tbuckley/cabot-search huggingface dataset:
AB0122 Regulatory t cell abnormalities and il-2 deficiency in patients with systemic lupus erythematosus
Authors: C. von Spee-Mayer, N. Wassermann, A. Rose, T. Alexander, J. Klocke, J. Y. Humrich, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Quantitative and qualitative aberrations of CD4+ Foxp3+ regulatory T cells (Treg) have been associated with systemic lupus erythematosus (SLE). In addition, impaired production of IL-2 by T cells has been described in patients with SLE. <h3>Objectives</h3> Here, we aim to substantiate the link between IL-2 deficiency and Treg abnormalities in SLE. <h3>Methods</h3> Phenotype, frequency and homeostatic proliferation of CD4+Foxp3+CD127lo Treg and CD4+Foxp3- conventional T cell (Tcon) subsets were analyzed by multi-color flow-cytometry in PBMCs from SLE patients and healthy donors <i>ex vivo</i> and after <i>in vitro</i> stimulation with varying doses of human IL-2 (Proleukin). IL-2 mRNA expression of CD4+ T cells <i>in vitro</i> was determined by real-time PCR. Disease activity was determined according to the SLE activity index (SLEDAI). <h3>Results</h3> The expression of CD25 in Foxp3+CD127lo Treg was significantly reduced in SLE patients compared to healthy donors. Proliferation of Tcon was significantly increased in SLE patients, resulting in a reduced Treg to Tcon proliferation ratio, which inversely correlated with disease activity. In contrast, the Treg to Tcon proliferation ratio positively correlated with the frequency of CD25+ Treg and with the <i>in vitro</i> IL-2 mRNA expression of CD4+ T cells. Spontaneous <i>in vitro</i> IL-2 mRNA expression of CD4+ T cells was significantly reduced in SLE patients compared to healthy controls. IL-2 stimulation of SLE PBMCs <i>in vitro</i> significantly augmented CD25 expression levels in Treg. The frequency of CD25high cells among Treg was most efficiently increased when the lowest dose of 1ng/ml IL-2 was applied. In parallel, IL-2 stimulation significantly amplified the expression of anti-apoptotic Bcl-2 in SLE Treg. <h3>Conclusions</h3> In analogy to our previous findings in lupus-prone mice (1), Treg from SLE patients show the classical hallmarks of IL-2 deficiency with loss of CD25 expression and a homeostatic imbalance between Treg and Tcon. These findings could be associated with a reduced IL-2 expression by CD4+ T cells in SLE patients. On the other hand, lowdose IL-2 stimulation <i>in vitro</i> could restore these defects, underlying the potential of IL-2 as a novel therapeutic option in SLE. <h3>References</h3> Humrich, JY et al, PNAS, 2010 <h3>Disclosure of Interest</h3> None Declared
PTU-253 Life without a bleeding rota: risk of late endoscopy?
Authors: R Dart, D Dewar
Journal: Gut (2012)

<h3>Introduction</h3> In the 2007 UK audit of acute upper gastrointestinal bleeding (AUGIB),<sup>1</sup> 44% of participant centres did not have facility for a dedicated bleeding rota. Gross measures of outcome, such as mortality, were found to be independent of the presence of a bleeding rota; however adherence to other aspects of guidance, such as time to endoscopy, in the absence of a bleeding rota, was not examined. We aimed to examine the performance in the absence of a dedicated bleeding rota, but with a “goodwill” out of hours service, against national guidelines and performance. <h3>Methods</h3> Data were collected prospectively for all cases of AUGIB over a 2-month period from September 2010 to November 2010. Cases were identified from request forms in the endoscopy department. Data were collected for all endoscopies; repeat endoscopy on the same admission was recorded separately. Rockall score, if not included with the original endoscopy request was calculated retrospectively. Results were analysed in Excel. Statistics performed using Fischer9s exact test. <h3>Results</h3> There were 35 patients identified, referred for 40 procedures for AUGIB, 39 of which were carried out. Median age at presentation was 64 (35–92), 14 years younger than the national audit. The proportion of patients presenting with documented cirrhosis 23% (n=8) was significantly greater than in the national audit p=0.0026. Furthermore the proportion of patients with varices, although not necessarily responsible for the bleed, was greater 17% vs 8% p=NS. Rockall score was documented in 23% cases compared with 19% in the national audit. Rockall score was ≥3 in 73% compared with 51% in the national audit p=0.01. Time to endoscopy, regardless of Rockall score was &lt;24 h in 72% and in patients with Rockall score ≥3 was 79% compared with 50% in both groups in the national audit. In the cases in our study for whom the Rockall score was documented, all had a Rockall score ≥3 and proceeded to endoscopy within 24 h. Mortality in both our study and the national audit was 10%. <h3>Conclusion</h3> Our patient group was younger than the national average with a higher proportion with pre-endoscopy Rockall score ≥3. We demonstrate ongoing difficulties in encouraging documentation of risk assessment scores, however in our experience when the Rockall score was documented the endoscopy happened in a timely fashion. We demonstrate with data from our centre that early endoscopy is achievable in the majority of cases in the absence of a dedicated bleeding rota. This does not appear to affect overall mortality however risk assessment and early endoscopy are important as we strive to improve the service we offer our patients. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <i>UK Comparative Audit of Upper Gastrointestinal Bleeding and the Use of Blood</i>. London: British Society of Gastroenterology, 2007. http://www.bsg.org.uk/pdf_word_docs/blood_audit_report_07.pdf
OP0272 Prevalence of Structural Lesions MRI-Spine in Patients with (Possible) Axial Spondyloarthritis (AXSPA) Included in the Space-Cohort
Authors: M. De Hooge, R. Van Den Berg, V. Navarro Compán, M. Reijnierse, F. van Gaalen, K. M. Fagerli, M. Turina, M. van Oosterhout, M. Lorenzin, T. Huizinga, D. Van Der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Little is known about the prevalence of structural lesions (erosions (ERO), (bridging) syndesmophytes, fatty lesions (FL)) on MRI of the spine (MRI-spine) in patients (pts) with chronic back pain. <h3>Objectives</h3> To investigate the prevalence of structural lesions on MRI-spine in pts with chronic back pain. <h3>Methods</h3> Pts with back pain (≥3 months, ≤2 years, onset &lt;45 years) recruited from 5 participating centres were included in the SPondyloArthritis Caught Early (SPACE)-cohort. Pts underwent MRI-spine scored independently by 3 blinded, well-calibrated readers for presence of ERO, FL and (bridging) syndesmophytes on T1-weighted images (STIR images viewed simultaneously). FL suggestive of spondylitis were scored when visible on ≥2 consecutive slices. For ERO or (bridging) syndesmophytes, suggestive of spondylitis, presence on ≥1 slice was sufficient. Agreement of 2/3 readers was used. Prevalence of structural lesions based on several cut-offs were calculated. <h3>Results</h3> All pts with complete MRI-spine data were included for analysis (n=306). Pts were grouped according to the ASAS axSpA criteria (radiographic, non-radiographic (imaging &amp; clinical arm), no-axSpA and possible SpA (not fulfilling ASAS axSpA)). Prevalence of FL was the highest of all structural lesions in the spine in all subgroups. With a cut-off of ≥3 FL, the 'false-positive' rate in the no-axSpA group was low (6.5%) with still a considerable prevalence in the imaging and radiographic axSpA groups. Prevalence of ERO and (bridging) syndesmophytes was generally low (table;*'weak' SpA features (low LR) are: IBD, heel pain, dactylitis, IBP, good response to NSAIDs, peripheral arthritis, psoriasis, elevated ESR/CRP). <h3>Conclusions</h3> FL (≥3) on MRI-spine are primarily present in pts with MRI-SI positive non-radiographic and radiographic axSpA, not in no-axSpA and possible axSpA pts. ERO and (bridging) syndesmophytes in the spine are equally present in all groups. FL are the only type of structural lesions that can potentially discriminate between pts with and without axSpA. <h3>Disclosure of Interest</h3> None Declared
Urinary Tract Disorders in Patients with Chronic Granulomatous Disease
Authors: Hossein Aliabadi, Ricardo Gonzalez, Paul G. Quie
Journal: New England Journal of Medicine (1989)

Twelve of the 25 patients with chronic granulomatous disease treated at our institution between 1957 and 1987 were found to have urinary tract disorders. All 12 patients were male and 22 years of age or younger when chronic granulomatous disease was diagnosed. Six patients had hydroureteronephrosis in association with recurrent episodes of pyelonephritis, retroperitoneal lymphadenitis, and granuloma formation. The other six patients had genital lesions or dysuria. Among the six patients with hydroureteronephrosis, a nephrectomy was performed in two, ureterolysis was used to relieve obstruction in one, and hydroureteronephrosis resolved after antibiotic therapy alone in three. We conclude that complications involving the genitourinary system occur frequently in patients with chronic granulomatous disease. Periodic imaging of the urinary tract may detect asymptomatic hydroureteronephrosis or other treatable genitourinary abnormalities in these patients. (N Engl J Med 1989; 321:706–8.)
Abstract 879: A functional promoter polymorphism (−1362G&amp;gt;T) of IL-6 gene is associated with the risk of squamous cell carcinoma of head and neck
Authors: Yu-Jing Huang, Jiangong Niu, Li-E Wang, Zhensheng Liu, Erich M. Sturgis, Qingyi Wei
Journal: Cancer Research (2011)

Abstract Interleukin-6, an immunoregulatory cytokine, plays a crucial role in the pathogenesis of a wide variety of human cancers, and the IL-6 levels have been shown to be associated with tumor progression in human squamous cell carcinoma of the head and neck (SCCHN). Because the presence of polymorphisms in the non-coding gene regulatory region may affect transcriptional regulation of IL-6, we hypothesized that such genetic variants of IL-6 might contribute to susceptibility to SCCHN. To assess the association between IL-6 polymorphisms and SCCHN risk, two independent IL-6 promoter SNPs, -1362 G&amp;gt;T (rs2069827) and -597 G&amp;gt;A (rs1800797), the latter being in nearly complete linkage disequilibrium with -173 C&amp;gt;G (rs1800795), were genotyped in 1,092 non-Hispanic White SCCHN patients and 1,126 age-and sex-matched cancer-free controls. After adjustment for age, sex, and smoking and drinking status, a significantly higher risk was observed for the -1362GT+TT genotypes (adjusted OR = 1.28, 95% CI = 1.01-1.62), compared with those carrying the -1362GG homozygotes, but not for the -597G&amp;gt;A SNP. Additional functional experiment demonstrated that the IL-6 SNP -1362 G-to-T allelic change was associated with an increased promoter activity in human head and neck cell lines, supporting the hypothesis that genetic polymorphism influencing IL-6 transcription may play a role in human SCCHN carcinogenesis. We conclude that the IL-6 promoter -1362 G&amp;gt;T (rs2069827) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites. Larger studies are needed to validate our findings. (Supported by NIH grants R01CA131274, R01ES011740 and P30 CA016672) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 879. doi:10.1158/1538-7445.AM2011-879
Abstract B29: Female reproductive cancers incidence in Bihar, India with the risk of xenoestrogenic arsenic in serum and in drinking water sources
Authors: Akhileshwari Nath, Jitendra Kumar Singh, S. Ezhil Vendan, Priyanka K
Journal: Cancer Research (2011)

Abstract Reproductive cancers are the most prevalent cancers among the women worldwide. Breast, ovary, uterine and cervix cancers are leading cancers in India. Hormonal carcinogens also known as endocrine disturbing chemicals (EDCs) are predominant factors causing reproductive cancer risks in women. Heavy metal Arsenic (As) is naturally found in Northern India. It is popularly known as EDC especially mimicking as estrogen (i.e., xenoestrogen). The present study aimed to assess the hormonal carcinogenic risk of As among women in Bihar, India. Cancer incidences in Bihar were recorded from the patient's clinical registry in Mahavir Cancer Sansthan hospital. Serum was collected from the different cancer patients and the level of As in serum was estimated by Atomic Absorption Spectroscopy. Drinking water samples were collected from different regions of Bihar and As was estimated by As kit. During the last ten years cervix and breast cancer incidence were very high followed by ovary, uterine and other cancers. Among the 38 districts of Bihar, those cancers incidence were highly marked in the Bhagalpur, Bhojpur, Chapra, East Champran, Gaya, Gopalanj, Jahanabad, Lakhisarai, Madobani, Muzaffarpur, Nalanda, Patna, Samastipur, Saran, Siwan and Vaishali districts. Maximum incidences were highly recorded in the age group of 36 to 45 years. More than 10 ppb level of As in serum was recorded in all the tested breast, ovary, uterine and cervix cancer cases. Highest concentration of As was recorded in cervix (17.6 ppb) followed by breast, uterine and ovary cases (13.3, 11.3 and 4.9 ppb respectively). WHO permits 10 ppb of As as maximum in drinking water sources, whereas in the present study we found that near to Gangetic region As level was high (more than 10 ppb) than the non-Gangetic region. Together, the results indicate that As contamination in drinking water shows a relationship between female reproductive cancers incidence and As occurrence in patients serum. In conclusion, As might be suppress female reproductive function by as environmental toxicant that is contra-mechanistic to that of estrogen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B29.
Cochlear Implants — Science, Serendipity, and Success
Authors: Gerard O'Donoghue
Journal: New England Journal of Medicine (2013)

Interview with Dr. Gerard O'Donoghue on the past and future development of cochlear implants. (11:53)Download Restoring hearing to people who are too deaf to benefit from hearing aids required an extraordinary, decades-long research endeavor. The 2013 Lasker–DeBakey Clinical Medical Research Award recognizes the contributions of three pioneers of cochlear implantation.
Case 77-1962
Authors: David C. Poskanzer, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A sixty-seven-year-old widow was referred to the hospital because of dyspnea.One week before entry the patient began to be dyspneic upon climbing one flight of stairs, with an associated sensation of lightheadedness and smothering. Despite restricted activities she continued to experience mild episodes of dyspnea once or twice daily, and paroxysmal nocturnal dyspnea developed. Two days before admission sharp pain in the left inframammary area on deep inspiration and a hacking, nonproductive cough appeared. On the night before entry she was unable to lie down because of marked dyspnea and a sensation of pounding . . .
FRI0338 Multicenter study of tumour necrosis factor alpha antagonists for refractory behçet’s uveitis in spain
Authors: M. Mesquida, M. V. Hernandez, G. Espinosa, D. Diaz Valle, M. Cordero Coma, A. Fonollosa, V. Llorenç, L. Pelegrin, B. Molins, A. Adan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Over the past decade, the off-label use of biologic agents such as TNF-a antagonists has improved the treatment armamentarium for refractory immune-mediated uveitis, with particular success in Behçet’s disease associated uveitis. <h3>Objectives</h3> To assess the long-term efficacy and safety of TNF-a antagonists (infliximab, [IFX]; adalimumab, [ADA]; and golimumab [GLM]) for the treatment of patients with Behçet’s disease (BD) and uveitis who failed to respond or did not tolerate conventional immunosuppressive (IS) treatment. <h3>Methods</h3> Retrospective study of patients with Behçet’s uveitis treated with anti-TNF therapy in four tertiary referral hospitals of Spain. Data analyzed were the following: demographic characteristics, disease duration and type of uveitis; best-corrected visual acuity (BCVA); previous treatments; type, regime and duration of each biological agent used; outcomes (remission, loss of efficacy, number of uveitis attacks). <h3>Results</h3> We included 59 eyes of 32 patients (16 males; mean age, 39±11.9 years old) with BD and refractory uveitis. Mean disease duration was 6.4±4.8 years. 18 patients (56.3%) were HLA-B51 positive. 66% of patients had panuveitis, 25% posterior, 6% anterior, and 3% intermediate uveitis. 84% of patients had bilateral ocular involvement. All patients received oral corticosteroids, and 63% had received ≥2 IS drugs at baseline. 25 patients (78%) were treated with IFX and 7 (22%) with ADA as initial therapy. 11/25 patients treated initially with IFX were switched to another anti-TNF agent due to adverse events (3 patients), loss of efficacy (3), patient’s choice (1), or uveitis relapse after IFX withdrawal (4): 9/11 were switched to ADA and 3/11 to GLM. Globally, 16/32 patients were treated with ADA and 3 with GLM. IFX was infused for a mean of 16.6 months (range, 2-48), ADA was administered for a mean of 30.2 months (range, 3-52), and GLM was given for a mean of 4 months (range, 3-6). Mean follow-up was 77.3 months (range, 8-276). 28 (87%) achieved uveitis remission. 12/32 patients were able to discontinue all systemic IS and CS. BCVA remained stable or improved in 53/59 eyes. Mean BCVA improved from 0.2±0.6 to 0.5±0.2 (p&lt;0.05), and ocular attacks per year dropped from 37 in the year before therapy to 5 at final follow-up visit (p&lt;0.05). 3 serious adverse events requiring IFX withdrawal were reported: 1 severe infusion reaction, 1 disseminated tuberculosis, and 1 prostatitis. <h3>Conclusions</h3> Anti-TNF agents are effective biological drugs for the treatment of Behçet’s uveitis. Treatments were generally well tolerated and only 3 patients required withdrawal. <b>Disclosure of Interest</b>: None Declared
Exosomes in stroke pathogenesis and therapy
Authors: Zheng Gang Zhang, Michael Chopp
Journal: Journal of Clinical Investigation (2016)

Stroke is one of the leading causes of death and disability worldwide. Stroke recovery is orchestrated by a set of highly interactive processes that involve the neurovascular unit and neural stem cells. Emerging data suggest that exosomes play an important role in intercellular communication by transferring exosomal protein and RNA cargo between source and target cells in the brain. Here, we review these advances and their impact on promoting coupled brain remodeling processes after stroke. The use of exosomes for therapeutic applications in stroke is also highlighted.
Effect of Avoidance on Peanut Allergy after Early Peanut Consumption
Authors: George Du Toit, Peter H. Sayre, Graham Roberts, Michelle L. Sever, Kaitie Lawson, Henry T. Bahnson, Helen A. Brough, Alexandra F. Santos, Kristina M. Harris, Suzana Radulovic, Monica Basting, Victor Turcanu, Marshall Plaut, Gideon Lack
Journal: New England Journal of Medicine (2016)

In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group).At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age.We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio.Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).