tbuckley/cabot-search huggingface dataset:
Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity
Authors: D. Simon, A. Cianferoni, J. M. Spergel, S. Aceves, M. Holbreich, C. Venter, M. E. Rothenberg, I. Terreehorst, A. Muraro, A. J. Lucendo, A. Schoepfer, A. Straumann, H.-U. Simon
Journal: Allergy (2016)

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures.
A phase I and pharmacokinetic (PK) study of weekly docetaxel (D), cisplatin (P), and daily capecitabine (C) (DPC) in patients with advanced solid tumors
Authors: M. G. Fakih, W. C. Zamboni, N. Ramnath, M. M. Javle, J. K. Schwarz, R. A. French, L. L. Regal, R. K. Gorenflo, P. J. Creaven
Journal: Journal of Clinical Oncology (2004)

2092 Background: D, P & C are 3 active chemotherapeutic agents with different mechanisms of activity. We investigated a weekly D & P with twice daily C regimen in patients (pts) with advanced solid tumors in a phase I study. Methods: Three pts were treated at each dose level (DL) given no dose-limiting toxicity (DLT) was noted. D & P were each given intravenously over 30 min on D1 & D8, and C was given orally BID on D1-D14; the cycle was repeated every 21 days. DL of D, P & C (mg/m2) were: 1) 20, 20, 600; 2) 20, 20; 825; 3) 27, 20; 825; 4) 27, 27; 825; 5) 36, 27; 825; 6) 36, 36; 825. DLT was defined as any treatment-induced grade (G) 4 neutropenia > 1 week, febrile neutropenia, G4 thrombocytopenia, G3 or higher non-hematologic toxicity (diarrhea must be > 1 day; nausea appropriately medicated), and delay in treatment of ≥ 2 weeks. CT scans were performed every 2 cycles. PK studies of D were performed on D1/cycle 1 with C and on D1/cycle 2 without C. D plasma concentrations were measured by an LC-MS/MS assay. Results: Twelve pts are evaluabe for toxicity (7/5 M/F; median age 57; 3 NSCL; 2 pancreatic carcinoma; and 1 each SCLC, gastric, anal, unknown, H & ENT, colon, and esophageal carcinomas; 10 pre-treated). Ten pts are evaluable for response. No DLT was noted at DL1–4 and accrual continues at DL 5. Treatment-related toxicities were G1 or G2 in the first cycle. G2 diarrhea occurred in 4 pts on DL 1–2. G2 stomatitis occurred in 1 pt on DL 2. No G2 or greater hand and foot syndrome was noted. Two patients had a confirmed partial response (gastric 8 months+; pancreatic 6 months+). Seven pts had stable disease (SD) lasting 12 or more weeks, 2 pts unconfirmed SD, and 1 patient (NSCL) progressed. A median of 6 cycles/pt has been administered to date. The mean +/- standard deviation of D clearance was 32 +/- 13.2 L/hr/m2 and 33 +/- 19.2L/hr/m2 on cycle 1 & 2 respectively. Conclusions: DPC is a well-tolerated combination with clinical activity in this phase I study. PK analysis suggests that C does not alter the disposition of D. This combination should be investigated further in efficacy studies once a phase II recommended-dose is identified. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Aventis Pharmaceuticals
Incidence and Remission of Nocturia: A Systematic Review and Meta-analysis
Authors: Jori S. Pesonen, Rufus Cartwright, Altaf Mangera, Henrikki Santti, Tomas L. Griebling, Alexey E. Pryalukhin, Jarno Riikonen, Riikka M. Tähtinen, Arnav Agarwal, Johnson F. Tsui, Camille P. Vaughan, Alayne D. Markland, Theodore M. Johnson, Riikka Fonsell-Annala, Charlie Khoo, Teuvo L.J. Tammela, Yoshitaka Aoki, Anssi Auvinen, Diane Heels-Ansdell, Gordon H. Guyatt, Kari A.O. Tikkinen
Journal: European Urology (2016)
Administration of further chemotherapy (CT) after capecitabine as first-line chemotherapy (CT) for metastatic breast cancer (MBC)
Authors: M. Debled, A. Trainaud, M. Durand, A. Floquet, V. Brouste, L. Mauriac
Journal: Journal of Clinical Oncology (2007)

1095 Background: Based on results of randomized trials of Xeloda (X) vs CMF or taxanes (T) as first-line CT for MBC, very favorable tolerability, and patients’ (pts) preference for oral therapy, front-line X is now often used in our institution, especially for slowly progressing disease. As other CT regimens, especially T, have demonstrated improved OS, we analyzed post-X CT in these pts. Methods: Analysis was restricted to pts who began X before Jan 05, all of whom have now discontinued because of progression or toxicity. Results: In 90 eligible pts, median TTF and OS from initiation of X are 9 [95% CI 7–11] and 26 [22–30] months, respectively. 75% of pts received second-line CT. Three subgroups can be analyzed: (A) 65 pts (median age 58y, range 34–84) received further CT (median 2 regimens, range 1–6) after stopping X, including T (85% of pts), anthracycline (a/c: 42%), vinorelbine (45%), or mitomycin C (20%). 24 pts received =2 regimens including a/c and T; 7 pts received neither T nor a/c (vinorelbine, n = 6; UFT, n = 1). Median OS from initiation of X was 30 months [95% CI 27–32]. 30 pts are alive after a 16-month median follow-up since X failure; they may receive another CT; (B) 3 pts are currently receiving endocrine therapy after X failure and may receive another CT later; (C) 22 pts (24%) (median age 77y, 19 =70y) died without receiving further CT. Median OS from initiation of X was 11 months (range 0.5–23). 4 of these pts (aged 57, 71, 74, and 84y) received endocrine therapy for 2–10 months. Ability to administer further CT varies with age: of pts &lt;75y, 89% received subsequent CT (T: 75%), whereas 37% of pts =75y received second-line CT. Conclusions: TTF and OS indicate that capecitabine is very active as first-line CT for MBC. For a large majority of pts &lt;75y, first-line X does not compromise administration of further CT including T. No significant financial relationships to disclose.
Minimum serum antibody levels associated with protection from human papillomavirus 16 (HPV 16) reinfection among placebo subjects
Authors: K. Ault, H. Sings, O. Bautista, R. Marchese, E. Barr
Journal: Journal of Clinical Oncology (2005)

5024 Background: We have shown that prophylactic administration of a prototype HPV 16 L1 coat protein virus-like particle (VLP) vaccine was 100% effective in preventing acquisition of persistent HPV 16 infection. Given this efficacy, a minimum protective anti-HPV 16 level could not be defined. Using such subjects within the placebo arm, we assessed the minimal anti-HPV 16 level needed to protect against reacquisition of HPV 16 infection. Methods: 2391 women aged 16–23 years were enrolled in a 4 year randomized, double-blind study of an HPV 16 L1 VLP vaccine, as part of the development of a quadrivalent HPV vaccine. Genital samples for HPV 16 DNA were obtained at Day 1, Month 7 and then every 6 months through Month 48. Serum was collected for anti-HPV 16 testing by immunoassay at Day 1 and Months 7, 12, 18, 30, 42, and 48. Antibody levels were reported in arbitrary units (mMU/mL). HPV 16 re-infection was defined as HPV 16 DNA detection in genital samples collected at ≥2 consecutive visits, or on the last visit on record. Results: At Day 1, 111 placebo subjects were free of HPV 16 DNA but anti-HPV 16 seropositive. Of these, 14 reacquired HPV 16 infection. Risk for reacquisition of HPV 16 infection was inversely related to Day 1 anti-HPV16 levels. Please see table below. Conclusions: Anti-HPV 16 levels >20 mMU/mL at baseline appeared to be generally protective against re-acquisition of HPV 16 infection over a 4-year interval. This observation is consistent with previously reported data, whereby HPV 16-naïve women who were vaccinated with an HPV 16 L1 VLP vaccine (and thus had anti-HPV 16 levels >20 mMU/mL) were protected from HPV 16-related infection or disease. These data suggest that anti-HPV16 levels >6 mMU/mL may confer some degree of protection, while anti-HPV16 levels >20 mMU/mL may predict protection against HPV 16 over a sustained interval. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck
<i>CDKN2A</i>mutations with p14 loss predisposing to multiple nerve sheath tumours, melanoma, dysplastic naevi and internal malignancies: a case series and review of the literature
Authors: M.R. Sargen, S.L. Merrill, E.Y. Chu, K.L. Nathanson
Journal: British Journal of Dermatology (2016)

An inherited germline mutation in CDKN2A is the most common cause of familial atypical multiple mole melanoma (FAMMM) syndrome. Although it is well known that CDKN2A mutations confer an increased risk for melanoma and pancreatic carcinoma, the association with an increased risk for nerve sheath tumours and other tumour types is under‐recognized. We report a family with a missense mutation (c.151–1G>C) at the acceptor splice site of intron 1 of CDKN2A, resulting in loss of function of both tumour suppressor proteins p16INK4 and p14ARF. This mutation is associated with a clinical phenotype of FAMMM syndrome in which patients develop numerous benign and malignant mutations, brain tumours, sarcomas and other solid tumours, in addition to melanoma and dysplastic naevi. Our proband initially presented with multiple nerve sheath tumours, leading to diagnostic confusion with Neurofibromatosis type 1. Loss of p14 expression results in increased MDM2‐mediated degradation of the tumour suppressor protein p53, and predisposes mutation carriers to multiple benign and malignant neoplasms. This article highlights the importance of considering CDKN2A mutations in patients with dysplastic naevi, melanoma and multiple nerve sheath tumours, specifically those with histological features of both neurofibromas and schwannomas. We also present a discussion of medical management for patients with this high‐risk cancer susceptibility syndrome.
Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation
Authors: P. Blanco-Lobo, E. Cordero, C. Martín-Gandul, M.A. Gentil, G. Suárez-Artacho, M. Sobrino, J. Aznar, P. Pérez-Romero
Journal: Journal of Infection (2016)
Economic burden of transfusion dependence in patients with myelodysplastic syndromes
Authors: J. R. Frytak, H. Henk, M. Nelson, C. Decastro
Journal: Journal of Clinical Oncology (2005)

6064 Background: Few studies have examined health economic burden in transfusion-dependent patients with myelodysplastic syndromes (MDS). Two-thirds of MDS patients are estimated to have anemia and require red blood cell transfusions, costing approximately $550/unit transfused. This study explored health care costs and utilization in this population. Methods: Administrative claims data from a large US health plan with commercial, Medicare, and Medicaid members were used to identify transfusion-dependent patients from 5/1/00 through 3/31/03 that were ≥ 55 years of age. Transfusion dependence (TD) was defined as ≥ 2 transfusion events in an 8-week period as indicated by procedure and/or revenue codes and service dates for whole or red blood cell transfusions, and a minimum of a third transfusion occurring 3–6 months from the initial transfusion. MDS was identified from medical claims data with an ICD-9-CM diagnosis code (238.7, 284.9, 285.0, 205.20, 208.20) in the 6 months prior to and up to 12 months following the index transfusion date. Patients with evidence of chemotherapy-induced anemia were excluded. Deferoxamine use was identified in all TD patients, regardless of MDS status, and one year of claims data following first administration was captured. Medical costs were defined as transfusion-related if costs occurred on the same day as a transfusion event. Results: A total of 338 transfusion-dependent MDS patients were identified. Average age was 73.6 years. Annualized average total medical and pharmacy costs were $58,457. 82.7% of transfusions occurred in an outpatient setting with an average of 11.03 outpatient transfusions per patient per year. Annualized transfusion-related medical costs in the outpatient setting were $9,270. 49.41% of patients had erythropoietin use and average costs per treated patient were $12,589. For 20 TD patients with deferoxamine use and one year of continuous follow-up, the average duration of therapy was 276.35 days; and average costs per year were $7,437. Conclusions: The economic burden in TD MDS patients is high. Significant opportunity exists to decrease economic burden if transfusion independence can be achieved in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Successful implementation of an asthma care bundle in a UK hospital
Authors: Alison Gill, Rehan Naseer, Alan Hart-Thomas, Annika Graham
Journal: European Respiratory Journal (2011)

Introduction:  A care bundle is a checklist of guidelines for clinicians. These have been successfully implemented in areas such as central line sepsis & ventilator-acquired pneumonia. We proposed that a care bundle would improve acute asthma care & outcomes by providing key clinical prompts. The 2009 British Thoracic Society (BTS) asthma audit highlighted areas for improvement, including PEFR and SpO2 documentation, inhaler technique review & use of written action plans.   Aims and objectives:  To assess the impact of an asthma care bundle on concordance with UK asthma standards.   Method:  A checklist sticker was created, piloted & implemented on acute medical wards, and the impact assessed using the 2010 BTS asthma audit.   Results:  Pre- and post-care bundle results are shown in Table 1 (care bundle elements shown in bold)   Conclusion:  Use of the care bundle improved acute asthma care, particularly pre-discharge education & planning. Further work is needed to assess longer-term impact e.g. readmission rates, and the bundle is being revised in light of the latest audit data.
Chromosomal Analysis of Lymphoblastoid Cell Lines After Heterosexual Cocultivation With Bone Marrow Fibroblasts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Benyesh-Melnick, M Macek, E H Seidel, V Macková
Journal: JNCI Journal of the National Cancer Institute (1971)
Fludarabine and Cytarabine Based Induction Therapy Is Associated With High Response Rate and Durable Remission With Low Treatment Related Mortality In Elderly Patients With Core-Binding Factor AML (CBF-AML)
Authors: Koichi Takahashi, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi, Stefan Faderl, Susan O'Brien, Hagop M Kantarjian, Gautam Borthakur
Journal: Blood (2013)
Phase II trial of gefitinib for recurrent or metastatic esophageal or gastroesophageal junction (GEJ) cancer
Authors: D. J. Adelstein, L. A. Rybicki, M. A. Carroll, T. W. Rice, T. Mekhail
Journal: Journal of Clinical Oncology (2005)

4054 Background: Conventional chemotherapeutic agents are of limited benefit in patients (pts) with recurrent or metastatic cancer of the esophagus or GEJ. We report preliminary results from an ongoing phase II trial of gefitinib, an oral epidermal growth factor receptor inhibitor, in this population. Methods: Eligibility for this trial requires a histologic diagnosis of esophageal or GEJ adenocarcinoma or squamous cell carcinoma which is either metastatic, or recurrent and incurable after initial definitive therapy. Pts may not have received more than one prior chemotherapy regimen, must have an ECOG performance status of 0–1, and must sign informed consent. Treatment consists of gefitinib 250 mg daily for a minimum of 8 weeks followed by clinical reassessment. Experimental therapy is discontinued if there is objective disease progression, subjective evidence of clinical deterioration or drug intolerance. Results: Between 4/03 and 10/04, 20 pts (17 men, 3 women) with a median age of 58 (range 45–73) years were entered on this trial. There were 12 pts with GEJ and 7 with distal esophageal adenocarcinoma; and 1 with a proximal esophageal squamous cell cancer. All but 4 pts had previously received chemotherapy. Toxicity was modest with grade I diarrhea in 10 pts (50%), a grade II gefitinib rash in 1 (5%), and a grade I rash in 14 pts (70%), and grade I-II nausea in 5 pts (25%). Compliance with the medication could be assessed in 16 of the 20 pts and was excellent. Pts took an average of 98% (range 89–100%) of the prescribed pills. There have been 3 partial responders and 3 pts with stable disease (30% response/stability) with a mean duration of benefit of 4.6 (range 2.2–7.9) months. The median survival for all 20 pts is 5.5 months, but has not yet been reached for the 6 responding or stable pts. Conclusions: Gefitinib is well tolerated and active in previously treated pts with recurrent or metastatic esophageal or GEJ cancer. The disease response or stability rate with this agent is similar to that achieved for other solid tumors. This study continues to accrue pts and is supported by AstraZeneca pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Lymph node density and number of adjuvant chemotherapy cycles for node-positive resected bladder cancer: University of Iowa experience
Authors: T. Abu Hejleh, M. O'Donnell, D. Vaena
Journal: Journal of Clinical Oncology (2009)

e16126 Background: Although its survival benefit is unclear, adjuvant chemotherapy (CT) is commonly utilized for node-positive bladder cancer after radical cystectomy (RC) and lymph node (LN) dissection. The ideal number of CT cycles is also unknown. Previous studies in patients with metastatic disease administered up to 6 cycles. Lymph node density (LND) (ratio of positive LN/total LN) has been shown to be more important than nodal TNM stage in predicting outcomes after RC, and suggested a 20% LND cutoff for prognosis. This finding also accounted for adjuvant chemotherapy (yes vs. no). We evaluated the long-term outcomes of node-positive pts after RC, according to the number of cycles of adjuvant CT received and adjusting for LND. Methods: The study was IRB approved. Patients still alive were required to give informed consent and accrual is ongoing. Pathological and survival variables of pathologically node-positive pts who underwent RC at the University of Iowa in the last 5 yrs and then received adjuvant CT were retrospectively evaluated. Results: 22 pts have been evaluated to date. Median age was 62 (37–86). Median number of LNs resected was 19.5 and median LND was 19% (3–47). Median survival was 17 mo (10–67). 21 pts received a platinum-gemcitabine combination. The table shows the pt distribution according to no. of CT cycles, LND and number of &gt; 2 yr survivors. Median survival was 17 mo both for pts with LND ≤ 20% and &gt;20% . Median survival of pts with ≤ 4 cycles of CT was 16.5 mo (11–67), with 4 patients still alive at 14–67 months. Median survival of pts who received &gt; 4 cycles of adjuvant CT was 17 mo (10–44), with 3 pts still alive at 29–39 months. Conclusions: The pt distribution table suggests that patients with high LND may have been sicker, and thus less able to receive as many CT cycles. This study is limited by its retrospective nature and small current sample. Accrual is ongoing and updated data will be available. Prospective adjuvant trials could stratify or randomize patients based on LND. [Table: see text] No significant financial relationships to disclose.
P0272 : Long-term inhibition of EGFR in human cholangiocarcinoma cells leads to the induction of an epithelial to mesenchymal transition program and activation of insulin/insulin growth factor 1 receptors
Authors: J. Vaquero, A. Clapéron, M. Mergey, C. Desbois-Mouthon, F. Praz, L. Fouassier
Journal: Journal of Hepatology (2015)
Abstract 19066: D-Dopachrome Tautomerase Provides a Novel Cardioprotective Mechanism Through its Modulation on AMPK Activation in Heart During Ischemia-reperfusion
Authors: Dake Qi, Kwame Atsina, Xiaoyue Hu, Xiaohong Wu, Lin Leng, Richard Bucala, Lawrence Young
Journal: Circulation (2012)

Endogenously released cardiac proteins or cardiokines regulate intracelluar signaling pathway and cardiac injury in response to stress. Macrophage migration inhibitory factor (MIF) modulates AMP-activated protein kinase (AMPK) activation and limits cardiac injury during ischemia-reperfusion. Genetic deletion of the MIF receptor, CD74, has more profound effects on ischemic tolerance and AMPK activation, than deletion of MIF alone, suggesting the possibility of a second receptor ligand. We recently identified D-dopachrome tautomerase (DDT) as a homolog of MIF, and the purpose of this study was to determine the actions of DDT in the heart. DDT perfusion in mouse heart increased AMPK in a dose-dependent manner (from 10 to 50ng/ml) without alterations in LV contractile function. Immunohistochemistry showed that DDT was highly expressed in cardiomyocytes in the mouse heart. DDT release from perfused mouse hearts (baseline: 2 ± 0.5 ng/min; post-ischemia: 4.5 ± 0.7 ng/min, p&lt;0.05) was triggered by brief episodes (15 min) of ischemia and the inhibition of DDT actions by perfusion with neutralizing antibody (anti-DDT vs. non-immune IgG) significantly attenuated AMPK activation during ischemia. Anti-DDT (100µg/ml) also resulted in more pronounced cardiac injury following ischemia-reperfusion. Parallel effects were observed in isolated rat heart papillary muscles: recombinant DDT treatment had a similar pharmacologic effect to induce AMPK activation in a dose-dependent manner. Hypoxia (15 min) also stimulated DDT release from rat papillary muscles and inhibition of extracellular DDT by DDT neutralizing antibodies impaired AMPK activation. These pharmacologic and physiologic effects of DDT were also observed in isolated rat cardiomyocytes, indicating that DDT has specific autocrine effects. DDT treatment (400ng/ml) increased intracellular calcium in cardiomyocytes and STO-609 (2µM), a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor attenuated DDT induced AMPK phosphorylation, suggesting that DDT induced AMPK activation is mediated by calcium-CaMKK pathway. Thus, DDT is a novel endogenous cardiac protein that modulates cardiac stress response pathways and protects against injury during ischemia.