tbuckley/cabot-search huggingface dataset:
Integrated analysis of efficacy and safety of palonosetron (PALO) 0.75 mg IV for preventing chemotherapy-induced nausea and vomiting (CINV) in anthracycline and cyclophosphamide (AC/EC) combination chemotherapy in Japan: PALO Japanese breast cancer cooperative study group.
Authors: Y Suzuki, Y Tokuda, K Inoue, K Aogi, M Saito, Y Yanagita
Journal: Cancer Research (2009)

Abstract Abstract #4099 Background: In the treatment of breast cancer, combination chemotherapy of AC/EC has been widely used for neoadjuvant, adjuvant chemotherapy or standard treatment of metastatic breast cancer. AC/EC frequently induces severe nausea and vomiting, that it is important to adequately prevent and control. PALO is the first novel serotonine antagonist approved for prevention of delayed nausea and vomiting in moderately emetogenic chemotherapy in US and other countries. Integrated analysis was done on the data from phase 2 and 3 trials that have been completed in Japan. The purpose of this analysis was to assess efficacy and safety of PALO for preventing CINV induced by AC/EC regimens.&amp;#x2028; Methods: Three Japanese studies with single/repeated IV dose of PALO in pts receiving AC/EC were used. In all these studies, PALO 0.75 mg IV was administrated 30 min prior to AC/EC. Dexamethasone was administrated before AC/EC on day 1, and also on days 2-3 for the phase 3 trial. This integrated analysis assessed the efficacy and safety by difference in regimens (AC or EC), assessed the efficacy by difference in FEC (EC with 5-FU) or EC regimen and by difference in epirubicin (E) dosage in EC. Apart from the integrated analysis, efficacy of PALO in repeated cycles of chemotherapy was assessed by different regimens (AC or EC).&amp;#x2028; Results: Total of 266 pts administrated AC/EC were evaluated for efficacy in single dose. Overall CR(CR = no emesis or rescue medication)% for PALO in acute phase was 70.7%. Overall CR% in delayed phase was 61.3%. CR% in acute and delayed phase for (a) AC (n=76) vs EC (n=190), (b) FEC (n=141) vs EC (n=49), (c) low (n=109) vs high (n=81) dosage of E (&amp;lt;=90, &amp;gt;90 mg/m2) in EC were as follows; (a) acute: 80.3 vs 66.8, delayed: 68.4 vs 58.4, (b) acute: 61.7 vs 81.6, delayed: 56.7 vs 63.3, (c) acute: 72.5 vs 59.3, delayed: 61.5 vs 54.3. Total of 155 pts administrated AC/EC were evaluated for efficacy of PALO in repeated cycles of chemotherapy, and similar efficacy between AC and EC was confirmed. Total of 474 pts administered AC/EC were evaluated for safety in all Japanese studies. There was no significant difference in the incidence of adverse drug reactions between AC and EC.&amp;#x2028; Conclusion: This integrated analysis suggested that high antiemetic activity of PALO in CINV was shown for breast cancer pts receiving either AC or EC. In addition, in the FEC regimen and high dosage of E, all showed CR rate of more than 50% in both acute and delayed phases in the efficacy analysis, revealing a long lasting antiemetic activity of palonosetron. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4099.
AB1151-HPR Can the Understanding of Disease Activity Score by Patients Lead to Better Satisfactions of the Rheumatoid Arthritis Treatment?
Authors: T. Kichikawa, H. Muramatsu, N. Takahashi, Y. Urushiyama, Y. Sato, Y. Takizawa, Y. Nakata, S. Sato, H. Ikeda, D. Kobayashi, S. Ito, Y. Miyagawa, A. Abe, H. Ishikawa, A. Murasawa, K. Nakazono
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> We have previously demonstrated that the improvements of disease activity and patients9 satisfaction did not show significant relationship in rheumatoid arthritis (RA). Here we hypothesized that the understanding of disease activity score 28 (DAS28) by patients may lead to better patients9 satisfaction. <h3>Objectives</h3> To assess the relationship between patient9s DAS28 understanding and treatment satisfaction in rheumatoid arthritis treatment. <h3>Methods</h3> The study was conducted in cross-sectional method. The questionnaire was collected between June 17, 2013 and July 26, 2013 from 1004 RA patients in our hospital. Newly visited patients were excluded from this study. Questionnaires included treatment satisfaction, experience of receiving DAS28 explanation, and understanding of DAS28. <h3>Results</h3> Patients were 203 male and 801 female, mean age of 61.5 years, mean disease duration of 10.9 years, and mean DAS28 (ESR) of 2.82. Administrations were 763 patients with conventional DMARDs and 241 patients with biological DMARDs. The overall satisfaction to the treatment was satisfied (23%), somewhat satisfied (54%), neutral (16%), somewhat unsatisfied (5%), and unsatisfied (2%). Patients experienced receiving the explanation of DAS28 (28%), unexplained (32%), and did not recall or unknown (45%). To compare the patients who did understood DAS28 (n=191) with the patients who did not and does not understand DAS28 (n=745), patients were stratified into two groups. The satisfaction from the patients who understood DAS28 was 89%, while the patients who did not and does not understand DAS28 was 76%. Patients who understood DAS28 showed significantly higher rate of satisfaction compared to the patients who did not and does not understood DAS28 (p=0.0013, Kruskal-Wallis test). <h3>Conclusions</h3> The treatment satisfaction of RA patients with the understanding of DAS28 was higher than that of the patients who does not know or did not understand DAS28. The portion of the patients who received DAS28 explanation was 28%, leaving most of the patients unexplained and not knowing of DAS28. These facts suggest that the educational approach including explanation of DAS28 to RA patients may lead to improve overall treatment satisfaction level in our hospital. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3542
CORONARY AORTA DIASTOLIC PRESSURE INDEX: A NEW NOVEL INDICATOR FOR PREDICTING SIGNIFICANT CORONARY STENOSIS. A VALIDATION AGAINST FRACTIONAL FLOW RESERVE
Authors: Khawaja Afzal Ammar, Mirza Nubair Ahmad, Arsalan Riaz, Fatima A Husain, Syed Shahab Kazmi, Haroon Yousaf, Imran Husain, Anjan Gupta
Journal: Journal of the American College of Cardiology (2015)
SAT0480 High Doses of Infliximab in the Management of Juvenile Idiopathic Arthritis
Authors: R. Q. Cron, A. Tramballi, T. Beukelman, P. Weiser, T. P. Atkinson, M. L. Stoll
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although biologics have revolutionized treatment of juvenile idiopathic arthritis (JIA), many patients have active disease despite therapy [1]. Studies have shown benefit of dose intensification of infliximab in several conditions, including inflammatory bowel disease, psoriasis, and idiopathic uveitis [2, 3]. However, the safety and effectiveness of infliximab dose intensification have not been evaluated in JIA. <h3>Objectives</h3> We routinely use high doses of infliximab (10–20 mg/kg/dose) in children with recalcitrant JIA or complications thereof. The objective of this study was to review our experiences with high-dose infliximab in JIA. <h3>Methods</h3> We performed a retrospective review of children with JIA who received infliximab at ≥10 mg/kg/dose. We recorded all serious adverse events (SAE), medically important infections, and infusion reactions. We also recorded the ESR, physician global assessment of disease activity (MD global), and active joint count (AJC) at initiation of high dose infliximab and 3, 6, and 12 months thereafter. Institutional Review Board approval was obtained from the University of Alabama at Birmingham for this study. <h3>Results</h3> 75 subjects received a total of 1,367 infusions over 126.8 person-years. There were a total of 11 SAEs (8.7 / 100 person-years), seven of which were potentially related to therapy; and 10 infusion reactions (0.7%), two constituting anaphylaxis. Statistically significant improvements were observed in the AJC (median 0 [range 0 – 31] versus 2 [0 – 39]) and MD global (12 [0 – 31] versus 21 [0 – 80]) assessments of disease activity over the first year. <h3>Conclusions</h3> High dose infliximab resulted in improvements in markers of JIA disease activity. The incidence of SAEs with high dose infliximab was similar to that reported in long-term outcome of a randomized clinical trial of standard dose infliximab for JIA [4], and the incidence of infusion reactions was even lower. High dose infliximab appears safe and effective in the management of JIA. Future studies are necessary to compare prospectively dose intensification with alternative therapeutic options. <h3>References</h3> Shenoi S, Wallace CA. Paediatr Drugs. 2010;12:367. Kahn P, et al. Ophthalmology. 2006;113:860. Reguiero M, et al. Inflamm Bowel Dis. 2007;13:1093. Ruperto N, et al. Ann Rheum Dis. 2010;69:718. <h3>Acknowledgements</h3> We thank the patients and families for agreeing to dose amplification of infliximab in medically refractory disease. <h3>Disclosure of Interest</h3> None Declared
PTH-005 Laparoscopy-assisted Ercp Following Bariatric Gastric Bypass Surgery: Initial Experience At A Uk Tertiary Referral Centre
Authors: B Paranandi, D Joshi, B Mohammadi, S Read, M Adamo, GJ Webster
Journal: Gut (2014)

<h3>Introduction</h3> Bariatric gastric bypass surgery is being increasingly performed, but ERCP in these patients poses a unique challenge because of lack of per-oral access to the stomach. Small series suggest a higher technical success rate, using Laparoscopy assisted ERCP (LA-ERCP), than with an enterosocpic approach via the Roux-en-Y anastamosis. We present the experience thus far of LA-ERCP at our UK tertiary referral Pancreaticobiliary unit. <h3>Methods</h3> Retrospective case series of consecutive patients undergoing LA-ERCP in our unit between September 2011 and June 2013. Data was retrieved from electronic, clinical and endoscopy records. <h3>Results</h3> All LA-ERCP procedures were undertaken in the operating theatre with a mobile endoscopy stack and Olympus TJF duodenoscopes equipped with standard ERCP accessories. The laparoscopic procedure involved formation of a closed pneumoperitoneum to a pressure of 12 mmHg with a Veress needle. A 15 mm trocar was placed in the epigastrium and two 5mm trocars were placed in the right and left flanks for surgical access. A 15 mm gastrostomy port was secured with purse-string sutures. The duodenoscope was inserted via the port into the gastric remnant and advanced conventionally into the duodenum. Standard therapeutic ERCP technique was then performed. Closure of the gastrostomy was achieved with a double layer of 2–0 vicryl sutures. Peri-procedural prophylactic intravenous antibiotics were administered routinely in all patients. <h3>Conclusion</h3> Five LA-ERCPs (on 5 patients) were performed. All patients were Female with median age 44 years (range 36–71). Indications included symptomatic bile duct stones (3/5), benign papillary fibrosis (1/5) and retained biliary stent (1/5). Duodenal access, biliary cannulation and completion of therapeutic aim were achieved in all patients. 4/5 (80%) patients required endoscopic sphincterotomy. The 5th patient had a prior sphincterotomy. The mean duration of procedures was approximately 94 min (range 70–135). Median post-op length of stay was 2 days (range 1–9). One patient developed mild post-procedural acute pancreatitis. Otherwise no procedure related complications were seen. <h3>Reference</h3> Our early experience of LA-ERCP is that it is safe and effective. The technique may require particular consideration, as bariatric surgery is increasingly performed, in a patient group at significant risk of bile duct stones. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3700: Proteomic credentialing in a model for chemoprevention studies of urinary bladder cancer
Authors: Reid R. Townsend, Henry Rohrs, Richard LeDuc, James P. Malone, Petra Erdman-Gilmore, Donald L. Hill, Clinton J. Grubbs, Ming You, Ronald A. Lubet
Journal: Cancer Research (2011)

Abstract Molecular markers for the development and response of tumors to agents are essential for efficacy assessment of cancer chemoprevention. The discovery, verification and validation of biomarkers for tumor monitoring require animal models that have been shown to share molecular features with human cancers. At the transciptomic level, the rat 4-hydroxybutyl(butyl) nitrosamine (OH-BBN) model has been shown to share many of the pathways that are commonly activated in human bladder cancer. To qualify the model at the proteomics level, global protein analyses on bladder tumors and on paired urine samples were performed, and the findings correlated with transcriptomic data and literature knowledge of upregulated proteins in human bladder cancer. We used a high-resolution LC-MS platform that consisted of optimized, reproducible sample preparation methods for tissue and urinary proteins, robust nano-LC hybrid (linear quadrupole-Orbitrap) mass spectrometry, and a data analysis pipeline to align and annotate differential peptides from LC-MS analyses of multiple samples. To date, samples from ∼ 150 individual animals have been analyzed using this quantitative proteomics platform. We have used this platform to correlate urinary candidate abundances with tumor burden and response to chemopreventive agents. In one experiment that compared the urine from control and tumor-bearing animals, it was found that 3,032 of the 15,557 detected peptides changed by &amp;gt; 3-fold. Among the proteins that were only detected in tumor-bearing animals (at least a 1000 fold increase) were Annexins (I, II and VII), S-100 proteins-4, 6 and 11, calpactin and galectin. 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 3700. doi:10.1158/1538-7445.AM2011-3700
Preservation of Function in Experimental Renal Disease by Dietary Restriction of Phosphate
Authors: Lloyd S. Ibels, Allen C. Alfrey, Lewis Haut, William E. Huffer
Journal: New England Journal of Medicine (1978)

We sought to determine the importance of calcium phosphate deposition in the functional deterioration of damaged or diseased kidneys. Using the remnant-kidney model in rats, we found that dietary phosphate restriction prevented proteinuria, renal calcification, histologic changes, functional deterioration and death in uremia. Histologic examination of the remnant kidney in the nonrestricted animals showed calcium and phosphorus deposits in the cortical tubular cells, basement membranes and interstitium. A similar degree and pattern of calcification have been found in preliminary studies of human end-stage kidneys. Our results suggest that the calcification produced by the altered phosphorus metabolism present in the uremic state incites an inflammatory and fibrotic reaction leading to destruction of the remnant kidney. Phosphate restriction prevents this response in the remnant kidney. The potential applicability of these findings to other forms of experimental renal disease and to clinical uremia remains to be explored.
AB1347 Influence of low socioeconomic status on autoimmune rheumatic diseases:
Authors: J.M. Anaya, J. Amaya-Amaya, M.J. Amador-Patarroyo, C. Herrera-Diaz, O.L. Quintero, J. Cardenas-Roldan, J. Giraldo-Villamil, C. Barragan-Ardila, J. Caro-Moreno, Z. De-San-Vicente, P. Cruz-Tapias, A. Rodriguez-Rodriguez, R.D. Mantilla, A. Rojas-Villarraga
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To analyze the influence of socioeconomic status (SES) on the course of autoimmune rheumatic diseases (AIRD) in an admixed and socio demographic heterogeneous population. <h3>Methods</h3> This was a cross-sectional analytical study in which 1096 consecutive patients with rheumatoid arthritis (RA, n=678), systemic lupus erythematosus (SLE, n=258), and Sjögren syndrome (SS, n=160) were included. SES was categorized according to the national legislation and was dichotomized as high (status 3 to 6) and low SES (status 1 and 2).Sociodemographic, clinical and laboratories variables were collected by means of a structured interview and a medical record review.Bivariate and logistic regression analyses were performed for each population sample. <h3>Results</h3> Significant association between low SES and a stronger autoimmune response was observed (Table). In addition, low SES influences the presence of arthritis, Raynaud's phenomenon, and discoid lupus in SLE. As expected, an association between low SES and low educational level was observed in SLE and SS, while in RA a low SES was also associated with housewives. <h3>Conclusions</h3> Our results indicate that SES influences the clinical presentation of AIRD. These results could be related to the admixture of our population, environmental factors, and the quality of health insurance, and deservefurther research. Also, the results might help to define public health policies in order to improve AIRD outcome in low SES patients. <h3>Disclosure of Interest</h3> None Declared
AB1211 Newborns of mothers with autoimmune disease. Outcome in a regional hospital
Authors: V. Ortiz-Santamaria, J. Sanchez-Manubens, M.T. Coll, R. Acal, J. Cuquet, J. Bermudez, X. Surís
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Pregnant women with autoimmune disease (AID), particularly systemic lupus erythematosus (SLE), have increased risks of disease exacerbation, pre/eclampsia and other maternal and fetal complications. Low birth weight (LBW) for gestational age, preterm delivery and neonatal lupus (NL), which occurs in 1.5% of newborns of mothers with SLE, are some of the associated fetal complications. <h3>Objectives</h3> To report the maternal and fetal morbidities associated with deliveries by women with AID at a regional hospital. <h3>Methods</h3> Retrospective data were collected between 2003 and 2010 at a regional hospital. The reference area included 300,000 inhabitants. We analyzed the clinical and laboratory characteristics of mothers with AID and the complications experienced by their newborns. We recorded the maternal and neonatal disorders arising from this disease. <h3>Results</h3> Over this 7-year period, 29 mothers were analyzed. There were 52 pregnancies, which resulted in 39 newborns. There were 13 miscarriage (45%), all of them in mothers with antiphospholipid syndrome (APS). The AIDs of the mothers were 19 SLE (67%), 3 cutaneous lupus, 3 primary Sjögren's syndrome, 2 mixed connective tissue disease, 1 primary APS and 1 systemic sclerosis. There were 8 instances of maternal complications (26%) during the pregnancies including 1 digital vasculitis, 1 pancreatitis, 1 outbreak of glomerulonephritis, 1 gestational diabetes, 3 preeclampsia and 1 eclampsia. One patient experienced significant improvement of her arthritis. During the postpartum period, there was 1 case of lupus fever and 1 case of eclampsia, pneumonitis and respiratory failure with a favorable outcome. Among the newborns, 7 were preterm (21%), 8 had LBW (35%) and 4 exhibited the transplacental passage of maternal antibodies (1anti-Sm [1], 1 anti-Ro, 1 anti-Ro plus anti-La and 1 anti-Ro plus anti-RNP). One newborn developed transient cutaneous NL with the transplacental passage of maternal anti-Sm antibodies [1]. Electrocardiography (ECG) was performed on 50% of the babies, and no abnormal results were observed. One of the daughters born to a mother with SLE was diagnosed with ANA negative self-limited oligoarthritis at 12 months of age. A son born to a mother with primary APS exhibited idiopathic thrombocytopenic purpura. <h3>Conclusions</h3> In our hospital, the rates of miscarriage, prematurity and LBW among the newborns of mothers with AID are similar to those reported in the literature. The observation of a case of NL with the transplacental passage of anti-Sm*, not previously reported in the literature, is remarkable. <h3>References</h3> Ortiz-Santamaria V, Olive A, Martinez-Cáceres E, Coll MT, Codina X, Surís X. Lupus 2010; 19: 659-61. <h3>Disclosure of Interest</h3> None Declared
NT-17 * TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) WITH AN ONCOLYTIC MEASLES VIRUS IN COMBINATION WITH INHIBITORS OF THE PI3-KINASE PATHWAY
Authors: S. Lal, S. Lawrence, C. Raffel
Journal: Neuro-Oncology (2014)

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a highly malignant pediatric brainstem tumor with less than 10% of patients surviving beyond 2 years. Surgical resection of this diffusely infiltrative tumor is not possible, radiation therapy is palliative not curative, and chemotherapy is ineffective. Clearly, more effective therapy for DIPG is necessary. The genomic analyses on tissue samples from biopsy and autopsy have frequently implicated amplification in the PI3K-mTOR pathway signaling in DIPG tumors. The vaccine strain of measles virus (MV) has been shown to be an effective oncolytic therapy in brain tumors in murine xenograft models. METHODS AND RESULTS: Flow cytometry showed that human DIPG cells abundantly express the CD46 receptor on the membrane that is preferentially utilized by MV for cellular entry. MV efficiently infects DIPG cells, replicates in these cells, and causes the formation of multinucleated syncytia. MV kills DIPG cells in dose and time dependent manner with more than 70% cell death observed at MOI of 0.5 after 96hrs. The mTORC1 inhibitor, rapamycin, and the Akt inhibitor, MK2206, individually attenuated the proliferation of DIPG cells (p < 0.05). Importantly, the killing of DIPG cells by MV was synergistically increased when used in combination with rapamycin or MK2206, as determined by the Chou-Talalay equation (synergism if combination index (CI) < 1). The CI values for MV-rapamycin and MV-MK2206 treatments were 0.4 and 0.8 respectively, at EC50. Cells treated with MV in combination with the inhibitor produced 10-times more virus than cells treated with the virus alone. The switch from apoptosis caused by MV alone to autophagy seen when inhibitors are used may be responsible for the increased virus titer. CONCLUSION: Measles virus has therapeutic potential in the treatment of DIPG tumors and the efficacy may be improved by simultaneously targeting the Akt-mTOR pathway.