tbuckley/cabot-search huggingface dataset:
Abstract 14905: Allele Specific Silencing Prevents Malignant Arrhythmias and Ultrastructural Abnormalities in Ryanodine Receptor Mutant Mice
Authors: Rossana Bongianino, Alessandra Vollero, Francesco Lodola, Marco Denegri, Simona Boncompagni, Silvia Fasciano, Andrea Mazzanti, Damiano Mangione, Serena Barbaro, Giulia Rizzo, Alberto Auricchio, Carlo Napolitano, Feliciano Protasi, Silvia G Priori
Journal: Circulation (2016)

Introduction:  Mutations in the cardiac Ryanodine Receptor gene (RYR2) are causative of dominant Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals when exposed to emotions or physical exercise.   Hypothesis:  We investigated the efficacy of allele specific silencing by RNA interference as an innovative therapeutic approach to attenuate clinical manifestations of dominant CPVT.   Methods:  We developed an  in vitro  mRNA and protein-based assays to screen multiple siRNAs for their ability to selectively silence the mutant RYR2-R4496C mRNA over the corresponding wild-type allele. For the most performant of these siRNAs (siRYR2-U10), we evaluated the specificity and efficacy of an adeno-associated serotype 9 viral vector (AAV9) expressing the homologous miRNA (miRYR2-U10) in correcting RyR2 function following  in vivo  delivery in pups RyR2 R4496C/+  mice (1.3 x 10 12  viral particles, 1 week after birth).   Results:  ECG analysis revealed a high incidence of adrenergically mediated ventricular tachycardia (VT) in AAV9-miRNA-scramble injected mice (SCR), but not in those treated with AAV9-miRYR2-U10 (U10; p   Conclusions:  The evidence that RNA interference of RyR2-R4496C transcripts preventing life-threatening arrhythmias in CPVT mice raises the possibility that mutant allele specific silencing might benefit CPVT patients.
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.
Authors: Sai-Hong Ignatius Ou, Marcello Tiseo, D. Ross Camidge, Myung-Ju Ahn, Rudolf M. Huber, Maximilian J. Hochmair, Sang-We Kim, Howard Jack West, Karen L. Reckamp, Julian R. Molina, Geoffrey Liu, Angelo Delmonte, Santiago Viteri Ramirez, Alessandra Bearz, Yvonne J. Summers, William Reichmann, David Kerstein, Scott N. Gettinger, Dong-Wan Kim
Journal: Journal of Clinical Oncology (2017)

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]
Synthesis of cADPR and NAADP by intracellular CD38 in heart: role in inotropic and arrhythmogenic effects of beta-adrenoceptor signaling
Authors: W K Lin, M Maciejewska, E L Bolton, Y Wang, F O'brien, M Ruas, M Lei, R Sitsapesan, A Galione, D A Terrar
Journal: Cardiovascular Research (2016)
Bevacizumab (Bev) or cetuximab (Cet) plus chemotherapy after progression with bevacizumab plus chemotherapy in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): Final analysis of a French randomized, multicenter, phase II study (PRODIGE 18)
Authors: J. Bennouna, S. Hiret, C. Borg, A. Bertaut, O. Bouche, G. Deplanque, E. Francois, T. Conroy, F. Ghiringhelli, G. des Guetz, J.-F. Seitz, P. Artru, T. Stanbury, S. Charpentier, M. Denis, A. Adenis
Journal: Annals of Oncology (2017)
KEYNOTE 029: Phase 1/2 randomized study of pembrolizumab (pembro) plus 2 dose regimens of ipilimumab (ipi) for advanced melanoma
Authors: M.B. Atkins, M.S. Carlino, A.G. Hill, C.M. McNeil, A. Ribas, V. Atkinson, J.S. Cebon, M.B. Jameson, W.-J. Hwu, J.A. Thompson, J. Anderson, B. Homet Moreno, N. Ibrahim, G.V. Long
Journal: Annals of Oncology (2017)
Impact of screening on presentation and survival of colorectal cancer
Authors: M. S. Beg, A. Gupta, R. Komrokji, M. Atiq, S. Ali, M. Safa
Journal: Journal of Clinical Oncology (2007)

1535 Background: There is an increasing emphasis and utilization of colorectal cancer (CRC) screening. We evaluated the effect of screening on CRC presentation and outcome. Methods: We reviewed all the invasive CRC cases diagnosed between Jan 1995-Dec 2005 at the Cincinnati Veteran’s Affairs hospital. Individual case records were reviewed and the data collected including patient demographics, treatment, outcome, mode of presentation as well as whether CRC was detected as a result of screening. Results: Altogether 288 patients were diagnosed with CRC during the study period. The median age at presentation was 69.3 years and 18.8% were African-Americans. Early stage CRC was diagnosed in 63.4% cases (stage 1: 32.7%, stage 2: 30.8%) and 33.3% were diagnosed at advanced stage (stage 3: 18.1% and stage 4: 15.3%). Seventy seven (26.7%) CRCs were asymptomatic at presentation and were diagnosed as a result of screening. Predominant screening modalities included fecal occult blood testing (46.8%) and flexible sigmoidoscopy (22.1%). The proportion of screen- detected cases increased from 19% in 1995–1999 to 32% in 2000–05 (p = 0.047). Demographics, including age and race, as well as the site of CRC were similar to symptomatic cases. Screen-detected cancers presented early, with 77.9% presenting at early stage (stage 1: 55.8%, stage 2: 22.1%), compared to 51.5% (stage 1: 21.0%, stage 2: 30.5%) of symptomatic cancers (p &lt;0.01). Only 1.3% of screen-detected CRC was found to be metastatic as compared to 21.0% of the symptomatic cases. The screen-detected cancers had significant survival advantage compared to symptomatic cases; with median survival being 81 months vs. 43 months in the latter (p =0.018). A proportional hazard regression analysis indicated that this improvement in survival was related to the fact that screening resulted in earlier stage at diagnosis. Only 20.3% of screen-detected CRC received adjuvant chemotherapy compared to 41.4% of symptomatic cases (p=0.002). Conclusions: An increasing proportion of CRC is being diagnosed as a result of screening. These cancers present at an earlier stage and are associated with a significantly improved survival. However, most CRC still presents symptomatically and more effective population screening is needed. No significant financial relationships to disclose.
Epidémie de gastroentérite à virus de Norwalk-like dans un hôpital de long et moyen séjour à Rotterdam
Authors: O Ronveaux, D Vos, A Bosman, K Brandwijk, J Vinjé, M Koopmans, R Reintjes
Journal: Eurosurveillance (2000)

Lors d’une epidemie de gastroenterite virale a un virus de Norwalk-like, 62% (74/120) des residents - personnes âgees et infirmes - d’un hopital de long et moyen sejour aux Pays-Bas et 32% du personnel (33/102) sont tombes malades. L’association temporelle des cas suggerait la transmission interhumaine. Le fait d’etre aide par les membres du personnel lors des repas a ete associe aux taux d’attaque plus eleves.
Could a New Method to Detect Coronary Inflammation Prevent Heart Attacks?
Authors: Jennifer Abbasi
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sunitinib (S) switch maintenance in advanced non-small cell lung cancer (NSCLC): An ALLIANCE (CALGB 30607), randomized, placebo-controlled phase III trial.
Authors: Mark A. Socinski, Xiaofei F. Wang, Maria Quintos Baggstrom, Lin Gu, Thomas E. Stinchcombe, Martin J. Edelman, Sherman Baker JR, Heather Dorothy Mannuel, Jeffrey Crawford, Everett E. Vokes
Journal: Journal of Clinical Oncology (2014)

8040 Background: This study compared switch maintenance with S versus placebo (P) in patients (pts) with advanced NSCLC following four cycles of first-line chemotherapy. The primary endpoint was progression-free survival (PFS) after randomization. Overall survival (OS) was a secondary endpoint. Methods: Stage IIIB/IV pts, PS 0-1 with stable/responding disease after 4 cycles of platinum-based therapy were randomized to S (37.5 mg po qd) vs P. Pts were assessed for progression every 6 weeks. PFS and OS were measured from the time of randomization. The trial was designed to have 90% power to detect a 6 week improvement in PFS using a log rank test at a 2-sided significance level of 0.05. Planned accrual was 244 pts. All p values are 2-sided. Results: The trial crossed the superiority boundary on the primary endpoint at an interim analysis. 210 pts were randomized (106 S, 104 P). Median age 66 yrs (range 25-89), 55.7% male, 60.5% ECOG PS 1, 87.6% stage IV, 22.4% received bevacizumab (which had to be discontinued at randomization), 91.7% current/past smokers. 45.9% had adenocarcinoma, 33.2% squamous, 13.7% undifferentiated NSCLC and 4.4% large cell. PFS was 4.3 mos on the S arm vs 2.8 mos on the P (HR 0.59, p=0.0008). PFS was improved for both squamous (4.3 S vs 2.4 P mos, HR=0.55, p=0.02) as well as non-squamous histology (4.3 S vs 2.8 P mos, HR=0.64, p=0.02). OS was not different (11.2 mos S vs 11.2 mos P, HR 1.05, p=0.77). Protocol treatment discontinuation was most commonly due to disease progression for P (90.6% for P vs 51.1% on S) and adverse event for S (28.7% for S vs 4.2% for P). Grade 3/4 toxicities (%) occurring in >5% of patients (S vs P) were anemia (6 vs 0), neutropenia (6 vs 1), thrombocytopenia (12 vs 0), hypertension (8 vs 0), fatigue (25 vs 4), rash (11 vs 0) and mucositis/stomatitis (11 vs 0). The rate of subsequent therapy was 74% on the P arm vs 61% on the S arm (p=0.049). Conclusions: CALGB 30607 met its primary endpoint by demonstrating a significant improvement in PFS for S switch maintenance therapy in advanced NSCLC. No effect on the secondary endpoint of OS was seen. Clinical trial information: NCT00693992.
Reproductive potential and performance of fertility-preserving procedures in BRCA mutation-positive (BRCA+) breast cancer (BC) patients (pts)
Authors: M. Lambertini, O. Goldrat, A.R. Ferreira, J. Dechene, J. Desir, A. Delbaere, M-D. t’Kint de Roodenbeke, E. De Azambuja, M. Ignatiadis, I. Demeestere
Journal: Annals of Oncology (2017)
Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators
Authors: Jaime Hernandez-Ojeda, Elena Arbelo, Roger Borras, Paola Berne, Jose M. Tolosana, Andrea Gomez-Juanatey, Antonio Berruezo, Oscar Campuzano, Georgia Sarquella-Brugada, Lluis Mont, Ramon Brugada, Josep Brugada
Journal: Journal of the American College of Cardiology (2017)
Impact of CYP3A4*22 on pazopanib pharmacokinetics in cancer patients
Authors: S.L.W. Koolen, A. Huitema, P. Laven, S. El Bouazzaoui, H. Yu, N.P. Erp, C.M.L. Herpen, P. Hamberg, H. Gelderblom, N. Steeghs, S. Sleijfer, R.H.N. van Schaik, R.H.J. Mathijssen, S. Bins
Journal: Annals of Oncology (2017)
A phase I/II study of pembrolizumab (P) with gemcitabine (G) in patients (Pts) with previously-treated advanced non-small cell lung cancer (NSCLC): Phase I safety results.
Authors: Rachel E. Sanborn, Regan M. Duffy, Brenda K Fisher, Kelly Shea Perlewitz, William L Redmond, Yoshinobu Koguchi, Bernard A. Fox
Journal: Journal of Clinical Oncology (2017)

e20605 Background: P, an anti-PD1 antibody active in advanced NSCLC, has optimal benefit in tumors with high PD-L1 expression. G may increase antigen cross-presentation and prime CD8 T cell responses via increased tumor cell apoptosis. The combination of antigen cross-presentation and T cell activation may have a synergistic effect with concurrent anti-PD1 immunotherapy. This study is evaluating P + G in pts with previously-treated advanced NSCLC with goal to establish feasible dosing prior to phase II evaluation. Methods: The phase I portion enrolled sequential cohorts of 2 pts each with advanced NSCLC (1-3 prior lines of therapy), regardless of PD-L1 status. Treatment consisted of G, 1250 mg/m2, Days (D) 1 &amp; 8 + P 200 mg D 1; 21-day cycles. Pts received G to max 6 cycles, P to max 2 years. Each cohort closed until pts completed 6 weeks therapy (2 cycles). Dose limiting toxicity (DLT) was defined as Gr 4 hematologic or Gr 3/4 non-hematologic toxicity at least possibly treatment-related within the first 6 weeks. Dose de-escalation would occur if ≥ 2 related DLTs occurred in the first 6 pts (accrual 6-36 pts); de-escalation was allowed for each drug independently based on toxicity attribution. Tumor tissue was collected for central PD-L1 testing and immune score analysis. Exploratory analysis of immune response via protein array and whole blood immunophenotyping is pending. Results: 6 pts were enrolled. Male/Female: 2/4; Age 53-73 (Median 67.5); ECOG 0/1: 1/5 pts, respectively. Median prior lines of therapy: 1 (Range 1-3). DLT: Gr 4 pulmonary hemorrhage with respiratory failure (1 pt, related to G). Other toxicities in DLT period: Gr 3 neutropenia (1), anemia (2 events in 1 pt). Other toxicities were Gr 1/2. 1 pt developed Gr 3 pneumonitis after DLT period ended (after cycle 3) and was removed from study treatment. Median cycles: 4 (Range 2-8). Primary reason for discontinuation was progression (4 pts). PD-L1 results by central analysis are pending. Conclusions: 1 DLT was observed in phase I; de-escalation was not triggered and the combination is considered feasible for phase II evaluation with G 1250 mg/m2 and P 200 mg (enrolling). Clinical trial information: NCT02422381.
Association between MRI-defined osteoarthritis, pain, function and strength 3–10 years following knee joint injury in youth sport
Authors: Jackie L Whittaker, Clodagh M Toomey, Linda J Woodhouse, Jacob L Jaremko, Alberto Nettel-Aguirre, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Background Youth and young adults who participate in sport have an increased risk of knee injury and subsequent osteoarthritis. Improved understanding of the relationship between structural and clinical outcomes postinjury could inform targeted osteoarthritis prevention interventions. This secondary analysis examines the association between MRI-defined osteoarthritis and self-reported and functional outcomes, 3–10 years following youth sport-related knee injury in comparison to healthy controls. Methods Participants included a subsample (n=146) of the Alberta Youth Prevention of Early Osteoarthritis cohort: specifically, 73 individuals with 3–10years history of sport-related intra-articular knee injury and 73 age-matched, sex-matched and sport-matched controls with completed MRI studies. Outcomes included: MRI-defined osteoarthritis, radiographic osteoarthritis, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain, knee extensor/flexor strength, triple-hop and Y-balance test. Descriptive statistics and univariate logistic regression were used to compare those with and without MRI-defined osteoarthritis. Associations between MRI-defined osteoarthritis and each outcome were assessed using multivariable linear regression considering the influence of injury history, sex, body mass index and time since injury. Results Participant median age was 23 years (range 15–27), and 63% were female. MRI-defined osteoarthritis varied by injury history, injury type and surgical history and was not isolated to participants with ACL and/or meniscal injuries. Those with a previous knee injury had 10-fold (95% CI 2.3 to 42.8) greater odds of MRI-defined osteoarthritis than uninjured participants. MRI-defined osteoarthritis was independently significantly associated with quality of life, but not symptoms, strength or function. Summary MRI-detected structural changes 3– 10 years following youth sport-related knee injury may not dictate clinical symptomatology, strength or function but may influence quality of life.
Equivalent efficacy of a biosimilar rituximab and reference rituximab in previously untreated advanced follicular lymphoma: Extended results of ASSIST-FL, a confirmatory phase III study
Authors: W. Jurczak, I. Moreira, K. Setty Govindbabu, E. Munhoz, M-A. Echeveste, P. Giri, N. Castro, J. Pereira, A. Luiza, S. Alexeev, D. Osmanov, P. Zhu, S. Alexandrova, A. Zubel, O. Harlin, J. Amersdorffer
Journal: Annals of Oncology (2017)
Landscape of DNA damage response (DDR) genes alterations in the prospective MOSCATO and MATCH R trials
Authors: Y. El Dakdouki, L. Verlingue, C. Massard, R. Bahleda, A. Hollebecque, L. Mahjoubi, E. Rouleau, L. Lacroix, N. Auger, J.-Y. Scoazec, E. Solary, A. Marabelle, F. André, J.-C. Soria, S. Postel-Vinay
Journal: Annals of Oncology (2017)
A phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: Primary analysis results
Authors: M. Ikeda, T. Sasaki, C. Morizane, N. Mizuno, F. Nagashima, S. Shimizu, N. Hayata, H. Ikezawa, T. Suzuki, R. Nakajima, C. Dutcus, M. Ueno
Journal: Annals of Oncology (2017)
FORWARD I: A phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRa)-positive, platinum-resistant epithelial ovarian cancer, primary peritoneal cancer, or primary fallopian tube cancer
Authors: K.N. Moore, I. Vergote, A. Oaknin, N. Colombo, S. Banerjee, A.M. Oza, P. Pautier, C.M. Kelly, K. Malek, M.J. Birrer
Journal: Annals of Oncology (2017)
Optimal Histologic Cutpoints for Treatment Response in Patients With Eosinophilic Esophagitis: Analysis of Data From a Prospective Cohort Study
Authors: Craig C. Reed, W. Asher Wolf, Cary C. Cotton, Spencer Rusin, Irina Perjar, Johnathan Hollyfield, John T. Woosley, Nicholas J. Shaheen, Evan S. Dellon
Journal: Clinical Gastroenterology and Hepatology (2017)
Cases of Neisseria meningitidis in Greece
Authors: J Kremastinou, G Tzanakaki, N Vakalis, A Velonaki
Journal: Eurosurveillance (1997)

In Greece, Neisseria meningitidis appears as sporadic cases with some seasonal local outbreaks. The notification of meningococcal disease to the local health authorities and the Ministry of Health is mandatory. In 1994, the National Reference Centre for M
Epidémie d'oreillons au Portugal malgré une couverture vaccinale importante - rapport préliminaire
Authors: J A Dias, M Cordeiro, M A Afzal, M G Freitas, M. R. Morgado, J. L. Silva, L. M. Nunes, M. G. Lima, F Avilez
Journal: Eurosurveillance (1996)

En 1987, le vaccin trivalent contre la rougeole, les oreillons et la rubeole (ROR) a ete ajoute dans le Programme National de Vaccination (PNV) portugais. Tous les vaccins sont donnes gratuitement dans des centres medico-sociaux. Toutefois, une epidemie d'oreillons a debute en 1995, affectant au debut le nord du Portugal puis s'etendant a d'autres regions.
Abstract 14045: Frailty as Assessed by Gait Speed is Associated With Peripheral Endothelial Dysfunction in Older Patients With ST-segment Elevation Myocardial Infarction
Authors: Ryosuke Satou, Yasushi Matsuzawa, Eiichi Akiyama, Hiroyuki Suzuki, Chika Kawashima, Masaaki Konishi, Katsutaka Hashiba, Nobuhiko Maejima, Noriaki Iwahashi, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Shinichi Sumita, Kazuo Kimura, Yuuichiro Kimura
Journal: Circulation (2016)

Introduction: Endothelial dysfunction plays a pivotal role in the progression of atherosclerosis and subsequent cardiovascular events. In older patients, decreased gait speed is associated with wor...
Labour seems to be watering down promise to abolish PFI
Authors: Andy Cowper
Journal: BMJ (2017)

High on their success in the general election, Jeremy Corbyn’s Labour Party headed to its annual conference in Brighton last week in buoyant confidence.

Though there was not a huge push on NHS issues (save for shadow health secretary Jonathan Ashworth’s call for an immediate extra £500m (€565m; $675m) to ease winter pressures1), two potentially important themes emerged.

The first was on public service funding and the private finance initiative (PFI). Shadow chancellor John McDonnell used his speech to promise that “based on our Fiscal Credibility Rule … to pay for our public services, we will close the tax loopholes and avoidance scams used by the mega-rich, and we will make sure the rich and the giant corporations pay their way.”2

Ashworth’s speech to the conference set out plans for £45bn extra funding for health and social care.3 To put this in fiscal context, a rise of one penny in the basic rate of income tax currently raises about £4bn.

Turning to PFI, McDonnell told the conference that on top of Labour’s existing commitment “that there will be no new PFI deals …
Hybrid minimally invasive vs. open esophagectomy for patients with esophageal cancer: Long-term outcomes of a multicenter, open-label, randomized phase III controlled trial, the MIRO trial
Authors: C. Mariette, S. Markar, T.S. Dabakuyo-Yonli, B. Meunier, D. Pezet, D. Collet, X.B. D'Journo, C. Brigand, T. Perniceni, N. Carrere, F. Bonnetain, G. Piessen
Journal: Annals of Oncology (2017)