tbuckley/cabot-search huggingface dataset:
Effectiveness of Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries Aged 70 to 79 Years
Authors: Xabier García-Albéniz, John Hsu, Michael Bretthauer, Miguel A. Hernán
Journal: Annals of Internal Medicine (2016)

Background: No randomized, controlled trials of screening colonoscopy have been completed, and ongoing trials exclude persons aged 75 years or older. The Medicare program, however, reimburses screening colonoscopy without an upper age limit. Objective: To evaluate the effectiveness and safety of screening colonoscopy to prevent colorectal cancer (CRC) in persons aged 70 to 74 and those aged 75 to 79 years. Design: Large-scale, population-based, prospective study. The observational data were used to emulate a target trial with 2 groups: colonoscopy screening and no screening. Setting: United States. Participants: 1 355 692 Medicare beneficiaries (2004 to 2012) aged 70 to 79 years at average risk for CRC who used Medicare preventive services and had no previous diagnostic or surveillance colonoscopies in the past 5 years. Measurements: 8-year risk for CRC and 30-day risk for adverse events. Results: In beneficiaries aged 70 to 74 years, the 8-year risk for CRC was 2.19% (95% CI, 2.00% to 2.37%) in the screening colonoscopy group and 2.62% (CI, 2.56% to 2.67%) in the no-screening group (absolute risk difference, −0.42% [CI, −0.24% to −0.63%]). Among those aged 75 to 79 years, the 8-year risk for CRC was 2.84% (CI, 2.54% to 3.13%) in the screening colonoscopy group and 2.97% (CI, 2.92% to 3.03%) in the no-screening group (risk difference, −0.14% [CI, −0.41 to 0.16]). The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1000 individuals (CI, 4.4 to 6.8) in the 70- to 74-year age group and 10.3 per 1000 (CI, 8.6 to 11.1) in the 75- to 79-year age group. Limitation: CRC-specific mortality was not available, but CRC incidence and stage were studied at diagnosis. Conclusion: Screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries. The risk for adverse events was low but greater among older persons. Primary Funding Source: National Institutes of Health.
Lipid-specific T cells and the skin
Authors: R. Jarrett, G. Ogg
Journal: British Journal of Dermatology (2016)

Langerhans cells express constitutively high levels of CD1a, a member of the CD1 family of molecules which are known to present lipid antigens to T cells. Whilst much human skin immunology research has focussed on the function of T cells which recognise peptides presented by HLA molecules, in contrast few studies have addressed the role of CD1a and lipid antigens in the pathogenesis of inflammatory skin disease. House dust mite and bee and wasp venom extracts were found to generate CD1a reactivity, but paradoxically this function was within the protein and not lipid fraction. This unexpected finding was explained by the presence of phospholipases within the house dust mite and insect venoms which generated antigenic lipids on contact with skin. The lipids then bind to CD1a on Langerhans cells which are recognised by T cells, which in turn contribute to skin inflammation. This newly identified pathway of skin inflammation defines several potential points for therapeutic intervention.
Neither Germinal Center (GC) vs Non-Germinal Center (Non-GC) Phenotype nor FOXP1 Expression Correlate with Outcome in AIDS-Associated Diffuse Large B-Cell Lymphoma (DLBCL): Study of Patients from AIDS Malignancies Consortium Trials 010 and 034.
Authors: Amy Chadburn, Xia Chen, April Chiu, Elizabeth Hyjek, Wayne Tam, Lawrence Kaplan, David T. Scadden, Daniel M. Knowles, Ethel Cesarman
Journal: Blood (2006)
P1028 : Impaired aerobic capacity and cardiac autonomic control in sedentary postmenopausal women with Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: S.M. Duarte, R.E. Rezende, J.T. Stefano, L.A. Perandini, T. Dassouki, A.L Sa-Pinto, H. Roschel, B. Gualano, F.J. Carrilho, C.P. Oliveira
Journal: Journal of Hepatology (2015)
Megakaryocyte/Platelet-Restricted FVIII Expression Using a Platelet Factor 4 Promoter: Determination of Activation State and In Vivo Efficacy during Thrombocytosis.
Authors: Andrea L. Damon, Jolyon Jesty, Lesley E. Scudder, Dmitri V. Gnatenko, Wadie F. Bahou
Journal: Blood (2007)
Re-recurrence after distal gastrectomy for recurrence caused by needle tract seeding during endoscopic ultrasound-guided fine-needle aspiration of a pancreatic adenocarcinoma
Authors: Tomoya Iida, Takeya Adachi, Yuki Ohe, Suguru Nakagaki, Takashi Yabana, Yoshihiro Kondo, Hiroshi Nakase
Journal: Endoscopy (2016)

A 78-year-old woman, who was suspected of having pancreatic cancer, underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Three punctures were applied using a 22-gauge needle (Boston Scientific, Tokyo, Japan) ([Fig. 1]). The procedure was completed without complication, and adenocarcinoma was diagnosed. Distal pancreatectomy was performed and the lesion was confirmed as an infiltrating pancreatic duct cancer pT3N0M0, pStage IIA.
Final results of study 20050181: A randomized phase III study of FOLFIRI with our without panitumumab (pmab) for the second‑line treatment (tx) of metastatic colorectal cancer (mCRC).
Authors: Alberto F. Sobrero, Marc Peeters, Timothy Jay Price, Yevhen Hotko, Andres Cervantes-Ruiperez, Michel Ducreux, Thierry Andre, Emily Chan, Florian Lordick, Ying Tian, Roger Sidhu
Journal: Journal of Clinical Oncology (2012)

3535 Background: The primary analysis of study 20050181 showed that in patients (pts) with wild-type (WT) KRAS mCRC, pmab plus FOLFIRI given as second-line therapy significantly improved progression-free survival (PFS) vs FOLFIRI alone. Here, we report on a prespecified descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts with mCRC, ECOG 0-2, who had one prior fluoropyrimidine-based chemotherapy regimen were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI (Arm 2). Co-primary endpoints were OS and PFS (central assessment). Secondary endpoints included objective response rate (ORR) and safety. Tumor KRAS status was determined by a blinded central lab. Results: 1186 pts were randomised and received tx: 591 in Arm 1, 595 In Arm 2. 1083 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown below. Conclusions: In pts with WT KRAS mCRC receiving pmab+FOLFIRI vs FOLFIRI, PFS and ORR were significantly improved, and there was a trend toward improved OS. Post-progression anti-EGFR tx may have attenuated any significant difference in OS between tx arms. In pts with MT KRAS mCRC, no difference in efficacy was observed between tx arms. KRAS testing is critical to select appropriate pts for tx with pmab. [Table: see text]
P158 The cost of steroid induced morbidity among severe asthma patients in the UK: Abstract P158 Table 1
Authors: L Barry, J Sweeney, C O’Neill, C Patterson, D Price, L Heaney
Journal: Thorax (2015)

<h3>Introduction</h3> Patients with severe asthma are estimated to comprise 5–10% of the total asthma population but contribute disproportionately to the overall burden of disease. A growing body of evidence exists that implicates steroid exposure in morbidity and healthcare costs among this group. <h3>Aim</h3> This study sought to quantify the additional healthcare costs associated with steroid exposure among patients with severe asthma. <h3>Methods</h3> Data on patients severe asthma (GINA treatment step 5 with ≥4 prescriptions/year oral corticosteroids, n = 808), was obtained from the Optimum Patient Care Research Database (OPCRD) database along with age and gender matched mild/moderate asthma patients (GINA treatment step 2/3, n = 3975) and non-asthmatic controls (rhinitis only, n = 1865) Data included details of all scheduled and unscheduled healthcare consultations and details of prescribed medicines. Data on service use were extracted for the two most recent years for which observations were available. Healthcare contacts were monetised using unit costs extracted from the Personal Social Services Research Unit’s reference costs and for drugs using Prescription Cost Analysis data. All costs were expressed in their 2013 equivalents. Sensitivity analyses related to identification of staff providing specific consultations or activity, and high/low estimates based on assumptions used were produced. Mean high/low healthcare costs over two years by group were estimated and compared as were costs estimated separately for healthcare contacts and prescribed medicines. <h3>Results</h3> As shown in Table 1 mean per patient drug, healthcare activity and combined drug and activity costs were significantly higher for the severe asthma group relative to the mild/moderate group with asthma and the non-asthma controls in both high and low cost scenarios. The mean difference in combined cost between the severe and non-asthma controls groups was between £5,031 (low cost) and £5,545 (high cost) depending on the cost scenario and £4,098 (low cost) and £4,510 (high cost) compared to the mild asthma group. <h3>Conclusions</h3> Patients with severe asthma matched by age and gender have significantly greater direct healthcare costs compared to patients with mild/moderate asthma and non-asthmatic subjects.
Thirty years of investigation on the ergogenic effects of sodium citrate: is it time for a fresh start?
Authors: Vitor de Salles Painelli, Antonio Herbert Lancha Junior
Journal: British Journal of Sports Medicine (2016)

Sodium citrate (SCit) supplementation has been studied for several years as a strategy to reduce the muscle fatigue induced by H+ ion accumulation within the skeletal muscle during high-intensity, short-duration exercise. Several investigations have been published on this matter, and appear to indicate that SCit is not effective as an ergogenic aid, despite its ability to increase extracellular buffering capacity. In this short report, we briefly discuss the SCit results previously published in the literature and consider them in light of new and promising findings, which appear to address issues associated with previous study designs. We also suggest possible reasons for the current lack of reported ergogenic effects from this nutritional strategy and make recommendations that may re-define research in this area.
Phase I clinical trial of antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of advanced pleural mesothelioma.
Authors: R. Hassan, E. Sharon, H. X. Chen, K. Conlon, A. Ling, S. M. Steinberg, I. Pastan
Journal: Journal of Clinical Oncology (2010)

e17518 Background: SS1P is a recombinant immunotoxin, composed of an antimesothelin Fv fused to a 38 kDa fragment of Pseudomonas exotoxin A, targeting mesothelin, a cell surface glycoprotein that is highly expressed in many cancers including malignant mesothelioma (MM). The safety and maximum tolerated dose (MTD) of SS1P was established in phase I clinical trials and the MTD was 45 μ g/kg every other day × 3 doses. Based on preclinical studies that show remarkable synergy when SS1P is given with chemotherapy we initiated a clinical trial of SS1P with pemetrexed (P) and cisplatin (C) for frontline treatment of pleural MM. Methods: Eligible patients (pts) had received no prior treatment, had stage III / IV disease, ECOG PS 0-2, and good organ function. Pts received P 500 mg/m2; C 75 mg/m2 on day 1 every 3 weeks for 6 cycles. SS1P was administered in a dose escalating manner as: 25 μ g/kg; 35 μ g/kg; 45 μ g/kg and 55 μ g/kg on days 1, 3 and 5 of cycle 1 and 2. CT scan was performed every 2 cycles and every 3 months after completion of treatment and tumor response was evaluated using the modified RECIST criteria for mesothelioma. Results: Twelve pts (11 males, 1 female) have been treated so far. Five were treated at SS1P dose of 25 μ g/kg; 3 at 35 μ g/kg; 3 at 45 μ g/kg and 1 at 55 μ g/kg. Two pts treated at 25 μ g/kg withdrew after only 1 cycle and this cohort was expanded to 5 pts. One pt treated at 55μ g/kg had Grade 3 fatigue that was considered a DLT. Adverse events that were possibly or probably related to SS1P included Grade 3 hypoalbuminemia (3 pts) and pain (2 pts) and Grade 2 toxicities of hypoalbuminemia (5 pt), edema (3 pt), pain (2 pt) and fatigue (6 pt). Of the 10 evaluable pts, 5 had partial response (lasting 10 mo; 8+ mo; 5 mo; 5+ mo; 4+ mo), 2 had stable disease (lasting 18+ mo; 4 mo) and 3 had progressive disease. All three patients treated at SS1P dose level of 45μ g/kg had partial response. Conclusions: SS1P given in combination with P and C is well tolerated and clinical benefit was noted in 7 of 10 evaluable pts (5 partial responses and 2 stable disease). Dose escalation at the 55 μ g/kg dose level is ongoing, to be followed by cohort expansion at the MTD. No significant financial relationships to disclose.
Allogeneic HCT with Reduced Intensity Conditioning Versus Autologous HCT for &gt;55 Years Old Patients with Acute Lymphoblastic Leukemia in First Complete Remission: An Analysis from Acute Leukemia Working Party of the EBMT
Authors: Sebastian Giebel, Myriam Labopin, Norbert Claude Gorin, Noel Milpied, Eefke Petersen, Michael N Potter, Jan J. Cornelissen, Denis Caillot, Dietger Niederwieser, Rovira Montserrat, Pavel Jindra, Ellen Meijer, Johan Maertens, Alessandro Rambaldi, Arnon Nagler, Mohamad Mohty
Journal: Blood (2014)
Comparative Analysis of NK Receptor and T-Cell Receptor Repertoires in Patients with Chronic Myeloid Leukemia Treated with Different Tyrosine Kinase Inhibitors
Authors: Gianni Binotto, Luca Frison, Elisa Boscaro, Renato Zambello, Federica Lessi, Anna Parolo, Francesco Piazza, Roberta Bertorelle, Laura Bonaldi, Gianpietro Semenzato
Journal: Blood (2014)
Upshaw-Schulman Syndrome: A Masqueraded Thrombocytopenia during Pregnancy.
Authors: Tomomi Matsuyama, Masanori Matsumoto, Seiji Kato, Nobu Akiyama, Junji Tomiyama, Kazuhiko Natori, Yasunobu Kuraishi, Yutaka Imamura, Nobumasa Inoue, Koichi Kokame, Toshiyuki Miyata, Yoshihiro Fujimura
Journal: Blood (2005)
A phase 2, open-label, multicenter study of durvalumab (MEDI4736) ± tremelimumab in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC): ALPS.
Authors: Eileen Mary O'Reilly, Do-Youn Oh, Myung Ah Lee, Neesha Dhani, Jon Armstrong, Riccardo Belli, Salvatore Ferro, Yong Ben
Journal: Journal of Clinical Oncology (2016)

TPS4150 Background: PDAC is a lethal malignancy; most patients present with metastatic disease and have a median survival of < 1 year with current standard cytotoxic therapies. Thus there is a major unmet need for new treatment approaches. Combined blockade of immune checkpoints is being explored across multiple malignancies. Dual blockade of programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways is the most promising immuno-oncology combination approach to date. Durvalumab (D) is a selective, high affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 and CD80. Tremelimumab (T) is a selective human IgG2 mAb inhibitor of CTLA-4. In a Phase 1/2 study (NCT01693562), D monotherapy showed preliminary evidence of antitumour activity in several tumor types, including PDAC1. Encouraging activity and manageable tolerability of the combination of D + T were reported in a Phase 1b NSCLC study (NCT02000947)2. Here we describe ALPS (NCT02558894), a Phase 2 study of D ± T in mPDAC. Methods: This is a Phase 2, open-label, multicenter, 2-part study to determine the efficacy and safety of D as monotherapy or in combination with T in pts with mPDAC whose disease has progressed on 5-fluorouracil- or gemcitabine-containing chemotherapy (CT). Eligible pts must not have had > 1 prior CT regimen or other systemic therapy for recurrent/mPDAC. Proximate archival or new tumor biopsy procurement is required for PD-L1 and biomarker analyses. In Part A (lead-in), pts will be randomized (1:1) to receive D 1500 mg i.v. q4w; or D 1500 mg i.v. q4w + T 75 mg i.v. q4w for 4 doses, followed by D 1500 mg i.v. q4w for a total of up to 12 months of treatment. The Part A primary endpoint is objective response rate using investigator assessments (RECIST v1.1). Secondary endpoints include DoR; disease control rate; PFS; OS; safety and tolerability; health-related QoL; PK; and immunogenicity. The design of Part B will be based on findings from Part A. Recruitment is ongoing in Part A. 1. Segal NH, et al. Ann Oncol 2014;25(Suppl. 4):1058PD; 2. Antonia SJ, et al. J Clin Oncol 2015;33(Suppl. 15):3014. Clinical trial information: NCT02558894.
Increased Gene Expression Of The Nr4A Family In Bone Marrow T Cells Of Patients With Early Stage Acquired Aplastic Anemia
Authors: Kohei Hosokawa, Takumi Nishiuchi, Takamasa Katagiri, Chizuru Saito, Hiroyuki Maruyama, Naomi Sugimori, Hirohito Yamazaki, Shinji Nakao
Journal: Blood (2013)
A phase II study of trabectedin (ET-743) as a second line therapy in patients with persistent or recurrent endometrial carcinoma
Authors: D. S. McMeekin, G. Manikas, M. Crispens, A. M. Orza, P. Braly, D. Doering, O. C. Trifan, B. Michiels, M. Markman
Journal: Journal of Clinical Oncology (2004)

5086 Background: Trabectedin (Yondelis) is a novel marine-derived agent binding at low nM concentration to the minor groove of DNA in a sequence specific manner. It specifically affects transcription-regulated genes, which requires an intact Transcription Coupled-Nucleotide Excision Repair protein complex. Activity in ovarian and other cancers suggested a use for ET-743 in the treatment of human endometrial carcinoma. Methods: Patients with measurable persistent or recurrent endometrial carcinoma after one prior chemotherapy regimen have been enrolled in this multicenter, open-label, phase II study. ET-743 was administered as a 3 hour iv infusion every 21 days at a starting dose of 1.3 mg/m2. Patients were pretreated with dexamethasone. Primary objective is the response rate; secondary endpoints are safety profile, time to progression, progression-free survival, and overall survival. Results: As of December 15, 2003, 23 patients received treatment. Responses where the following: Eleven (47.83%) of the patients where treated within 3 months from their previous therapy. Median actual vs. planned dose (RDI) is 93.9%. For the 23 treated patients, notable grade 3–4 adverse-events were: elevated ALT 43%, neutropenia 9% and asthenia 4%. One patient developed transient rhabdomyolysis, toxic hepatitis, dyspnea and upper GI hemorrhage. A total of 9 cycles were delayed due to adverse events. Conclusions: ET-743 administered as a single agent in 3 hours infusion every 3 weeks is a reasonably well-tolerated drug with activity in endometrial carcinoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson PRD Johnson & Johnson PRD Johnson & Johnson
The AfFIRM Study: A multicenter phase 2 study of single-agent filanesib (ARRY-520) in patients with advanced multiple myeloma.
Authors: Sagar Lonial, Michel Delforge, Hermann Einsele, Philippe Moreau, Martin Kaiser, Meletios A. Dimopoulos, Albert Oriol, Martin Gyger, Brandi Hilder, Ann M. Ptaszynski, Roger Aitchison, Robert Z. Orlowski
Journal: Journal of Clinical Oncology (2015)

TPS8613 Background: An unmet medical need exists for patients (pts) with multiple myeloma (MM) whose disease has progressed despite prior exposure to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), particularly if their disease has become refractory to carfilzomib (CFZ) and/or pomalidomide (POM). Filanesib is a highly selective, targeted kinesin spindle protein (KSP) inhibitor that has shown promising activity and a manageable safety profile as a single agent in heavily pretreated pts with MM. Due to a distinct mechanism of action, filanesib is expected to be active in cells that have become resistant to IMiDs and PIs, potentially addressing a significant unmet need in the treatment of patients with refractory MM. Nonclinical and prior clinical data have suggested that pts with high serum levels of α 1-acid glycoprotein (AAG) may not obtain therapeutic benefit from filanesib as a result of decreased unbound fraction of drug and ineffective therapeutic exposure. The correlation between Baseline AAG and clinical response to single-agent filanesib will be evaluated. Methods: This single-arm Phase 2 study is designed to assess the efficacy and safety of single-agent filanesib in ~160 pts with MM at centers in North America and Europe (NCT02092922). Eligible pts have received at least 2 prior lines of therapy; have received prior bortezomib and lenalidomide; and have disease refractory to CFZ and/or POM. Filanesib (1.50 mg/m2/day) is administered intravenously on Days 1, 2, 15 and 16 in continuous 28-day cycles with prophylactic filgrastim until disease progression or unacceptable toxicity. Objective response is assessed by independent central review and classified per International Myeloma Working Group (IMWG) criteria. AAG is measured by a central laboratory using a validated immunoturbidimetric assay. The primary endpoint is objective response rate (ORR) in pts with low Baseline AAG. Secondary endpoints are ORR in pts with high Baseline AAG, duration of response, time to best response, clinical benefit rate, disease control rate, progression-free survival, time to next treatment, overall survival and safety. The study includes a 25-pt pharmacokinetics/QT substudy. Clinical trial information: NCT02092922.
High Frequency of HPA-2B Allele in Brazilian Apheresis Blood Donors Detected by Sequence Specific PCR.
Authors: Marcia C.Z. Novaretti, Silvia L. Bonifacio, Reinaldo Manhani, Pedro E. Dorlhiac-Llacer, Alfredo Mendrone, Dalton A.F. Chamone
Journal: Blood (2004)
Simultaneous Isolation and Enrichment of Multi Specific and Multi Functional T-Cells Populations for Treatment of Patients Undergoing Allogeneic Hematopoetic Stem Cell Transplantation,
Authors: Meike Kruse, Halvard Bonig, Markus Kapp, Lothar Germeroth, Hermann Einsele, Götz Ulrich Grigoleit
Journal: Blood (2011)