tbuckley/cabot-search huggingface dataset:
Lymphadenectomy in carcinoma stomach: Experience from a regional cancer centre
Authors: V. Mahajan
Journal: Journal of Clinical Oncology (2006)

14121 Background: Carcinoma stomach is the most common cancer in males in chennai city. Lot of controversy exists regarding the need for extended lymphadenectomy because of the morbidity and mortality associated. Methods: A retrospective analysis was done to assess the benefit of extended lymphadenectomy. The records of all the patients operated at Cancer Institute from 1991 to 2004 were analysed. Out of 5050 cases of carcinoma stomach seen, only 570 cases were taken up for some form of treatment. 400 cases underwent resection, of which 366 patients records were retreived from the tumor registry for analysis. Followup ranged from 1 year to 10 years. Results: Male to female ratio was 3:1, most patients were in 40 - 60 year age group (60%). 60% patients had antral tumors and the rest were evenly distributed. 79 patients (21%) underwent conventional gastrectomy (D1), 243 patients (66%) underwent extended lymphadenectomy and 44 patients (12%)underwent palliative gastrectomy. 280 patients underwent subtotal gastrectomy, 54 patients total gastrectomy, 28 esophago gastrectomy and 5 had transhiatal esophagectomies. Stage wise distribution was IA 4.9%, IB 9.8%, II 21%, IIIA 29.4%, IIIB 12.8%, IV 22.1%. The total number of nodes dissected in the Extended nodal dissection group was less than or equal to 15 in 12% patients, 15 to 30 nodes in 48% patients and &gt;30 nodes in 40% patients. 72% patients had node positive disease. Overall Survival at 5years was 38.9% for all the cases. 5year ovarall survival for conventional gastrectomy group was 37% and was 48% for the extended lymphadenectomy group which was statistically significant(p =0.06) .On substratification for T status and stage, the difference in survival between conventional and extended lymphadenectomy arms was not found to be significant.However,there was a trend towards improved survival in the lymphadenectomy arm.There were 7 post operative deaths in the lymphadenectomy arm,5 of which were in the first year of starting extended lymphadenectomies, which points to the learning curve for these procedures. Conclusions: Larger trials may be required to prove the advantage of extended lymphadenectomies in Gastric cancer. In addition neoadjuvant chemotherapy and Intraoperative radiotherapy may need to be studied to improve survival in gastric cancer. No significant financial relationships to disclose.
Norman Henry Birch
Authors: Robert Birch
Journal: BMJ (2016)

Norman Henry Birch was born in Leeds on 19 November 1923. He was from a humble background that few would have guessed would foretell of an exciting and interesting medical career across continents. One of two children, he attended Leeds Grammar School and obtained his school certificate in July 1940. At the age of only 17 he went to Leeds University Medical School and qualified as a doctor in September 1945, before his 21 birthday.

After university, Norman undertook his national service in Germany as a medical officer before returning to Britain for surgical training and achieving his FRCS in …
Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial
Authors: Christian Carrie, Ali Hasbini, Guy de Laroche, Pierre Richaud, Stéphane Guerif, Igor Latorzeff, Stéphane Supiot, Mathieu Bosset, Jean-Léon Lagrange, Véronique Beckendorf, François Lesaunier, Bernard Dubray, Jean-Philippe Wagner, Tan Dat N'Guyen, Jean-Philippe Suchaud, Gilles Créhange, Nicolas Barbier, Muriel Habibian, Céline Ferlay, Philippe Fourneret, Alain Ruffion, Sophie Dussart
Journal: The Lancet Oncology (2016)
Ponatinib Is Well Tolerated and Active In Patients With Relapsed/Refractory Philadelphia Positive Acute Lymphoblastic Leukemia (PH+ ALL) and Advanced Phase Of Chronic Myelogenous Leukemia (CML) Harbouring T315I Mutation: The Bologna Experience
Authors: Cristina Papayannidis, Caterina De Benedittis, Simona Soverini, Ilaria Iacobucci, Maria Chiara Abbenante, Chiara Sartor, Maria Teresa Bochicchio, Anna Ferrari, Claudia Venturi, Valentina Robustelli, Andrea Ghelli Luserna Di Rorà, Viviana Guadagnuolo, Emanuela Ottaviani, Nicoletta Testoni, Carmen Baldazzi, Simona Luatti, Sarah Parisi, Stefania Paolini, Cristina Clissa, Alberto Conficoni, Federica Frabetti, Elisa Lani, Silvia Piccari, Paolo Di Bartolomeo, Roberto Di Lorenzo, Renato Fanin, Giuseppe Cimino, Giovanni Martinelli
Journal: Blood (2013)
PI3 kinase/mTOR inhibition increases sensitivity of ER positive breast cancers to CDK4/6 inhibition by blocking cell cycle re-entry driven by cyclinD1 and inducing apoptosis
Authors: M.T. Herrera-Abreu, U.S. Asghar, R. Elliot, A. Pearson, M.A. Nannini, A. Young, D. Sampath, M. Dowsett, L.A. Martin, N. Turner
Journal: Annals of Oncology (2015)
Safety, pharmacokinetics, and pharmacodynamics of avoralstat, an oral plasma kallikrein inhibitor: phase 1 study
Authors: M. Cornpropst, P. Collis, J. Collier, Y. S. Babu, R. Wilson, J. Zhang, L. Fang, J. Zong, W. P. Sheridan
Journal: Allergy (2016)

Abstract Background Avoralstat is a potent small‐molecule oral plasma kallikrein inhibitor under development for treatment of hereditary angioedema (HAE). This first‐in‐human study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of avoralstat. Methods This double‐blind, placebo‐controlled, ascending‐dose cohort trial evaluated avoralstat single doses of 50, 125, 250, 500, and 1000 mg and multiple doses up to 2400 mg daily (100, 200, 400, and 800 mg every 8 h [q8 h] up to 7 days). Results Avoralstat ( n = 71) was generally well tolerated with no signals for a safety concern; there were no serious adverse events (AEs) or discontinuations due to AE s, and compared to placebo ( n = 18), no notable difference in AE s. Four moderate severity AE s were reported in two subjects; syncope after a single 250 mg dose (one subject) and abdominal pain, back pain, and eczema after multiple doses of 800 mg avoralstat (one subject). For multiple‐dose cohorts, the incidence of gastrointestinal AE s was highest at the 2400 mg/day dose. Elimination of avoralstat was bi‐exponential with a terminal half‐life of 12–31 h. Inhibition of plasma kallikrein was observed at all doses, and the degree of inhibition was highly correlated with avoralstat concentrations ( R = 0.93). Mean avoralstat concentrations at doses ≥400 mg q8 h met or exceeded plasma kallikrein EC 50 values throughout the dosing interval. Conclusion Avoralstat was well tolerated, and drug exposure was sufficient to meet target levels for inhibition of plasma kallikrein. Based on these results, the 400 mg q8 h dose was selected for further evaluation in patients with HAE.
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection
Authors: Wouter A. A. de Steenhuijsen Piters, Santtu Heinonen, Raiza Hasrat, Eleonora Bunsow, Bennett Smith, Maria-Carmen Suarez-Arrabal, Damien Chaussabel, Daniel M. Cohen, Elisabeth A. M. Sanders, Octavio Ramilo, Debby Bogaert, Asuncion Mejias
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem.To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity.We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling.Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
Safety of Seasonal Influenza Vaccination in Hospitalized Surgical Patients
Authors: Sara Y. Tartof, Lei Qian, Gunter K. Rieg, Kalvin C. Yu, Lina S. Sy, Hung Fu Tseng, Rulin C. Hechter, Steven J. Jacobsen
Journal: Annals of Internal Medicine (2016)

Despite recommendations to vaccinate surgical inpatients against influenza, vaccination rates remain low in this population, due in part to concerns about potential negative effects on postsurgical care.To evaluate whether influenza vaccination in the perioperative period increases health care utilization and evaluations for postsurgical infection after discharge.Retrospective cohort study.Members of Kaiser Permanente Southern California.Patients aged 6 months or older who had inpatient surgery with admission and discharge between 1 September and 31 March from 2010 to 2013.All influenza vaccinations administered between 1 August and 30 April in the 2010-2011, 2011-2012, and 2012-2013 influenza seasons. Outcomes included rates of outpatient visits, readmission, emergency department (ED) visits, fever (temperature ≥38.0 °C), and clinical laboratory evaluations for infection (urine culture, complete blood count, blood culture, and wound culture) in the 7 days after discharge.Of the 42 777 surgeries included in adjusted analyses, vaccine was administered during hospitalization in 6420. No differences were detected between the vaccinated and unvaccinated groups in risk for inpatient visits (rate ratio [RR], 1.12 [95% CI, 0.96 to 1.32]), ED visits (RR, 1.07 [CI, 0.96 to 1.20]), postdischarge fever (RR, 1.00 [CI, 0.76 to 1.31]), or clinical evaluations for infection (RR, 1.06 [CI, 0.99 to 1.13]). A marginal increase in risk for outpatient visits (RR, 1.05 [CI, 1.00 to 1.10]; P = 0.032) was found.The study did not distinguish between planned and unplanned readmissions or outpatient visits.No strong evidence of increased risk for adverse outcomes was found in comparisons of patients who received influenza vaccine during a surgical hospitalization and those who did not. The data support the recommendation to vaccinate surgical inpatients against influenza.Centers for Disease Control and Prevention.
Lithium-induced nephrotic syndrome
Authors: I K Wood, D X Parmelee, J W Foreman
Journal: American Journal of Psychiatry (1989)

The nephrotic syndrome is a rare, idiosyncratic adverse renal effect of lithium that can occur with therapeutic plasma lithium levels. The syndrome is usually reversed by discontinuation of lithium treatment but may require corticosteroids. Renal biopsies reveal fusion of the foot processes of renal epithelial cells, referred to as "minimal change disease." No particular variable identifies individuals at risk for developing the nephrotic syndrome while taking lithium. The authors review the eight published cases in the English-language literature and present the case of an adolescent who developed lithium-induced nephrotic syndrome.
GeDDiS: A prospective randomised controlled phase III trial of gemcitabine and docetaxel compared with doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft tissue sarcomas (EudraCT 2009-014907-29).
Authors: Beatrice M. Seddon, Jeremy Whelan, Sandra J Strauss, Michael Gordon Leahy, Penella J. Woll, Fiona Cowie, Christian Alexander Rothermundt, Zoe Wood, Sharon Forsyth, Iftekhar Khan, Stephen Nash, Paul Patterson, Sandra Beare
Journal: Journal of Clinical Oncology (2015)

10500 Background: Standard first-line treatment of locally advanced/metastatic soft tissue sarcoma (STS) is Dox. GemDoc has activity in STS and is used in relapsed STS after failure of at least one line of chemotherapy. Our aim was to compare GemDoc with Dox as first-line treatment of locally advanced/metastatic STS. Methods: Patients (pts) from 24 UK sites and 1 Swiss site were randomised to receive 6 cycles of Dox 75 mg/m2 intravenously (IV) day 1 every 3 weeks, or Gem 675 mg/m2 IV days 1 and 8 and Doc 75 mg/m2 IV day 8 every 3 weeks (wks). Pts had locally advanced/metastatic STS, Trojani grade 2 or 3, disease progression prior to enrolment, no prior chemotherapy for sarcoma, no prior Dox, WHO performance status 0-2, age ≥ 13 years. Pts were stratified by age ( ≤ 18 or > 18 years) and histological subtype (uterine leiomyosarcoma [uLMS], synovial, pleomorphic, and other). Primary endpoint was progression free survival (PFS) rate (PFR) at 24 wks. Results: From Dec 2010 - Jan 2014, 257 pts were randomised (n = 129 Dox; n = 128 GemDoc). Median follow up was 19 months. 61% of pts were female; median age was 55 years. Baseline characteristics were balanced. Histology was 27% uLMS, 4% synovial, 12% pleomorphic, 56% other. PFR at 24 wks was 46.1% v 46.0%, median PFS was 23 v 24wks, for Dox v GemDoc, but the hazard ratio (HR) was 1.28 (95% CI 0.98-1.67, P = 0.07) in favour of Dox. Median OS was 71 v 63 wks (HR = 1.07; 95% CI 0.77-1.49) for Dox v GemDoc. Although the PFS Kaplan-Meier curves did not violate the proportional hazards assumption (p = 0.53), they initially overlapped, and then separated after 24 wks in favour of Dox. Best response (CR/PR/SD) was 65.9% (Dox) v 58.6% (GemDoc). Mean dose intensity was 94.6% (Dox) v 83.3% (GemDoc). 46% (Dox) v 61% (GemDoc) of pts had at least one dose delay; 1 pt (2%) on Dox v 13 pts (16%) on GemDoc stopped treatment early due to toxicity. Conclusions: Although the PFR at 24 wks was the same for Dox and GemDoc, the HR indicated superiority of Dox. Dox was less toxic and easier to deliver than GemDoc, and should remain standard first-line treatment for locally advanced/metastatic STS. Clinical trial information: ISRCTN07742377.
The Presence Of 1 / 8 HLA Mismatch Do Not Hamper Survival After Allogeneic Stem Cell Transplantation Using Immunoprophylaxis With Sirolimus-Tacrolimus
Authors: Rocío Parody, Lucía López-Corral, Oriana Lopez Godino, Irene García Cadenas, Vazquez Lourdes, Rodrigo Martino, Carmen Martinez, Carlos Solano, Ariadna Perez Martinez, Pere Barba, David Valcarcel, Jose F. Falantes, Francisco J Márquez-Malaver, Dolores Caballero, Jose Antonio Perez-Simón
Journal: Blood (2013)
Simplified regimen for the prevention of paclitaxel-associated hypersensitivity reactions.
Authors: M Markman, A Kennedy, K Webster, G Peterson, B Kulp, J Belinson
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.12.3517 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9396407 Simplified regimen for the prevention of paclitaxel-associated hypersensitivity reactions. M MarkmanxM MarkmanSearch for articles by this author , A KennedyxA KennedySearch for articles by this author , K WebsterxK WebsterSearch for articles by this author , G PetersonxG PetersonSearch for articles by this author , B KulpxB KulpSearch for articles by this author , J BelinsonxJ BelinsonSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.12.3517 PDF "Simplified regimen for the prevention of paclitaxel-associated hypersensitivity reactions.." Journal of Clinical Oncology, 15(12), p. 3517© 1997 by American Society of Clinical Oncology
Psoriasin (S100A7) promotes stress-induced angiogenesis
Authors: J. Vegfors, A.-K. Ekman, S.W. Stoll, C. Bivik Eding, C. Enerbäck
Journal: British Journal of Dermatology (2016)

Summary Background Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease. Objectives To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis. Methods The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated. Results Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways. Conclusions These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.
Individual and Neighborhood Socioeconomic Status and the Association between Air Pollution and Cardiovascular Disease
Authors: Gloria C. Chi, Anjum Hajat, Chloe E. Bird, Mark R. Cullen, Beth Ann Griffin, Kristin A. Miller, Regina A. Shih, Marcia L. Stefanick, Sverre Vedal, Eric A. Whitsel, Joel D. Kaufman
Journal: Environmental Health Perspectives (2016)

Background:Long-term fine particulate matter (PM2.5) exposure is linked with cardiovascular disease, and disadvantaged status may increase susceptibility to air pollution-related health effects. In addition, there are concerns that this association may be partially explained by confounding by socioeconomic status (SES).Objectives:We examined the roles that individual- and neighborhood-level SES (NSES) play in the association between PM2.5 exposure and cardiovascular disease.Methods:The study population comprised 51,754 postmenopausal women from the Women's Health Initiative Observational Study. PM2.5 concentrations were predicted at participant residences using fine-scale regionalized universal kriging models. We assessed individual-level SES and NSES (Census-tract level) across several SES domains including education, occupation, and income/wealth, as well as through an NSES score, which captures several important dimensions of SES. Cox proportional-hazards regression adjusted for SES factors and other covariates to determine the risk of a first cardiovascular event.Results:A 5 μg/m3 higher exposure to PM2.5 was associated with a 13% increased risk of cardiovascular event [hazard ratio (HR) 1.13; 95% confidence interval (CI): 1.02, 1.26]. Adjustment for SES factors did not meaningfully affect the risk estimate. Higher risk estimates were observed among participants living in low-SES neighborhoods. The most and least disadvantaged quartiles of the NSES score had HRs of 1.39 (95% CI: 1.21, 1.61) and 0.90 (95% CI: 0.72, 1.07), respectively.Conclusions:Women with lower NSES may be more susceptible to air pollution-related health effects. The association between air pollution and cardiovascular disease was not explained by confounding from individual-level SES or NSES.Citation:Chi GC, Hajat A, Bird CE, Cullen MR, Griffin BA, Miller KA, Shih RA, Stefanick ML, Vedal S, Whitsel EA, Kaufman JD. 2016. Individual and neighborhood socioeconomic status and the association between air pollution and cardiovascular disease. Environ Health Perspect 124:1840–1847; http://dx.doi.org/10.1289/EHP199
Epithelial-to-Mesenchymal Transition Defines Feedback Activation of Receptor Tyrosine Kinase Signaling Induced by MEK Inhibition in <i>KRAS</i>-Mutant Lung Cancer
Authors: Hidenori Kitai, Hiromichi Ebi, Shuta Tomida, Konstantinos V. Floros, Hiroshi Kotani, Yuta Adachi, Satoshi Oizumi, Masaharu Nishimura, Anthony C. Faber, Seiji Yano
Journal: Cancer Discovery (2016)

KRAS is frequently mutated in lung cancer. Whereas MAPK is a well-known effector pathway of KRAS, blocking this pathway with clinically available MAPK inhibitors is relatively ineffective. Here, we report that epithelial-to-mesenchymal transition rewires the expression of receptor tyrosine kinases, leading to differential feedback activation of the MAPK pathway following MEK inhibition. In epithelial-like KRAS-mutant lung cancers, this feedback was attributed to ERBB3-mediated activation of MEK and AKT. In contrast, in mesenchymal-like KRAS-mutant lung cancers, FGFR1 was dominantly expressed but suppressed by the negative regulator Sprouty proteins; MEK inhibition led to repression of SPRY4 and subsequent FGFR1-mediated reactivation of MEK and AKT. Therapeutically, the combination of a MEK inhibitor (MEKi) and an FGFR inhibitor (FGFRi) induced cell death in vitro and tumor regressions in vivo These data establish the rationale and a therapeutic approach to treat mesenchymal-like KRAS-mutant lung cancers effectively with clinically available FGFR1 and MAPK inhibitors.Adaptive resistance to MEKi is driven by receptor tyrosine kinases specific to the differentiation state of the KRAS-mutant non-small cell lung cancer (NSCLC). In mesenchymal-like KRAS-mutant NSCLC, FGFR1 is highly expressed, and MEK inhibition relieves feedback suppression of FGFR1, resulting in reactivation of ERK; suppression of ERK by MEKi/FGFRi combination results in tumor shrinkage. Cancer Discov; 6(7); 754-69. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.