tbuckley/cabot-search huggingface dataset:
THU0016 Trans-Ethnic Genome-Wide Analysis Reveals MHC Variability in Rheumatoid Arthritis Genetic Susceptibility
Authors: M. Teruel, J.E. Martin, L. Rodriguez-Rodriguez, A. Balsa, D. Pascul-Salcedo, I. Gonzalez-Alvarez, A.M. Ortiz, E.M. Acevedo-Vazquez, M.H. Cardiel, J.A. Esquivel-Valerio, M.A. Maradiaga-Ceceña, J.L. Musuruana, C.E. Graf, A.J. Alvarellos, M.A. Gonzalez-Gay, B. Pons-Estel, M.E. Alarcon-Riquelme, J. Martin
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previous trans-ethnic meta-analysis including samples from European and Asian individuals support the hypothesis that the genetic component of rheumatoid arthritis is shared. However, our knowledge about populations such as the native population of Americans, also called Amerindians or Native Americans, is poor. Few genetic studies have been conducted in Amerindian populations. <h3>Objectives</h3> We conducted a meta-analysis of Latin American, with Amerindian-European (primarily South European) admixed individuals and Spanish, in order to find new risk <i>loci</i> for RA susceptibility shared and specific for each one of them. <h3>Methods</h3> A total of 5,533 subjects were genotyped with the immunochip custom array and included in the final data set. The OR of the meta-analysis of both populations was performed using the inverse variance method under fixed-effects model. The imputation process of the MHC region was performed with a dense reference panel using the Beagle software. <h3>Results</h3> We confirm the association in this population at genome-wide significant level of the <i>HLA</i> and <i>PTPN22</i>. The MCH analysis showed that four amino acids in positions 11, 13, 70 and 86 of the HLA-DRβ1 explain all the association in our combined analysis. Interestingly, we observed differential associations in each cohort separately. In the Spanish cohort, only amino acids 13 and 86 of HLA-DRβ1 were necessary to explain all the association in the MHC region, while for the Latin American population, amino acids at positions 13 and 70 were the important ones. Outside of the HLA region, the most interesting signals observed were on 2p25.3, 3q25.33 and 7p12.2 where the <i>MYTL1</i>, <i>IL12A</i> and <i>IKZF1</i> genes are located, respectively. <h3>Conclusions</h3> Our results show that the comparative use of two populations provides clues on the diversity and the history of the genetic susceptibility behind a complex disease such as RA. <h3>References</h3> Kim, K. et al. Ann. Rheum. Dis. (2014). doi:10.1136/annrheumdis-2013-204749 Jia, X. et al. PloS One 8, e64683 (2013). Raychaudhuri, S. et al. Nat. Genet. 44, 291–296 (2012). <h3>Acknowledgements</h3> This work was supported by the followuing grants: Instituto de Salud Carlos III (ISCIII) from Spanish Health Ministry RETICS Program RD12/0009 and PI12/02558, the C2A Andalusian recruitment program from Junta de Andalucía (Spain), the European IMI BTCure Program and the Swedish Research Council. MT is supported by the Instituto de Salud Carlos III (Spanish Health Ministry), through the Sara Borrell subprogram [CD13/00316]. <h3>Disclosure of Interest</h3> None declared
Histochemical Demonstration of Proteolytic Activity in Human Neoplasms
Authors: M. S. Burstone
Journal: JNCI Journal of the National Cancer Institute (1956)

Histochemical Demonstration of Proteolytic Activity in Human Neoplasms Get access M. S. Burstone M. S. Burstone National Institute of Dental Research,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 5, April 1956, Pages 1149–1161, https://doi.org/10.1093/jnci/16.5.1149 Published: 01 April 1956 Article history Received: 28 November 1955 Published: 01 April 1956
The impact of the summer 2003 heat waves on mortality in four Italian cities
Authors: P Michelozzi, F de Donato, L Bisanti, A Russo, E Cadum, M DeMaria, M D'Ovidio, G Costa, C. A. Perucci
Journal: Eurosurveillance (2005)

This study evaluates the impact of the 2003 heat wave on cause-specific mortality and the role of demographic characteristics and socioeconomic conditions that may have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome and Turin. Daily mortality counts, for the resident population by age, sex and cause of death were considered. Daily excess mortality was calculated as the difference between the number of deaths observed and the smoothed average. The impact of heat on health is measured in terms of maximum apparent temperature. The greatest excess in mortality was observed in the north west of Italy (Turin, +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were the age groups most affected, and when stratifying by sex, the increase in mortality seemed to be greater among females. The greatest excess in mortality was registered in those with low socioeconomic status in Rome (+17.8%) and in those with lower education levels in Turin (+43%). The analysis of cause-specific mortality not only confirms results from previous studies of an increase in heat-related mortality by respiratory and cardiovascular diseases, but also shows a significant excess in mortality for diseases of the central nervous system and for metabolic/endocrine disorders. Results from 2003 highlight the necessity of targeting future prevention programmes at the susceptible sub-groups identified. The introduction of warning systems alongside efficient preventive plans and the monitoring of mortality during heat waves may represent a valid tool for the reduction of heat-related deaths.
Endoscopic management of obstructive pancreatitis with a metal stent in two family members with hereditary cationic trypsinogen (PRSS1) deficiency
Authors: Marine Camus, Sarah Leblanc, Dominique Debray, Ulriikka Chaput, Stanislas Chaussade, Frédéric Prat
Journal: Endoscopy (2015)

We report here the case of a 37-year-old woman and her daughter (now 12 years old) with genetically proven hereditary cationic trypsinogen (PRSS1) deficiency pancreatitis. The two patients were treated in a similar manner: endoscopic extraction of large obstructive stones located mainly in the head of the pancreas upstream of a stricture of the distal (cephalic) pancreatic duct and associated with extreme dilation (10 – 15 mm) of the pancreatic duct, manifesting as bouts of mild acute pancreatitis and abdominal pain that could not relieved with analgesics ([Fig. 1 – 3]).
Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): update from a phase Ia study.
Authors: Leora Horn, David R. Spigel, Scott N. Gettinger, Scott Joseph Antonia, Michael S. Gordon, Roy S. Herbst, Lecia V. Sequist, Colombe Chappey, Marcin Kowanetz, Alan Sandler, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

8029 Background: NSCLC exhibits mutational complexity, which is associated with increased tumor immunogenicity. PD-L1 expression in the tumor microenvironment can inhibit antitumor immunity. MPDL3280A blocks PD-L1 and can restore tumor-specific T-cell immunity. Methods: In this dose-escalation and -expansion study, pts with NSCLC were enrolled from Oct 25, 2011 to Sep 24, 2013 and received MPDL3280A IV ≤ 20 mg/kg q3w (data cutoff Sep 2, 2014). ORRs were assessed by RECIST v1.1. PD-L1 expression on tumor-infiltrating immune cells (ICs) and tumor cells (TCs) was centrally evaluated by an IHC assay based on the SP142 antibody with pts scored as IC 0, 1, 2 or 3 and TC 0, 1, 2 or 3. Results: 88 NSCLC pts were safety- and efficacy-evaluable: 57% of pts were male, 28% were ECOG PS 0 and 72% were ECOG PS 1. The median age was 61 y (range, 24-84 y), and the majority of pts had 3 lines of therapy. Pts received MPDL3280A for a median duration of 15 wks (range, 0-129 wks). Treatment-related all grade AEs occurred in 73% of pts, most often fatigue (21%), nausea (15%) and decreased appetite (14%). 11% of pts had a related G3-4 AE, most often dyspnea, hypoxia, fatigue and hyponatremia (2% each). One related G5 AE due to cardio-respiratory arrest was seen. ORRs, DOR, PFS and OS were assessed by PD-L1 status (Table). Of note, pts with PD-L1 expression of TC3 or IC3 (n = 20) had an ORR of 45% (95% CI, 23-68%) vs 14% (95% CI, 6-25%) for pts with PD-L1 expression of TC 0/1/2 and IC 0/1/2 (n = 58). Conclusions: PD-L1 expression in the tumor microenvironment appeared to be a predictive biomarker for MPDL3280A clinical benefit with median OS not yet reached. Treatment with MPDL3280A was generally well tolerated. Phase III trials are ongoing. Clinical trial information: NCT01375842.Efficacy results. Pts TC0/1/2 and IC0/1/2 TC3 or IC3 Alla n 58 20 88 ORR (95% CI), % 14 (6-25)b 45 (23-68)c 21 (13-30) 24-wk PFS (95% CI), % 36 (24-49) 45 (23-67) 42 (32-53) Median DOR (range), wk 108 (38+-110) 64 (31-80+) 67 (31-110) 1 y OS (95% CI), %d 78 (65-91) 89 (75-100) 82 (72-91) a10 pts with unknown TC and IC status were included. b4 pts with missing or unevaluable response. c1 pt with missing or unevaluable response. d Median OS not yet reached for all groups.
PTU-158 Magniview zoom endoscopy for the detection of markers of coeliac disease: a feasibility study
Authors: PD Mooney, M Burden, DS Sanders
Journal: Gut (2015)

<h3>Introduction</h3> Coeliac disease (CD) remains underdiagnosed. Previous studies have shown that 5–13% of patients with CD have undergone a previous gastroscopy where the opportunity to take duodenal biopsies and make a diagnosis had been missed. Clinicians may rely on the presence of endoscopic markers of CD to guide biopsy however these have been shown to lack the required sensitivity. A routine duodenal biopsy approach may solve this problem but this is time consuming and expensive. Methods to improve the macroscopic detection of CD at endoscopy to guide biopsy would seem advantageous. Magniview endoscopes are capable of 136x optical zoom without loss of definition. At this level of magnification it should be possible to identify blunting and absence of villi. We aimed to assess the feasibility of magniview in patients with suspected CD. <h3>Method</h3> Patients with attending for a duodenal biopsy to diagnose CD were invited to take part. Appearances were graded on a 3 point scale: normal, partial villous atrophy or marked villous atrophy. All patients received 4 biopsies from the second part of the duodenum and at least 1 biopsy from the bulb. Concurrently serum for endomysial (EMA) and tissue transglutaminase (tTG) antibodies were taken at the time of endoscopy. Macroscopic markers of CD are compared VA on histology as the gold standard. Sensitivity of endoscopic markers was compared to a control group CD who had standard endoscopy using the Fisher exact test. <h3>Results</h3> 27 patients (52% female, mean age 49.6) have been recruited to date. 14 (51.9%) patients tested had positive serology. In total 13 (48%) patients were diagnosed with CD. All 13 patients diagnosed with CD were correctly identified on Magniview. 4 patients had a false positive Magniview assessment. Of these 3 (75%) were felt to have partial villous atrophy. A single further patient with a positive EMA and tTG was felt to have marked villous atrophy in the bulb but normal D2 however biopsies were normal from both D1 and D2. In summary Magniview to detect VA demonstrated sensitivity, specificity, PPV and NPV of 100% (72–100), 71% (42–90), 76% (50–92) and 100% (66–100) respectively. The sensitivity of Magniview for detecting VA was superior to a standard endoscopy cohort of 89 patients with CD (100% vs. 41.6%, p &lt; 0.0001). <h3>Conclusion</h3> The addition of Magniview to standard endoscopy to aid the diagnosis of CD is feasible and currently has 100% sensitivity and negative predictive value. However a larger study in a lower prevalence population is required to fully elucidate the utility of Magniview in clinical practice. <h3>Disclosure of interest</h3> None Declared.
SAT0571 Persistence with Anti-Tumor Necrosis Factor Therapies in Patients with Psoriatic Arthritis in Routine Practice
Authors: J. Morel, B. Combe, C. Daien, C. Lukas
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Until now, anti-TNF therapies represent major improvement in the treatment of severe psoriatic arthritis. However, in France, little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice. <h3>Objectives</h3> The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a cohort of psoriatic arthritis patients and to identify factors associated with drug discontinuation. <h3>Methods</h3> Patients with psoriatic arthritis (PsA) were identified in the database of the Teaching hospital of Montpellier using IC code. A total of 124 patients treated with anti-TNF drug were selected (first anti-TNF agent: etanercept, n=40; infliximab, n=47; and adalimumab, n=37). Persistence with treatment was examined using Kaplan-Meier survival analysis. Log-rank (Mantel Cox) analyses were used to examine potential predictors of withdrawals. <h3>Results</h3> At baseline, the mean (standard deviation) age of patients was 47.4±12.3 years, 38% were female. Anti-TNF was combined with sDMARD in 38 patients. Median drug survival was 60 months (36.6-84.5) and 1-year and 2-year drug survival rates were 78.4% and 65% respectively. Infliximab had a significantly longer median drug retention with 99±9.7months vs 54.5±6.9 for etanercept and 23.8±6.2 for adalimumab (p&lt;0.05) (figure). Gender, age, concomitant sDMARD were not associated with longer drug survival. The mean duration of (standard deviation) follow-up was 2.5 years ±3.8. During the period of follow-up, 65 patients received a second anti-TNF therapy (etanercept, n=22; infliximab, n=15; and adalimumab, n=22). Median drug survival was 35.5±7 months. Drug retention was not different across the three anti-TNF drugs. Again, age, gender and combination with a sDMARD were not predictive of maintenance. <h3>Conclusions</h3> Psoriatic arthritis patients show high persistence rates with anti-TNF therapies. Surprisingly, infliximab had the best maintenance in this cohort. The 5mg/kg dose per injection and intraveinous administration may explain this longer drug retention. <h3>Disclosure of Interest</h3> J. Morel Grant/research support from: PFIZER, Consultant for: PFIZER, ABBVIE, MSD, B. Combe Grant/research support from: PFIZER, Consultant for: PFIZER, MSD, ABBVIE, C. Daien Grant/research support from: PFIZER, Consultant for: PFIZER, ABBVIE, MSD, C. Lukas Grant/research support from: PFIZER, Consultant for: PFIZER, ABBVIE, MSD
Soundings: Student selected caesareans
Authors: James Owen Drife
Journal: BMJ (2004)

2004 is my 40th year in medical education, as student or teacher. Back in 1964 our class was special—the first to experience the New Curriculum. The idea had been to reduce factual learning and make the course more integrated.

I now know that reducing factual learning is a tradition stretching back to the 19th century. Each generation of educators discovers that designing a fully integrated and really challenging course is fun. It certainly beats teaching.

Our last new curriculum in Leeds had special study modules (SSMs). Our current one has student selected components (SSCs). When I asked about these damn fool initials, I was told they came from the General Medical Council (GMC). Ah yes. Back in Hallam Street it had seemed a good idea to let students choose subjects for in-depth study.

When the Leeds ethics theme team asked for topics for a third year SSC, I suggested: “Should women be allowed to choose caesarean section?” Later the emails started arriving, asking: “When can we meet?” That's when the magic started. After decades of force-feeding students the basics I had five lively undergraduates talking to me by choice.

Never having done obstetrics, they soaked up background information about indications and risks. I tried (but not too hard) to disguise my own opinion that a well-informed woman can choose how to have her baby. Then off they went to surf the literature.

Most of the stuff on the internet is written by people who believe that pushing a baby through your pelvic floor is a harmless and fulfilling experience. The students, rather pro-choice to begin with, were persuaded that caesarean section is risky, bad for bonding, and too expensive for the NHS. People who like it don't say so on the web.

The climax of the SSC was dramatised presentations. Emily wore a pregnancy belly with an umbilical ring. Hinaa was the NHS obstetrician and Imran the hospital manager. David played the suave Brazilian husband and Aysha provided the commentary.

They wrote the script but let me direct. “Now, luvvies, let's do the moves. Autonomy here... Beneficence here... Marvellous, darlings!” I got a text message when they were about to start. They were terrific. I went home a happy medical academic. Now that is new.
Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit
Authors: T Kasugai, M Okada, M Morimoto, N Arizono, K Maeyama, M Yamada, H Tei, K Dohmae, H Onoue, GF Newlands
Journal: Blood (1993)
Relative Amount of Ammonia Evolved from Digests of Isomeric Peptides with Aqueous Tissue Extracts
Authors: Jose M. Gonçalves, Vincent E. Price, Jesse P. Greenstein
Journal: JNCI Journal of the National Cancer Institute (1947)

Journal Article Relative Amount of Ammonia Evolved from Digests of Isomeric Peptides with Aqueous Tissue Extracts Get access Jose M. Gonçalves, Jose M. Gonçalves research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar Vincent E. Price, Vincent E. Price assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse P. Greenstein Jesse P. Greenstein chief biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 8, Issue 1, August 1947, Pages 31–34, https://doi.org/10.1093/jnci/8.1.31 Published: 01 August 1947 Article history Received: 02 June 1947 Published: 01 August 1947
The dexamethasone suppression test in adolescent psychiatric inpatients
Authors: S D Targum, A E Capodanno
Journal: American Journal of Psychiatry (1983)

The dexamethasone suppression test (DST) was administered to 120 adolescent psychiatric patients at the time of hospitalization, and cortisol levels were measured at 4:00 p.m. and 11:30 p.m. on the day after a 1-mg oral dose of dexamethasone was given. Failure to suppress serum cortisol (i.e., cortisol level less than 5 micrograms/dl) was noted in 25 patients: 7 of 17 patients who met DSM-III criteria for major depressive disorder, 7 of 38 patients with dysthymic disorder, 7 of 47 patients with conduct disorder, and 4 of 15 schizophreniform patients. The predictive value of the DST for major depressive disorder was only 28%. Although adolescent patients with abnormal DSTs may eventually develop affective symptoms consistent with a major depressive disorder, the DST did not discriminate between major depression and other psychiatric diagnoses in these hospitalized adolescents.
PTU-261 Surgery for benign colorectal polyps: the impact of an advanced colonic endoscopic mucosal resection (EMR) service in a large tertiary centre
Authors: R Sringeri, N Gautam, A Bohan, S Sen, AD Farmer, S Hebbar
Journal: Gut (2015)

<h3>Introduction</h3> Advances in endoscopy training and endoscopic resection techniques have facilitated the development of advanced EMR service in few regional centres. This should equate to a reduction in the number of surgery for benign colorectal polyps. Interestingly, a previous study of hospital episode statistics database for national trends in benign colorectal polyp surgery had showed no significant difference in the reduction of surgery over a 10 year period.<sup>1</sup>We aimed to assess the impact of a new advanced EMR service on the need for surgical intervention for benign polyps in a tertiary care centre. <h3>Method</h3> The advanced EMR service (including level 3 and 4 polyps)<sup>2</sup>was set up in May 2013. We retrospectively looked at the MDT outcomes 20 months prior and after setting up of the service to identify patients requiring external referral or surgery for benign polyps. Hospital electronic records were reviewed to ascertain details concerning polyp size, complications and bed days. <h3>Results</h3> In the period before the EMR service, 51 patients underwent surgery for benign polyps requiring 285 bed days. 8 complications were encountered. The average polyp size was 3.2 cms (Range 1–8 cms). 6 patients were referred externally for advanced EMR. Between May 2013 and Dec 2014, since the setting up of the service, 8 patients have had surgery requiring 46 bed days. During the same time, 180 polyps were encountered in 168 patients. The mean polyp size varied from 1.5 cms to 12 cms. Excluding patients who had surgery for invasive cancer, 91% of patients avoided surgery. Of 139 completely resected benign polyps, 66 (47%) polyps were level 4 and 89% polyps achieved complete endoscopic clearance with one procedure. 4 complications required 9 bed days. <h3>Conclusion</h3> An advanced EMR service decreases the need for surgical intervention, reduces the number of bed days and complications. Moreover, such a service also offers important savings for local healthcare economies. This study also emphasise the need for the development of regional benign polyp MDT. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Almoudaris AM, <i>et al</i>. Surgery for benign colorectal polyps in England – trends and outcomes from 1997 to 2007. Gut 2011;<b>60</b>:A4 Gupta S, <i>et al</i>. The “SMSA” scoring system for determining the complexity of a polyp. Gut 2011;<b>60</b>:A129
Centralised paediatric intensive care beds are blocked
Authors: I. James
Journal: BMJ (1996)

7.6 cases in the month after immunisation in the United Kingdom, based on the typical reported annual incidence of 1/100 000 ).1We questioned 103 patients with Guillain- Barre or Miller Fisher syndrome, 98 household controls, and 93 hospital controls in south east England in 1992-4 (before the measles/rubella immunisation programme).2Thirteen patients, and nine household and five hospital controls reported being immunised within 12 weeks before onset of neuropathy in the index case.The immunisations were for influenza in 10 patients and eight household and three hospital controls, typhoid/cholera in one patient and one household control, typhoid alone in one patient, tetanus toxoid booster in one patient, diphtheria/ tetanus/pertussis in one hospital control, and