Journal of Thoracic Oncology (2018)
<i>In vivo</i> growth of 60 non-screening detected lung cancers: a computed tomography study
Authors: Onno M. Mets, Kaman Chung, Pieter Zanen, Ernst T. Scholten, Wouter B. Veldhuis, Bram van Ginneken, Mathias Prokop, Cornelia M. Schaefer-Prokop, Pim A. de Jong
Journal: European Respiratory Journal (2018)

Current pulmonary nodule management guidelines are based on nodule volume doubling time, which assumes exponential growth behaviour. However, this is a theory that has never been validated in vivo in the routine-care target population. This study evaluates growth patterns of untreated solid and subsolid lung cancers of various histologies in a non-screening setting. Growth behaviour of pathology-proven lung cancers from two academic centres that were imaged at least three times before diagnosis (n=60) was analysed using dedicated software. Random-intercept random-slope mixed-models analysis was applied to test which growth pattern most accurately described lung cancer growth. Individual growth curves were plotted per pathology subgroup and nodule type. We confirmed that growth in both subsolid and solid lung cancers is best explained by an exponential model. However, subsolid lesions generally progress slower than solid ones. Baseline lesion volume was not related to growth, indicating that smaller lesions do not grow slower compared to larger ones. By showing that lung cancer conforms to exponential growth we provide the first experimental basis in the routine-care setting for the assumption made in volume doubling time analysis.
Toenails as the “Hemoglobin A<sub>1c</sub>” of Functional Independence—Beyond the Polished Wingtips
Authors: Ariela R. Orkaby, Andrea Wershof Schwartz
Journal: JAMA Internal Medicine (2018)

This article argues that the physical examination finding of long toenails should alert the clinician to other possible care needs and help guide questions as to the underlying differential diagnosis of the untrimmed toenails.
Tumor sideness and mutational status: The potential effects on mCRC pts survival and treatment outcomes.
Authors: Emel Sezer, Kadir Eser, Arif Hakan Onder, Banu Ozturk
Journal: Journal of Clinical Oncology (2018)

682 Background: The treatment of mCRC has been changed with identification of different clinical behaviour of right and left sided tumors. Right-sided primary was associated with high mutational burden, worse prognosis and poor anti-EGFR response. We aimed to investigate the association between tumor site and survival, mutational status and treatment outcome of mCRC pts. Methods: The data of mCRC pts in two-cancer center in South Anatolia were retrospectively analyzed. The effects of tumor sidedness, treatment, braf on survival of mCRC pts were investigated using the log rank test. The Kaplan- Meier survival estimates were calculated. Results: A total of 210 (F/M=128/82) pts were included to study. Median age was 59.5 (range: 23-88) years. Right and left-sided tumour rates were 45 (21.7%) and 153 (72.9%), respectively. Kras, nras and braf mutation rates were 32.9, 5.5 and 6.7 %, respectively. Median follow-up was 27.5 (range: 1.3-274.3) months. In the right-sided tumors, kras (52.5 vs. 33.8 %, p=0.0034) and braf (33.3 vs. 11.1%, p=0.022) mutation rates were more than left-sided ones. Median PFS (15.1 vs. 14.2 months) and OS (27.5 vs. 23.9 months) were higher in the pts with left-sided tumors, the difference was not significant. First line bevacizumab was used in 76 (55%) in left, 15 (36%) in right, anti-EGFR was used in 27 (20%) in left, 11 (25%) in right-sided tumors. According to tumor side, there was no significant survival difference between treatment arms. In the pts with left-sided tumors, median OS was 39.3 months with anti-EGFR, 27.3 months with bevacizumab. Right-sided primary was associated with worse survival. Median OS was similar between braf wild and mutant tumours. Conclusions: Our mutation rates were similar with the literature. Braf mutations were more frequent in right-side tumors. Right-sided primary was associated with poor prognosis. However, the survival difference was not significant. Best survival rates were found with first-line anti-EGFR treatment in the pts with left-sided tumors, but only 20% pts used anti-EGFR at first line in this group. Due to low anti-EGFR usage at first line, survival rates were similar between treatment arms.
Diagnostic accuracy of molecular tumor profiling in determining the tissue of origin in adult patients with cancer of unknown primary: A meta-analysis.
Authors: Rowena Torres Inocencio, Kavitha Kesari, Susan Smith
Journal: Journal of Clinical Oncology (2017)

20 Background: Appropriate cancer treatment requires determination of the primary site of origin. The standard of care for diagnosing Cancer of unknown primary (CUP) based on the 2016 NCCN Guidelines is a comprehensive clinical work-up including biopsy and immunohistochemistry (IHC). However, IHC was able to identify a primary tumor in only 25% of CUP. Molecular tumor profiling (MTP) validation studies demonstrated sensitivities of 74-89% and specificities of 95-99%. Only a few studies with small sample sizes using MTP to diagnose the primary in CUP have been performed yielding variable results. This study aims to evaluate the diagnostic accuracy of MTP in determining the tissue of origin in adult patients with CUP. Methods: Literature search included articles published in any language indexed in MEDLINE and Cochrane. A Google Scholar search and a review of all published articles’ references were performed. Unpublished studies and abstracts from conference proceedings were also reviewed. Studies involving adult patients with CUP who underwent both MTP and clinical evaluation with IHC were identified. Articles were included if they had primary data sufficient to calculate both sensitivity and specificity. Methodological qualities of the included studies were evaluated using the QUADAS-2 tool. Data was analyzed using Review Manager 5.3 and MetaDiSc 1.4. Results: Seven studies with 549 patients were analyzed. MTP was found to have a pooled sensitivity of 89% (95% CI 0.85-0.92)and pooled specificity of 74% (95% CI 0.67-0.80)with pooled positive and negative likelihood ratios of 2.97 (95% CI 1.17-7.63) and 0.20 (95% CI 0.07-0.51), respectively. Area under the curve was measured to be 0.9107. Conclusions: This meta-analysis suggests that MTP could be useful in determining the tissue of origin in adult patients with CUP. With an area under the curve of 0.9107, it is an excellent diagnostic test. The results showed considerable heterogeneity as expected in meta-analyses of diagnostic test accuracy. In this case, it may be due to variability among the MTP assays used which may reflect different cutoffs.
176P PrediCare: A new diagnostic tool predicting imminent disease progression in advanced NSCLC patients by machine-learning integration of three serum biomarkers
Authors: Y. Kogan, M. Kleiman, S. Shannon, M. Elishmereni, E. Taub, L. Aptekar, R. Brenner, R. Berger, H. Nechushtan, Z. Agur
Journal: Journal of Thoracic Oncology (2018)
Donor T Cells Genetically Modified with a Novel Suicide Gene (inducible Caspase 9, iC9) Expand and Persist over Time after Post-Allograft Infusion in Patients Given αβ T-Cell and B-Cell Depleted HLA-Haploidentical Allogeneic Stem Cell Transplantation (αβ haplo-HSCT) Contributing to Accelerate Immune Recovery
Authors: Pietro Merli, Valentina Bertaina, Federica Galaverna, Mattia Algeri, Matilde Sinibaldi, Luisa Strocchio, Giuseppina Li Pira, Daria Pagliara, Sonia De Murtas, Giuseppe Palumbo, Vincent O'Neill, David M. Spencer, Aaron Foster, Alice Bertaina, Franco Locatelli
Journal: Blood (2017)
Abstract 137: Gab Family Scaffolding Adaptor Proteins are Essential for Postnatal Maintenance of Cardiac Function via Neuregulin-1/ErbB Signaling
Authors: Yoshikazu Nakaoka, Atsunori Kamiya, Takashi Minami, Hirofumi Sawa, Yasushi Fujio, Tatsuya Koyama, Hisao Hirota, Keiko Yamauchi-Takihara, Kinya Otsu, Masatsugu Hori, Toshio Hirano, Naoki Mochizuki
Journal: Circulation (2007)

Backgrounds: Grb2-associated binder (Gab) family proteins belong to scaffolding adaptor proteins and undergo tyrosine-phosphorylation after stimulation with various growth factors and cytokines. Tyrosine-phosphorylated Gab family proteins associate with tyrosine phosphatase SHP2 and p85 phosphatidylinositol-3 kinase subunit, leading to activation of extracellular signal-regulated kinase (ERK) and AKT, respectively. Among Gab family proteins, mRNAs of Gab1 and Gab2 were detected in the murine heart by RT-PCR. Since Gab1 and Gab2 are capable of complementing each other in some signaling pathways, we tried to elucidate the role of Gab family proteins in the myocardium by creating cardiomyocyte-specific Gab1/Gab2-double knockout (DKO) mice. Methods &amp; Results: DKO mice were generated by crossing cardiomyocyte-specific Gab1-knockout mice with conventional Gab2-knockout mice. Although DKO mice were viable, they exhibited marked ventricular dilatation and deteriorated contractility with aging. Approximately 70% of DKO mice died of heart failure between 3 and 72 weeks. Among various growth factors, neuregulin-1β (NRG-1β), a paracrine factor shed from endocardial and microvascular endothelium in the heart, most strongly induced tyrosine-phosphorylation of both Gab1 and Gab2 and subsequent association of Gab1/Gab2 with SHP2 and p85. NRG-1β induced activation of ERK and AKT in the hearts of control mice, but not in those of DKO mice. Intriguingly, endocardial fibroelatsosis and abnormally dilated vessels were observed exclusively in the ventricles of DKO mice, suggesting the endothelial dysfunction in the heart. To explore the molecular target of NRG-1β/ErbB/Gab1/Gab2-signaling pathway in the myocardium, we performed DNA microarray analysis and found that administration of NRG-1β upregulated expression of an endothelium-stabilizing factor, angiopoeitin-1, in the myocardium of control mice, but not in those of DKO mice, which presumably accounted for the pathological abnormalities in the DKO mice hearts. Conclusion: In the NRG-1β/ErbB signaling, Gab1 and Gab2 of the myocardium are essential for both maintenance of myocardial function and stabilization of cardiac capillary/endocardial endothelium in the postnatal heart.