tbuckley/cabot-search huggingface dataset:
SAT0442 Which AEs of Biological Therapy Led to Discontinuation of Treatment in an Open Monocentric Long-Term Prospective Study of 377 JIA Patients.
Authors: I. Pontikaki, M. Romano, M. Gattinara, A. Salmaso, P. Meroni, V. Gerloni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To report adverse events (AEs), which led to discontinuation of biologics, in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with biological therapy (BT). <h3>Methods</h3> All patients with JIA, non responder or intolerant to DMARDs, treated with BT at the pediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to November 2012, were enrolled in an open, single-centre, long-term prospective study. All AEs were recorded on a unique registration form. <h3>Results</h3> 377 pts (208 etanercept, 89 infliximab, 55 adalimumab, 5 golimumab, 2 certolizumab, 9 abatacept, 7 anakinra, 2 rituximab) were enrolled. Median onset age was 5.8 yrs (mean 6.9, range 0.4-18.0). Median disease duration was 7.5 yrs (mean 9.2, range 0.2-41.4). Median period of follow-up was 5.5 yrs (mean 5.6, range 0-12.7). A total of 220 (58.4%) pts (110 etanercept, 77 infliximab, 25 adalimumab, 5 abatacept, 3 anakinra) failed to respond to or did not tolerate the first therapy and 149 (39.5%) switched to a second one. A total 750 courses of BT (634 anti-TNF, 57 anti-IL-1ra and 59 anti-cells treatments) were administered; 157 (20.9%) AEs occurred and the frequency was 0.09 AEs/patient/year. Infusion reactions led to discontinuation in 38 (24.2%) courses and were the most common AEs in our pts treated with infliximab. The most frequent AEs occurred in pts with JIA on etanercept were important behavioural alterations (depression, anxiety, aggressiveness). One case of hypoglossal paralysis and 2 suspected demielinating disease were reported. New onset of inflammatory bowel disease (9 etanercept and 1 adalimumab) and new onset or flare-up of chronic iridocyclitis (15 etanercept, 1 infliximab, 1 certolizumab) were also reported. Dermatological AEs occorred in 15 (9.6%) courses, most of them were recorded in adalimumab. 9 (6%) cases of injection site reaction were also described. <h3>Conclusions</h3> In our 13-year, study BT were well tolerated and safe; most of AEs reported were reversible by discontinuation of therapy. In case of active disease it was necessary to switch to another biological agent. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during BT as much as possible. <h3>Disclosure of Interest</h3> None Declared
Nocardia Brain Abscess Identification with Tl-201 SPECT
Authors: FRANCISCO GARCIA-MORALES, VASEEM U. CHENGAZI, ROBERT E. O’MARA
Journal: Clinical Nuclear Medicine (2001)

GARCIA-MORALES, FRANCISCO M.D.; CHENGAZI, VASEEM U. M.D., Ph.D.; O’MARA, ROBERT E. M.D. Author Information
FRI0510 Elbow pathology in patients with inflammatory arthropathies: a clinical, sonographic and radiographic study
Authors: J. Uson, R. Miguélez-Sánchez, M. J. Martinéz-Blasco, C. Fernández-Espartero, V. Villaverde García, J. Garrido, E. Naredo-Sánchez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasonography is widely used in Rheumatology practice to detect articular and periarticular lesions. To date, elbow clinical findings have not been compared with ultrasonography (US) and conventional radiography (RX) in patients with different inflammatory arthropathies (IA). <h3>Objectives</h3> To study the associations and agreement between clinical, US and RX elbow abnormalities in patients with IA. <h3>Methods</h3> 243 elbows of 122 consecutive patients ( 86 women/37 men, 54.4 ±13.2 years old ) with rheumatoid arthritis (62), spondyloathritis (20) psoriatic arthritis (19) and other IA (21) from a University Hospital Rheumatology Clinic gave informed consent to enroll in the study. The clinical rheumatologists recorded local elbow pain, tenderness, swelling, motion loss, specific resisted maneuvers and established a clinical based diagnosis of elbow arthritis, olecranon bursitis, cubital bursitis, common extensor entesopathy, common flexor entesopathy and/or triceps entesopathy. A systematic EULAR elbow B-mode and Doppler ultrasound (US) examination (Logic 9, probe ML12 General Electric, Wauwatosa, Wisconsin,) was performed by one expert rheumatologist-sonographer (JU) blinded to patients diagnosis and clinical examination. OMERACT definitions for synovitis and entesopathy were used (J Rheumatol 2005;32:2485-7). Anterior and lateral elbow radiographs (RX) were read by one rheumatologist (RM) blinded to clinical information. Descriptive statistics, Fisher´s exact test and kappa indexes were computed to study association and concordance between clinical, US and RX findings. <h3>Results</h3> In 176 painless elbows, clinical joint exam (CJE) was normal in 170 (96%) whereby pathology was found in 92 (52%) US exams and 37 (22%) RX. In 65 elbows with local pain, CJE was pathologic in 57 (86%) however, normal US and RX was recorded in 12 (19 %) and 27 (44.3%) elbows respectively. Clinical, US and RX findings were associated with pain (p &lt; 0.0005). Despite that agreement was strong with clinical findings(ƙ = 0.8) it was poor, though significant with US (ƙ = 0.16) and RX (ƙ =0.24) findings. US synovitis was found in 63 elbows and clinically suspected in 21 (p&lt;0.0005, ƙ= 0.5). US extensor tendon entesopathy was detected in 38 elbows and clinically suspected in 14 (p&lt; 0.0005, ƙ= 0.3). US entesophyts and intra-articular erosions were detected 3 times more with US than RX. Common flexor entesopathy, triceps entesopathy and olecranon bursitis were rare. Cubital bursitis was not found. <h3>Conclusions</h3> Strong associations were found between clinical, US and RX findings although agreement was poor. US detects more elbow articular and periarticular pathology than joint examination and radiographs <h3>Disclosure of Interest</h3> None Declared
PTU-048 Rifaximin for the treatment of hepatic encephalopathy; a meta-analysis of randomised studies
Authors: M Y Morgan, R W Morris
Journal: Gut (2012)

<h3>Introduction</h3> The non-absorbable antibiotic rifaximin has been used to treat hepatic encephalopathy (HE) since the 1980s. Interest in its use increased following a recent Phase III study showing that treatment with rifaximin over 6-months resulted in a relative reduction in the risk of breakthrough HE of 58% compared to placebo (Bass <i>et al</i>, 2010). The aim of this study was to evaluate the efficacy and safety of rifaximin for the treatment of all types of HE in patients with cirrhosis against a variety of comparative regimens. <h3>Methods</h3> A language unrestricted search for papers published between January 1983 and September 2011 was undertaken utilising 11 databases. All HE treatment trials were scrutinised and randomised trials identified. Raw data were obtained from six trials. Data were extracted on (1) the numbers of patients showing improvement overall; (2) the means (±1SD) for mental state, asterixis, number connection tests (NCT), EEG and blood ammonia; and (3) adverse events. Fixed effect model meta-analyses were applied, subdivided by population type. Random effects analyses were used when statistically significant heterogeneity of results occurred. Overall relative proportions were calculated for binary outcomes and standardised mean differences (SMD) for quantitative outcomes. <h3>Results</h3> 17 trials were identified comparing rifaximin to non-absorbable disaccharides (9 trials), other antibiotics (6 trials) or “no treatment” (2 trials) in patients with either “acute” (4 trials), “chronic” (8 trials), or “minimal” (3 trials) HE or else for the “prevention of HE recurrence” (2 trials). Most trials were of adequate quality; the total sample size was 1037 patients, but data were not extractable for all outcomes. The relative proportion of patients experiencing clinical improvement with rifaximin, compared to all control regimen, was 1.26 (95% CI 1.05 to 1.52, p=0.014). Broadly consistent benefits were shown for individual outcome variables for example, asterixis (SMD −0.32, 95% CI −0.62 to −0.02, p=0.038, 5 trials); EEG (SMD −0.49, 95% CI −0.92 to −0.07, p=0.023, 2 trials) and blood ammonia (SMD=−0.25, 95% CI −0.48 to −0.02, p=0.034, 8 trials), although not for mental status (SMD −0.19, 95% CI −0.47 to 0.10, p=0.20, 5 trials) or NCTs (SMD 0.05, 95% CI −0.19 to 0.28, p=0.8, 7 trials). SMDs were stronger in the eight trials in chronic hepatic encephalopathy (asterixis −0.34; EEG −0.56; blood ammonia −0.26; mental state −0.45; NCTs 0.36). No significant differences were observed in side-effects between rifaximin and control regimens. <h3>Conclusion</h3> Rifaximin is an efficacious and safe treatment for HE when compared to a variety of other treatments regimens; the benefits are most marked in patients with chronic HE. <h3>Competing interests</h3> None declared.
DXA Variations and Fractures After Simultaneous Pancreas-Renal Transplantation
Authors: José-Vicente Torregrosa, Ana Sánchez-Escuredo, David Fuster, Xoana Barros, Francisco Campos, África Muxí, Pilar Perlaza, Maria Cristina Marzola, Sotirios Chondrogiannis, Patrick M. Colletti, Domenico Rubello, María José Ricart
Journal: Clinical Nuclear Medicine (2014)

Simultaneous pancreas-kidney transplant (SPKT) has been associated with an increased risk of fracture. We prospectively evaluated the long-term effects of SPKT on bone mineral density (BMD) and fracture risk. During 1998 to 1999, 29 participants were consecutively monitored, and 18 completed the 10-year follow-up. Laboratory blood parameters, lumbar-dorsal radiography, and DEXA were determined at baseline, 1 year, and 10 years. The medical record was reviewed for peripheral fragility fractures. The BMD revealed no changes between baseline and 1 or 10 years after SPKT. Lumbar-dorsal radiography showed 0% asymptomatic vertebral fractures at baseline and after 1 year with 16.7% at 10 years. Vertebral asymptomatic fractures were correlated with acute rejection episodes (P = 0.025). During the first year, no nonvertebral fractures were identified. At the end of the follow-up, 5 nonvertebral fractures in 4 patients were reported. Dorsal and lumbar spine fractures correlated with lumbar spine t score (r = -0.591, P =0.022) and peripheral fractures with femoral neck t score (r = -0.633, P = 0.013). Patients with SPKT did not show long-term significant loss of BMD. The incidence of vertebral fractures was low and related to steroid treatment; the incidence of peripheral fractures was higher and independent of clinical or biochemical parameters.
Single, Circumscribed, Intrathoracic Densities
Authors: Hans Abeles, David Ehrlich
Journal: New England Journal of Medicine (1951)

IN THE course of mass chest x-ray surveys for the detection of pulmonary tuberculosis, single, circumscribed densities are found that offer difficult problems in diagnosis and management. In the early years of the surveys, it was the usual procedure to follow these lesions by periodic examinations. Whenever an increase in the size of the lesion was noticed, the patient was referred for surgical treatment. All too often, the surgeon was then confronted with a malignant tumor that had become inoperable. Obviously, the opportunity for early removal had been missed. There were two reasons for the delay in the advice of . . .
Tuberculosis in Patients with Human Immunodeficiency Virus Infection
Authors: Diane V. Havlir, Peter F. Barnes
Journal: New England Journal of Medicine (1999)

Tuberculosis remains an important problem in patients with human immunodeficiency virus (HIV) infection in the United States, with an estimated 6000 to 9000 new cases annually.1 The case rates are extraordinarily high among indigent patients and substance abusers, and one third of these patients are also infected with HIV.2 Much has been learned about the pathogenesis, clinical presentation, treatment, and prevention of tuberculosis in HIV-infected persons over the past several years. We summarize recent developments in these areas, as well as the effects of new antiretroviral therapies on antituberculosis regimens.HIV Infection and Susceptibility to TuberculosisHIV-infected persons are at . . .
Abstract 2996: DNA-damaging agents disrupt telomere structure
Authors: Oumar Samassekou
Journal: Cancer Research (2011)

Abstract Telomeres are found at chromosome ends. When these ends are not protected by telomeric capping, the telomeres are recognized as double-strand breaks and the consequent recruitment of DNA repair machinery may affect cellular fate. Furthermore, telomeric capping proteins have been shown to interact with some of the proteins involved in DNA repair. A direct link thus exists between DNA repair and telomeres. However, few data are available on the changes in telomere structure associated with the different modes of DNA repair. To study the effects of three DNA-damaging agents on telomere structure, we exposed normal human primary fibroblasts to H202, gamma radiation, or UVB rays. The cells were then harvested at different times over a period of 24 hours. First the telomere nuclear architecture was studied by quantitative fluorescence in situ hybridization with a telomere-specific peptide nucleic acid probe followed by 3D telomere imaging. H202 treatment induced a significant reduction of telomere signals and a disruption of the nuclear volume that became normal after 24 hours of recovery. Also, telomere positioning was positively correlated to nuclear volume that disrupted over time. For gamma irradiation, the nuclear volume was positively correlated to the number of telomere signals and negatively correlated to telomere average intensity for each time point. UVB lead to a significant formation of telomeric aggregates and disruption of telomere nuclear shape by forming ellipsoid instead of circular shape. Next, we studied the effects of these different DNA damage agents on the expression profile of telomere shelterin genes. The most affected genes were TRF1, POT1, TIN2 and Rap1. For instance, while the three agents showed a high induction of TIN2, gamma and H202 treatments presented high induction for POT1 and only H202 treatment induced significant increase of TRF1. In conclusion, certain DNA-damaging events alter telomere structure by acting on nuclear telomere architecture and the expression profile of some telomere shelterin genes. The disruption of telomere structure due to acute insults might have an influence on cell homeostasis and the pathways involved can shed light for a better understanding of some pathological and therapeutic processes. 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 2996. doi:10.1158/1538-7445.AM2011-2996
FRI0024 Antagonizing endosomal toll-like receptors diminishes inflammatory arthritis
Authors: S. Herman, A. Fischer, M. Hoffmann, G. Steiner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA), the most common chronic inflammatory joint disease, has a definite autoimmune background. There is evidence that release of endogenous nucleic acids triggers autoimmune reactions important for the onset of RA. In recent years, endosomal Toll-like receptors (TLRs, i.e. TLR3, TLR7, TLR8 and TLR9) have been implicated in autoimmune processes due to their ability to recognize these nucleic acids. <h3>Objectives</h3> We study the role of TLR7 and TLR9 in the pathogenesis of arthritis by antagonizing them in the pristane-induced arthritis (PIA) model in DA rats. <h3>Methods</h3> Different immunoregulatory sequences (IRS) known to inhibit TLR7/9-activity were tested in cultured rat splenocytes. Using the PIA model, these IRS were also tested for their efficiency in inhibiting arthritis development compared to placebo animals. The IRS' were applied twice a week subcutaneously at the base of the tail. Arthritis score and weight changes were assessed during the experiment. Paws, lymph nodes and spleen were taken for further protein-, RNA- and histological analysis. Furthermore, the impact of the IRS' was analyzed in an <i>in vitro</i> osteoclast formation assay using murine bone marrow-derived macrophages. <h3>Results</h3> IRS against TLR7, TLR9 and TLR7/9 displayed a dose-dependent inhibition of pre-activated rat splenocytes. Interestingly, the combined TLR7/9 inhibitor did not diminish arthritis severity. However, antagonizing TLR9 alone led to reduced arthritis severity, which was also confirmed by diminished protein expression levels in paws and lymph nodes compared to the placebo group and the TLR7 inhibition therapy group. Moreover, bone destruction was strongly reduced in paws of rats treated with the TLR9-antagonist, as revealed by histological analysis of bone erosion, inflammation and number of osteoclasts of paws. Furthermore, in an <i>in vitro</i> osteoclast formation assay it could be shown that treatment with the combined TLR7/9 inhibitor and the TLR9 antagonist led to reduced osteoclastogenesis. <h3>Conclusions</h3> We could show that DNA plays an important role in a rat model of inflammatory arthritis. Despite its role in the PIA rat model, DNA might also play an important role in the pathogenesis of human RA and antagonizing TLR9 might become a useful therapeutic option for RA. <h3>Disclosure of Interest</h3> None Declared
Commentary: non-HIV hypotheses must be studied more carefully
Authors: P. Duesberg
Journal: BMJ (1996)

Patients with haemophilia treated with commercial factor VIII and zidovudine are at risk of developing AIDS defining immunodeficiency diseases like pneumonia, candidiasis, and toxoplasmosis but not Kaposi's sarcoma or dementia. Their risk of these diseases is proportional to their lifetime dosages of factor VIII and cytotoxic DNA chain terminators like zidovudine.*RF 1, 1a*

Haemophilia specific AIDS diseases have been explained in terms of two hypotheses. A non-infectious hypothesis holds that the long term administration of immunosuppressive foreign proteins contaminating commercial factor VIII and zidovudine causes AIDS. An infectious hypothesis holds that HIV causes AIDS.1

### Still no evidence for infection

Based on inadequate tests, Sabin et al reject the foreign protein-zidovudine hypothesis.2 However, their data and those of others actually support the hypothesis.

Sabin et al claim that HIV causes AIDS because all of their haemophilic patients had antibodies against the virus. But HIV cannot be enough for AIDS because six of their 17 HIV positive patients (table 2) remained healthy for 10 years. Likewise 12000 out of 15000 HIV positive American haemophilic patients have remained …
ERCP-guided cholangioscopy using a single-use system: nationwide register-based study of its use in clinical practice
Authors: Jeanne Lübbe, Urban Arnelo, Lars Lundell, Fredrik Swahn, Björn Törnqvist, Eduard Jonas, J.-Matthias Löhr, Lars Enochsson
Journal: Endoscopy (2015)

Single-operator peroral cholangioscopy enables direct visualization of duct lesions, biopsy, and therapeutic interventions in the biliary and pancreatic ductal systems. The aim of this study was to address the use and outcome of this technology in wider clinical practice.A nationwide study of endoscopic retrograde cholangiopancreatography (ERCP) procedures, with or without cholangioscopy, was conducted. Procedures that were registered in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks), between 2007 and 2012 were included. The primary outcome was ERCP-specific adverse events.Data from 36 352 ERCP procedures were analyzed, including 408 cholangioscopy procedures. Postprocedural adverse events were more prevalent when cholangioscopy was used (19.1 % vs. 14.0 %). Pancreatitis (7.4 % vs. 3.9 %) and cholangitis (4.4 % vs. 2.7 %) were ERCP-specific adverse events that were elevated in the cholangioscopy group. However, in multivariate analysis, the risks of intraprocedural and postprocedural adverse events were significantly increased in the cholangioscopy group whereas the risks of pancreatitis and cholangitis, when adjusted for confounders, were not.The single-operator peroral cholangioscopy technique is an advanced technique for intraluminal visual inspection, and for therapeutic intervention of the biliary and pancreatic ducts. However, there is a significantly increased risk of intra- and postprocedural adverse events. Thus, this method should preferably be performed at tertiary referral centers in carefully selected patients.
Abstract 4522: Oncogenic stress-induced cell death following Imatinib deprivation in Bcr-Abl overexpressing Imatinib-resistant ALL cells
Authors: Michael A. Dengler, Annette M. Staiger, Matthias Gutekunst, Walter E. Aulitzky, Heiko van der Kuip
Journal: Cancer Research (2010)

Abstract Imatinib resistance is a major problem in treatment of Bcr-Abl positive leukemias, particularly in patients with ALL and advanced CML. One of the major mechanisms of this resistance is overexpression of Bcr-Abl. We investigated the effects of Imatinib deprivation in Bcr-Abl overexpressing Imatinib-resistant ALL cell lines. Removal of Imatinib from culture medium led to a huge induction of Bcr-Abl autophosphorylation and concomitant overstimulation of PI3K-, MAPK-, and JAK/STAT signalling leading to an elevated cell size and cellular protein content. Massive induction of cell death was then observed at later time points (48 hours after Imatinib deprivation) accompanied by loss of outer and inner mitochondrial membrane integrity. Using a protein kinase inhibitor library, we identified inhibitors of glycogen synthase kinase-3 (GSK3) and p38-MAPK as the most potent compounds which completely prevented induction of cell death upon removal of Imatinib whereas the same inhibitors had synergistic effects with Imatinib in Imatinib-sensitive ALL cells. In contrast to GSK3- and p38, inhibition of PI3K had no effect on oncogenic stress upon Imatinib withdrawal in the resistant clones. Importantly, oncogenic stress-induced cell death could not be blocked by the pan-caspase inhibitor z-VAD-fmk whereas the RIP1 inhibitor Necrostatin partially rescued the cells upon Imatinib deprivation. We also detected a posttranslational modification of RIP1 upon Imatinib withdrawal that was completely absent in cells pre-treated with GSK3- or p38 inhibitors indicating a central role of RIP1 for oncogenic stress-induced cell death. In conclusion, we found a massive induction of a necroptosis-like cell death in Bcr-Abl overexpressing ALL cells as a consequence of oncogenic stress upon Imatinib deprivation. GSK3 and p38 turned out to play the most prominent role for oncogenic stress induced cell death. These data implicate that a discontinuous treatment with Imatinib (periods of Imatinib treatment followed by short periods without Imatinib) may prevent the appearance of cell clones with Bcr-Abl overexpression. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4522.
GENDER INFLUENCE ON THE PROGNOSTIC VALUE OF CORONARY ARTERY DISEASE DETECTED BY CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Marcio Sommer Bittencourt, Edward Hulten, Natalie Bello, John Groarke, Michael Cheezum, Brian Ghoshhajra, Suhny Abbara, Khurram Nasir, Udo Hoffmann, Marcelo Di Carli, Ron Blankstein
Journal: Journal of the American College of Cardiology (2015)