tbuckley/cabot-search huggingface dataset:
FRI0482 Cost effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before anti-tnf therapy
Authors: C. François, B. Granger, G. Carcelain, P. Ravaud, X. Mariette, B. Fautrel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> New more sensitive and specific immunologic tests – Interferon γ Release Assays (IGRA) – for diagnosis of latent tuberculosis infection (LTBI) have been developed, but their higher cost needs to conduct cost-effectiveness (CE) assessment to determine how they can be implemented in the diagnostic strategy. <h3>Objectives</h3> To evaluate the CE of different IGRA-based LTBI diagnostic strategies comparatively to tuberculin skin test (TST) in patients before starting anti-TNF therapy. <h3>Methods</h3> 429 patients with rheumathoid arthritis, spondylarthropaty or Crohn’s Disease with an indication for initial biological treatment with anti TNF therapy were included in the ETAT study<sup>1</sup>. All patients were tested by TST and 2 different IGRA: QUANTIferon TB Gold in tube (QTF-Gold IT) and T-SPOT.TB. A decision tree was used to represent the different strategies: (a) TST alone (reference) and 5 alternative strategies(see table). The model was filled with probability values from ETAT study and direct medical costs (TST, IGRA and LTBI treatment including monitoring in case of positive LTBI detection; in euros (€)) from the French health care payers’ perspective. The effectiveness was measured in terms of percentage of patients without LTBI treatment. The incremental cost effectiveness ratio (ICER) was expressed in terms of cost in € per LTBI treatment avoided. Construction of decision tree and analysis was performed using TreeAge Pro 2012. <h3>Results</h3> Data were available for 392 patients and none of them developed a TB. The effectiveness of the different strategies was: 65% (a), 82% (b, c, e), 81% (d), and 89% (f). The cost of the strategies was: 172€ (a), 329€ (b), 345€ (c), 345€ (d), 277€ (e) and 146€ (f). Results are shown in the table. The dominant strategy was (f) and the ICER was assessed at -104€ by LTBI treatment avoided. For the other strategies the ICER were assessed: 924 (b), 1020 (c), 999 (d), 530 (e). <h3>Conclusions</h3> According to the good specificity of QTF Gold IT and TSPOT.TB, the absence of a real gold standard for the LTBI diagnosis and the absence of active TB under Anti-TNF during this study, using the percentage of patient without preventive TB treatment for the effectiveness must be considered as a good option. In this case the dominant strategy was based on QTF Gold ITalone or with TSTwhen the result of QTF Gold ITwas indeterminated. <h3>References</h3> Mariette X et al., Influence of replacing TST with ex vivo IGRA on decision to administer prophylactic antituberculosis antibiotics before anti-TNF therapy. Ann Rheum Dis. 2012 Nov;71(11):1783-90. <h3>Disclosure of Interest</h3> None Declared
Abstract 1966: Regulation of RKIP function by Helicobacter pylori in gastric cancer cells
Authors: Erika Moen, Talha Anwar, Sicheng Wen, Omobola Onikoyi, Steven Moss, Devasis Chatterjee
Journal: Cancer Research (2011)

Abstract Raf kinase inhibitory protein (RKIP) is a negative regulator of the mitogen activated protein kinase (MAPK) cascade initiated by Raf-1 and nuclear factor kappa B (NF-κB) and is an activator of apoptosis in human cancers. STAT3 (signal transducer and activators of transcription) is often constitutively phosphorylated in gastric cancer. RKIP is a negative regulator of STAT3 and has been positively correlated with a higher survival rate in gastric cancer patients (Chatterjee, et al., Clin. Cancer Res., 14:2994-3001, 2008). Helicobacter pylori (H. pylori) infection is associated with high levels of activated STAT3 as well as activation of the transcription factor NF-κB in gastric epithelial cells, through mechanisms involving macrophage-derived IL-6. H. pylori infection led to a dose- and time-dependent increase in STAT3 activation and Snail, a protein that is a negative regulator of RKIP transcription. In addition, H. pylori and IL-6 treatment stimulated the phosphorylation of RKIP in a protein kinase C- (PKC) dependent manner. Interestingly, H. pylori stimulated RKIP transcription which was enhanced in the presence of the histone acetyl transferase, CBP, and inhibited in the presence of the PKC inhibitor. Surprisingly, RKIP stimulated STAT3 transcription in gastric cancer cells, an effect that was reversed in the presence of CBP. After H. pylori infection, RKIP localized to the nucleus and enhanced H. pylori-mediated apoptosis. Collectively, these results indicate that RKIP function is regulated by phosphorylation after H. pylori infection and acetylation by CBP. Moreover, our study demonstrates that RKIP post translational modifications regulate apoptosis induction (via phosphorylation) and inhibition of cell survival (via acetylation) in gastric cancer. These results also suggest the existence of a feedback loop between RKIP, H. pylori infection and STAT3 in gastric cancer. Supported, in part, by NIH COBRE Investigator Award Grant P20 RR17695 (DC and SM). 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 1966. doi:10.1158/1538-7445.AM2011-1966
James Wilson Fleming
Authors: J. Wood
Journal: BMJ (2014)

James Wilson Fleming (“Jimmy”) died on 29 September. Coincidentally, 74 years earlier on this date he graduated from Glasgow University as a medical doctor.

He was born in the Scottish Highlands, the son of the local butcher. His academic record was such that he was sent to a boarding school outside Glasgow. He would travel there and back by steamer, hence his abiding interest in Scottish steamers.

He joined Glasgow University to undertake his medical studies. Used to gory sights, he was the only medical student to last the first round of visits …
AB1115 A novel mutation in the CIAS1/NLRP3 gene associated with an unexpected phenotype of caps
Authors: A. Insalaco, P.S. Buonuomo, I. Ceccherini, C. Bracaglia, M. Pardeo, R. Nicolai, F. De Benedetti
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by heterozygous mutations of CIAS1/NLRP3 gene. Affected patients may present three different phenotypes: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and CINCA syndrome. Common symptoms include sporadic or cold-induced non pruritic urticarial rash and fever. Severe cases suffers from deafness, meningitis, articular contracture and secondary amyloidosis <h3>Objectives</h3> To identify the genotype-phenotype correlation of our patient. <h3>Methods</h3> We describe a 13-year-old female who presented, starting at 12 years of age, recurrent episodes of high fever, pericarditis, arthralgia, arthritis of the knees, abdominal pain and marked increase in inflammatory markers (5 episodes in the first 5 months of disease). Symptoms were poorly responsive to therapy with NSAIDs and colchicine but responded to steroid therapy. Molecular analysis of the MEFV, TNFR and MVK genes did not show any pathogenic mutations. Serumamyloidlevel was normal. In the subsequent months she developed recurrent (up to daily) episodes of chest pain, skin rash and swelling of the subcutaneous tissue of limbs, trunk, joints and lips, in the absence of fever, with spontaneous resolution. <h3>Results</h3> Molecular analysis of the CIAS1 gene revealed the presence of a c.1105C&gt;A mutation in the heterozygous state,that predicts a L369M amino acid substitution. To the best of our knowledge this variant has never been reported. One-Hundred chromosomes were examined and the variant was not found. In order to verify the potential pathogenic effects of the L369M amino acid substitution, daily therapy with anakinra (2 mg/kg/day) was started with rapid disappearance of clinical symptoms and normalization of CRP levels in 24 hours <h3>Conclusions</h3> The fast response to IL-1 inhibtion suggests that the disease of this patient is driven by IL-1 and support the conclusion that this novel mutation is pathogenic and may be associated with a new CAPS phenotype <h3>References</h3> Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, Hoyer J, Gattorno M, Gul A, Smith J, Leslie KS, Jiménez S, Morell-Dubois S, Davis N, Patel N, Widmer A, Preiss R, Lachmann HJ. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011 Dec;70(12):2095-102. Epub 2011 Aug 21. <h3>Disclosure of Interest</h3> None Declared
OP0099 Toll-like receptor 4 agonists MRP 8 and MRP 14 act as endogenous enhancers of MSU-crystal induced IL-1 secretion in vitro and reflect disease activity in gout patients in vivo
Authors: D. Holzinger, N. Nippe, K. Marketon, N. Dalbeth, T. Merriman, D. Baeten, N. Busso, T. Vogl, D. Foell, C. Gabay, J. Roth
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Monosodium urate (MSU) crystal induced interleukin-1 (IL-1β) secretion is a critical pathogenic factor in the development of gout and serves as a therapeutic target in these patients. Nevertheless, without co-stimulation by a pro-IL-1β inducing factor, such as lipopolysaccharides, MSU alone does not induce IL-1β secretion <i>in vitro</i>. The endogenous Toll-like receptor 4 (TLR-4) agonists myeloid related protein (MRP) 8 and MRP14 play a significant role in human inflammatory and infectious diseases, reflect disease activity and have been shown to be an important pathogenic factor in murine arthritis models. <h3>Objectives</h3> To analyze the co-stimulatory properties of MRP8 and MRP14 that lead to enhancement of MSU crystal induced IL-1β secretion, verify their expression in gout patients and test their value as biomarkers in gout patients. <h3>Methods</h3> The co-stimulatory effects of MRP8 and MRP14 on MSU-induced IL-1β secretion were tested <i>in vitro</i> on primary human monocytes and macrophages, and on murine macrophages, with confirmation by ELISA and Western Blot. Furthermore MSU-induced release of MRPs from human neutrophils and monocytes was measured by ELISA. MRP8 and MRP14 was measured in paired serum and synovial fluid samples (n=15) and in synovial tissue (n=10) of gout patients. The relationship between disease activity and MRP expression was analyzed in the serum of acute and convalescent gout patients (each n=40). <h3>Results</h3> MRP8 and MRP14 were released by MSU-activated human neutrophils and monocytes and induced pro-IL-1β production in monocytes. MSU-induced IL-1β secretion was significantly increased by MRP co-stimulation in human and murine monocytes and macrophages. MRP was found in the synovia and synovial fluid of active gout patients and levels were significantly elevated compared to those in osteoarthritis patients. Moreover, the serum levels of MRPs in gout patients were positively associated with disease activity (mean ± 95% CI, acute: 2020±420 ng/ml, convalescent: 920±70 ng/ml, controls: 430±100 ng/ml; p&lt;0.001 acute vs. convalescent and acute vs. control; p&lt;0.05 control vs. convalescent). <h3>Conclusions</h3> MRP8 and MRP14 are endogenous enhancers of MSU crystal-induced IL-1β secretion by induction of pro-IL-1β via TLR-4. These proteins are found at the site of inflammation in patients with acute gout and their serum levels reflect disease activity in these patients. These findings indicate a new role of endogenous TLR-4 ligands in the pathogenesis of gout. <h3>References</h3> [1]Martinon et al., Nature. 2006 Mar 9;440(7081):237-41. [2]Vogl et al., Nat Med. 2007 Sep;13(9):1042-9. [3]van Lent et al., Ann Rheum Dis. 2008 Dec;67(12):1750-8. <h3>Disclosure of Interest</h3> None Declared
Abstract 192: MiR-34c has an anti-apoptotic role in non-small-cell lung carcinoma
Authors: Silvia Catuogno, Laura Cerchia, Giulia Romano, Sara Laudato, Maria Matarese, Gerolama Condorelli, Vittorio de Franciscis
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively regulate the expression of their target genes. They are involved in many biological processes, including cell proliferation, apoptosis and differentiation, and are considered as promising new therapeutic targets for cancer. However, the identity of miRNAs involved in apoptosis and their respective targets remain largely unknown. Given the elevated complexity of miRNA regulation of gene expression, we performed a functional screening as an alternative strategy to identify those miRNAs that in lung cancer cells may interfere with the apoptotic process. To this aim we generated a derivative of the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical upstream initiator of apoptosis, can be activated by the administration of the small dimerizer drug AP20187. We found a number of miRNAs that may rescue cell viability from caspase-8 activation. They included miRNAs already described as oncogenic such as miR-17, miR-135, miR-520, but also some miRNAs such as miR-124a and miR-34c for which a tumor suppressive role has been instead described or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel induced apoptosis. We demonstrate that Bmf (Bcl-2 modifying factor) is a target of miR-34c-5p and that its silencing, together with that of c-myc, a known target of miR-34c-5p, contributes to resistance to apoptosis induced by paclitaxel via p53 downregulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 192. doi:1538-7445.AM2012-192
Abstract 3379: Overexpression of CTGF is associated with chemoresistance in esophageal adenocarcinoma.
Authors: Zhuwen Wang, Lin Lin, Dafydd G. Thomas, Mark B. Orringer, Andrew C. Chang, David G. Beer, Jules Lin
Journal: Cancer Research (2013)

Abstract Esophageal adenocarcinoma is the most rapidly increasing solid malignancy with an overall 5-year survival of only 19%. Neoadjuvant chemoradiation is standard practice in most large centers but results in a complete pathologic response in only 21%, although this subset has an improved 5-year survival. In this study, connective tissue growth factor (CTGF), which is associated with increased cell migration, tissue invasion, and angiogenesis, was evaluated for its role in chemoresistance in esophageal adenocarcinoma. CTGF was found to be overexpressed in 33.3% (5 of 15; mean 3.1-fold) of esophageal adenocarcinomas on oligonucleotide microarray relative to Barrett's metaplasia. Elevated expression of CTGF was also found in 5/5 advanced stage IV esophageal adenocarcinomas on Western blot. Overexpression of CTGF was observed in 70.6% of chemoresistant esophageal adenocarcinomas (n=17) as determined using qRT-PCR and was significantly higher compared to chemo-naïve esophageal adenocarcinomas (n=102; p&amp;lt;0.0005). Stable inhibition with an shRNA against CTGF in the esophageal adenocarcinoma cell line Flo, which expresses endogenous CTGF, led to a significantly increased response to the chemotherapeutic agents 5-FU (9.4-fold increase), cisplatin (5.5-fold), and etoposide (4.4-fold) at 24 hours (p&amp;lt;0.005). These findings suggest that CTGF may be important in mediating chemoresistance in esophageal adenocarcinoma and that inhibition of CTGF could be useful in modulating chemoresistance to current neoadjuvant regimens in esophageal adenocarcinomas overexpressing CTGF. Citation Format: Zhuwen Wang, Lin Lin, Dafydd G. Thomas, Mark B. Orringer, Andrew C. Chang, David G. Beer, Jules Lin. Overexpression of CTGF is associated with chemoresistance in esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3379. doi:10.1158/1538-7445.AM2013-3379
Bacterial and Protozoal Gastroenteritis
Authors: R L Guerrant, D A Bobak
Journal: New England Journal of Medicine (1992)

IN recent years there have been numerous advances in our understanding of the increasingly varied range of microorganisms that infect the gastrointestinal tract. These agents range from newly identified bacterial pathogens, such as Helicobacter pylori, and a still growing range of types of Escherichia coli to protozoal, algal, and fungal enteric pathogens. This overview will provide an update and a practical approach to the understanding, diagnosis, and management of nonviral infectious diarrhea. It is particularly important to understand the epidemiologic setting and pathogenesis of these infections, because they provide a clinical basis for diagnosis and management. A highly selective . . .
Hemostatic Effect of Tranexamic Acid Mouthwash in Anticoagulant-Treated Patients Undergoing Oral Surgery
Authors: Steen Sindet-Pedersen, Göran Ramström, Stener Bernvil, Margareta Blombäck
Journal: New England Journal of Medicine (1989)

We carried out a placebo-controlled, double-blind, randomized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis, a prosthetic cardiac valve, or a vascular prosthesis. Surgery was performed with no change in the level of anticoagulant therapy, and treatment with the anticoagulant agent was continued after surgery. Before it was sutured, the operative field was irrigated in 19 patients with 10 ml of a 4.8 percent aqueous solution of tranexamic acid (an inhibitor of fibrinolysis) and in 20 patients with a placebo solution. For seven days thereafter, patients were instructed to rinse their mouths with 10 ml of the assigned solution for two minutes four times a day. There were no significant differences between the two treatment groups in base-line variables, including the level of anticoagulation at the time of surgery. Eight patients in the placebo group had a total of 10 postoperative bleeding episodes, whereas only 1 patient in the tranexamic acid group had a bleeding episode (P = 0.01). There were no systemic side effects. We conclude that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants.
Tapered-tip Teflon catheter: another device for sequential dilation in endoscopic ultrasound-guided hepaticogastrostomy
Authors: V. Prachayakul, P. Aswakul, U. Kachinthorn
Journal: Endoscopy (2011)

We report the case of a 54-year-old man who had previously undergone a gastrojejunostomy due to a perforated gastric ulcer. He developed hilar cholangiocarcinoma and underwent endoscopic retrograde cholangiopancreatography (ERCP), but duodenal intubation failed because of his surgically altered anatomy. He was therefore scheduled to undergo biliary drainage by endoscopic ultrasound (EUS)-guided hepaticogastrostomy using a therapeutic curved linear echo endoscope (GF-UC 140P; Olympus, Tokyo, Japan).
P10.01 * PARANEOPLASTIC BRAINSTEM ENCEPHALITIS AS PRESENTING SYMPTOM OF MERKEL CELL CARCINOMA (MCC) FOLLOWED BY INTRACRANIAL AND LEPTOMENINGEAL DIFFUSION
Authors: D. Ferrandi, C. Prevost, M. Mascolo, R. Bottaro, M. Melato, M. Palermo, P. Varese, E. Traverso, L. Ruiz
Journal: Neuro-Oncology (2014)

CASE REPORT: A 52 years-old man was hospitalized for dizziness and dysarthria, followed by sleepiness, ataxia and dysphagia with forced rest in bed and need of parenteral nutrition. Neurological examination revealed bilateral lateral nystagmus, positive Romberg's sign, gait ataxia. Magnetic resonance imaging (MRI) of the brain was negative. Cerebrospinal fluid examination showed increased protein and normal count cells; PCR for neurotropic viruses was negative. Neoplastic markers and onconeuronal antibodies resulted negative. Findings on computed tomography of the chest and abdomen were normal. PET scan showed high metabolic activity in axillary and inguinocrural right lymph nodes. Excisional biopsy of the inguinal lymph node documented metastasis from a malignant neuroendocrine cutaneous neoplasia cromogranina A, CK 20 EMA and Synaptophysin positive. This profile was consistent with metastatic MCC. No skin lesions were detected. A diagnosis of paraneoplastic brainstem encephalitis was formulated: the patient was treated with intravenous infusion of immunoglobulins with partial benefit. The primitive neoplasm was treated with a combination therapy of Etoposide 100 mg/mq administered for three days and Cisplatin 75 mg/mq for one day in a 21-day-cycle. One month after the first cycle the patient recovered autonomous deambulation and normal feeding. About five months later the patient complained of dysarthria, dysphagia and ataxia. A brain MRI revealed a pineal lesion with contrast enhancement. Cerebrospinal fluid examination revealed 50 mononucleate cells per field, protein level of 47 mg/dl. Cytofluorimetric study of CSF showed 7% of CD45 negative cells, EMA (epithelial membrane antigen) positive cells consistent with leptomeningeal invasion. The patient deteriorated rapidly: he presented an epileptic seizure followed by coma and a few days after he deceased. Discussion and conclusion Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neurondocrine tumor. Literature reports few cases of paraneoplastic complications and also CNS metastasis are rare. In this case report, the onset of neurological symptoms lead to a diagnosis of a MCC. A paraneoplastic disease was supposed because of normal neuroradiological and laboratory findings although onconeuronal antibodies were absent. The rapid clinical response to treatment (both intravenous immunoglobulins and chemotherapy) seemed to confirm that view. The relapse of symtoms was caused by intracranial and leptomeningeal localization with poor prognosis. In the case described the MCC reveals a high affinity for CNS, both indirectly (an immune response against neuronal proteins expressed by the tumor cells is supposed to be the cause of the paraneoplastic syndrome) and directly with neurometastatic progression. In our knowledge this is the first case described of MCC with this high tropism for CNS.