tbuckley/cabot-search huggingface dataset:
PWE-116 Gp210 and/or sp100 antibodies in primary biliary cirrhosis: predictors of cirrhosis/autoimmune (aih) overlap syndromes?
Authors: O Taiwo, S Mathew, J Van Vlymen, A Correa, SJ Deacock, P Berry, K Cheent, H Lewis, A Ala
Journal: Gut (2015)

<h3>Introduction</h3> Primary Biliary Cirrhosis (PBC) is a progressive cholestatic liver disease, with Anti-mitochondrial antibodies (AMA) found in ∼ 95% of patients. Anti-GP210 and SP100 are suggested as additional markers in AASLD guidance, and may help in predicting disease prognosis. However, the role and benefit of anti-GP210 and SP100 testing in routine clinical practice is unclear. <h3>Method</h3> We conducted a retrospective study of all PBC patients (diagnosed according to AASLD criteria), across 3 hospitals in Surrey, England; serving a population 1.1million. Prospective ELISA testing for GP210 and SP100 antibodies were undertaken on all active PBC-patients in follow-up. Baseline characteristics (laboratory/clinical) and progression during follow-up were analysed and compared between both groups. <h3>Results</h3> 51 PBC patients were identified, with anti-GP210/SP100 demonstrated in 14 patients (27%); 9 with anti-SP100, 5 with anti-GP210. Demographic characteristics were similar between both groups: age 64 vs. 61 years, Females 80% vs. 70% in the PBC and GP210/SP100 groups. Consistent with the high sensitivity of AMA in PBC, only 1 (1/51) patient was AMA negative, and also negative for M2, GP210 and SP100. Baseline cirrhosis (imaging/biopsy) was present in 3/27 patients (11%) in the PBC group vs. 3/12 (25%) in the GP210/SP100 group. Quantitative mean M2 values were similar (100 vs. 96), as were baseline mean laboratory values (Bilirubin, ALT, ALP, GGT and IgM). Cirrhosis was present at follow-up (range 0.5–10 years) in 5/37 patients (13.5%) vs. 4/13 (31%) in the GP210/SP100 group. Treatment response to UDCA at one year (Barcelona criteria) was similar: 10/24 (42%) vs. 5/13 (38%) in the GP210/SP100 group. Post-treatment mean alkaline phosphatase levels were higher in the GP210/SP100 group 231 vs. 174 (p = 0.84). 8/51 PBC patients (16%) had diagnosed Autoimmune hepatitis (AIH)/PBC Overlap Syndrome (OS) (based on histological/serological features). OS cases were seen in 2/37 (5%) in the non-ANA group vs. 6/14 (43%) of those in the GP210/SP100 group, reaching statistical significance (p = 0.05); with no significant difference in ALT levels between the OS/non-OS groups. <h3>Conclusion</h3> Although a small sample, our findings support the role of anti-GP210/SP100 as possible markers of disease severity (cirrhosis), and suggest a role for these auto-antibodies in identifying patients with PBC/AIH overlap syndromes; even in the absence of a significant transaminitis. <h3>Disclosure of interest</h3> None Declared.
AB0738 Onset or Exacerbation of Uveitis and Psoriatic Skin Lesions by TNF Antagonists in Patients with Spondyloarthritis
Authors: F. Mechid, F. Hanni, M. Beggar, E.H. Ali, R. Benaziez, H. Sahel, C. Dahou
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Tumor necrosis factor (TNF) antagonists are successfully utilized in the treatment of a wide variety of chronic auto immune diseases and inflammatory conditions. Psoriasis, uveitis or refractory chronic inflammatory bowel disease (IBD), are an indication of TNF antagonists which may paradoxically appear under this treatment. <h3>Objectives</h3> The objective of this study was to report the paradoxical manifestations observed in patients with spondyloarthritis treated by TNF antagonists. <h3>Methods</h3> We identified prospectively all cases of psoriasis and uveitis occurring in patients receiving TNF antagonists for spondyloarthritis in our centre between 2009 and 2014. We collected demographic data, type of TNF antagonist, exposure duration, and the different paradoxical events. <h3>Results</h3> Eighty two (82) patients, 59 males/33 females (mean age 38.33 years), received TNF antagonists for ankylosing spondylitis (SA) in 80.48%, psoriatic arthritis (12.2%), and Crhon disease (7.31%). There where history of uveitis in 8.53%. Type of TNF antagonist was etanercept, infliximab and adalimumab in respectively 37.8%, 31.7% and 30.5%. Mean exposure duration was 14.41 months ±10.16 Three patients with SA developed uveitis worsening while receiving TNF antagonist (adalimumab in two cases and etanercept in another case). We also identified 2 cases of new onset uveitis under etanercept in patients with respectively SA and psoriatic arthritis. Another patient receiving etanercept presented an exacerbation of psoriasis and a relapse of uveitis, and we noted psoriasiform skin lesions in SA patients under adalimumab (two cases) or etanercept (one case.) In all the patients, TNF antagonist was effective on the rheumatic disorder, but was stopped in two of them. <h3>Conclusions</h3> Paradoxical reactions may occur during TNF antagonist treatment. Worsening of psoriasis and new onset uveitis may appear with etanercept <h3>References</h3> Viguier M and al.Paradoxical cutaneous manifestations during anti-TNF-alpha therapy.Ann Dermatol Venereol. 2010;137:64-71 Hernández MV and al. Skin Lesions and Treatment With Tumor Necrosis Factor Alpha Antagonists. Reumatol Clin. 2013; 9(1):53–61 London Nikolas JS and al. Drug-induced uveitis. Journal of Ophthalmic Inflammation and Infection. 2013, 3:43 <h3>Disclosure of Interest</h3> None declared
Cellular Localization of Glucocorticoid Receptor mRNAs in Human CNS Tumors by In Situ Hybridization
Authors: Lorenzo Magrassi, Enrico Silini, Gian Luigi Brambilla, Roberto Assietti, Gabriele Milanesi, Giorgio Butti
Journal: Neuro-Oncology (1991)

Glucocorticoid hormone high affinity binding activity has been demonstrated in human brain tumor cell extracts by radiolabelled ligand assay. To determine the molecular species responsible for this activity and their cellular distribution, we studied by in situ hybridization, with a human glucocorticoid receptor (hGR) cDNA digoxigenin probe, the expression of hGR mRNA in 10 brain tumors (3 astrocytomas, 1 glioblastoma, 1 neurinoma, 3 meningiomas, 1 choroid plexus papilloma, 1 ependymoma). All tumors, with the exception of the glioblastoma and one fibroblastic meningiomas, contained hGR positive neoplastic cells. The intensity of positivity varied between different tumors and within the same tumor. These results indicate, for the first time, the presence of true hGR receptor mRNA in human brain tumor cells.
Soundings: Words failed me
Authors: Liam Farrell
Journal: BMJ (1999)

When you English first came to Ireland you despoiled our relics, cut down all our ancient trees, pillaged our women, and made rude noises at our menfolk. But we got the better of you; we loved, relentlessly, every second of it, and as a bonus we got the English language, the heritage of Shakespeare and Milton, with all its capacity for bombast and subtlety, pageantry, and nuance, a star crossed marriage of a people gifted with a wild imagination with a vehicle sufficiently complex and idiosyncratic to allow them expression.

Even so, the vagaries of general practice can yet leave us lost for words; the skill of extemporaneous dissembling is not taught in the textbooks.

“I'm bucked, Doctor,” said Jimmy from his sick bed.

“Don't worry, man,” I said, faking a heavy Jamaican accent in a despairing attempt at humour, caught as I was between the Scylla and Charybdis of trying to reassure him without actually telling him lies. “The fluid tablets will help your breathing and the antibiotics will take care of the chest infection; you'll feel much better in the morning, and I'll see you then.”

I went outside to find the whole family assembled.

“How is he, Doctor?” asked his wife anxiously.

I paused, aware that they were hanging on my every word. I was also aware that words are inadequate here. Even the English language in all its meandering glory and richness of texture cannot quite seem to convey that there is a sick old man in there. I'm sure he's dying, body falling apart, all systems are failing, heart, lung, kidneys, brain, you name it.

Although I'm doing my best to keep him comfortable I don't really know what's going on, perhaps only that doing nothing heroic is the right thing; don't really know what's wrong with him; pay no attention to what I write on the death certificate, only guessing; and most of all I don't know how to explain my sense of uncertainty and inadequacy to you because I know it's not what you want to hear right now. You want someone strong and certain and positive, someone who knows what is happening, someone in control.

So: “Mary,” I said gravely, placing a firm, supportive hand on her shoulder, in the hope that my body language might help disguise the poverty of my words, “I'm afraid he's bucked.”
Outbreak of trichinellosis in Cáceres, Spain, December 2001–February 2002
Authors: M Cortés-Blanco, A García-Cabañas, F Guerra-Peguero, J- M Ramos-Aceitero, D Herrera-Guibert, J. F. Martinez Navarro
Journal: Eurosurveillance (2002)

An outbreak of trichinellosis by T. britovi occured in Cáceres, Spain, between 18 December 2001 and 11 February 2002, following the consumption of insufficiently cooked meat from a domestic pig. Among the 56 people exposed, 26 cases of trichinellosis were diagnosed, of which 17 serologically confirmed. The mean incubation period was 23.5 days (3–45). Among the foodstuffs suspected, salami-type sausages were associated with an attack rate of 93.3% (14/15), and a dose-response relationship was observed. Trichinella britovi is essentially a sylvatic species, but this study suggests a change in the epidemiology of trichinellosis.
AB0418 Effectiveness of Rituximab as First and Second Line Therapy in Patients with Rheumatoid Arthritis
Authors: I. Mahmoud, S. Jradi, O. Saidane, S. Rekik, H. Sahli, M. Elleuch, R. Tekaya, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The order of use of biologic agents after failing a TNF inhibitor is still a question for debate. Recent clinical practice guidelines recommend the use of Rituximab after previous failure of one anti-TNF. <h3>Objectives</h3> This study aims to compare the efficacy of first and second line of Rituximab and factors associated with, in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Retrospective analysis of 40 Tunisian RA database was included. RA patients initiating a first line either anti-TNF (adalimumab (ADA), etanercept (ETA) or infliximab (INF)) or Rituximab (RTX) were identified and followed forward in time. Anti TNF was then switched with Rituximab, which has become the second line. Baseline demographics included age, disease duration, fatigue and pain visual analogical scale evaluations (VAS) and DAS 28 ESR. The therapeutic efficacy was assessed on the EULAR response criteria. <h3>Results</h3> The analyzed cohort comprised patients with average age of 53,85 years (80% female). 21 patients initiating a first line anti TNF (ADA (n=2), ETA (n=7), INF (n=10), ETA then ADA in one case and INF then ETA in another one case). The evolution marked by a primary therapy failure in 6 cases and a secondary therapy failure in 8 cases. Anti TNF was then switched to RTX. The reason for the switch was therapy failure (n=12) and adverse effects (n=8). In this group, the EULAR response criteria were positive in 57% (Good in 6 cases and moderate in 6 cases). For patients (n=19) who have started in a first line RTX, the EULAR response criteria were positive in 94% (Good in 8 cases and moderate in 10 cases). Seven patients had positive antinuclear antibodies whose 57% had positive EULAR response criteria (Good in 1 case and moderate in 3 cases) and whose 3 patients were under second line RTX therapy who have not developed therapy response. Total, 75% of patients developed positive EULAR response criteria under RTX, whose 50% were under Methotrexate, 43% received more than one course of RTX whose 53% maintained therapeutic efficacy at week 16. <h3>Conclusions</h3> As a first line agent, RTX demonstrates a better retention rate than in second line. <h3>Disclosure of Interest</h3> None declared
Desperate Appliance
Authors: George E. Thibault
Journal: New England Journal of Medicine (1994)

A 64-year-old man presented to the emergency room with fever, chills, nausea, malaise, and left-leg pain that had lasted for four days. For the past two days he had been unable to lift his left leg.I assume he has been unable to lift his left leg because of pain. Acute pain that limits the ability to move a leg makes me think about a vascular catastrophe, trauma, or a fracture. We don't have a lot of history, except a nonspecific febrile illness that may or may not involve the gastrointestinal tract.He had a right-hip fracture . . .
PTU-245 Rectopexy for rectal prolapse
Authors: NN Alam, SK Narang, IR Daniels, NJ Smart
Journal: Gut (2015)

<h3>Introduction</h3> Ventral mesh rectopexy (VMR) is a recognised treatment for posterior compartment pelvic organ prolapse (POP). A variety of synthetic meshes have been used for a wide range of POP surgery but there have been reports of high rates of pelvis sepsis, as well as concerns regarding mesh erosion, dyspareunia, fistulation and stricturing. It has been postulated that biological mesh may cause fewer complications in comparison to synthetic mesh in certain high-risk circumstances. The aim of this review is to provide a synopsis of the evidence for biologic mesh use in VMR, the most widely recognised surgical technique for posterior compartment POP. <h3>Method</h3> A systematic search of PubMed was conducted using the search terms ‘VMR’, ‘ventral mesh rectopexy’ or ‘mesh rectopexy’. Inclusion criteria were studies that described a ventral rectopexy using a biological mesh in either an open or laparoscopic technique. Studies were excluded if only synthetic mesh was used or if there was no mention of a mesh. Furthermore, studies on patients under the age of 18 were excluded as well as non-English language studies, technical tips or duplicates series from the same research group. Overall, the search yielded 6 studies for analysis after the exclusion of review articles. <h3>Results</h3> From 6 case series, 268/324 patients underwent ventral rectopexy using biological mesh with a further 6 patients having a combination of synthetic mesh and biological mesh. Overall, 155 patients underwent VMR using additionally cross-linked porcine dermal collagen (PermacolTM or PelvicolTM) and 89 using porcine intestinal submucosa (Surgisis©). Recurrence was reported in 20 patients; however, 6 of these were from studies where data on biological mesh could not be extracted. One study did not report recurrence. There are no randomised controlled trials in VMR surgery generally and no studies have directly compared types of biologic mesh e.g. cross-linked <i>vs.</i>non-cross-linked. Cross-linked porcine dermal collagen is the most commonly used mesh and has not been associated with mesh erosion, infection or fistulation in this current review. The level of evidence available on the use of biologic mesh in VMR is of low quality (level 4). <h3>Conclusion</h3> VMR has become prevalent for posterior compartment POP. The evidence base for its implementation is not strong and the quality of evidence to inform choice of mesh is poor. <h3>Disclosure of interest</h3> None Declared.
Shelved 4-1BB Antibodies Make Comeback
Authors: Janet Colwell
Journal: Cancer Discovery (2015)

New trials are reexamining 4-1BB antibodies for a variety of cancers. Development of the drugs had stalled due to concerns about toxicity, but recent studies in animals, as well as early-phase trials, suggest that new formulations of the drugs may be less toxic-and potentially more potent-when combined with other therapies.
THU0111 Prevalence and Cross-Sectional Associations of Neuropathic-Like Pain Features in Rheumatoid Arthritis
Authors: S.M. Koop, P.M. Ten Klooster, H.E. Vonkeman, L.M. Steunebrink, M.A. van de Laar
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Pain control in rheumatoid arthritis (RA) is often inadequate and clinically significant pain persists in a substantial proportion of patients, even when inflammation appears to be well controlled. This suggests that inflammation or subsequent joint damage might not be the only factor causing pain in RA. Accumulating evidence suggests that features of neuropathic pain may also be present in patients with rheumatic pain conditions. <h3>Objectives</h3> To estimate the prevalence and factors associated with neuropathic-like pain symptoms in patients with rheumatoid arthritis (RA). <h3>Methods</h3> A cross-sectional sample of 159 RA patients completed the painDETECT questionnaire along with other self-reported measures before their visit to the rheumatology outpatient clinic. Univariate analyses and multivariable logistic regression were used to identify factors associated with neuropathic pain features. <h3>Results</h3> The large majority of patients (88%) were in remission or had low disease activity, but 44% of the patients continued to report clinically significant pain. According to the painDETECT, 27 patients (17.0%) were classified as having likely neuropathic pain and 34 patients (21.4%) as having possible neuropathic pain. Besides reporting more intense pain, patients with likely or possible neuropathic pain were more likely to meet the diagnostic criteria for fibromyalgia, to use analgesics, and to have more tender joints and worse physical and mental health status as measured by the SF-36. In multivariable analysis, physical (P&lt;0.001) and mental health status (P=0.006) remained significantly associated with neuropathic pain features, even after controlling for pain severity. <h3>Conclusions</h3> Neuropathic-like pain symptoms are present in a substantial number of patients with RA and are associated with worse physical and mental health. These symptoms may represent central sensitization and underscore the need for further research and screening of pain mechanisms in RA patients. <h3>Disclosure of Interest</h3> None declared
Combined Treatment With 131I-MIBG and Sunitinib Induces Remission in a Patient With Metastatic Paraganglioma Due to Hereditary Paraganglioma-Pheochromocytoma Syndrome From an SDHB Mutation
Authors: William Makis, Karey McCann, Alexander J.B. McEwan, Michael B. Sawyer
Journal: Clinical Nuclear Medicine (2015)

A 22-year-old woman with rapidly progressing metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome from an SDHB mutation, who recurred after neoadjuvant chemotherapy, was found to be MIBG avid. She was treated with 2 131I-MIBG treatments and concurrent sunitinib, achieving a complete response. She was in full remission for 9 months before developing bone metastases.
Neurological examination abnormalities in neuroleptic-naive patients with first-break schizophrenia: preliminary results
Authors: R D Sanders, M S Keshavan, N R Schooler
Journal: American Journal of Psychiatry (1994)

The authors report preliminary findings from an ongoing prospective study of neuroleptic-naive patients with first-break schizophrenia. They evaluated 17 of these patients and 15 normal subjects with a structured neurological examination before the patients received any medical treatment. The patients with schizophrenia showed significantly greater neurological impairment than did the normal comparison subjects.
Prediction of Human Herpesvirus 6 Infection After Allogeneic Bone Marrow Transplantation
Authors: Tetsushi Yoshikawa, Kyoko Suzuki, Masaru Ihira, Hiroshi Furukawa, Sadao Suga, Yoshizo Asano, Seiji Kojima, Koji Kato, Takaharu Matsuyama
Journal: Blood (1998)
Survival of Patients with Gastrointestinal Cancers Can Be Predicted by a Surrogate microRNA Signature for Cancer Stem–like Cells Marked by DCLK1 Kinase
Authors: Nathaniel Weygant, Yang Ge, Dongfeng Qu, John S. Kaddis, William L. Berry, Randal May, Parthasarathy Chandrakesan, Edwin Bannerman-Menson, Kenneth J. Vega, James J. Tomasek, Michael S. Bronze, Guangyu An, Courtney W. Houchen
Journal: Cancer Research (2016)

Doublecortin-like kinase 1 (DCLK1) is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a miRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/miRNA-sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic, and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies. Cancer Res; 76(14); 4090-9. ©2016 AACR.
Soundings: Prevention is better than cure
Authors: Imre Loefler
Journal: BMJ (2004)

One may think that “prevention is better than cure” is a quote from the goddess Hygiene, yet the vintage is recent and the wisdom is more limited than it appears.

What is “better?” Vaccination against whooping cough has its dangers, but these are negligible in comparison with whooping cough itself. As whooping cough does not give pleasure to anyone, it is reasonable to say that the prevention of whooping cough is “better” than whooping cough. But is the prevention of atherosclerosis by the combination of dietary measures, exercise, and avoidance of smoking “better” than the risk of myocardial infarction or obliterative arterial disease? And if incisive changes in lifestyle are proposed, would not the prohibition of horse riding, parachuting, mountain climbing, and skiing be “better” than the risks associated with these pastimes?

Tobacco, alcohol, drugs, coffee, chocolate, sugar, salt, red meat, raw fish, oysters, dairy products, smoked food, and food cooked in aluminium pots have been shown to constitute risks, as do walking in forests, living with mites, bats, dogs, cats, reptiles, or birds, or riding a motorcycle, sunbathing, or touching other people's genitals without gloves. One is told to move one's bowels regularly and inspect stools, monitor blood pressure, breasts, testicles, cholesterol... What is the fate of a person who lives by these rules? Such a person will die a non-preventable death, as opposed to all those who die a “premature death,” because they did not follow the doctor's advice. Could it be that people who die a “non-preventable death” die later than those who, foolishly, die from preventable causes? Or could it be that healthy people are more injury prone because, in their exuberance, they are likely to indulge in dangerous activities? Do healthy people have a better life? True, a healthier society is more productive in terms of material wealth.

But is there an observable link between health and creativity? Great art has always been associated with suffering. The putative elimination of disability, of pain, and of anguish and the fear of death may well impoverish human experience. The two outstanding healthist societies of history, Sparta and Hitler's Germany, were philistine. There is no evidence that a healthier society generates more thought, more beauty.