tbuckley/cabot-search huggingface dataset:
Prevalence of BRCA1/2 mutations among an Irish cohort unrestricted by testing eligibility thresholds.
Authors: Michael Conroy, David James Gallagher, Michael P. Farrell
Journal: Journal of Clinical Oncology (2017)

e13013 Background: Diagnostic criteria for BRCA1/2 genetic testing vary worldwide. Different eligibility thresholds for testing are used in different healthcare systems. In the public system in Ireland, this threshold is based on the Manchester Score (MS), with a score of ≥16 (approximately 10% likelihood of BRCA1/2 mutation) required for testing. Individuals unaffected by cancer are not eligible for diagnostic testing. Testing is also available privately by self-paying. We reviewed all self-pay patients in Ireland who were unrestricted by national guidelines. Methods: We performed a retrospective chart review of results from BRCA1/2 genetic testing in the Mater Private Hospital genetics clinic. Outcomes were recorded as ‘positive’, ‘wild type’ or ‘variant of uncertain significance’ (VUS). Results: 276 patients underwent testing between 2011 and 2016. 203 were affected with a median age of diagnosis of 48 (range 14-76), and 73 were unaffected individuals with a median age of 45 (range 30-74) at testing. 103 affected patients had a MS of ≥ 16: 7(6.8%) tested positive for BRCA1 mutation and 11(10.7%) tested positive for a BRCA2 mutation. Seven (6.8%) had a VUS characterised. 100 affected patients had an MS of &lt;16: 3(3%) tested positive for a BRCA1 mutation and 5(5%)tested positive for a BRCA2 mutation. Eight (8%) had a VUS identified. 39 unaffected individuals had a MS ≥ 16: 6(15.4%) tested positive for a BRCA1 mutation, and 1(2.6%) for a BRCA2 mutation. 5(12.8%) had a VUS. 34 unaffected patients had an MS of &lt;16: 2 (5.8%) tested positive for a BRCA2 mutation and 1 (2.9%) had a VUS. A total of 134 patients had a MS&lt;16, and the prevalence of BRCA1/2 mutation in this group was 7% (n=10). Conclusions: The mutation detection rate was higher than expected in unaffected individuals and individuals belonging to families with MS &lt; 16. Scoring systems such as the MS help to prioritise resources but miss many BRCA1/2 mutation carriers. [Table: see text]
Letters to the Editor: Reply
Authors: Karl H. Schütte
Journal: JNCI Journal of the National Cancer Institute (1969)

Letters to the Editor: Reply Karl H. Schütte Karl H. Schütte Department of Botany University of Cape TownRondebosch C. P. Cape Town South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 43, Issue 2, August 1969, Page v, https://doi.org/10.1093/jnci/43.2.v Published: 01 August 1969
Abstract #2544: miR191 reprogrames gene expression to control invasiveness of breast cancer
Authors: Gianpiero Di Leva, Apollinaire Ngankeu, Pierluigi Gasparini, Meng Li, Cristian Taccioli, Michela Garofalo, Marilena Iorio, Claudia Piovan, Kenneth Nephew, Carlo Croce
Journal: Cancer Research (2009)

MicroRNA are small non coding RNAs of 19-22nt that control gene expression post-transcriptionally. We have previously shown that microRNAs are aberrantly expressed in breast cancer and correlate with different bio-pathologic phenothypes, such as Estrogen Receptor status. Several studies also demonstrated that microRNAs regulate the invasiveness of breast cancer cells. Here, we show that miR191 is strongly down-regulated in highly aggressive breast cancer cell lines and its expression level has high prognostic significance. We found that restoration of miR191 expression in highly aggressive cells reduces their tumorigenicity by inhibiting their growth and invasiveness  in vitro  and  in vivo . Moreover, gene expression profile of miR191-expressing MDA-MB-231 revealed altered expression of    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2544.
02.01 Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumour necrosis factor inhibitors: A systematic review and meta-analysis
Authors: Hussien Ahmed, Abdelrahman Ibrahim Abushouk, Ammar Ismail, Ahmed Elmaraezy, Ahmed Said Badr, Mohamed Gadelkarim, Mohammed Elnenny
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or TNF inhibitors. <h3>Materials and methods</h3> We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. <h3>Results</h3> Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of the American college of rheumatology (ACR20, ACR50, and ACR70) improvement criteria (p&lt;0.00001), disease activity score 28-ESR (RR=3.77, 95% CI [2.47, 5.74], p&lt;0.00001), and Sharp/van der Heijde radiological improvement score (RR=1.63, 95% CI [1.43, 1.85], p&lt;0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR=1, 95% CI [0.78, 1.28], p=0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR=2.13, 95% CI [1.69, 2.68], p&lt;0.00001), compared to placebo group. <h3>Conclusion</h3> The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.
Abstract 14732: Vortex Formation Time in Patients With Hypertrophic Cardiomyopathy
Authors: Dimitrios Maragiannis, Robert C Schutt, Paulino A Alvarez, Karen Chin, John M Buergler, Stephen H Little, Dipan J Shah, Sherif F Nagueh
Journal: Circulation (2015)

Introduction: Vortex formation time (VFT) is an index reflecting optimal vortex formation and efficiency in blood volume transport. The objective of this study was to investigate the association of VFT index with LV diastolic function and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM) and examine its changes after septal reduction therapy. Methods: We studied 116 HCM patients (median age 57.5 [49-65], 39.7% female) who underwent exercise stress testing with measurement of peak O2 consumption within 2 months of imaging. VFT index was calculated and the cohort was divided into 2 groups (cutoff based on prior work and our own normal controls [n=12]): VFT&lt;3.3 (n= 70) and VFT 3.3-5.5 (n=46). Comparisons were made in the subgroup of HCM patients before and after septal reduction therapy (n=31). Results: Patients with VFT &lt; 3.3 had evidence of more advanced diastolic dysfunction grade (p&lt;0.01) and a more advanced NYHA class in comparison with patients with a VFT in the 3.3 to 5.5 range (p=0.048). In addition, patients with VFT 3.3-5.5 achieved a higher workload (7.5 vs 5.7 METs, p=0.016) and maximal oxygen consumption (21.7 vs. 17.7, p=0.003). Following septal reduction therapy VFT increased significantly from 2.8 to 3.7 (p &lt; 0.001). LVEDV (100.9 to 112.9 mL, p=0.003) and LA volume index (50.6 to 40.0 mL/m2, p &lt; 0.001) remodeling were observed as well as reduced septal thickness (1.9 to 1.5 cm, p&lt;0.001) along with improvement in NYHA class (p&lt;0.001). The change in peak O2 consumption related well to the change in VFT (r =0.9, P&lt;0.001). Conclusions: Patients with HCM and VFT 3.3-5.5 are less symptomatic and have better exercise tolerance. VTF increases after septal reduction therapy in keeping with the NYHA class improvement and the change in peak O2 consumption. VFT appears to be a useful parameter to evaluate cardiac function, its relation to exercise tolerance as well as the response to treatment in HCM patients.
Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles
Authors: Pakorn Kraisit, Sontaya Limmatvapirat, Manee Luangtana-Anan, Pornsak Sriamornsak
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10-20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10-30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.
Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer.
Authors: Myong Cheol Lim, Suk-Joon Chang, Heong Jong Yoo, Byung-Ho Nam, Robert Bristow, Sang-Yoon Park
Journal: Journal of Clinical Oncology (2017)

5520 Background: Cytoreductive surgery followed by taxane and platinum-based chemotherapy is standard treatment for advanced ovarian cancer. We compared results of randomly allocated HIPEC in primary advanced epithelial ovarian cancer who have optimal cytoreductive surgery in this prospective randomized multicenter trial. The study endpoint is to evaluate progression free survival (PFS) and overall survival (OS). Methods: 184 patients staged III and IV were randomly allocated to trial arm (HIPEC, cisplatin 75 mg/m 2 , 90 min) or control arm (no HIPEC), intraoperatively based on residual tumor (size &lt;1cm) from July 2010 to January 2016. The groups were well balanced according to the age, body mass index, performance status, stage, histology, serum CA125 level, and use of neoadjuvant chemotherapy (NAC) at study entry. Results: 184 pts (HIPEC, 92; control, 92) were included in this preplanned analysis. No mortality after surgery ± HIPEC was identified in both groups. Postoperative outcomes including extent of surgery, estimated blood loss, residual tumor, and hospitalization day were not different between both group, except operation time (487 vs. 404 min, p&lt;0.001) due to HIPEC procedure. The most common adverse event was anemia: 67.4% in HIPEC and 50% in control group (p=0.025). The other toxicity common in HIPEC group is the elevation of creatinine (15.2% vs. 4.3%, p=0.026). There were no differences between both groups for transfusion (35.9 vs. 29.3, p=0.432), neutropenia (19.6 vs. 10.9%, p=0.151), and thrombocytopenia (9.8 vs. 3.3%, p=0.136). Two-year PFS was 43.2% and 43.5% and 5-year PFS was 20.9% and 16.0% in HIPEC and control group, respectively (p=0.569). Five-year OS was 51.0% and 49.4% in HIPEC and control group, respectively (p=0.574). In women who received NAC, the median PFS for HIPEC and control group were 20 and 19 months, respectively (log-rank test, p = 0.137) and the median OS for HIPEC and control group were 54 and 51 months, respectively (log-rank test, p = 0.407). In the subgroup with NAC, 2-year PFS was 37.2% in HIPEC group and 29.5% in control group and 5-year OS was 47.9% in HIPEC group and 27.7% in control group. After 20 months in PFS and 30 months in OS, two survival curves in women who received NAC showed the trend of gradual distinction, favoring HIPEC group. Conclusions: No mortality was identified and postoperative morbidities were not statistically different between two groups except anemia and creatinine elevation in HIPEC group. The survival analysis did not show the statistical superiority of the HIPEC arm. More follow-up is required to confirm the impact of HIPEC on long-term survival outcome in ovarian cancer, especially in NAC group. Clinical trial information: NCT01091636.
Refinement of prespecified cutoff for genomic loss of heterozygosity (LOH) in ARIEL2 part 1: A phase II study of rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC).
Authors: Robert L. Coleman, Elizabeth M. Swisher, Amit M. Oza, Clare L. Scott, Heidi Giordano, Kevin K. Lin, Gottfried E. Konecny, Anna Tinker, David M. O'Malley, Rebecca Sophie Kristeleit, Ling Ma, Katherine M. Bell-McGuinn, James D. Brenton, Janiel M. Cragun, Ana Oaknin, Isabelle Laure Ray-Coquard, Scott H. Kaufmann, Sandra Goble, Lara Maloney, Iain A. McNeish
Journal: Journal of Clinical Oncology (2016)

5540 Background: ARIEL2 (NCT01891344) prospectively evaluated a tumor-based next-generation sequencing (NGS) LOH assay and novel algorithm to predict sensitivity to rucaparib based on BRCAmutstatus and degree of genomic LOH. Methods: Pts with measurable, platinum-sensitive HGOC were classified as BRCAmut, BRCAwt/LOHhigh (BRCA-like), or BRCAwt/LOHlow by NGS analysis of tumor tissue DNA. The primary objective of this analysis was to compare progression-free survival (PFS) of BRCAmut vs LOHhigh and LOHlow tumors. A planned post hoc analysis identified a refined genomic LOH cutoff to differentiate PFS of pts with LOHhigh vs LOHlowtumors. Results: ARIEL2 part 1 completed enrollment in December 2014; the data cutoff date was January 18, 2016. In 204 treated pts, median age was 65 years; median number of prior regimens was 1. Efficacy data are shown in the Table. The confirmed radiologic objective response rate (rORR) for germline (n=20) and somatic (n=20) BRCAmut pts was 85% and 75%, respectively. Refinement of the LOH cutoff improved median PFS and PFS HR in the LOHhigh vs LOHlowgroup. Common treatment-related AEs included nausea (71%; grade ≥3: 3%), fatigue (59%; grade ≥3: 6%), ALT/AST increased (41%; grade ≥3: 11%), and anemia (30%; grade ≥3: 19%). Three pts died due to disease progression. Conclusions: Refinement of the genomic LOH cutoff improves selection of BRCAwt/LOHhigh pts more likely to benefit from rucaparib. Clinical trial information: NCT01891344. BRCAmut Prespecified LOH Cutoff BRCAwt/LOHhigh BRCAwt/LOHlow n* 40 82 70 rORR, % 80.0 35.4† 12.9† DOR‡ 11.2 (7.4–13.7) 10.8 (5.5–12.0) 5.9 (4.6–8.5) PFS‡ 12.8 (9.0–14.7) 5.7 (5.3–7.6) 5.2 (3.6–5.5) PFS HR§ 0.27 (0.16–0.44); P<0.001 0.62 (0.42–0.90); P=0.011 − BRCAmut Refined LOH Cutoff BRCAwt/LOHhigh BRCAwt/LOHlow n* 40 69 83 rORR, % 80.0 39.1† 13.3† DOR‡ 11.2 (7.4–13.7) 10.8 (7.6–20.6) 5.7 (1.9–7.4) PFS‡ 12.8 (9.0–14.7) 7.2 (5.5–9.6) 5.0 (3.6–5.4) PFS HR§ 0.25 (0.15–0.42); P<0.001 0.51 (0.34–0.74); P<0.001 − DOR, duration of response; HR, hazard ratio. *LOH not determined for 12 pts. †Both confirmed and unconfirmed responses (RECIST v1.1). ‡Median months (95% confidence interval [CI]). §HR (95% CI) vs BRCAwt/LOHlow.
Endoscopy-guided surgery of an atrio-esophageal fistula after failure of self-expandable metal stents
Authors: Ignacio Couto-Worner, Pedro Alonso-Aguirre, Emilio Estévez-Prieto, Benito González-Conde, Carlos Velasco-García, José Cuenca-Castillo, Salvador Fojón-Polanco
Journal: Endoscopy (2017)

A 34-year-old man presented at the emergency department with syncope and atrial fibrillation. He had undergone atrial fibrillation ablation 3 weeks earlier. He was initially treated with anti-arrhythmic agents but developed seizures. A computed tomography scan revealed air embolisms on the brain and an atrio-esophageal fistula in the mediastinum ([Fig. 1]). Because of hemodynamic instability, surgeons asked the Gastroenterology Department to place an esophageal stent.
Phenotype Analysis and Clinical Management in a Large Family with a Novel Truncating Mutation in RASGRP2, the Caldag-GEFI Encoding Gene
Authors: Amrita Desai, Wenche Jy, Wolfgang Bergmeier, Mathias Canault, Marie-Christine Alessi, Paquita Nurden, Yeon-Soong Ahn, Alan T. Nurden
Journal: Blood (2016)
Association Between Structured Physical Activity and Sedentary Time in Older Adults
Authors: Amal A. Wanigatunga, Walter T. Ambrosius, W. Jack Rejeski, Thomas M. Gill, Nancy W. Glynn, Catrine Tudor-Locke, Todd M. Manini
Journal: JAMA (2017)

This post hoc exploratory analysis of Lifestyle Interventions and Independence for Elders (LIFE) trial data examines the association between the trial’s physical activity intervention and sedentary time in older adults.
Asthma in the elderly and late-onset adult asthma
Authors: R. M. Dunn, P. J. Busse, M. E. Wechsler
Journal: Allergy (2017)

Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis, and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be underdiagnosed and undertreated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (ie, corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population.
The impact of dietary regimen compliance on outcomes for head and neck cancer patients treated with definitive radiation therapy.
Authors: Madhur Garg, Rafi Kabarriti, Amanda Bontempo, Maria Romano, Nitin Ohri, Shankar Viswanathan, Daniel Mark, Hilda Haynes, Bradley A Schiff, Stuart Packer, Richard V Smith, Missak Haignentz, Chandan Guha, Shalom Kalnicki
Journal: Journal of Clinical Oncology (2015)

e17100 Background: We have initiated a nutritional program where all patients treated with definitive radiation therapy are evaluated and closely followed by a registered oncologic dietitian. In this report, we analyze nutritional factors and compliance with dietary recommendations as related to overall survival (OS) and progression free survival (PFS). Methods: We identified 352 patients with non-metastatic oropharyngeal (206) and laryngeal (146) cancer who were treated with definitive RT between 2004-2013. Individual patient data including compliance with nutritional program were tabulated. Adherence to the nutritional program was scored weekly and patients were deemed non-compliant with nutritional program if they cancelled > 25% of their appointments with the dietitian, refused nutritional counseling or did not follow recommendations. Descriptive analyses, logrank test and Cox regression model was fitted to examine predictors of OS and PFS. Results: The median follow-up was 22.86 (0.56-116) months. The probability of survival was 0.91, 0.86 and 0.73 at year 1, 2 and 5, respectively. 85.8% of patients met with a dietitian during their course of RT and 62.5% of these patients were compliant with the nutritional program. Compliance with nutritional program resulted in 27% (HR: 0.73, 95%CI: 0.43-1.26) and 31% (HR: 0.69, 95%CI: 0.50-0.94) protection from death and disease progression. Lower pretreatment BMI was associated with a higher risk for death (HR: 0.94, 95%CI: 0.90-0.99) and disease progression (HR: 0.96, 95%CI: 0.93-0.99). Though not statistically significant, PEG tubes use increased risk for overall death and disease progression. Conclusions: Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with an aggressive nutritional program appear to have improved PFS. Given that patients with low pre-treatment BMI appear to have worse outcomes, further studies exploring ways to increase compliance with nutritional programs are warranted.
Neurofibromatosis Type 1–Associated MPNST State of the Science: Outlining a Research Agenda for the Future
Authors: Karlyne M. Reilly, AeRang Kim, Jaishri Blakely, Rosalie E. Ferner, David H. Gutmann, Eric Legius, Markku M. Miettinen, R. Lor Randall, Nancy Ratner, N. L. Jumbé, Annette Bakker, David Viskochil, Brigitte C. Widemann, Douglas R. Stewart
Journal: JNCI Journal of the National Cancer Institute (2017)

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma for which the only effective therapy is surgery. In 2016, an international meeting entitled "MPNST State of the Science: Outlining a Research Agenda for the Future" was convened to establish short- and long-term research priorities. Key recommendations included the: 1) development of standardized, cost-efficient fluorodeoxyglucose positron emission tomography and whole-body magnetic resonance imaging guidelines to evaluate masses concerning for MPNST; 2) development of better understanding and histologic criteria for the transformation of a plexiform neurofibroma to MPNST; 3) establishment of a centralized database to collect genetic, genomic, histologic, immunohistochemical, molecular, radiographic, treatment, and related clinical data from MPNST subspecialty centers in a standardized manner; 4) creation of accurate mouse models to study the plexiform neurofibroma-to-MPNST transition, MPNST metastasis, and drug resistance; 5) use of trial designs that minimize regulatory requirements, maximize availability to patients, consider novel secondary end points, and study patients with newly diagnosed disease. Lastly, in order to minimize delays in developing novel therapies and promote the most efficient use of research resources and patient samples, data sharing should be incentivized.
French comment on article Clinical implications of low grade dysplasia found during inflammatory bowel disease surveillance: a retrospective study comparing chromoendoscopy and white-light endoscopy1 Conséquences cliniques de la mise en evidence de dysplasie bas de grade dans le suivi les maladies inflammatoires chroniques de l’intestin: Analyse retrospective comparant la chromoendoscopie à l’endoscopie en lumière blanche
Journal: Endoscopy (2017)

Les recommandations actuelles de surveillance des patients atteints de maladie inflammatoire chroniques de l’intestin (MICI) reposent sur l’utilisation d’une chromoendoscopie (CE) pancolique. Cependant, on ne sait pas si le risque de transformation des lésions de dysplasie de bas grade (DBG) en dysplasie de haut grade (DHG) ou cancer colo-rectal (CCR) diagnostiquées lors de la CE est supérieur à celui des procédures utilisant simplement l’endoscopie en lumière blanche (ELB). Le but de ce travail était donc de comparer le risque de néoplasie avancée (DHG ou CCR) lors du suivi après détection en CE versus détection en ELB.