tbuckley/cabot-search huggingface dataset:
FRI0185 Impact of Tocilizumab on Neutrophil Survival and Function
Authors: T. Gaber, M. Hahne, C. Strehl, P. Hoff, Y. Dörffel, E. Feist, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL) 6 receptor pathway by tocilizumab is a potent treatment for RA, it may also cause unwanted effects such as an occasionally high grade neutropenia. <h3>Objectives</h3> Here, we analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of neutrophils under normoxic versus hypoxic conditions. <h3>Methods</h3> Human neutrophils were purified, pre-treated with varying doses of tocilizumab and, for comparison, dexamethasone or vehicle/human IgG and stimulated with lipopolysaccharide (LPS) alone, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18%O<sub>2</sub>) or hypoxic (1%O<sub>2</sub>) conditions and subsequently analysed. <h3>Results</h3> Both neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in LPS-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. <h3>Conclusions</h3> Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of a hypoxia-induced oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and alteration of mediator secretion. <h3>Acknowledgements</h3> This study has been supported by an unrestricted educational grant by Roche/Chugai now Chugai Pharma. We thank Manuela Jakstadt for technical assistance. This work was supported by the Berlin-Brandenburg Center of Regenerative Therapies (BCRT) to TG and by the Berlin-Brandenburg School of Regenerative Therapies (BSRT) to MH. <h3>Disclosure of Interest</h3> T. Gaber: None declared, M. Hahne: None declared, C. Strehl: None declared, P. Hoff: None declared, Y. Dörffel: None declared, E. Feist Grant/research support from: Roche/Chugai, Consultant for: Roche/Chugai, Paid instructor for: Roche/Chugai, G.-R. Burmester Consultant for: Roche, Paid instructor for: Roche, F. Buttgereit: None declared
Educating the Primary Care Clinician on Preexposure Prophylaxis for Human Immunodeficiency Virus
Authors: Paul Matthew Lu, Lee S. Shearer, E. Jennifer Edelman
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PTH-353 Surgeon specific outcome data in colorectal cancer surgery - the patient perspective
Authors: WAH Maclean, S Park, JS Knight
Journal: Gut (2015)

<h3>Introduction</h3> NHS England requires trusts to report individual outcomes in ten clinical specialties. In September 2013, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) published individual surgeon and hospital outcomes detailing 90-day mortality rates after elective resection for bowel cancer. This data is available to view online. Our aims were to investigate patients’ awareness and perspective of surgeon specific outcome data and to find out what was important to them about their upcoming operation. <h3>Method</h3> Over a 6 month period, all consecutive patients attending preoperative assessment prior to resection for colorectal cancer at a teaching hospital were asked to complete the survey. <h3>Results</h3> Of the 67 patients asked to complete the survey 66 (98.5%) responded. 13 of 66 (20%) patients stated they were aware of the surgeon specific outcome data and of those, 6 said they would know how to find it. 52 (79%) patients said the surgeon was more important than the hospital, 9 stated the hospital and 5 were undecided. When asked about other factors, 41 (67%) stated the reputation of the surgeon was the most important. Only 2 patients chose surgeon specific mortality rate, 18 said the number of times the operation had been performed by the surgeon in the preceding year and 5 did not answer the question. <h3>Conclusion</h3> Most patients undergoing surgery for bowel cancer are unaware of the published outcome data for their surgeon. Of those that are aware less than half would know how to find it. However the overwhelming most important factor for the patient is the perceived reputation of the surgeon. <h3>Disclosure of interest</h3> None Declared.
SAT0345 Lifestyle, Clinical and Psychosocial Predictors of Good Response to Methotrexate Therapy in the Rheumatoid Arthritis Medication Study (RAMS)
Authors: J.C. Sergeant, H.F. Hope, J. Anderson, A. Barton, K.L. Hyrich, S.M.M. Verstappen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Methotrexate (MTX) is the disease modifying drug of first choice for most patients with rheumatoid arthritis (RA). However, response to MTX varies and attempts to identify predictors of response have proved inconsistent. <h3>Objectives</h3> To evaluate potential lifestyle, clinical and novel psychosocial predictors of response to MTX in the Rheumatoid Arthritis Medication Study (RAMS), a cohort of RA patients commencing MTX therapy for the first time. <h3>Methods</h3> RAMS is a multi-centre observational study recruiting RA patients from across the UK who are ≥18 years old and starting MTX for the first time. Predictors of response to MTX are acquired via questionnaires and from case notes at baseline 3, 6 and 12 months after MTX commencement. Response to treatment was defined at 6 months using the EULAR definition of good response: disease activity score-28 (DAS28) ≤3.2 and reduction in DAS28 from baseline &gt;1.2. Associations between good response at six months and baseline measures of body mass index (BMI), smoking status (current/former/never), alcohol intake, symptom duration, DAS28, functional disability (Health Assessment Questionnaire, HAQ), C-reactive protein (CRP), creatinine, rheumatoid factor (RF), socioeconomic status (Index of Multiple Deprivation, IMD), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), beliefs about medicines (Beliefs about Medicines Questionnaire, BMQ) and illness representation (Brief Illness Perceptions Questionnaire (BIPQ)) were assessed using chi-square or Mann-Whitney tests and adjusted for age and sex using multiple logistic regression. <h3>Results</h3> Complete data on baseline predictors and response at six months was available on 460 participants: 338 female (73%), median age 60 (IQR 48-68) years, median symptom duration 9 (IQR 5-30) months. 130 participants (28%) were good responders. Baseline measures for good responders and non-good responders, together with group comparisons and adjusted odds ratios are shown in Table 1. Good response was negatively associated with BMI, current smoking and anxiety and depression, and positively associated with baseline DAS28, elevated CRP, RF positivity and positive illness representation. <h3>Conclusions</h3> Lifestyle, clincial, and novel psychosocial factors were found to be predictors of response to MTX at six months. Notably those with higher values of baseline disease activity and serological and inflammatory markers were more likely to be good responders, perhaps reflecting a greater potential to improve. Prediction models of individual MTX response in RA may need to consider the potential role of such factors in personalising treatment decisions. <h3>Disclosure of Interest</h3> None declared
FRI0007 The Importance of Somatic Hypermutation for the Immunoreactivity Towards Neutrophil Extracellular Traps (NETS)-Citrullinated Autoantigens of Ra Synovial Monoclonal Antibodies
Authors: E. Corsiero, E. Carlotti, C. Pitzalis, M. Bombardieri
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> We previously showed that anti-citrullinated peptide/protein antibodies (ACPA) targeting citrullinated antigens contained in neutrophils extracellular traps (NETs) can be manufactured within ectopic germinal center-like structure (GC-LS) in the rheumatoid arthritis (RA) synovium. <h3>Objectives</h3> To characterise a) whether the RA synovial anti-NETs antibodies had undergone antigen-driven affinity maturation and b) the importance of somatic hypermutations (SHM) within the V<sub>H</sub> and V<sub>L</sub> chain for their binding. <h3>Methods</h3> 66 full recombinant monoclonal antibodies (RA-syn-rmAbs) were generated from single CD19+ B cells FACS-sorted from fresh GC-LS+ synovial cell suspensions following IgV<sub>H</sub>+V<sub>L</sub> genes cloning. RA-syn-rmAbs for reversion experiments (n=9) were chosen according to their level of reactivity towards NETs. Reversion of the IgV genes into germ-line (GL) and generation of hybrid clones (where V<sub>H</sub>, V<sub>L</sub> or selected CDRs/FRs were reverted into GL, n=5) was performed by overlap-PCR. Further characterization of the mature vs GL RA-syn-rmAbs sequence was performed by structural alignment via an <i>in silico</i> prediction model using the root-mean-square-deviation (RMSD) score to measure the similarity between the mature and GL structures (1). Anti-NETs immunoreactivity was detected using cell-based immunoassays with activated peripheral blood or RA synovial fluid neutrophils. <h3>Results</h3> Structural alignment showed some differences in the 3D structure between mature vs GL sequences in 3 RA-syn-rmAbs suggesting that SHM is critical for antigen binding. Accordingly, the anti-NETs immunoreactivity of the RA-syn-rmAbs was dependent on affinity maturation within GC-LS and was completely abrogated when the full IgV<sub>H</sub>+V<sub>L</sub> genes were reverted to GL. Conversely, when only the IgV<sub>L</sub> gene was reverted to GL, 2 out of 5 RA-syn-rmAbs displayed a residual reactivity toward NETs suggesting that in some clones the V<sub>H</sub> chain plays a dominant role in conferring the reactivity towards NETs. <h3>Conclusions</h3> Importantly, our data showed that SHM is necessary for the development of high-affinity NETs-binding antibodies in synovial GC-LS. The importance of defining the contribution of individual CDRs and FRs to the affinity of antigen-binding sites may help to engineer new therapeutic Abs and design of CDRs/FRs-specific peptides for tolerogenic strategy. <h3>References</h3> Lyskov S, et al. Serverification of molecular modeling applications: the Rosetta Online Server that Includes Everyone (ROSIE). PloS one. 2013;8(5):e63906. <h3>Disclosure of Interest</h3> None declared
Changes in brain ventricular size with repeated CAT scans in suspected Alzheimer's disease
Authors: S D Brinkman, J W Largen
Journal: American Journal of Psychiatry (1984)

The interpretation of brain ventricular size in CAT scans of patients with dementia is made difficult by the marked variability in ventricular size that occurs with normal aging. Five patients with probable Alzheimer's disease had serial CAT scans. Published normative data were interpolated to estimate the normal rate of change in ventricular size. Over a period of 15 to 35 months, four of the five patients had increases in ventricular size that were remarkably greater than the norms. The data suggest that the rate of change in ventricular size may be of considerable interest in longitudinal analyses and as a neurodiagnostic parameter.
Women at a Disadvantage in Fluorouracil Treatment—Reply
Authors: Valérie Boige, Marc Vincent, Pierre Laurent-Puig
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Race/Ethnicity and Economic Differences in Cost-Related Medication Underuse Among Insured Adults With Diabetes
Authors: Chien-Wen Tseng, Edward F. Tierney, Robert B. Gerzoff, R. Adams Dudley, Beth Waitzfelder, Ronald T. Ackermann, Andrew J. Karter, John Piette, Jesse C. Crosson, Quyen Ngo-Metzger, Richard Chung, Carol M. Mangione
Journal: Diabetes Care (2008)

To examine racial/ethnic and economic variation in cost-related medication underuse among insured adults with diabetes.We surveyed 5,086 participants from the multicenter Translating Research Into Action for Diabetes Study. Respondents reported whether they used less medication because of cost in the past 12 months. We examined unadjusted and adjusted rates of cost-related medication underuse, using hierarchical regression, to determine whether race/ethnicity differences still existed after accounting for economic, health, and other demographic variables.Participants were 48% white, 14% African American, 14% Latino, 15% Asian/Pacific Islander, and 8% other. Overall, 14% reported cost-related medication underuse. Unadjusted rates were highest for Latinos (23%) and African Americans (17%) compared with whites (13%), Asian/Pacific Islanders (11%), and others (15%). In multivariate analyses, race/ethnicity significantly predicted cost-related medication underuse (P = 0.048). However, adjusted rates were only slightly higher for Latinos (14%) than whites (10%) (P = 0.026) and were not significantly different for African Americans (11%), Asian/Pacific Islanders (7%), and others (11%). Income and out-of-pocket drug costs showed the greatest differences in adjusted rates of cost-related medication underuse (15 vs. 5% for participants with income <or=$25,000 vs. >$50,000 and 24 vs. 7% for participants with out-of-pocket costs >$150 per month vs. <or=$50 per month.One in seven participants reported cost-related medication underuse. Rates were highest among African Americans and Latinos but were related to lower incomes and higher out-of-pocket drug costs in these groups. Interventions to decrease racial/ethnic disparities in cost-related medication underuse should focus on decreasing financial barriers to medications.
Dose-Response Relations in Experimental Transmission of Avian Erythromyeloblastic Leukosis. III. Titration of the Virus&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Eckert, Edward A., Beard, Dorothy, Beard, J. W.
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Dose-Response Relations in Experimental Transmission of Avian Erythromyeloblastic Leukosis. III. Titration of the Virus Get access Edward A. Eckert, Edward A. Eckert Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy Beard, Dorothy Beard Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Beard J. W. Beard Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 5, April 1954, Pages 1055–1066, https://doi.org/10.1093/jnci/14.5.1055 Published: 01 April 1954 Article history Published: 01 April 1954 Received: 27 November 1963
Sigmoidoscopically Induced Pneumatosis Cystoides Coli in Crohn's Disease Manifested by Collar Subcutaneous Emphysema
Authors: G Gösi, F Huoránszki
Journal: Endoscopy (2001)

A 32-year-old female patient had been treated for colonic inflammatory bowel disease with suspicion of ulcerative colitis for 9 years. As a result of marked weight loss, abdominal pain, and newly developed perineal fistulas, colonoscopy was attempted, but not completed because of an ulcerated, narrowed rectum with significant stenosis at 20 cm. About 3 hours after the uneventful proctosigmoidoscopy, the following clinical signs appeared: collar subcutaneous emphysema, abdominal distension, and pain. Radiographic findings revealed pneumoperitoneum, pneumoretroperitoneum, and pneumomediastinum. An emergency exploration revealed a rigid left colon, strictured ileum characteristic of Crohn's disease, diffuse peritonitis, pneumoretroperitoneum, pneumatosis cystoides of the right colon, and a small area of biliary retroperitoneal imbibition of the hepatic flexure. A total colectomy with Brooke ileostomy and rectal mucuous fistula were made. The macroscopic examination of the specimen revealed a solitary acute ulcer on the otherwise unaffected hepatic flexure (Figure [1]). The histological results confirmed Crohn9s disease. An elective proctectomy (Figure [2]) and extirpation of the fistulas were performed 5 months later. Currently the patient is complaint-free.
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
Authors: Silvia Affo, Le-Xing Yu, Robert F. Schwabe
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver. Cholangiocarcinoma (CCA), in contrast, is characterized by a strong desmoplasia that typically occurs in response to the tumor, suggesting a key role of cancer-associated fibroblasts (CAFs) and fibrosis in its tumor microenvironment (TME). Here, we discuss the functional contributions of myofibroblasts, CAFs, and fibrosis to the development of HCC and CCA in the hepatic PME and TME, focusing on myofibroblast- and extracellular matrix-associated growth factors, fibrosis-associated immunosuppressive pathways, as well as mechanosensitive signaling cascades that are activated by increased tissue stiffness. Better understanding of the role of myofibroblasts in HCC and CCA development and progression may provide the basis to target these cells for tumor prevention or therapy.
Changing epidemiology of tardive dyskinesia: an overview
Authors: D V Jeste, R J Wyatt
Journal: American Journal of Psychiatry (1981)

Dyskinesia is found significantly more often among neuroleptic-treated psychiatric patients than among non-neuroleptic-treated patients. The epidemiology of tardive dyskinesia is changing; its reported prevalence among neuroleptic-treated psychiatric inpatients has been progressively rising and has reached 25% during the past five years. The prevalence of persistent tardive dyskinesia that may be attributable to neuroleptics is about 13%. Tardive dyskinesia is not restricted to old, brain-damaged inpatients but also occurs with a noticeable frequency among younger patients, including outpatients, treated neuroleptics. Yet neuroleptics are the most effective available treatment for schizophrenia; hence, any drastic curtailment of their use in the treatment of chronic schizophrenic patients may not be justified. Cautious use of these drugs, along with intensified research on tardive dyskinesia is warranted.