tbuckley/cabot-search huggingface dataset:
SP0166 Joint Distraction and Cartilage Regeneration – What is the Basis for Structural Repair?
Authors: S. Mastbergen
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Knee joint distraction is an experimental treatment for knee OA, aimed at temporarily unloading the joint cartilage and subchondral bone by use of an external fixation frame. The technique proved to be clinically long-term effective for end-stage ankle OA. This clinical improvement was supported by structural tissue changes significant improvement of the joint space width and normalization of bone sclerosis as evaluated by digital X-ray analysis. Since knee OA occurs more often and has a greater socio-economical impact than ankle OA, joint distraction as a therapy was applied for the knee. So far two years follow-up results of the first study on knee joint distraction are available demonstrating significant cartilage repair, as analyzed by quantitative MRI analysis. Additionally, X-rays were taken under full weight bearing, demonstrating the mechanical competence of the formed tissue. Collagen type II biomarkers showed a significant increase in synthesis, suggesting the newly formed cartilaginous tissue is hyaline cartilage. Importantly, this structural cartilage repair is accompanied by significant clinical improvement in pain and function, sustaining for at least two years. These clinical data are supported by several OA animal studies also demonstrating both structural changes and clinical improvement. As this cartilage repair activity is unique, this provides for the first time the opportunity to study the unknown mechanism required for cartilage repair. Acquiring this knowledge will open new frontiers to establish actual treatment of a still incurable joint disease. The cartilage repair activity as observed by joint distraction cannot be solely the result of the matrix synthesis by the resident chondrocytes. It is anticipated that intrinsic mesenchymal stem cells (MSCs) activity plays a crucial role in the observed cartilage repair activity. MSCs can originate from (peri-articular) bone marrow, cartilage, synovium, synovial fluid, and infrapatellar/sub-synovial fat pad. Apparently, joint distraction provides the appropriate biomechanical intra-articular milieu, facilitating MSCs in their cartilage repair activity. <h3>Disclosure of Interest</h3> None Declared
Abstract 680: Loss of miR-34a as measured by quantitative in situ hybridization on a tissue microarray is associated with poor outcome in breast cancer
Authors: Seema Agarwal, Jason A. Hanna, David L. Rimm
Journal: Cancer Research (2012)

Abstract Introduction: MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of cancers as either oncogenes or tumor suppressors. It has been shown that the loss of miR-34a leads to tumor progression and metastasis using cell lines and a limited number of patient samples by RT-PCR. Lack of a robust, reproducible and quantitative method has limited large scale analysis and assessment of miR-34a as tumor suppressor marker in cancer. Herein, we have developed and validated a method for the quantitative analysis of miRNA expression by in situ hybridization (qISH) allowing for the direct assessment of tumor epithelial expression of miR34a in breast cancer. Method: Expression level of miR-34a was measured in a retrospective breast cancer (n=461) cohort with 20 year follow-up using quantitative immunofluorescence (AQUA) technology for ISH in a tissue microarray (TMA) format. The assay was performed in two-fold redundancy with a 40 case index TMA for reproducibility and standardization. Averaged AQUA scores for miR34a were correlated with clinical and pathological characteristics and 10 year disease-free survival in this cohort. Results: Since miR-34a is a tumor suppressor, we determined the threshold at which no specific hybridization was seen (AQUA score =16.89). Reproducibility between two different builds (cores) of the TMA was R*2 = 0.59. Using overall survival as an endpoint in Kaplan Meier analysis with the threshold of expression as the cutpoint, the group with loss of miR-34a had significantly worse survival (log rank p = 0.0264). Cox univariate analysis for miR-34a showed hazard ratio of 1.53 (95% CI: 1.05-2.22, p=0.0276). Cox multivariate analysis including age, nuclear grade, nodal status, ER, PR and Her2 showed miR34a is not an independent marker (p=0.0908). An independent breast cancer cohort will be used to validate this result. Conclusions: The microRNA miR-34a has been proposed to be a tumor suppressor using mechanistic and functional data. This result, showing loss of miR-34a is associated with worse outcome in a large breast cancer cohort provides clinical evidence of the tumor suppressor function of miR-34a. 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 680. doi:1538-7445.AM2012-680
AB0781 Very early morphological capillary changes during the transition from primary to secondary raynaud’s phenomenon
Authors: C. Pizzorni, F. Ravera, A. Sulli, G. Zampogna, E. Alessandri, V. Smith, C. Ferrone, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Nailfold videocapillaroscopy (NVC) analysis can definitely distinguish between primary (PRP) and secondary (SRP) Raynaud's phenomenon by identifying the "early" scleroderma-pattern of microangiopathy (giant capillaries and microhaemorrhages) (1). <h3>Objectives</h3> The aim of the study was to evaluate, in recent SRP patients, who developed the "early" pattern of nailfold microangiopathy (and SRP) the evolution of very early non-specific morphological capillary alterations by a follow up of their previous NVC microvascular status. <h3>Methods</h3> After informed consent and Ethical Committee approval, fifty patients with early diagnosis of SRP (mean age 47±16 years; mean SRP duration 7±8 years) based on the new finding of "early" NVC scleroderma-pattern of microangiopathy were evaluated (one year retrospective follow-up), to study the evolution of not specific capillary abnormalities possibly present at previous NVC examinations, in particular capillary ectasias (diameter between 20-50 microns). Two fields per finger (from the 2nd to the 5th finger) of both hands were analyzed and the average semiquantitative scores for the capillaroscopic parameters (i.e. capillary number, ectasias, giant capillaries, microhaemorrhages, ramified capillaries), as previously reported (2-3). The statistical examination was performed by non-parametric tests. <h3>Results</h3> All the SRP patients showed two or more giant capillaries, identifying the "early" scleroderma-pattern of microangiopathy at the moment of inclusion. In 74% of patients the "ectasia score" remained the same during one-year follow-up, despite the appearance of giant capillaries, while in 26% of patients the "ectasia score" increased from 1 to 2 (p=0.005). 42% of patients showed a one-point increment of the microhaemorrhage score (from 0 to 1 or from 1 to 2) (p=0.005). At first NVC examination, 9% of patients showed a mild capillary number reduction, which did not change during the subsequent follow-up (score 1); in 16% of cases a not statistically significant reduction of capillary number (score from 0 to 1) was observed at last NVC visit. Capillaries ramifications were not observed at follow-up. <h3>Conclusions</h3> The results confirm that the transition from PRP to SRP is characterised by the appearance of giant capillaries, at NVC. However, the very early identification of nailfold capillary ectasias in a subgroup of PRP patients suggests the need for close NVC monitoring of these patients, in order to early detect the onset of giant capillaries and related diseases, such as systemic sclerosis, especially when other clinical features of the disease are not evident. <h3>References</h3> Cutolo, M. et al. Nature Rev Rheumatol 2010; 6, 578–587. Cutolo M, et al. Rheumatology 2004; 43: 719-26. 3. Sulli A, et al. Ann Rheum Dis 2008; 67:885-7. <h3>Disclosure of Interest</h3> None Declared
FRI0335 Preliminary activity and severity criteria for juvenile idiopathic arthritis-related uveitis
Authors: C. Birolo, M.E. Zannin, G. Martini, F. Vittadello, F. Zulian
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anterior uveitis (AU) is the most important extra-articular complication of juvenile idiopathic arthritis (JIA) but to date, there are no universally accepted criteria for defining its activity and severity in children. <h3>Objectives</h3> Aim of this study was to define activity and severity criteria for JIA-related AU by a consensus-based methodology. <h3>Methods</h3> The project was conducted in three phases. <i>1.First Delphi:</i> A detailed questionnaire on activity and severity criteria used in clinical practice for JIA-related uveitis was sent to pediatric rheumatologists and ophthalmologists from 23 Pediatric Rheumatology referral Centers in Italy 2. <i>Consensus meeting (CM):</i> criteria where 80% consensus among participants was not reached have been discussed during a one-day-meeting and consensus reassessed (Nominal Group Technique) <i>3. Second Delphi:</i> to establish the final set of criteria, the only group of ophthalmologists were then asked to re-rate, after 2 weeks thinking time, their level of agreement on a few criteria in which agreement was not reached at CM. <h3>Results</h3> High agreement was reached for the following criteria of AU activity: white keratic precipitates, new onset of endothelial traces, anterior chamber cells (≥1+), anterior chamber <i>flare,</i> new onset/progression of complications such as posterior synechiae, CME or increased ocular pressure. For AU Severity criteria a uniform consensus was reached on posterior synechiae, cataract, band keratopathy, vitreitis, glaucoma, no. ≥3 AU relapses/year and ≥2 weeks uveitis duration of each AU episode. For two severity criteria (Best Corrected Visual Acuity reduction rate and uveitis bilaterality) agreement among investigators was reached and they have been temporarily excluded. <h3>Conclusions</h3> These preliminary criteria for JIA-related uveitis will help standardize classification of patients for clinical research, epidemiology, outcome studies and therapeutic trials. A prospective validation of these criteria using the OMERACT filter is ongoing. <h3>References</h3> Jabs DA et al. Standardization of uveitis nomenclature for reporting clinical data. Result of the first international workshop. J Ophthalmol 2005; 140: 509-16 Black N, et al. Consensus development methods: a review of best practice in creating clinical guidelines. J Health Serv Res Policy, 1999; 4: 236-48 Tappeniner C et al. Elavated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis, Acta Ophtalmol, 2011 <h3>Disclosure of Interest</h3> None Declared
Eliminate Prophylactic Platelet Transfusions?
Authors: Sherrill J. Slichter
Journal: New England Journal of Medicine (2013)

Studies have clearly shown that the threshold for prophylactic platelet transfusions can be reduced from the previous guideline of 20,000 platelets per cubic millimeter to 10,000 per cubic millimeter1 and that the standard platelet-transfusion dose can be reduced by half,2 without increasing the risk of bleeding in patients with hypoproliferative thrombocytopenia. The next logical question, addressed in the study by Stanworth et al. in this issue of the Journal, 3 is whether prophylactic transfusions are really necessary or whether patients with thrombocytopenia can be effectively supported with only therapeutic platelet transfusions given with the onset of a bleeding event of World . . .
TEMPORAL TRENDS IN ACUTE DECOMPENSATED HEART FAILURE HOSPITALIZATIONS IN THE U.S., 1998-2011
Authors: Sunil K. Agarwal, Lisa Wruck, Pedro M. Quibrera, Kunihiro Matsushita, Laura Loehr, Patricia Chang, Wayne Rosamond, Jacqueline Wright, Gerardo Heiss, Josef Coresh
Journal: Journal of the American College of Cardiology (2015)
PTU-018 Cystatin C and protein: creatinine ratio; potential predictors of early acute kidney injury, renal replacement therapy and in-hospital death in patients with cirrhosis
Authors: A Slack, J Wendon, M J McPhail, R Sherwood, R Musto, M Heneghan
Journal: Gut (2012)

<h3>Introduction</h3> Acute kidney injury (AKI) is common, but difficult to predict in patients with cirrhosis as lower baseline serum creatinine can mask significant chronic kidney dysfunction. Cystatin C is a biomarker of glomerular filtration rate (GFR), which may overcome this weakness. Quantifying proteinuria using the widely available protein:creatinine ratio (PCR) may better the degree of structural glomerular damage. <h3>Methods</h3> 34 patients with cirrhosis and mean (SD) age 51 (14) years and, median (range) Child-Pugh Turcotte (CPT) score 11 (9–11) were prospectively assessed for 10 days or until AKI, developed. Baseline iohexol clearance was performed to calculate GFR and urine underwent PCR analysis. Daily urine and serum samples were collected for determination of novel serum and urine biomarkers of kidney injury, including Cystatin C. Biomarkers were assessed by area under the receiver operating curve (AUROC) for predicting AKI stage 1, renal replacement therapy (RRT) and death. <h3>Results</h3> 16 (47%) patients developed AKI defined by an increase of &gt;26.4 umol/l from baseline serum creatinine (median 73 range (37–120 umol/l)). Estimated GFR overestimated GFR with median eGFR 95 (47–181) ml/min/1.73 m<sup>2</sup> compared to a median iohexol derived GFR of 55 (20–115) mL/min/1.73 m<sup>2</sup>, p&lt;0.0001. Median PCR was 55 (36–189) compared to 17 (13–29) in the AKI and Non-AKI groups, p&lt;0.0005. Liver disease severity scores were not significantly different between AKI groups for both CTP (p=0.86) or model for end-stage liver disease (MELD, p=0.14). Plasma cystatin C at 48 h prior to AKI predicted its subsequent development with an AUROC of 0.82 (sensitivity 86%, specificity 75%, p=0.004, cut off 1.18 mg/l). A random urine PCR of &gt;30 predicted AKI during that hospital admission with an AUROC of 0.72 (sensitivity, 77%, specificity 63%, p=0.001). Plasma cystatin C at 48 h prior to AKI predicted death with an AUROC of 0.88 (sensitivity 100%, specificity 76%, p≤0.0001, cut off 1.18 mg/l). PCR &gt;49 predicted the need for RRT with an AUROC of 0.85 (sensitivity 73%, specificity 86%, p≤0.0001). <h3>Conclusion</h3> Estimated GFR using serum creatinine based equations overestimates GFR, therefore an accurate assessment requires a gold standard measure, like iohexol, in patients with advanced liver disease. Cystatin C and the widely available urine PCR measurement can be used to assess the risk of AKI. They both demonstrate potential for predicting AKI 48 h prior to onset, the need for RRT and hospital survival. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Slack A</b>, Yeoman A, Wendon J. Renal dysfunction in chronic liver disease. <i>Crit Care</i> 2010;<b>14</b>:214.
Abstract 4367: IP6: A potential novel therapy for cancer stem cells
Authors: Toshie Nata, Hieu Cong Tran, Joseph L. Bryant, Eugene Ateh, Yanto Lunardi-Iskandar, Ivana Vucenik
Journal: Cancer Research (2011)

Abstract Background and Aims: We recently discovered that inositol hexaphosphate (IP6), a new anticancer agent, killed malignant cancer stem cells (CSC) such as: CD133+, CD44+ and CD24+ cells via apoptotic pathways, but did not kill normal epithelial cells, fibroblasts, lymphocytes and macrophages. The effects of IP6 on malignant CSC have not been known. To clarify the molecular mechanism of IP6 destruction of CSC cells, we studied its effects in several CSC from malignant KS-Y1, B-NHL, prostate cancer (PCA) and breast cancer (BCA) cell lines. Methods and Results: CSC were isolated from KSY-1, B-NHL/HIV Tg26 mice, PCA and BCA cancer cell lines using magnetic beads conjugated with MoAbs and analyzed by flow cytometry for CD133, CD44 and CD24 cells. CSC cells were cultured using liquid and semisolid techniques for tumorigenesis assay and were treated with IP6 at doses of 100, 300 and 500 µg/ml, untreated (PBS) and control treatment with 10-100 µg/ml of Taxol. Cell viability was determined by trypan blue at 1 hr-24 hrs. FACS analyses were performed for apoptotic activities by detection of death molecules such as Annexin V-FITC and PI-CD95, and apoptosis assessed by 3D confocal microscopy. Significant killing of malignant CSC with IP6 in a dose-dependent manner were shown ex vivo in proliferation/differentiation tumorigenesis assay, in quantitative/qualitative FACS analyses and 3D confocal microscopy. In contrast, Taxol molecule with doses 10-100 µg/ml did not kill the CSC. Since it is known that CSC are resistant to Taxol treatment and radiation therapy, and IP6 significanly decreased proliferation and induced apoptosis in malignant and metastatic CSC, the results from our experiments suggest that IP6 may be an excellent new drug for treatment of CSC. 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 4367. doi:10.1158/1538-7445.AM2011-4367
The Challenges with Chronic Angina
Authors: E. Magnus Ohman, Karen P. Alexander
Journal: New England Journal of Medicine (2014)

Should therapies to treat chronic stable angina reduce the risk of major cardiovascular events such as death and myocardial infarction? Although this may be a laudable target, the majority of treatments that are currently in use, such as nitrates, calcium-channel blockers, and beta-blockers, have not been proved to achieve this goal. Still, these agents have been recommended as first-line therapy for angina1 because of their presumptive safety in this context and their ability to lower blood pressure, reduce symptoms, and improve quality of life.The occurrence of angina is associated with reduced quality of life and increased resource use.2 Angina, . . .
EUS-guided implantation of radioactive iodine-125 seeds in retroperitoneal metastatic adenocarcinoma
Authors: Y. Guo, Y. Liu, Z. Li, D. Wang, Y. Du, J. Chen, Z. Jin
Journal: Endoscopy (2009)

EUS-guided implantation of radioactive seeds of iodine-125 combined with chemotherapy was used to treat a case of inoperable retroperitoneal metastatic adenocarcinoma. Complete local remission was achieved.
Abstract P4-11-16: Accelerated Partial Breast Irradiation for Ductal Carcinoma In Situ: An Analysis of the Susan G Komen Clinical Trial
Authors: AM Abbott, J Gay, L Han, M Kinney, T Washington, TM. Tuttle
Journal: Cancer Research (2010)

Abstract Introduction In 2002 the Food and Drug Administration approved a device, MammoSite, that delivers accelerated partial breast irradiation (APBI). Our aim was to determine outcomes with MammoSite in the treatment of ductal carcinoma in situ (DCIS). Methods We conducted a prospective multi-center trial between 2003 and 2009. Inclusion criteria included age &amp;gt; 18 years, biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities (according to the EROTC/RTOG Acute Radiation Morbidity Scoring Criteria), cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results We enrolled 45 patients into the study. APBI was not initiated in 5 patients due to inadequate distance from tumor cavity to the skin. Toxicities were observed in 30 patients (75%). Grade 1 toxicity was the most common (78%); most were subcutaneous and cutaneous changes. Cosmetic outcome at 12 months was reported as good to excellent in 93% of surgeon and 90% of patient responses. Median follow up was 36.5 months. Among treated patients, 4 (10%), developed an IBTR, (all DCIS). All IBTRs were outside the treatment field. Among patients with IBTRs the mean age was 49.8 years and the mean time to recurrence was 29.8 months. Conclusions APBI, using MammoSite, appears to provide a safe cosmetically acceptable outcome; however the 10% IBTR rate with median follow up of only 36.5 months is concerning. Randomized trials are necessary before use of APBI for DCIS. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-16.
False-Positive Positron Emission Tomographic Scan for Recurrent Breast Cancer Resulting From a Bee Sting
Authors: D S Johnson, J T Wong, M N Coel
Journal: Clinical Nuclear Medicine (1999)

A 38-year-old woman who had a bilateral modified radical mastectomy for breast cancer of both breasts was evaluated for recurrence or metastatic disease. Whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomographic scans revealed only a small focal abnormality in the left axilla, which was too superficial to represent a lymph node. When we questioned the patient regarding the abnormality, she reported a recent bee sting at the area in question. Active inflammatory cells readily take up FDG, and thus insect stings and other acute local inflammatory lesions should be considered when a superficial abnormality is seen on a positron emission tomographic scan and should not readily be interpreted as a metastatic lesion.