tbuckley/cabot-search huggingface dataset:
P012 Peptidyl arginine deiminase immunisationinduces anti-citrullinated protein antibodies in HLA-DRB1*04:01 transgenic mice
Authors: I Auger, F Arnoux, C Mariot, E Peen, NC Lambert, N Balandraud, J Roudier
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Autoantibodies to citrullinated proteins (ACPAs) are highly associated with rheumatoid arthritis (RA). ACPAs are produced in the absence of T cell responses to citrullinated proteins. <h3>Objectives</h3> Peptidyl arginine deiminase 4 (PAD4), which binds numerous different proteins and citrullinates them, is the target of autoantibodies in early RA. This suggests a model to explain the production of ACPAs in the absence of T cells to citrullinated proteins. ACPAs could arise because, at first, PADs are recognised by T cells, which, in turn help the production of autoantibodies to proteins being citrullinated by PADs, through a hapten/carrier model. Here, we test this model in mice. <h3>Methods</h3> HLA-DRB1*04:01 transgenic mice were immunised subcutaneously with PADs or phosphate buffered saline (PBS) in Freund's complete adjuvant (CFA). Three booster injections of PAD or PBS in Freund' incomplete adjuvant (IFA) were given subcutaneously 15, 35 and 55 days later. Mice were: tested for anti-PAD antibodies by ELISA. tested for T cell responses to PADs, native or citrullinated fibrinogen 65 days after PAD immunisation. tested for anti-citrullinated fibrinogen antibodies by ELISA using fibrinogen peptides under citrullinated and native form. <h3>Results</h3> HLA-DRB1*04:01 transgenic mice immunised with PADs developed antibodies and T cells to PADs and IgG antibodies to citrullinated peptides from fibrinogen, in the absence of T cell response to native or citrullinated fibrinogen. <h3>Conclusions</h3> T cell immunisation to PAD proteins triggers ACPAs through a hapten carrier mechanism in which the carrier is PAD which performs citrullination and the hapten any protein being citrullinated by PAD. <h3>Disclosure of interest</h3> None declared
Role of ITU experience in surgical training
Authors: Girish Chawla
Journal: BMJ (2006)

Traditionally, patients in the intensive treatment unit (ITU) have been looked after mainly by anaesthetists, and intensive care medicine has been considered an essential part of anaesthetic training. But now things are changing. Having worked in ITU as part of my surgical training, I would like to share my experiences. I think it would have been better if I had worked in ITU as a house officer. Generally speaking, it teaches you how to manage critically ill patients.

A job in ITU is beneficial to junior doctors from all specialties. With the new foundation programmes, more junior doctors will have the opportunity to get ITU experience and improve their skills. Here are some of the ways it helped me.

Physiology —It improves your understanding of applied physiology, for example cardiac function, respiratory function, renal function. The best part of it is that you learn things in real time. In other words, you can see the effects of any intervention, for example how increasing intravenous fluids affects central venous pressure, increasing oxygen concentration …
Sentinel node biopsy in clinical stage I testicular cancer.
Authors: Joost Marijn Blok, Richard Paul Meijer, Jan M. Kerst, Erik Vegt, Ruud Bosch, Axel Bex, Henk Van Der Poel, Simon Horenblas
Journal: Journal of Clinical Oncology (2018)

550 Background: Approximately 20 – 30% of patients with testicular germ cell tumors (TGCTs) in clinical stage I (CS I) have occult metastatic disease at the time of presentation and will relapse under surveillance. The availability of a sentinel node procedure would enable early identification of patients with occult metastases. We report the long-term results of the sentinel node approach in CS I testicular tumor patients in our facility. Methods: Between 2001 and 2015, patients suspected of CS I TGCT in our third echelon referral center were asked to participate. SNs were identified using SPECT/CT and/or lymphoscintigraphy. Participants underwent laparoscopic retroperitoneal SN excision together with inguinal orchiectomy. Patients with a SN positive for occult metastases were treated with adjuvant chemotherapy. Follow-up was according to then current guidelines and consisted of clinical examination, tumor markers, abdominal/thoracic CT-scanning and chest X-rays. Results: Twenty-seven patients were included. In two patients, no sentinel nodes were visualized on scintigraphy. In twenty-five patients, a median of 3 SNs (range 1 – 4) per patient were removed. Two patients showed no malignancy on histopathologic examination of the testis. Of the 23 patients diagnosed with TGCT, three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median follow-up of 62.2 months (range 22.3 – 143.4). Conclusions: The SN procedure enables early identification of patients with occult metastatic disease in CS I TGCT. Clinical trial information: M00LMT.
PROGNOSTIC VALUE OF THE COMBINATION OF CARDIAC POWER INDEX AND MODEL OF END-STAGE LIVER DISEASE EXCLUDING INR (MELD-XI) SCORE IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Kazuya Tanabe, Kiyomi Kayama, Masatsugu Kawahira, Makoto Abe, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
Prevalence, risk factors and prognosis of nontuberculous mycobacterial infection among people with bronchiectasis: a population survey
Authors: Michal Shteinberg, Nili Stein, Yochai Adir, Shifra Ken-Dror, David Shitrit, Danielle Bendayan, Leonardo Fuks, Walid Saliba
Journal: European Respiratory Journal (2018)

The incidence of nontuberculous mycobacteria (NTM) infection among people with bronchiectasis varies between different geographical areas and accordingly between different series [1, 2]. Studies are largely based on bronchiectasis referral centres, which routinely screen for NTM in respiratory secretions. Therefore, the reported estimates of NTM prevalence in bronchiectasis may be exaggerated. Studies from bronchiectasis centres show conflicting results regarding risk factors for NTM: older age was found to increase risk in some but not other centres [1–4]. Due to the small numbers of patients in these studies, it is usually not possible to determine the effect of NTM infection on prognosis. Culture of NTM from people with bronchiectasis is negatively associated with smoking and low socioeconomic status <http://ow.ly/E3jR30j553X> This work was presented at the second World Bronchiectasis Conference in July 2017 (Milan, Italy).
NON-EMERGENT PERCUTANEOUS CORONARY INTERVENTION ON AN UNPROTECTED LEFT MAIN CORONARY ARTERY SUPPORTED WITH IMPELLA® HEART PUMP IN PATIENTS INELIGIBLE FOR SURGICAL REVASCULARIZATION
Authors: Perwaiz M. Meraj, Jonathan Hill, Simon Dixon, Theodore Schreiber, Jeffrey Moses, Andreas Schaefer
Journal: Journal of the American College of Cardiology (2018)
From Preoperative Assessment to Preoperative Optimization of Frailty
Authors: Liane S. Feldman, Franco Carli
Journal: JAMA Surgery (2018)

Frailty is a multidimensional syndrome of decreased physiologic reserve that describes an older person's vulnerability to health stressors. Frail patients have higher rates of morbidity, mortality, and hospital readmission and take longer to recover.1,2
CLINICAL SIGNIFICANCE OF PLAQUE RUPTURE AND VASCULAR REMODELING IN ACUTE MYOCARDIAL INFARCTION ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND
Authors: Masahiro Hoshino, Taishi Yonetsu, Yoshihisa Kanaji, Eisuke Usui, Masahiro Hada, Hiroaki Ohya, Yohei Sumino, Rikuta Hamaya, Tetsumin Lee, Yoshinori Kanno, Tadashi Fukuda, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2018)
Anaesthetists warn that patient care is undermined by lack of resources
Authors: Abi Rimmer
Journal: BMJ (2016)

A third of UK anaesthetists find it hard to deliver safe and effective patient care because of a lack of resources, the Royal College of Anaesthetists has found.

A survey by the college found that over a third of members thought that factors such as inadequate facilities and a demoralised, fatigued workforce made it harder to deliver …
Abstract 15099: Acculturation and Lifestyle Risk Behaviors in Korean Immigrants: Mediating Effects of Acculturative Stress and Body Image Discrepancy
Authors: Chorong Park, Soohyun Nam, Robin Whittemore
Journal: Circulation (2016)

Introduction: Due to genetic predisposition and acculturation experiences, Korean immigrants (KIs) are vulnerable to developing obesity and cardiovascular complications. However, few studies have e...
PDTM-34. COMBINED BET BROMODOMAIN AND CDK2 INHIBITION IN MYC-DRIVEN MEDULLOBLASTOMA
Authors: Sara Bolin, Anna Borgenvik, Camilla Persson, Anders Sundström, Jun Qi, James Bradner, William Weiss, Yoon-Jae Cho, Holger Weishaupt, Fredrik Swartling
Journal: Neuro-Oncology (2017)

Misexpression of MYC genes (MYC and MYCN) occurs commonly in medulloblastoma (MB), the most frequent malignant childhood brain tumor. We previously showed that tumors are addicted to MYCN and that MYCN stabilization is required for MB development in mice (Swartling et al, Genes & Dev, 2010; Cancer Cell, 2012). BET bromodomains recognize acetylated lysine residues and are known to promote and maintain MYC transcription. Moreover, some cyclin-dependent kinases (CDKs) are known to support MYC stabilization in tumor cells. In this study MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. The combination treatment worked synergistically and caused cell cycle arrest as well as programmed cell death. Immediate transcriptional changes from this combination treatment were found using RNA-Seq profiling and showed remarkable similarities to changes in MYC target gene expression when MYCN was turned off with doxycycline in our MYCN-inducible Group 3 MB animal model. Importantly, our combination treatment approach significantly prolonged survival, as compared to single agent therapy, in mice orthotopically transplanted with MYC-amplified human Group 3 MB. Our data suggests that dual inhibition of CDK2 and BET bromodomains could be a novel treatment approach for suppressing MYC-amplified medulloblastoma.
Aid agencies call for access to besieged Eastern Ghouta
Authors: Anne Gulland
Journal: BMJ (2018)

Aid agencies have urged the Syrian government to allow doctors and medical supplies into the Eastern Ghouta area in the suburbs of Damascus after a bombing campaign resulted in the destruction of hospitals and other healthcare facilities.

The rebel held area, which has been under siege since 2013, has been subject to a heavy bombing campaign by the Syrian government since the beginning of February. The United Nations Human Rights Office reported 1200 civilian casualties in the area between 4 and 21 February, including 346 deaths. Some 92 of these deaths reportedly occurred in just one 13 hour period on 19 February. The UN …
Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer.
Authors: Daisuke Takahari, Takeru Wakatsuki, Tetsuo Mashima, Keisho Chin, Takashi Ichimura, Mariko Ogura, TOMOHIRO MATSUSHIMA, Hiroki Osumi, Izuma Nakayama, Yumiko Ota, Eiji Shinozaki, Mitsukuni Suenaga, Naomi Kawata, Yuki Horiike, Hiroyuki Seimiya, Naoya Fujita, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2018)

81 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. Recently we reported early elevation of plasma VEGF-A was associated with shorter survival as a preliminary result. We will report the results of final analysis. Methods: Patients with advanced gastric cancer who received ramucirumab combined with paclitaxel or single use were enrolled. Plasma samples were collected at pre-treatment and day 8 after administration. Nine kinds of plasma biomarker involved in angiogenesis, VEGF-A, C, D, PlGF, VEGFR1, 2, Angiopoietin 1, stromal cell derived factor-1α (SDF1α), and Neuropirin-1, were measured by means of ELISA. Patients were dichotomized by optimal cut-off value. Univariate and multivariate analysis were done by Cox proportion hazard model. Results: Forty-one patients were enrolled. Thirty-nine patients (95.1%) received ramucirumab with paclitaxel. Plasma VEGF-A, D, PlGF, and VEGFR2 levels were significantly increased one week after administration compared with baseline levels, while plasma VEGFR1 and NRP1levels were significantly decreased. Median PFS and OS were 5.6 (95% CI 4.66-6.54) and 9.8 (95% CI 5.41-14.19) months, respectively. In univariate analysis, higher baseline SDF1α and PlGF levels resulted in shorter OS with HR 2.71 95% CI 1.23-6.00, p =0.013 for SDF1α and HR 2.78 95% CI 1.16-6.65, p =0.022 for PlGF. Higher D8 VEGF-A was associated with shorter PFS with HR 2.77 95% CI 1.39-5.51, p =0.004. While higher D8 VEGF-D was associated with better PFS with HR 0.39 95% CI 0.20-0.77, p =0.007. In multivariate analysis, higher baseline SDF1α and PlGF were independent negative prognostic factor for OS with HR 2.45 95% CI 1.10-5.42, p =0.028 for SDF1α and HR 2.48 95% CI 1.03-5.96, p =0.043. With respect to PFS, higher D8 VEGF-A was also independent negative prognostic factor with HR 2.32 95% CI 1.13-4.77, p =0.022, while higher D8 VEGF-D was favorable predictor for PFS with HR 0.47 95% CI 0.23-0.96, p =0.038. Conclusions: Higher base line SDF1α and PlGF levels may be negative prognostic marker. While early VEGF-A and D elevation after ramucirumab administration may be predictive marker of ramucirumab.
PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke
Authors: Ranjeet K. Sinha, Yaoming Wang, Zhen Zhao, Xiao Xu, Laurent Burnier, Naveen Gupta, José A. Fernández, Greg Martin, Sergey Kupriyanov, Laurent O. Mosnier, Berislav V. Zlokovic, John H. Griffin
Journal: Blood (2018)
Indoleamine 2,3-dioxygenase (IDO1), PD-L1, and overall survival (OS) of patients diagnosed with esophageal cancer.
Authors: Ari Rosenberg, Derek Wainwright, Alfred Rademaker, Carlos Galvez, Matthew Genet, Lijie Zhai, Kristen Lauing, Victoria Meucci Villaflor
Journal: Journal of Clinical Oncology (2018)

50 Background: Immune checkpoint inhibition of PD-L1 is emerging as an important therapeutic target for patients with advanced esophageal cancer. However, response rates to therapy remain low. IDO1 is a rate-limiting immunosuppressive enzyme that has emerged as an important immunotherapeutic target in human cancer. The role, expression pattern, and relevance of IDO1 in esophageal cancer are currently unknown. Here, we utilize gene expression analysis of the cancer genome atlas and quantitative immunohistochemistry (IHC) to understand whether IDO1 contributes to a poor esophageal cancer patient prognosis. Methods: mRNA expression was assessed using Hi-RNA sequencing in an esophageal squamous cell carcinoma (SCC) cohort of 87 patients and an adenocarcinoma (AC) cohort of 97 patients. Survival data was obtained from the Cancer Genome Atlas. Patient survival was analyzed by the Kaplan-Meier Method. IHC for a second cohort of 93 cases of esophageal SCC were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic immunoscoring analysis. Correlation between markers was analyzed using Fisher’s exact test. Results: The median OS for high versus low IDO1 mRNA levels was 15.9 months vs 41.5 months, respectively (p =0.02) in the SCC cohort. The median OS was 20.1 months and 58.6 months in the high vs low IDO1 mRNA levels, respectively (p = 0.036) in the esophageal AC cohort. High co-expression for IDO1 and PD-L1 vs low co-expression of these markers, demonstrated a median OS of 15.1 months and 41.5 months, respectively, in the SCC cohort, and 13.7 months and 41.5 months, respectively, in the AC cohort. IHC for IDO1 SCC showed a significant correlation with PD-L1 (p = &lt; 0.0001) and CD3ε (p = &lt; 0.0001). PD-L1 expression also significantly correlated with CD3ε expression (p = &lt; 0.0001). Conclusions: Esophageal cancer with high IDO1 and PD-L1 levels is associated with significantly decreased survival. The expression of IDO1 and PD-L1 is significantly enhanced by the coincident intratumoral increase of T cells. These data suggest that combinatorial approaches for combination therapies that simultaneously inhibit IDO1 and PD-(L)1 may enhance T-cell mediated control of esophageal cancer in patients.
Development and External Validation of Prediction Models for 10-Year Survival of Invasive Breast Cancer. Comparison with PREDICT and CancerMath
Authors: Solon Karapanagiotis, Paul D.P. Pharoah, Christopher H. Jackson, Paul J. Newcombe
Journal: Clinical Cancer Research (2018)

To compare PREDICT and CancerMath, two widely used prognostic models for invasive breast cancer, taking into account their clinical utility. Furthermore, it is unclear whether these models could be improved.
INITIATION OF DISEASE-MODIFYING ANTIRHEUMATIC DRUGS AND BIOLOGICAL AGENTS LEADS TO EARLY RESOLUTION OF PERICARDIAL DELAYED HYPERENHANCEMENT IN PATIENTS WITH RECURRENT PERICARDITIS
Authors: Kimi Sato, Arnav Kumar, Beni Verma, Chandra Ala, Vivek Menon, Rory Hachamovitch, Deborah Kwon, Apostolos Kontzias, Allan Klein
Journal: Journal of the American College of Cardiology (2018)
Patients with severe wet AMD regain vision after stem cell treatment
Authors: Abi Rimmer
Journal: BMJ (2018)

Two patients with very severe wet age related macular degeneration (AMD) who received stem cell treatment have regained reading vision.

The findings, from a phase I trial by the London Project to Cure Blindness, were published in Nature Biotechnology .1 The project is a partnership between Pete Coffey of University College London and Lyndon da Cruz, a retinal surgeon at Moorfields Eye Hospital NHS Foundation Trust.

The study described the implantation of a specially engineered patch of retinal pigment epithelium cells derived from stem cells, to treat people with sudden severe …
Association Between Grade of Acute on Chronic Liver Failure and Response to Terlipressin and Albumin in Patients With Hepatorenal Syndrome
Authors: Salvatore Piano, Hartmut H. Schmidt, Xavier Ariza, Alex Amoros, Antonietta Romano, Anna Hüsing-Kabar, Elsa Solà, Alexander Gerbes, Mauro Bernardi, Carlo Alessandria, Bernhard Scheiner, Marta Tonon, Miriam Maschmeier, Cristina Solè, Jonel Trebicka, Thierry Gustot, Frederik Nevens, Vicente Arroyo, Pere Gines, Paolo Angeli
Journal: Clinical Gastroenterology and Hepatology (2018)
Association of stromal lymphocyte infiltration with tumor invasion depth and high-grade T1 bladder cancer.
Authors: Mathieu Rouanne, Reem Betari, Camélia Radulescu, Nicolas Signolle, Yves Allory, Aurelien Marabelle, Julien Adam, Thierry Lebret
Journal: Journal of Clinical Oncology (2018)

488 Background: Morphological assessment of tumor-infiltrating lymphocytes (TIL) has been shown to provide prognostic and potentially predictive significance in many different tumor types. Large studies investigating TIL in urothelial carcinoma are lacking. We investigated in a homogenous population of patients with high-grade T1 (HGT1) bladder cancer the association of TIL with clinico-pathological parameters and clinical outcomes. Methods: Pretreatment index tumors were collected between 2000 and 2015 from 147 patients with primary high-grade cT1N0M0 bladder cancer. The density of stromal TIL was evaluated using hematoxylin and eosin (H&amp;E)-based staining on whole tissue sections. Stromal TIL density was scored as percentage of stromal area infiltrated by mononuclear cells. Inter-reader assessment and stromal TIL correlation with a subset of CD3+ stained sections were evaluated. The main endpoint was correlation with overall survival (OS). Hazard ratios (HRs) and 95% CIs associated with stromal TIL were estimated through a multivariable Cox model. Results: Median follow-up was 8.2 years (6.1-9.5). Induction BCG therapy was followed by 126 patients (86%). Recurrence and progression were respectively observed in 67 patients (46%) and 40 patients (27%). Stromal TIL density was high (≥10%) in 82 tumors (56%). The overall agreement was good between the two readers (κ = 0.75). Correlation between stromal TIL density analyzed on H&amp;E-sections and CD3+ IHC staining was high (ρ = 0.71, p &lt; 1.10 -5 ). Stromal TIL were positively associated with variant histology (p = 0.01) and tumor invasion depth (p = 0.03). For the OS analysis, intense (≥10%) vs. non-intense ( &lt; 10%) stromal TIL unadjusted HR (95% CI, p) was 1.30 (0.75-2.24, p = 0.34) and adjusted HR was 1.25 (0.72-2.16, p = 0.43). Conclusions: Density of stromal TIL was associated with tumor invasion depth and variant histology, but not with prognosis of patients with HGT1 bladder cancer. These data suggest that tumor progression is associated with an increased adaptive immune response but other factors may influence outcome of patients. Characterization of TIL subpopulations may be required to identify immune-related prognostic factors.
Abstract P5-21-05: Withdrawn
Authors: LM Smyth, M Oliveira, E Ciruelos, K Tamura, A El-Khoueiry, A Mita, B You, DJ Renouf, M-P Sablin, A Lluch, IA Mayer, H Bando, H Yamashita, H Ambrose, E de Bruin, TH Carr, C Corcoran, A Foxley, JPO Lindemann, R Maudsley, M Pass, A Rutkowski, G Schiavon, U Banerji, M Scaltriti, BS Taylor, S Chandarlapaty, J Baselga, DM Hyman
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (P) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC): Subgroup analysis of LATITUDE trial.
Authors: Satoshi Fukasawa, Hiroyoshi Suzuki, Fuminori Sato, Katsuyoshi Hashine, Hisashi Hasumi, Hiroaki Matsumoto, Tomohiro Tsuchiya, Hirotsugu Uemura, Mototsugu Oya, Hiroomi Kanayama, Kazushiro Kawaguchi, Hidehisa Noguchi, Kentaro Enjo, Namphuong Tran, Mary Beth Todd, Karim Fizazi, Nobuaki Matsubara
Journal: Journal of Clinical Oncology (2018)

286 Background: Patients with high-risk mHNPC have a poor prognosis. In Japan, mHNPC accounts for approximately 10% of newly diagnosed prostate cancers. AAP was approved for the treatment of castration-resistant prostate cancer in Japan in July 2014. We now report the clinical benefit of AAP with ADT in Japanese patients with newly diagnosed, high-risk mHNPC. Methods: Interim analysis of the multinational, randomized, double-blind, placebo-controlled, phase 3 study, LATITUDE, was previously reported at ASCO2017. We evaluated the superiority of AA 1g + P 5 mg + ADT (AAP group) to ADT+PBOs of AA and P (P group) in mHNPC with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) for the subgroup of Japanese patients. Results: Of 1199 total patients in LATITUDE trial, 70 patients were Japanese (AAP group, n = 35; P group, n = 35). The hazard ratio (HR) for overall survival in the AAP group versus the P group was 0.635 (95% confidence interval [CI], 0.152 to 2.659) and HR for radiographic progression-free survival was 0.219 (95%CI, 0.086 to 0.560). The incidence of adverse events (AE) was 97% (34/35) in both groups. AEs that occurred in the AAP group at a frequency ≥10% compared with the P group included hypertension, hypokalemia, rib fracture, hematuria and hyperbilirubinemia. The incidence of Grade 3 and 4 AEs was 66% in the AAP group and 20% in the P group. As a whole, efficacy and safety of Japanese patients in LATITUDE were shown to be consistent with those of overall population. Conclusions: AAP has shown a favorable risk/benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk prognostic factors. Clinical trial information: NCT01715285.