tbuckley/cabot-search huggingface dataset:
Association of tumor infiltrating CD8 positive T cells and PDL-1 expression with survival after conversion surgery for unresectable gastric cancer.
Authors: Hiroaki Tanaka, Junya Nishimura, Yuichiro Miki, Tatsuro Tamura, Kazuya Muguruma, Masatsune Shibutani, Go Ohira, Sadaaki Yamazoe, Hisashi Nagahara, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira
Journal: Journal of Clinical Oncology (2018)

62 Background: Conversion surgery after chemotherapy responds to unresectable gastric cancer has long-term prognosis, however, chemotherapy after surgery should also be considered to improve treatment outcome. The effectiveness of immune checkpoint inhibitors for gastric cancer has been proved. In this study, we investigated the association between PDL-1 expression and CD8 + T cell infiltration in the primary tumor and prognosis of patients who underwent conversion surgery after S-1-based multidrug chemotherapy in unresectable gastric cancer. Methods: We evaluated PDL-1 expression and CD8 T cell infiltration by immunohistochemical staining and examined the relationship with prognosis in 90 patients with Stage IV gastric cancer who underwent gastrectomy in our department from 2007 to 2015. Results: 90 cases included 47 cases of palliative resection, 26 cases of CY1P 0cases and 17 cases of conversion surgery. Among Conversion Surgery cases, 11 (65%) patients underwent R0 surgery, and the 5-year survival rate was 66%. The 5-year survival rate of non-curative resected cases was 16%. In immunohistochemical examination, PDL-1 high expression was a poor prognostic factor in palliative surgery and CY1P0 cases. Meanwhile, in the case of Conversion Surgery, the 5-year survival rate was 58%, 32%, 61%, and 30% in the order of PDL-1 high expression group, low expression group, CD8 T cell high infiltration, and low infiltration group, respectively. Prognosis of PDL-1 high expression group and CD8 T cell infiltration group was good. There was no association between curative resection and neither of CD8 T cell infiltration or PDL-1 expression. Conclusions: We found that the prognosis was relatively good in patients where local immune response was enhanced, regardless of R0 excision. Our results suggested that infiltration of CD8 T cells in the primary tumor may be a prognostic predictor, and it is expected to use an immune check point inhibitor after conversion surgery for unresectable gastric cancer.
PROGNOSTIC VALUE OF BIOMARKER OF COLLAGEN TURNOVER (C-TERMINAL TELOPEPTIDE) IN PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROMES: INSIGHTS FROM MERLIN-TIMI 36
Authors: Thomas Zelniker, Petr Jarolim, Benjamin Scirica, Eugene Braunwald, Jeong-Gun Park, Saumya Das, Marc Sabatine, David A. Morrow
Journal: Journal of the American College of Cardiology (2018)
Diploma in Tropical Medicine and Hygiene
Authors: Craig Davies
Journal: BMJ (2009)

Any qualified doctor with an interest or career in tropical and infectious diseases. It is indispensable for those who want to practise in resource poor settings, particularly in sub-Saharan Africa. As a new foundation year 2 doctor, I was one of the more junior members on the course. The other attendees were from over 30 different nations, many in Africa, and were diverse in specialty and interests. Ages ranged from 26 to 65 years plus, with retired general practitioners alongside lots of infectious disease doctors. Many people had worked in resource poor settings or intended to do so.

The course at the London School of Hygiene and Tropical Medicine runs annually from early January to the end of March, with exams in the final days of March. Courses also run in Liverpool, Sheffield, and Glasgow on different dates. I attended the course during a year out between foundation years 1 and 2, having applied a whole year before the course began. About 70 places are available and demand is high.

I have worked and travelled in developing …
Big Data and Machine Learning in Health Care
Authors: Andrew L. Beam, Isaac S. Kohane
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
NHS workforce management is flawed, costly, and inefficient, NAO says
Authors: Matthew Limb
Journal: BMJ (2016)

Efforts by the NHS in England to manage the supply of doctors and other clinical staff are seriously flawed and “fragmented,” the National Audit Office has concluded.

The public spending watchdog said that attempts by the health secretary, Jeremy Hunt, to rein in the £3.3bn in spending on agency staff were “unlikely to address fully the underlying causes of increased demand.” It also said that efforts to fill shortfalls in staffing were “unnecessarily costly and inefficient” and that there was no comprehensive modelling of doctor supply and demand. There was an “increased risk of duplication and incoherence” in the arrangements for managing the supply of clinical staff.

Amyas Morse, head of the National Audit Office, said, “Given the size of the NHS, workforce planning will never be an exact science, but we think it clearly could be better than it is. Since clinical staff are the NHS’s main resource and cost, these shortcomings are serious, and the current arrangements do not achieve value for …
NHS England plans to review all PMS contracts in 2013-14
Authors: Helen Jaques
Journal: BMJ (2013)

NHS England plans to review all personal medical services (PMS) GP contracts in 2013-14 to “identify ways of improving value for money for the future.”

The aims of the review are to establish equitable “core” funding between general practices on PMS contracts and those on general medical services (GMS) contracts and to ensure value for money from investment in non-core “enhanced” services. NHS England has said, however, that it does not plan to change the “quantum” of PMS funding this year while the review is under way.

NHS England has instructed its local …
Stress and sexual reproduction affect the dynamics of the wheat pathogen effector AvrStb6 and strobilurin resistance
Authors: Gerrit H. J. Kema, Amir Mirzadi Gohari, Lamia Aouini, Hesham A. Y. Gibriel, Sarah B. Ware, Frank van den Bosch, Robbie Manning-Smith, Vasthi Alonso-Chavez, Joe Helps, Sarrah Ben M’Barek, Rahim Mehrabi, Caucasella Diaz-Trujillo, Elham Zamani, Henk J. Schouten, Theo A. J. van der Lee, Cees Waalwijk, Maarten A. de Waard, Pierre J. G. M. de Wit, Els C. P. Verstappen, Bart P. H. J. Thomma, Harold J. G. Meijer, Michael F. Seidl
Journal: Nature Genetics (2018)
Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis
Authors: Christopher Maximilian Arends, Joel Galan-Sousa, Kaja Hoyer, Willy Chan, Marten Jäger, Kenichi Yoshida, Ricarda Seemann, Daniel Noerenberg, Nils Waldhueter, Helga Fleischer-Notter, Friederike Christen, Clemens A. Schmitt, Bernd Dörken, Uwe Pelzer, Marianne Sinn, Tomasz Zemojtel, Seishi Ogawa, Sven Märdian, Adrian Schreiber, Annegret Kunitz, Ulrike Krüger, Lars Bullinger, Elena Mylonas, Mareike Frick, Frederik Damm
Journal: Leukemia (2018)
Genomics and emerging biomarkers for immunotherapy of colorectal cancer
Authors: Jakob Nikolas Kather, Niels Halama, Dirk Jaeger
Journal: Seminars in Cancer Biology (2018)

Colorectal cancer (CRC) is a common and lethal disease with a high therapeutic need. For most patients with metastatic CRC, chemotherapy is the only viable option. Currently, immunotherapy is restricted to the particular genetic subgroup of mismatch-repair deficient (MMRd)/microsatellite instable (MSI) CRC. Anti-PD1 therapy was recently FDA-approved as a second-line treatment in this subgroup. However, in a metastatic setting, these MMRd/MSI tumors are vastly outnumbered by mismatch-repair proficient (MMRp)/microsatellite stable (MSS) tumors. These MMRp/MSS tumors do not meaningfully respond to any traditional immunotherapy approach including checkpoint blockade, adoptive cell transfer and vaccination. This resistance to immunotherapy is due to a complex tumor microenvironment that counteracts antitumor immunity through a combination of poorly antigenic tumor cells and an immunosuppressive tumor microenvironment. To find ways of overcoming immunotherapy resistance in the majority of CRC patients, it is necessary to analyze the immunological makeup in an in-depth and personalized way and in the context of their tumor genetic makeup. Flexible, biomarker-guided early-phase immunotherapy trials are needed to optimize this workflow. In this review, we detail key mechanisms for immune evasion and emerging immune biomarkers for personalized immunotherapy in CRC. Also, we present a template for biomarker-guided clinical trials that are needed to move new immunotherapy approaches closer to clinical application.
The long tail of oncogenic drivers in prostate cancer
Authors: Joshua Armenia, Stephanie A. M. Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K. Chatila, Debyani Chakravarty, G. Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E. Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M. Bielski, Alexander V. Penson, Charlotte Tolonen, Franklin W. Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A. Garraway, Francesca Demichelis, Philip W. Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S. Taylor, Howard I. Scher, Peter S. Nelson, Johann S. de Bono, Mark A. Rubin, Charles L. Sawyers, Arul M. Chinnaiyan, Nikolaus Schultz, Eliezer M. Van Allen
Journal: Nature Genetics (2018)
cHCC‐CCA
Authors: Elizabeth Brunt, Shinichi Aishima, Pierre‐Alain Clavien, Kathryn Fowler, Zachary Goodman, Gregory Gores, Annette Gouw, Alex Kagen, David Klimstra, Mina Komuta, Fukuo Kondo, Rebecca Miksad, Masayuki Nakano, Yasuni Nakanuma, Irene Ng, Valerie Paradis, Young Nyun Park, Alberto Quaglia, Massimo Roncalli, Tania Roskams, Michiie Sakamoto, Romil Saxena, Christine Sempoux, Claude Sirlin, Ashley Stueck, Swan Thung, W.M.S. Tsui, Xin‐Wei Wang, Aileen Wee, Hirohisa Yano, Matthew Yeh, Yoh Zen, Jessica Zucman‐Rossi, Neil Theise
Journal: Hepatology (2018)

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular‐cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation. Conclusion: It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113‐126).
Recognising risk and improving patient safety (R²IPS)
Authors: Manav Bawa, Kerry Carlin
Journal: BMJ (2011)

The recognising risk and improving patient safety (R²IPS) course is a one day theoretical course organised by the Countess of Chester NHS Foundation Trust. It aims to teach a strategy that will enable trainees to identify, intervene in, and prevent the components of personal and team behaviours that contribute to increased risk for patients and adverse outcomes. It also helps junior doctors to challenge situations where they believe that a medical error may occur. The course is new but is becoming more and more popular with junior trainees.

This course is mainly aimed at newly qualified foundation doctors, as it complements a part of the foundation curriculum, but it is useful for any grade.

The day …
Simulation-based benchmarking of isoform quantification in single-cell RNA-seq
Authors: Jennifer Westoby, Marcela Sjöberg Herrera, Anne C. Ferguson-Smith, Martin Hemberg
Journal: Genome biology (2018)

Single-cell RNA-seq has the potential to facilitate isoform quantification as the confounding factor of a mixed population of cells is eliminated. However, best practice for using existing quantification methods has not been established. We carry out a benchmark for five popular isoform quantification tools. Performance is generally good for simulated data based on SMARTer and SMART-seq2 data. The reduction in performance compared with bulk RNA-seq is small. An important biological insight comes from our analysis of real data which shows that genes that express two isoforms in bulk RNA-seq predominantly express one or neither isoform in individual cells.
The impact of pre-operative chemotherapy in patients with peritoneal lavage cytology positive or localized peritoneum metastasis for gastric cancer: A multicenter retrospective study.
Authors: Rie Makuuchi, Toshifumi Yamaguchi, Atsuo Takashima, Kengo Nagashima, Tatsuya Yamada, Takahiro Kinoshita, Hiroaki Hata, Yasuyuki Kawachi, Ryohei Kawabata, Toshikatsu Tsuji, Naoki Hirabayashi, Takeshi Sakamoto, Takao Inada, Koshiro Ishiyama, Takeo Fukagawa, Narikazu Boku, Hitoshi Katai
Journal: Journal of Clinical Oncology (2018)

95 Background: Peritoneal lavage cytology of positive and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Patients (pts) with CY1 and/or P1 have poor prognosis after removing all macroscopically visible disease by standard gastrectomy followed by S1. The aim of this study was to investigate the efficacy of pre-operative chemotherapy (Pre-Cx) in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: no distant metastasis other than CY1 or P1, no prior treatment for GC. The subjects were divided to two groups according to treatment strategy with/without Pre-Cx before surgery. In the Pre-Cx group, status of CY and P was diagnosed by laparoscopy before and after Pre-Cx, and indication of surgical resection was decided by each physician. Results: A total of 824 pts were collected from 34 institutions. Of the 713 eligible pts, 150 pts received Pre-Cx (Pre-Cx group) and 563 pts underwent surgery followed by Cx (Post-Cx group). Proportions of P0CY1/P1CY0/P1CY1 were 69/12/19% and 69/17/14% in the Pre- and Post-Cx. Cx regimen for Pre-Cx were S1 plus cisplatin/ docetaxel and cisplatin plus S1/others (n=90/37/23). In the Pre-Cx, 57 (38%) pts who achieved P0CY0 after Pre-Cx showed better survival than the remaining 92 pts (overall survival (OS), 31.0 vs. 19.9 months (M), HR=1.99, 95% CI 1.32-2.93, p=0.001). OS was 24.8 and 24.0 M in the Pre- and Post-Cx (HR 1.07; 95% CI 0.87-1.32, p=0.502). In multivariate analysis, P1CY1, over 65 years old and clinical N3 lymph node metastasis were identified as the independent prognostic factor for OS (p&lt;0.05). Conclusions: Although Pre-Cx showed favorable survival in case of achieving P0 and CY0, Pre-Cx did not show a survival benefit for GC pts with CY1 and /or P1.
O023 Rare seronegative destructive RA: identification of somatic mutations in the expanded CD8+ lymphocytes
Authors: T Kelkka, P Savola, K Paalanen, T Sokka-Isler, S Mustjoki
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Clonally expanded CD8 +lymphocytes harbour somatic mutations in RA patients.<sup>1</sup> Seronegative RA, that often displays milder symptoms and slower disease progression, does not share the genetic linkage to the MHC II locus. Thus, we hypothesise that somatic mutations in the clonal CD8 +lymphocytes could modulate inflammation in these patients. <h3>Objectives</h3> Our aim was to validate the concept of somatic mutations as regulators of chronic inflammation. <h3>Methods</h3> We collected blood samples from seronegative RA patients (n=8) who displayed unusually aggressive, progressive disease that was refractory to treatment and had led to severe joint erosions.<sup>2</sup> Flow cytometry was used to screen lymphocyte clonality in both CD4 and CD8 lymphocytes and to enrich the mutated clone. TCR-repertoire analysis was performed by TCRB-deep sequencing. Somatic variants were called from deep sequencing data (panel of 1000 immunological genes and exome sequencing) and the data was confirmed by capillary sequencing. <h3>Results</h3> Similarly as in our earlier work, there were more suggestive clonal expansions in CD8 +lymphocytes than in CD4 +lymphocytes. The overall clonality of CD8 +cells did not statistically differ between our seronegative destructive RA cohort and age-matched healthy controls (n=19), seropositive (n=53) or seronegative diagnostic phase patients (n=12). Sequencing of one of the seronegative RA patients' CD4 and CD8 T cells with the targeted gene panel, revealed novel somatic mutations in the CD8 +cell pool. The expanded T cell clone was enriched using flow cytometry and from this clone, 22 mutations were identified in genes that are expressed in healthy CD8 +cells. Eight of these mutations were selected and confirmed using capillary sequencing. Based on computational prediction algorithms, we hypothesise that the identified mutations (in <i>PIK3CG, KPNA1, PLCG2, ITGAE, NKAP</i> genes) may regulate the clonal properties, immunological phenotype and even contribute to the regulation of chronic inflammation. <h3>Conclusions</h3> We identified somatic mutations in the clonally expanded CD8 lymphocytes from a patient with unusual, aggressive seronegative RA. More work is warranted to elucidate the biological and clinical consequences of the identified mutations. <h3>References</h3> . Savola P, et al. Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis. Nature Communications2017;8:15869. . Nikiphorou E, et al. Long-term outcomes of destructive seronegative (rheumatoid) arthritis: Description of four clinical cases. BMC Musculoskelet Disord2016;17:246. <h3>Disclosure of interest</h3> None declared
Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.
Authors: Teresa Mercade Macarulla, Jens T. Siveke, Andrew Peter Dean, Richard Hubner, Jean-Frédéric Blanc, David Cunningham, Li-Tzong Chen, Beloo Mirakhur, Jie Chen, Floris A de Jong, Andrea Wang-Gillam
Journal: Journal of Clinical Oncology (2018)

379 Background: We report an exploratory, post hoc subgroup analysis in pts with BPI and BAU data receiving nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1 (NCT01494506). In this pivotal trial, nal-IRI+5-FU/LV improved median OS (mOS) vs. 5-FU/LV (6.1 vs. 4.2 mo [HR=0.67; p=0.012]). Methods: BPI/BAU included an average of 3-7 days pt-recorded data before randomisation. Greater values indicated greater pain for BPI using a 100 mm visual analogue scale. BAU was converted to morphine equivalent mg/day. Results: Of 417 ITT pts, 295 had BPI and 299 had BAU data. Mean and median BPI were 28.6 and 25.0, respectively, and BAU were 33.3 and 8.1 mg/day, respectively. The percentage of pts with KPS ≥ 80 was higher in ≤ mean/≤ median (n=159/148) BPI groups vs. &gt; mean/&gt; median (n=136/147) BPI groups (96-97 vs. 83%) and in ≤mean/≤median (n=207/150) BAU groups vs. &gt; mean/&gt; median (n=92/149) BAU groups (95-97 vs. 82-85%). mOS and median PFS (mPFS) were higher for nal-IRI+5-FU/LV vs 5-FU/LV in all groups, with ≤ mean/≤ median BPI or BAU showing better outcomes vs. &gt; mean/&gt; median BPI or BAU (Table). Conclusions: BPI and BAU appear to have a prognostic effect on outcomes in mPDAC pts in the NAPOLI-1 study. No predictive effect was observed, with nal-IRI+5-FU/LV showing higher mOS vs. 5-FU/LV in all groups. Clinical trial information: NCT01494506. [Table: see text]
Integration of multi-omics datasets enables molecular classification of COPD
Authors: Chuan-Xing Li, Craig E. Wheelock, C. Magnus Sköld, Åsa M. Wheelock
Journal: European Respiratory Journal (2018)

Chronic obstructive pulmonary disease (COPD) is an umbrella diagnosis caused by a multitude of underlying mechanisms, and molecular sub-phenotyping is needed to develop molecular diagnostic/prognostic tools and efficacious treatments. The objective of these studies was to investigate whether multi-omics integration improves the accuracy of molecular classification of COPD in small cohorts. Nine omics data blocks (comprising mRNA, micro RNA, proteomes and metabolomes) collected from several anatomical locations from 52 female subjects were integrated by similarity network fusion (SNF). Multi-omics integration significantly improved the accuracy of group classification of COPD patients from healthy never-smokers and from smokers with normal spirometry, reducing required group sizes from n=30 to n=6 at 95% power. Seven different combinations of four to seven omics platforms achieved &gt;95% accuracy. For the first time, a quantitative relationship between multi-omics data integration and accuracy of data-driven classification power has been demonstrated across nine omics data blocks. Integrating five to seven omics data blocks enabled 100% correct classification of COPD diagnosis with groups as small as n=6 individuals, despite strong confounding effects of current smoking. These results can serve as guidelines for the design of future systems-based multi-omics investigations, with indications that integrating five to six data blocks from several molecular levels and anatomical locations suffices to facilitate unsupervised molecular classification in small cohorts.