tbuckley/cabot-search huggingface dataset:
Correlation of genetic polymorphisms in folate metabolic pathway genes with clinical outcomes in pemetrexed-treated advanced NSCLC patients.
Authors: J. Kim, J. Yun, J. Kong, S. Lee, S. Kim, J. Lee, J. Ahn, K. Park, M. Ahn
Journal: Journal of Clinical Oncology (2010)

7616 Background: Pemetrexed has been widely used in patients with advanced NSCLC, or malignant mesothelioma. It is an antifolate antineoplastic agent which inhibits multitargeted enzymes, TYMS, DHFR, GARFT, and ATIC. The clinical relevance of polymorphisms of pathway genes for pemetrexed metabolism have not been fully elucidated yet. The main goal of this study was to evaluate the association between polymorphisms in the genes possibly involved in the metabolic pathways of pemetrexed and clinical outcome in NSCLC patients treated with pemetrexed. Methods: Total 113 patients with advanced NSCLC who had been treated with pemetrexed at Samsung Medical Center between January 2007 and December 2008 were included. Patients were treated with 500mg/m2 of pemetrexed until progression or intolerable toxicity. Clinical data, including patient characteristics, response rate, progression free survival (PFS), and overall survival (OS) were collected retrospectively. Genomic DNA obtained from peripheral blood was analyzed for 64 single nucleotide polymorphisms (SNPs) from 13 genes (ABCB1, ABCC1, ABCC2, ATIC, DHFR, FPGS, GARFT, GGH, MTHFR, PPAT, SHMT1, SLC19A1, TYMS,). Results: A SNP (rs12995526) in ATIC was significantly associated with OS ; Patients carrying CC or CT genotype had significantly longer OS than those with TT genotype (p < 0.001 Hazard ratio = 7.404, 95% CI= 2.570-21.328). Significant associations with PFS were detected for 2 SNPs ; rs17279558 in GGH and rs2176785 in PPAT. The CC haplotype for A1298C and C677T polymorphisms in MTHFR showed better overall response rate than other MTHFR haplotype (p = 0.013), but did not confer survival benefit. We found a significant effect of ATIC, ABCB1, PPAT, SHMT haplotype combinations on OS or PFS. Conclusions: This study suggests that several genetic variations associated with folate metabolic pathway and the downstream events have significant correlation with clinical outcome in patients treated with pemetrexed. Further prospective studies will be needed to validate these polymorphisms as a useful biomarker in pemetrexed treated NSCLC patients. No significant financial relationships to disclose.
BMA calls for chief inspector of general practice to resign
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Doctors’ leaders have called for Steve Field, chief inspector of general practice at the regulator for England the Care Quality Commission, to resign, after he made “unjustified” comments that have “undermined” the profession.

The BMA’s General Practitioners Committee passed a motion on 17 December saying that it had no confidence in Field and calling for his immediate resignation.

The Royal College of General Practitioners also took the unusual step of openly critcising a high profile medical figure in the NHS to say that the GP profession had lost confidence in Field after “baffling, unfounded, and scaremongering” comments he made about GPs.

Field was interviewed for an article in the Daily Mail on 12 December in which he said, “I believe that we’ve failed as a …
Multiplatform molecular profiling of pancreatic adenocarcinomas to identify BRCA1/2 mutations and PD-1/PD-L1 status with therapeutic implications.
Authors: Sherri Z. Millis, Brian L. Abbott, Erin H Baker, Ryan Bender, Jeffrey Swensen, Zoran Gatalica, Sandeep K. Reddy, Alexander Rosemurgy, David A Iannitti
Journal: Journal of Clinical Oncology (2015)

4124 Background: Pancreas adenocarcinoma (PAC) is a challenging disease with overall single digit 5-year survivorship. BRCA1 and BRCA2 germline mutations are associated with increased risk of PC. Recent retrospective studies have described response of BRCA patients to platinum agents and PARP inhibitors. Additionally, immune therapies targeting the programmed cell death pathway in other cancers have shown promise; evaluating the incidence of aberrations of these markers in PAC impact therapeutic decisions. Methods: 450 PAC’s were evaluated at a commercial CLIA laboratory using a combination of sequencing (Sanger or next generation sequencing (NGS)) and protein expression (immunohistochemistry). BRCA1/2 mutations that could be germline or somatic, co-incidence with other mutations identified in the tissue, and expression levels of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL’s) were evaluated. Results: Mutations (MT) in BRCA1 and BRCA2 were identified in 5 and 17% percent of tissues, respectively. BRCA1 and BRCA2 MT had different rates of concurrence with other gene alterations, which was also different from the general PC population (table). Overexpression of PD-L1 and PD-1 TIL’s were also identified in 7% and 37% of PAC cases, respectively. BRCA1 MT cases had a higher incidence of PD-1 TIL’s, while BRCA2 MT cases had a higher percent of overexpressed PD-L1 than the overall population. Conclusions: The different frequencies of KRAS, TP53, PIK3CA and SMAD4 MT between the overall PAC population and BRCA MT populations may inform driver differences and may help select drugs and refine treatment decision making for certain patients. Evaluating the profiles of the BRCA MT populations with clinical outcomes will provide valuable insight into the clinical behavior in genomically defined subsets and may facilitate in developing rational combinations of targeted agents in PAC. Biomarker MT BRCA1 MT BRCA2 MT Overall PC Population % Coincidence APC 14 0 3 BRAF 0 0 1 KRAS 71 77 85 PIK3CA 14 0 3 SMAD4 0 10 16 TP53 43 60 59 PD-1 38 50 37 PD-L1 13 8 7
Molecular epidemiologic analysis of a Pneumocystis pneumonia outbreak among renal transplant patients
Authors: N. Urabe, Y. Ishii, Y. Hyodo, K. Aoki, S. Yoshizawa, T. Saga, S.Y. Murayama, K. Sakai, S. Homma, K. Tateda
Journal: Clinical Microbiology and Infection (2015)
NT-proBNP in assessment of pulmonary hypertension in COPD patients
Authors: Marcin Grabicki, Halina Batura-Gabryel, Barbara Kuznar-Kaminska, Beata Brajer-Luftmann
Journal: European Respiratory Journal (2013)

INTRODUCTION : COPD affects lungs and coexists with some comorbidities. Pulmonary hypertension (PH) is one of them. It is important to have a simple and available test to determine COPD patients with increased pulmonary pressure. NT-proBNP may meet these criteria. However there is limited information on the role of NT-proBNP in assessment of PH in COPD patients.

AIM: The goal of the study was to evaluate the usefulness of detecting NT-proBNP as a marker of PH in patients with COPD.

METHODS: 40 patients with moderate to very severe stage of COPD were enrolled into the study (GOLD 2010). Patients with evident and significant left-sided heart pathologies, arrhythmias and renal failure were excluded. Every subject underwent echocardiography, pulmonary function tests, 6- minute walk test, arterial blood gases and ECG. NT-proBNP was measured.

RESULTS: The average age was 62.4 ± 8.3 years. There were no significant differences in NT-proBNP concentration between subgroups distinguished based on RVSP and PV-AccT in the whole study population. The higher concentration of NT-proBNP was found in the subgroup of patients with RVSP > 36 mmHg and GOLD (III+IV) stages (p= 0.045). There was a significant positive correlation between NT-proBNP and RVSP (p= 0.021) in GOLD (III+IV). There was not such a relation in the entire population. The cut-off value of NT-proBNP was determined (31.1 pg/ml), separating the ranges of probability of PH presence based on RVSP (≤ vs > 36 mmHg), for patients with GOLD (III+IV) stages.

CONCLUSIONS: The results indicate that NT-proBNP can be a clinically useful screening tool for PH in patients with at least severe stage of COPD without any significant left heart pathologies, arrhythmias and renal failure.
Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy
Authors: Priscilla K. Brastianos, Ganesh M. Shankar, Corey M. Gill, Amaro Taylor-Weiner, Naema Nayyar, David J. Panka, Ryan J. Sullivan, Dennie T. Frederick, Malak Abedalthagafi, Pamela S. Jones, Ian F. Dunn, Brian V. Nahed, Javier M. Romero, David N. Louis, Gad Getz, Daniel P. Cahill, Sandro Santagata, William T. Curry, Fred G. Barker
Journal: JNCI Journal of the National Cancer Institute (2015)

We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient’s blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment.
FAMILIAL MAMMARY TUMORS IN THE RABBIT
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1939)

The pathological histories of two types of familial mammary cancer in the rabbit have been described. One type was distinguished by characteristic antecedent mammary changes similar to those found in Schimmelbusch's disease in women and by a distinctive papillary structure. The second type originated in normal breast tissue and was characterized histologically by an atypical proliferation of acini.
An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy
Authors: Eva-Maria Nichols, Thomas D. Barbour, Isabel Y. Pappworth, Edwin K.S. Wong, Jeremy M. Palmer, Neil S. Sheerin, Matthew C. Pickering, Kevin J. Marchbank
Journal: Kidney International (2015)

Abnormal regulation of the complement alternative pathway is associated with C3 glomerulopathy. Complement factor H is the main plasma regulator of the alternative pathway and consists of 20 short consensus repeat (SCR) domains. Although recombinant full-length factor H represents a logical treatment for C3 glomerulopathy, its production has proved challenging. We and others have designed recombinant mini-factor H proteins in which 'non-essential' SCR domains have been removed. Here, we report the in vitro and in vivo effects of a mini-complement factor H protein, FH1-5^18-20, using the unique factor H-deficient (Cfh-/-) mouse model of C3 glomerulopathy. FH1-5^18-20 is comprised of the key complement regulatory domains (SCRs 1-5) linked to the surface recognition domains (SCRs 18-20). Intraperitoneal injection of FH1-5^18-20 in Cfh-/- mice reduced abnormal glomerular C3 deposition, similar to full-length factor H. Systemic effects on plasma alternative pathway control were comparatively modest, in association with a short half-life. Thus, FH1-5^18-20 is a potential therapeutic agent for C3 glomerulopathy and other renal conditions with alternative pathway-mediated tissue injury.
Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact
Authors: Armand Mekontso Dessap, Florence Boissier, Cyril Charron, Emmanuelle Bégot, Xavier Repessé, Annick Legras, Christian Brun-Buisson, Philippe Vignon, Antoine Vieillard-Baron
Journal: Intensive Care Medicine (2015)
Randomized phase III study of S-1 alone versus S-1 + cisplatin in the treatment for advanced gastric cancer (The SPIRITS trial) <i>SPIRITS:</i> S-1 plus cisplatin vs S-1 in RCT in the treatment for stomach cancer
Authors: H. Narahara, W. Koizumi, T. Hara, A. Takagane, T. Akiya, M. Takagi, K. Miyashita, T. Nishizaki, O. Kobayashi
Journal: Journal of Clinical Oncology (2007)

4514 Background: S-1 has been widely used against advanced gastric cancer (AGC) not only as monotherapy but also in combination with other cytotoxic compounds. Results of a phase I/II study combining S-1 + cisplatin (CDDP) were very encouraging with a high response rate (RR) of 76%, and the MST (Median Survival Time) of 383 days (Koizumi W et al, Br J Cancer, 2003). Based on these results, a phase III study comparing S-1 alone with S-1 + CDDP has been conducted to further evaluate the efficacy and safety for S-1 + CDDP as a standard treatment for AGC. Methods: This is a randomized, controlled, open-label, parallel, multicenter study. Patients (pts) are randomized to one of two treatment arms. Arm A: Pts receive oral S-1 (40 mg/m 2 ) twice daily 28 days followed by 14 days rest. Arm B: Pts receive oral S-1 (40 mg/m 2 ) twice daily 21 days followed by 14 days rest plus CDDP (60 mg/m 2 ) iv on day 8. Eligibility criteria included unresectable/recurrent AGC, age 20–74, no prior chemotherapy for AGC. Primary endpoint was overall survival (OS). Main secondary endpoints included RR, time to treatment failure (TTF) and toxicity. Based on planned sample size of 284 pts, the trial was designed to have 90% power to detect an improvement in median OS from 8 to 12 months (2-sided log-rank test; significance level 0.05). Results: 305 pts (Arm A/B, 152/153) were randomized between Mar 2002 and Nov 2004. The eligible pts were 299 (Arm A/B, 150/149). Median age was 62.0/61.5 yrs. At a 2 yrs follow-up since last patient in, the MST for Arm A was 335.5 days (95%CI: 292.0 - 402.0) and for Arm B was 396.0 days (95%CI: 342.0 - 471.0). The OS for Arm B was superior to Arm A (log-rank p=0.0366, hazard ratio: 0.774, 95% CI: 0.608 - 0.985). RR was 31.1% for Arm A and 54.0% for Arm B. In Arm A vs Arm B, the most common grade 3/4 toxicities were: leucopenia, 2.0% vs 11.5%; neutropenia, 10.7% vs 39.9%; anemia (decreased Hb), 4.0% vs 25.7%; nausea, 1.3% vs 11.5%; anorexia, 6.0% vs 30.4%. No treatment related death was observed. Conclusions: The combination treatment of S-1 and CDDP met primary endpoint of OS, and was found to be effective and well tolerated in pts with AGC. Accordingly, this regimen can be regarded as one of first-line standard treatment for AGC. No significant financial relationships to disclose.
Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma
Authors: Kyuichi Kadota, Jun-ichi Nitadori, Hideki Ujiie, Daniel H. Buitrago, Kaitlin M. Woo, Camelia S. Sima, William D. Travis, David R. Jones, Prasad S. Adusumilli
Journal: Journal of Thoracic Oncology (2015)
Refugee crisis demands European Union-wide surveillance!
Authors: Mike Catchpole, Denis Coulombier
Journal: Eurosurveillance (2015)

Preview this article: Refugee crisis demands European Union-wide surveillance!, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/20/45/eurosurv-20-30063-1-1.gif
THE IMMUNOGLOBULINS OF MICE
Authors: John L. Fahey, John Wunderlich, Robert Mishell
Journal: The Journal of Experimental Medicine (1964)

Two subclasses of mouse 7S γ2-globulins are identified, and are designated γ2a- and γ2b-globulins. They are distinguished from 7S γ1-globulins, γ1A (ß2A)-globulins, and γ1M-globulins of mouse serum. Antibody activity was detected among the γ2a-globulins and γ2b-globulins of hyperimmune mouse serum. γ2a- and γ2b-myeloma proteins were identified. The genetically determined isoantigen, Iga-1, was present on γ2a-myeloma proteins, but not on γ2b-myeloma proteins. These findings indicate a complexity among the 7S γ2-globulins which must be taken into account in structural, functional, and genetic studies of immunoglobulins.
Improvement in the signs and symptoms of dry eye disease with dobesilate eye drops
Authors: Pedro Cuevas, Luis Antonio Outeiriño, Carlos Azanza, Javier Angulo, Guillermo Giménez-Gallego
Journal: Military Medical Research (2015)

Dry eye is a multifactor disease of the tear film and ocular surface that substantially affects quality of life.Dobesilate administered as eye drops was well tolerated and effective in treating both the objective signs and subjective symptoms of dry eye disease in this 2-week study.To the best of our knowledge, this is the first clinical report of using dobesilate in eye drops. Dobesilate may provide a novel approach to treating drying diseases of the eye.
Highs and Lows in the Peripheral Vasculature
Authors: Michael H. Criqui, Joachim H. Ix
Journal: Journal of the American College of Cardiology (2012)

In recent years, we have come a long way from categorizing all ankle-brachial indices (ABIs) above 0.90 as normal. Both borderline low and high ABIs present significant risk ([1][1]). In this issue of the Journal , Arain et al. ([2][2]) at the Mayo Clinic document the risk of a high ABI with the
Primary Pulmonary NUT Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterizations
Authors: Lynette M. Sholl, Mizuki Nishino, Saraswati Pokharel, Mari Mino-Kenudson, Christopher A. French, Pasi A. Janne, Christopher Lathan
Journal: Journal of Thoracic Oncology (2015)
P0791 : Daclatasvir (DCV) combined with sofosbuvir (SOF) or simeprevir (SMV) in liver transplant (LT) recipients with severe recurrent HCV genotype 1 infection
Authors: R.J. Fontana, R. Brown, J. Herzer, K. Stauber, R.E. Moreno-Zamora, A. Londono, M.-C. Prieto, M. Castells, L. Chacko, K. Ferenci, P. Jafri, S.-M. Knop, V. Bahirwani, R. Durand, C. Lionetti, R. Loiacono, L. Berg, C. Joshi, S. Montalbano, M. Mubarak, A. Pellicelli, A. Elsharkawy, A. Stenmark, S. Torti, C. Vekeman, F. Ionescu-Ittu, R. Edmond, B. Reddy
Journal: Journal of Hepatology (2015)
Fibroblasts Enhance Migration of Human Lung Cancer Cells in a Paper‐Based Coculture System
Authors: Gulden Camci‐Unal, David Newsome, Brenda K. Eustace, George M. Whitesides
Journal: Advanced Healthcare Materials (2015)

A multilayered paper-based platform is used to investigate the interactions between human lung tumor cells and fibroblasts that are isolated from primary patient tumor samples. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Role of Type 1 Diabetes–Associated SNPs on Autoantibody Positivity in the Type 1 Diabetes Genetics Consortium: Overview
Authors: Stephen S. Rich, Patrick Concannon
Journal: Diabetes Care (2015)

OBJECTIVE Type 1 diabetes (T1D) arises from the autoimmune destruction of the β-cells of the pancreas, resulting in dependence on exogenously administered insulin for survival. Key biomarkers of the autoimmune process in T1D are the occurrence of autoantibodies directed against β-cells and other antigens. The Type 1 Diabetes Genetics Consortium (T1DGC) assembled collections to 1) discover genes that modify the risk of T1D, 2) conduct phenotyping related to risk, and 3) make available biologic and genetic resources for research. The goal of the T1DGC Autoantibody Workshop was to use T1DGC phenotypic, genotypic, and autoantibody data on affected sibling pair (ASP) families to discover genes accounting for variation in presence of autoantibodies. RESEARCH DESIGN AND METHODS The T1DGC provided the working groups with autoantibody and genetic data on 9,976 subjects from 2,321 ASP families. Data were distributed to numerous working groups for analyses of specific autoantibody subsets and targets. RESULTS Seven groups analyzed the joint autoantibody and genetic data within the ASP families. Six reports are provided in this collection, ranging from candidate gene analyses of selected autoantibodies to evaluation of regions of genetic variants associated with autoimmunity on the collection of autoantibodies. CONCLUSIONS Although selected variants in the available genes remain important genetic predictors for prevalence of T1D, other genes and nongenetic factors are expected to contribute to the initiation of islet autoimmunity, the first step in the pathogenesis of T1D.
Abstract 16237: Zero Fluoroscopy Ablation of Atrial Fibrillation: A Safety and Feasibility Study
Authors: Luigi Di Biase, Rodney Horton, Chintan Trivedi, Prasant Mohanty, Sanghamitra Mohanty, Rong Bai, Javier Sanchez, G. Joseph Gallinghouse, Jason Zagrodzky, Amin Al-Ahmad, Patrick Hranitzky, J. David Burkhardt, Andrea Natale
Journal: Circulation (2014)

Introduction: Radiofrequency catheter ablation of atrial fibrillation is performed under fluoroscopic guidance and therefore carries radiation risk exposure for the both the patient and the operator. Three-dimensional mapping systems and newer technologies to allow non-fluoroscopic catheter visualization together with intracardiac echo have reduced but not abolished the fluoroscopy exposure. We aim to demonstrate the feasibility, the safety and the efficacy of catheter ablation for atrial fibrillation without the use of fluoroscopy. Methods: A totally fluoro-less approach was developed for AF ablation at our Institution. 94 consecutive AF patients underwent zero fluoroscopy catheter ablation for atrial fibrillation. In the zero fluoroscopy cases, the fluoroscopy arm was kept far away from the patient table. Access including double trans-septal, mapping with the Carto 3 system and ablation were all performed without fluoroscopy with the use of ICE and the Carto 3 system. These 94 patients were compared with 94 control patients matched for age, sex and type of AF who underwent AF ablation by the same operator with the use of fluoroscopy. Results: Baseline characteristics were similar between fluoroless (N=94, Age=64.5 ± 10.1, 75.5% male, 48% paroxysmal) and control (N=94, Age=65.1 ± 9.9, 72.3% male, 50% paroxysmal) group. Non-PV triggers were detected and ablated in 51 (54.3%) and 56 (59.6%) patients in fluoroless and control group respectively (p=0.5). Average fluoro time in control group was 10.1 ± 4.7 minutes. Procedure duration was comparable (120.4 ± 25.8 vs. 122.2 ± 28.7, p =0.6). After the short term median follow-up of 4.5 (4 – 6.5) months, 10 (10.6 %) patients in flourless and 9 (9.6%) patients in control group experienced recurrences (p=0.8).One pericardial effusion requiring pericardiocenteis occurred in the fluoroless group. Conclusions: Our series show that zero fluoroscopy ablation of atrial fibrillation with the use of newer technologies is feasible, safe and efficacious at the short term follow up. Importantly in our series the double transeptal was performed without fluoroscopy and the ablation was not limited to the pulmonary veins only but included ablation of the posterior wall, the coronary sinus and the left atrial appendage.