tbuckley/cabot-search huggingface dataset:
Phase I trial using toxicity severity weights for dose finding of gemcitabine combined with radiation therapy and subsequent surgery for patients with extremity and trunk soft tissue sarcomas
Authors: P. W. Pisters, M. T. Ballo, N. Bekele, P. F. Thall, B. W. Feig, P. Lin, J. N. Cormier, R. S. Benjamin, S. R. Patel
Journal: Journal of Clinical Oncology (2004)

9008 Background: To determine the maximum tolerated dose (MTD) of gemcitabine when provided concurrently with external beam radiation (EBRT) for patients with extremity and superficial trunk soft tissue sarcomas (STS). Methods: Preoperative EBRT (50 Gy, 25 daily fractions Mon-Fri) was given for 5 weeks. Gemcitabine was administered at 10 mg/m2/min on days 1, 8, 22, 29, 43, and 50 at a starting dose of 400 mg/m2 and escalated or de-escalated between cohorts in increments of 100 mg/m2 using a new method based on severity weights for each grade of each of 5 different toxicities (myelosuppression, dermatitis, nausea/vomiting, liver, and fatigue). This toxicity severity weight method (TSWM) is a Bayesian procedure that repeatedly assesses the data to find the dose having mean posterior total toxicity burden (TTB) closest to a clinician-defined target of 3.04. Results: Eighteen (of 36 planned) patients with radiologically measureable intermediate or high-grade STS have been treated; 16 had completed all therapy at analysis. Histologies included MFH (7), unclassified STS (5), synovial STS (3), and liposarcoma (3). The gemcitabine dose has been progressively escalated to 700 mg/m2 at which the current estimated posterior probability of the TTB is 3.19 (analysis of 15 patients). Five patients have completed treatment at 700 mg/m2 with observed grade 3 or 4 toxicities that included: myelosuppresion without fever (n=2), dermatitis in the radiation field (n=1), hepatotoxicity (n=2), and fatigue (n=2). All 16 patients have undergone surgical resection with microscopically negative surgical margins. Pathological complete responses were observed in 4 tumors, 3 additional tumors had ≥95% tumor necrosis. Conclusions: Gemcitabine-based concurrent chemoradiation appears feasible for extremity and trunk STS. The currently targeted MTD is 700 mg/m2, accrual continues. The TSWM permitted efficient and safe dose escalation using weighted assessment of 5 different, clinically relevant toxicities. Observed histologic responses associated with this regimen are encouraging. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly; Schering-Plough Eli Lilly
Obesity in Low- and Middle-Income Countries: Burden, Drivers, and Emerging Challenges
Authors: Nicole D. Ford, Shivani A. Patel, K.M. Venkat Narayan
Journal: Annual Review of Public Health (2017)

We have reviewed the distinctive features of excess weight, its causes, and related prevention and management efforts, as well as data gaps and recommendations for future research in low- and middle-income countries (LMICs). Obesity is rising in every region of the world, and no country has been successful at reversing the epidemic once it has begun. In LMICs, overweight is higher in women compared with men, in urban compared with rural settings, and in older compared with younger individuals; however, the urban–rural overweight differential is shrinking in many countries. Overweight occurs alongside persistent burdens of underweight in LMICs, especially in young women. Changes in the global diet and physical activity are among the hypothesized leading contributors to obesity. Emerging risk factors include environmental contaminants, chronic psychosocial stress, neuroendocrine dysregulation, and genetic/epigenetic mechanisms. Data on effective strategies to prevent the onset of obesity in LMICs or elsewhere are limited. Expanding the research in this area is a key priority and has important possibilities for reverse innovation that may also inform interventions in high-income countries.
P1.02-051 Concomitant Driver Mutations in Advanced Stage Non-Small-Cell Lung Cancer of Adenocarcinoma Subtype with Activating EGFR-Mutation
Authors: Jens Benn Sørensen, Morten Grauslund, Linea Melchior, Jan Jakobsen, Eric Santoni-Rugiu
Journal: Journal of Thoracic Oncology (2017)
P1.03-073 Predictors for Pathological N1 and N2 Disease in Clinical N1 Non-Small-Cell Lung Cancer
Authors: Takayuki Fukui, Toshiki Okasaka, Koji Kawaguchi, Koichi Fukumoto, Shota Nakamura, Shuhei Hakiri, Naoki Ozeki, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2017)
Endoscopic ultrasound of splenic artery pseudoaneurysm
Authors: Malay Sharma, Piyush Somani, Maryam Al Khatry, Amol Patil
Journal: Endoscopy (2017)

A 48-year-old man was referred from an outside hospital with a recent episode of acute pancreatitis and hematemesis for the evaluation of a cystic lesion in the body of the pancreas, which was noted on computed tomography (CT) of the abdomen.
Abstract B18: Development of human STING agonists for prostate cancer immunotherapy
Authors: Jian Hui Wu
Journal: Clinical Cancer Research (2017)

Abstract Recent studies have identified the host STING pathway as a critical mechanism of innate immune sensing of cancer, that drives type-I interferons (IFNs) production and promotes aggressive antitumor responses. Thus, STING agonists could be candidates for testing as stimulants for anticancer immune activity. Although DMXAA binds and activates mouse STING, it cannot activate human STING (hSTING). This species specificity is thought to be the reason that DMXAA showed dramatic effect against solid tumor in rodent models, but failed in human clinical trials. In this project, we aim to identify novel chemical compounds as agonists of hSTING. By combining in silico screening and in vitro assays, we have discovered two novel chemical compounds that activate hSTING. Direct binding of our compounds with hSTING was confirmed by Surface plasmon resonance (SPR) analysis. We demonstrated that our hSTING agonist activated interferon signaling pathway in monocytic human THP-1 cells, which express endogenous hSTING. Further, our compound itself is not cytotoxic to 22Rv1 prostate cancer cells, but the spent supernatants of the THP-1 cells exposed to our compound are cytotoxic to 22Rv1 cells. Chemical optimization of initial active compounds is in progress. We aim to generate compound candidates as potent hSTING agonists for in vivo evaluation in rodent models. Note: This abstract was not presented at the conference. Citation Format: Jian Hui Wu. Development of human STING agonists for prostate cancer immunotherapy. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B18.
Adolescent and Young Adult Patients Treated with Modified Augmented Berlin-Frankfurt-Muenster Therapy
Authors: Michael E. Rytting, Hagop M. Kantarjian, Deborah A Thomas, Elias Jabbour, Anna Franklin, Farhad Ravandi, Stefan Faderl, Rebecca Garris, Tapan Kadia, Kurt Schroeder, Susan O'Brien
Journal: Blood (2010)
Comparable Survival between HIV+ and HIV- Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) Patients Undergoing an Autologous Peripheral Blood Stem Cell Transplantation (ASCT). A Retrospective Analysis of the EBMT Lymphoma Working Party.
Authors: Jose L. Diez-Martin, Pascual Balsalobre, Alessandro Re, Pierre Biron, Eulogio Conde, Anne Rosselet, Bernardino Allione, Ildefonso Espigado, Philippe Genet, Josep-Maria Ribera, Augustin Ferrant, Gaelle Gillerm, Dirk Meyer, M. Rupolo, Rosario Varela, Marcus Hentrich, Ann E. Hunter, Carmen Canals, Goli Taghipour, David Serrano, Anna Sureda
Journal: Blood (2007)
Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy
Authors: Shruti Rawal, Pujika Emani Munasinghe, Amol Shindikar, Jono Paulin, Vicky Cameron, Patrick Manning, Michael J.A. Williams, Gregory T. Jones, Richard Bunton, Ivor Galvin, Rajesh Katare
Journal: Cardiovascular Research (2016)

Microangiopathy due to endothelial dysfunction is a major contributing factor to the development of diabetes-induced cardiovascular disease (CVD). Dysregulation of endothelial-specific microRNAs (miRs) is correlated with impaired angiogenesis and cell survival. We investigated the profile of two angiomiRs, miR-126, and miR-132, in the plasma of type 2 diabetic individuals without any known history of CVD as well as in the cardiac tissues collected from diabetics undergoing cardiac surgery.The presence of diabetes alone significantly decreased both angiomiRs in the plasma and the myocardium. The down-regulation of angiomiRs was also associated with reduced capillaries and arterioles and increased endothelial cell apoptosis, the hallmark of microangiopathy. Importantly, a time course study in a type 2 diabetic mouse model confirmed that the down-regulation of angiomiRs preceded endothelial apoptosis as well as alterations in the density of the microvasculature. Finally, therapeutic overexpression of both angiomiRs in diabetic aortic rings and human umbilical vein endothelial cells exposed to high glucose (HG) abrogated the deleterious effects of diabetes and HG on cell survival and proliferation and restored their angiogenic potential.These novel findings demonstrate that the down-regulation of angiomiRs is a major underlying mechanism for the development of microangiopathy in diabetic hearts. Therefore, therapeutic restoration of angiomiRs could become a potential approach to combat the cardiovascular complications of diabetes.
The CXCR4/STAT3/IL-10 Pathway Controls the Immunoregulatory Function of Chronic Lymphocytic Leukemia (CLL) and Can be Modulated By Lenalidomide
Authors: Hila Shaim, Zeev Estrov, Takuya Sekine, Kayo Kondo, Peter P. Ruvolo, Philip Thompson, Anushruti Sarvaria, Muharrem Muftuoglu, Nobuhiko Imahashi, Enli Liu, Catherine Sobieski, William Wierda, Michael J. Keating, Nina Shah, Chitra M. Hosing, Abdullah Alsuliman, Rafet Basar, Alessandra Ferrajoli, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Blood (2015)
OA05.01 Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer: Updated Survival Results from KEYNOTE-028
Authors: Patrick Ott, Enriqueta Felip, Sandrine Hiret, Dong-Wan Kim, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Janice Mehnert
Journal: Journal of Thoracic Oncology (2017)
P240 Low ige and not blood eosinophils predicts lack of response to omalizumab in uhsm cohort
Authors: TB Morris, HV Patel, M Demirbag, LJ Holmes, R Daly, D Ryan, RM Niven
Journal: Thorax (2016)

<h3>Background</h3> Omalizumab is an anti-IgE monoclonal antibody therapy used in patients with inadequately controlled persistent allergic IgE mediated asthma who require continuous or frequent treatment with oral corticosteroids. Previous studies have tried to predict a patient’s response to omalizumab based on pre-treatment baseline characteristics. Most recent data has suggested that baseline blood eosinophils, serum periostin or FeNO may be predictive of response to omalizumab in the T<sub>H</sub>2 phenotype. <h3>Aims</h3> This study will attempt to identify a characteristic that may explain why some patients suffering with severe asthma in a single severe asthma centre do not achieve a response when treated with the anti-IgE monoclonal antibody, omalizumab. <h3>Methods</h3> The target population was represented by all patients previously treated or undergoing treatment with omalizumab at the Severe Asthma Service at University Hospital South Manchester (n = 185). The study population was those for whom records could be found within the study period (n = 154). Demographic and clinical data was collected retrospectively from patient medical records. <h3>Results</h3> 16.2% of patients at UHSM did not show response to omalizumab at 16 weeks. Baseline serum IgE levels in the non-response group were on average 77.28 kU/L lower than those in the response group, statistical analysis of the two groups show that this difference was significant (<i>P</i><i> = </i><i>0.04</i>). Mean eosinophils in the true non-responder group were actually higher than those in the true responder group, however this difference was not statistically significant. No other demographic or disease specific measures predicted a lack of response to omalizumab. <h3>Discussion</h3> The results from the study indicate that a lower baseline serum IgE may predict non-response to treatment with omalizumab. The results also show that non-response rates at the NWLC were lower than those demonstrated in clinical trials (INNOVATE), were consistent with other real life studies (PERSIST/APEX I and APEX II) but markedly lower than those quoted in the eXpeRience registry.
T<scp>ranslational</scp> A<scp>dvances</scp> <scp>in the</scp> F<scp>ield</scp> <scp>of</scp> P<scp>ulmonary</scp> H<scp>ypertension</scp>Bench to Bedside: How Fundamental Discoveries in Science Are Advancing Our Understanding and Therapy of Pulmonary Arterial Hypertension
Authors: Mark T. Gladwin
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
P130 Prevalence and clinical outcomes of fungal sensitive asthma in a severe asthma population
Authors: N Swaminathan, A Mansur
Journal: Thorax (2016)

<h3>Introduction</h3> It has been proposed that severe asthma patients with fungal sensitisation might endure worse clinical outcomes than non-sensitised patients. However, the extent of fungal sensitisation and its influence on the disease severity remain unconfirmed. This study explores the prevalence of severe asthma with fungal sensitisation (SAFS) and its clinical effect. <h3>Methods</h3> Consecutive patients referred to a severe asthma centre has been put through systematic assessment protocol to establish their asthma diagnosis, severity, and clinical outcome measures that includes lung function, biomarkers, exacerbations and hospital admissions frequency. Total and specific serum immunoglobulin E (IgE) and skin prick testing to 27 allergens including 5 fungal allergens were undertaken. <h3>Results</h3> A total of 263 patients with a mean age of 45.5 yrs (SD ± 14.6), 72% females, mean age at onset of asthma 21.52 years (range 0.0–69 years), mean pre FEV1% predicted 69.8 (SD ± 24.5) and FEV1/FVC ratio of 66.1 (SD ± 15.3) were considered for the analysis. Allergic characterisation demonstrated atopic status in 182/256 (71.1%), positive sensitisation to alternaria 27/256 (10.5%), aspergillus 57/256 (22.3%), candida 24/256 (9.4%), cladosporium 24/256 (9.4%), penicillium 16/256 (6.2%), meeting SAFS criteria 93/254 (36.4%), and allergic bronchopulmonary aspergillosis (ABPA) 18/247 (7.3%). The SAFS group had higher total IgE than non SAFS group: mean total IgE 974.5 ng/l vs 330.1. However, we observed no statistically different outcomes for the SAFS versus non SAFS groups, ACQ 3.17 vs 3.515, AQLQ 4.0 vs 3.52, FeNO 36.4 ppb vs 32.9, peripheral blood eosinophils (PBE) 385 cells/µl vs 361, annual hospital admissions 1.28 vs 0.97 and annual OCS burst therapy of 5.7 vs 5.9. In contrast the ABPA versus non ABPA cohort had higher PBE 585 cells/µl vs 364, total IgE 2882ng/L vs 326, lower% predFEV1 60.2L vs 71 L, and ever ITU admissions 0.9 vs 0.46. <h3>Conclusion</h3> Fungal sensitisation is relatively common in severe asthma but it did not seem to influence overall clinical outcomes. ABPA is less common with worse outcomes.
P1.03-012 Experience with BioSentryTM Tract Sealant System for Percutaneous CT-Guided Lung Nodule Biopsies in an Oncology Population
Authors: Patricia De Groot, Girish Shroff, Judy Ahrar, Garrett Gladish, Bradley Sabloff, Cesar Moran, Sanjay Gupta, Joe Chang, Gregory Gladish, Jeremy Erasmus
Journal: Journal of Thoracic Oncology (2017)
A case of pulsatile tinnitus
Authors: Karan Jolly, Pawanjit Hare, Richard Irving, Peter Monksfield
Journal: BMJ (2017)

A 32 year old man presented to his primary care doctor with an eight month history of hearing loss and a pulsatile noise that sounded like a heartbeat in his left ear. In the previous four months he had experienced otalgia in the left ear and headaches. On examination, the doctor noticed a mass behind the left tympanic membrane, with pulsation of the membrane. Tuning fork tests identified a conductive hearing loss in the left ear. Other than headaches, there were no red flag symptoms such as weight loss, fever, or other signs of raised intracranial pressure. The patient was referred to an ear, nose, and throat specialist, who noted that the left tympanic membrane was intact and facial nerve function on both sides was normal. There was an obvious pulsating mass behind the left tympanic membrane (fig 1⇓). Endoscopic examination of the larynx showed normal vocal cord movement, but there was evidence of a hypoglossal palsy on the left side, with unilateral tongue wasting. The patient had some difficulty articulating speech but reported no dysphagia. Audiometry confirmed a conductive hearing loss in the left ear. Contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI) (fig 2⇓) of the base of the patient’s skull showed an enhanced jugular fossa mass on the left side.



Fig 1  Left tympanic membrane





Fig 2  T2 weighted magnetic resonance image of the head





### 1. What are the differential diagnoses for pulsatile tinnitus?

#### Short answer

Differential diagnoses include vascular stenosis due to atherosclerotic plaques; arteriovenous fistula; vascular tumours (including paragangliomas), and intracranial hypertension. Alternatively, the tinnitus can result from increased sensitivity to normal bodily noises such as blood flow. This can be due to conductive hearing loss caused by wax obstruction …
Early Consolidation with High Dose Therapy and Autologous Stem Cell Transplantation in HIV-Associated Non Hodgkin Lymphoma At High Risk (Aaipi 2–3). an Interim Report of a Multicenter Phase II Trial.
Authors: Alessandro Re, Mariagrazia Michieli, Bernardino Allione, Salvatore Casari, Chiara Cattaneo, Michele Spina, Andrea Gori, Elisa Garlassi, Luisa Verga, Camillo Almici, Pierino Ferremi, Mario Mazzucato, Alessandro Levis, Umberto Tirelli, Giuseppe Rossi
Journal: Blood (2012)
Over 1000 doctors sign letter calling for new tobacco plan for England
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

More than 1000 doctors and other healthcare workers, including five former presidents of royal colleges, have written an open letter to the prime minister, Theresa May, and England’s health secretary, Jeremy Hunt, urging them to publish a new Tobacco Control Plan “without further delay” to address inequalities in health.1

The letter, which was organised by Nick Hopkinson, reader in respiratory medicine at Imperial College London, pointed out that the government’s previous tobacco strategy for England expired at the end of 2015 and that despite …
Pre-Clinical In Vitro Evaluation of BCL-2 Antisense Compound GenasenseTM (G3139; Genta, Inc.) as a Targeted Pro-Apoptotic Agent for Leukemias with t(4;11)(q21;q23) Translocations.
Authors: Blaine W. Robinson, Kathyrn C. Behling, Jeffrey S. Barrett, Manish Gupta, Jessicca M. Rege, Jonni S. Moore, Andrew D. Bantly, Junhyong Kim, George Hii, Cheryl L. Willman, Jeffrey Potter, Peter C. Adamson, Carolyn A. Felix
Journal: Blood (2005)
P3.01-044 Splicing Variant of Estrogen Receptor Alpha is Associated with Pathological Invasiveness in Smoking Independent Lung Cancer
Authors: Ayumi Suzuki, Katsuhiro Okuda, Motoki Yano, Satoru Moriyama, Hiroshi Haneda, Osamu Kawano, Tadashi Sakane, Risa Oda, Ryoichi Nakanishi
Journal: Journal of Thoracic Oncology (2017)
CD34+CD38-CD58- leukemia-Propagating Cells at Diagnosis Could Identify Patients at High-Risk for Relapse in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yuan Kong, Lan-Ping Xu, Yan-Rong Liu, Ya-Zhen Qin, Yu-Qian Sun, Yu Wang, Huan Chen, Hao Jiang, Qian Jiang, Ying-Jun Chang, Xiao-Jun Huang
Journal: Blood (2014)
Evidence for an Underestimation of the Prognostic Impact of Poor Cytogenetics within the IPSS.
Authors: Detlef Haase, Ulrich Germing, Julie Schanz, Michael Pfeilstoecker, Barbara Hildebrandt, Michael Luebbert, Aristoteles Giagounidis, Carlo Aul, Lorenz Truemper, Thomas Mueller, Peter Valent, Norbert Gattermann, Christa Fonatsch, Otto Krieger, Reinhard Stauder, Christian Steidl
Journal: Blood (2006)
P56 Efficacy and safety of long-acting beta agonists + long acting muscarinic antagonists vs. long-acting beta agonists + inhaled corticosteroids in COPD: a meta-analysis
Authors: RE Villalobos, A David-Wang, J Magallanes
Journal: Thorax (2016)

<h3>Background and significance</h3> Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the use of long-acting beta agonists (LABA) plus inhaled corticosteroids (ICS), or long-acting muscarinic antagonists (LAMA) for the treatment of patients with moderate to severe COPD. The combination of LABA+LAMA is recently indicated for COPD patients with severe symptoms; however, its role in reducing exacerbations is less clear. <h3>Methods</h3> We performed a meta-analysis of randomised controlled trials that compared efficacy and safety of LABA+LAMA versus LABA+ICS in moderate to severe COPD patients. The primary outcome is the rate of COPD exacerbations. Other outcome measures include improvement in trough FEV1, St. George Respiratory Questionnaire for COPD (SGRQ-C) scores, transition dyspnea index (TDI) scores, rescue medication use and pneumonia risk. Analysis was performed in accordance with the Quality of Reporting of Meta-Analyses (QUORUM) guidelines. <h3>Results</h3> A total of 6 RCTs with 3370 patients were included. Over-all exacerbation rates were 21% lower in those treated with LABA+LAMA versus LABA+ICS (RR 0.79, [95% CI: 0.66–0.94]). This effect is more pronounced in patients who had &gt;1 exacerbation per year, showing 25% lower exacerbation rates (RR 0.75 [0.60–0.95]) compared to those with no history of prior exacerbations (RR 0.85 [0.61–1.14]). Patients given Indacaterol+Glycopyrronium also experienced lower rates exacerbation versus LABA+ICS (RR 0.71 [0.57–0.59]) compared to those given Umeclidinium+Vilanterol (RR 1.16 [0.68–2.00]). There were also statistically significant improvements in FEV1 (mean difference 70 mL [95% CI: 0.07–0.07 Liters]), improvement in SGRQ-C (mean difference −0.92 points [−0.95, −0.90]), improvement in TDI scores (mean difference 0.24 [0.23–0.25]) and decrease in use of rescue medications (mean difference −0.20 puffs/day[−0.21, −0.20]). Pneumonia risk was 41% lower in patients given LABA+LAMA compared LABA+ICS (RR 0.59 [0.43 – 0.80]). <h3>Conclusions</h3> The combination of LABA+LAMA is safer and more effective in reducing exacerbations and improving clinical outcomes compared with LABA+ICS in patients with moderate to severe COPD.