tbuckley/cabot-search huggingface dataset:
Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802.
Authors: W Tester, R Caplan, J Heaney, P Venner, R Whittington, R Byhardt, L True, W Shipley
Journal: Journal of Clinical Oncology (1996)

PURPOSE This phase II study was designed to evaluate effectiveness and toxicity of a combined chemoradiotherapy program with selective bladder preservation in the management of patients with invasive bladder cancer. PATIENTS AND METHODS Ninety-one eligible patients with invasive bladder cancer stages T2M0 to T4AM0 suitable for radical cystectomy received two courses of methotrexate, cisplatin, and vinblastine (MCV regimen) followed by radiotherapy with 39.6 Gy and concurrent cisplatin. After complete urologic evaluation, operable patients who achieved complete response were selected for bladder preservation and treated with consolidation cisplatin-radiotherapy. RESULTS Of 91 eligible patients, 85 underwent complete urologic evaluation and 68 (75%; 95% confidence interval [CI], 59% to 84%) had documented complete responses. Fourteen operable patients with residual tumor underwent immediate cystectomy. Of 70 patients treated with consolidation cisplatin-radiotherapy, 36 subsequently developed bladder recurrences, 23 of which were invasive. Patients with invasive recurrence (n = 16), extensive noninvasive recurrence (n = 6), or severe treatment complications (n = 1) underwent salvage cystectomy. Thus, a total of 37 of 91 patients (40%) required cystectomy. The 4-year cumulative risk of invasive local failure (which includes induction failures) was 43% (95% CI, 33% to 53%). The 4-year actuarial risk of distant metastasis was 22% (95% CI, 13% to 31%). The 4-year actuarial survival rate of the entire group was 62% (95% CI, 52% to 72%). The 4-year actuarial rate of survival with bladder intact was 44% (95% CI, 34% to 54%). CONCLUSION Initial results of this combined chemoradiotherapy program show that bladder preservation can be achieved in the majority of patients, and that overall survival is similar to that reported with aggressive surgical approaches. Long-term survival and quality-of-life assessments require longer follow-up study.
Net Clinical Benefit for Oral Anticoagulation, Aspirin, or No Therapy in Nonvalvular Atrial Fibrillation Patients With 1 Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex)
Authors: Gregory Y.H. Lip, Flemming Skjøth, Lars Hvilsted Rasmussen, Peter B. Nielsen, Torben Bjerregaard Larsen
Journal: Journal of the American College of Cardiology (2015)
Patterns of relapse during adjuvant trastuzumab therapy
Authors: Z. Tomasevic, Z. Rakocevic, S. Milosevic, Z. Tomasevic, Z. Zdrale, S. Vasovic, M. Matijasevic, N. Borojevic, V. Lukic
Journal: Journal of Clinical Oncology (2008)

11540 Background: It is well known that adjuvant trastuzumab (Herceptin [H]), significantly affects the natural history of HER2 3+ breast carcinoma. However, it is less known, what is the pattern of relapse in patients treated with H. The aim of this paper is to determine the incidence and pattern of relapse in high-risk breast cancer patients during adjuvant H treatment. Methods: From September 2006 to September 2007, 86 patients with HER2 3+ early breast cancer were treated with three weekly adjuvant H, after breast surgery, six cycles of FAC chemotherapy.,± postoperative irradiation. Median time to H initiation was 8 weeks (range 7–9 weeks) after the last chemotherapy cycle ± postoperative irradiation. All patients were premenopausal, median age 43 yrs (range 28–53); 29 % were node negative, while median number of positive nodes was 6 (range 1–25); 17.4 % has 4 or more lymph nodes involved; 22% patients has ER+/PGR+ tumors. At the time of this analysis, median number of H was 9 (range 1–17) and median time after initial breast cancer diagnosis was 13 months (range 8–25). All patients had regular clinical examination while radiographic and US/CT procedures were performed at the beginning and end of treatment, or any time upon relapse or symptoms development. Results: Eight patients (9.3%) experienced disease relapse. Median number of H doses at the time of relapse was 13 (range 6–17). Five pts developed local recurrence. Two local relapses were not resectable because of lenticular skin involvement. In one patient contra-lateral breast carcinoma was registered after 8 doses of H. One pt developed bone metastases during last dose of H Only one patient (1.1%) developed multiple visceral metastases (lung, liver and CNS) after 7 cycles of H. After relapse, H was continued only in a patient with HER2 3+ contra lateral breast carcinoma. Conclusions: In our group of 86 high-risk premenopausal patients, 8 (9,3%) developed relapse during adjuvant H treatment. All relapses were clinically detectable or symptomatic. The pattern of relapses confirms the enormous significance of clinical examination, hence 6/8 relapses were detected by simple physical examination and 4/6 pts could be re-treated with potentially curative surgery. No significant financial relationships to disclose.
Abstract 18805: Prediction of Pre-procedural TIMI Flow Grade and Post-procedural Cardiac Troponin Elevations by 320-raw Multidetector Computed Tomography Myocardial Perfusion Imaging
Authors: Makoto Araki, Takayuki Niida, Junji Matsuda, Asami Suzuki, Tadashi Murai, Tetsumin Lee, Yoshito Iesaka, Tsunekazu Kakuta
Journal: Circulation (2014)

Backgrounds: Computed tomography perfusion imaging (CTPI) is feasible, and the findings may be used as a diagnostic tool for predicting coronary TIMI flow grade or cardiac marker elevation after percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). We sought to investigate if detection of qualitative CTPI abnormality combined with CT coronary angiography (CTCA) findings can stratify the risk of NSTE-ACS patients before PCI.

Methods: The coronary CTCA and CTPI datasets of 130 NSTE-ACS patients (NSTEMI: 85, UA: 45) using 320-raw CT before percutaneous coronary intervention (PCI) were visually evaluated for the presence of coronary artery stenosis and perfusion defects. All patients underwent PCI within 48 hours from admission and CT examination. We excluded patients with cardiogenic shock, severe congestive heart failure, renal insufficiency. We also excluded patients without identifiable culprit lesions and/or suitable lesions for PCI. Perfusion defect (PD) was classified as none, inconclusive, or definite, and when inconclusive or definite PD judge was done, the PD location was assigned to RCA, LAD or LCX as culprit vessel based on a 16-segment American Heart Association model except for apex.

Results: Peak cardiac troponin I levels after PCI was 4.33 [0.84-10.5] ng/mL in total. Perfusion assessment was normal in 37, inconclusive in 53, and definite in 40 patients. In normal CTPI patients, initial TIMI flow grade 0 or 1 was detected in 3 patients out of 37 (8.1%), 6 out of 53 (11.1%) in inconclusive CTPI group, and 13 (32.5%) out of 40 in definite PD group (P=0.016). TIMI flow grade at the PCI completion ≦2 was detected in 1 patient out of 37 (3.0%) in normal group, 3 out of 53 (5.7%) in inconclusive group, and 5 (12.5%) out of 40 in definite group (P=0.042). Peak cardiac troponin I levels after PCI was 4.02 [1.02-9.83] ng/mL in normal group, 6.87 [1.02-23.4] ng/mL in inconclusive group, and 10.1 [3.25-24.2] ng/mL in definite group (P=0.016).

Conclusion: Myocardial perfusion detected by CTPI before PCI was associated with TIMI flow grade, and peak troponin I levels after PCI. CTPI, when added to CTCA, may help identify patients who may benefit from early coronary intervention and have high risk for PCI.
Outcome of extensive evaluation before adjuvant therapy in women with breast cancer and 10 or more positive axillary lymph nodes.
Authors: M Crump, P E Goss, M Prince, C Girouard
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the effect of extensive screening of women with high-risk, node-positive breast cancer on the detection of occult metastatic disease and patient eligibility for a randomized trial of the addition of high-dose chemotherapy and autologous bone marrow support (ABMT) to standard adjuvant therapy. PATIENTS AND METHODS Women with resected T1-3N1,2 primary breast cancer and &gt; or = 10 positive axillary lymph nodes referred for possible trial participation were evaluated for this report. All had normal chest x-ray, bone scan, and liver ultrasound performed by the referring physician. Those who provided informed consent for the randomized trial were further evaluated according to protocol with computed tomographic (CT) scans of the head, chest, abdomen, and pelvis and bilateral bone marrow biopsies; those with metastatic disease detected by any of these tests were excluded from study registration. RESULTS Forty-four women were evaluated between February 1993 and April 1995. Fourteen did not undergo further protocol staging because of refusal to participate or the presence of metastatic disease on clinical assessment or review of outside radiologic studies. The remaining 30 underwent additional investigations, and seven (23%; 95% confidence interval [CI], 12% to 41%) had metastases detected by CT scanning (four patients) or bone marrow biopsy (three patients) not detected by routine screening. CONCLUSION Although the number of patients evaluated is small, these data suggest that some of the improvement in outcome of women with &gt; or = 10 positive axillary lymph nodes who receive ABMT as part of adjuvant chemotherapy in phase II trials may be from the exclusion of patients with occult metastatic disease. The importance of these exclusions can only be determined by ongoing, randomized controlled trials.
Abstract 12933: A Genome-Wide Association Analysis to Identify Genomic Modulators of Rate Control Therapy in Patients with Atrial Fibrillation
Authors: Raafia Muhammad, Babar Parvez, Marylyn D Ritchie, Michiaki Kubo, Naoyiki Kamatani, Toshihiro Tanaka, Dan M Roden, Dawood Darbar
Journal: Circulation (2011)
Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio‐Functionality to Meshes
Authors: Olivier Guillaume, Andreas Herbert Teuschl, Simone Gruber‐Blum, René Hartmann Fortelny, Heinz Redl, Alexander Petter‐Puchner
Journal: Advanced Healthcare Materials (2015)

Abdominal wall hernia is a recurrent issue world‐wide and requires the implantation of over 1 million meshes per year. Because permanent meshes such as polypropylene and polyester are not free of complications after implantation, many mesh modifications and new functionalities have been investigated over the last decade. Indeed, mesh optimization is the focus of intense development and the biomaterials utilized are now envisioned as being bioactive substrates that trigger various physiological processes in order to prevent complications and to promote tissue integration. In this context, it is of paramount interest to review the most relevant bio‐functionalities being brought to new meshes and to open new avenues for the innovative development of the next generation of meshes with enhanced properties for functional abdominal wall hernia repair.
Abstract 3133: Firts-in Man Study with Bevacizumab-Eluting Stent: A New Approach for the Inhibition of Plaque Neovascularization.
Authors: Konstantinos Toutouzas, Eleftherios Tsiamis, Manolis Vavouranakis, Elli Stefanadi, Ioannis Karabelas, Nicholas Kipshidze, Christodoulos Stefanadis
Journal: Circulation (2007)

Introduction : Neovascularization is mainly mediated by vascular endothelial growth factor. Bevacizumab is a monoclonal antibody specific for this growth factor. In this study we investigated the safety and efficacy of bevacizumab-eluting stent, a dedicated stent for inhibition of plaque neovascularization.   Methods : Patients with acute coronary syndromes and ≥ 2 angiographically significant coronary artery stenoses were included in the study. The culprit lesions were successfully treated percutaneously. The non-culprit lesions were less than 20 mm in length, producing a significant stenosis (≥ 50%, in vessels with reference diameter ≥ 2.25mm). Local delivery of bevacizumab was accomplished via BiodivYsio stents, which bear a phosphorylcholine coating that adsorbs the drug with a “sponge-like” mechanism. Patients were discharged under drug treatment including aspirin (indefinitely) and clopidogrel for 12 months. All patients were scheduled for clinical and angiographic follow-up at 12 months. Intravascular ultrasound of the target vessel was performed immediately after the procedure and at 12 months.   Results : Twenty consecutive patients were included. All stents were successfully delivered (mean stent length 13.4±3.8mm) and all patients were discharged without any complication. During a follow-up period of 11.45 ± 0.73 months there were no adverse cardiac event such as death, myocardial infarction and target vessel revascularization. Angiographic and intravascular ultrasound follow-up were performed in all patients. Acute, subacute or late thrombosis was not observed. Angiographic and intravascular ultrasound follow-up did not reveal any restenosis (50% vessel narrowing) in any target vessel. Stent malapposition was not observed in any patient. In-stent late loss was 0.15±0.9 mm, and in-lesion late loss was 0.16±0.09 mm. Mean neointimal hyperplasia area in stented segments as measured with intravascular ultrasound was 0.7±0.39 mm 2 .   Conclusions : The implantation of bevacizumab-eluting stents in human coronary arteries is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results.
Dysregulated miRNAs and their predicted mRNA targets in emphysematous lungs
Authors: Santiyagu Savarimuthu Francis, Morgan Davidson, Rayleen Bowman, Nicholas Hayward, Kwun Fong, Ian Yang
Journal: European Respiratory Journal (2011)

There is increasing recognition of the importance of microRNAs (miRNAs) as short non-coding RNAs that post-transcriptionally regulate gene expression. Identifying the role of miRNAs in COPD would enable better understanding of disease pathogenesis and use as biomarkers for diagnostic purposes or therapeutic targets. Our aims were i) to identify miRNAs dysregulated in mild and moderate emphysema, and ii) to identify mRNAs modulated by miR-34c-5p in BEAS-2B and HFL cell lines.   Methods:  i) miRNA microarray profiling (Agilent Human miRNA profiler G4470 V1.0) was performed on 29 non-tumour lung tissues obtained from The Prince Charles Hospital tissue bank. Patients were classified as mild (n=9) and moderate (n=20) emphysema according to lung function measurements (KCO and FEV 1 ). Technical validation was performed on the selected miRNAs using quantitative real-time PCR. ii) Genomic mRNA expression changes from transient transfection of miR-34c-5p (candidate miRNA) in BEAS-2B and HFL cells were measured using Illumina HumanHT-12 V3 arrays.   Results:  COPD patients had mean (SD) age 68 (6) years, FEV 1  72 (17)% predicted and KCO 70 (10)% predicted. Five miRNAs were identified ( p    Conclusions:  We have shown that miRNAs are associated with COPD severity and modulate expression of their predicted mRNAs.  Support: NHMRC Biomedical Scholarship (SF), NHMRC Career Development Award (IY), The Prince Charles Hospital Foundation, Australian Lung Foundation/Boehringer Ingelheim COPD Research Fellowship.
A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma
Authors: Ji-Yeon Lee, Sung-Woo Park, Hee Kyoung Chang, Ho Young Kim, TaiYoun Rhim, June-Hyuk Lee, An-Soo Jang, Eun-Suk Koh, Choon-Sik Park
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

ADAM33 has been identified as a novel asthma susceptibility gene in genomewide screening and association studies. High-level expression in smooth muscles and fibroblasts suggests that ADAM33 plays a role in airway remodeling in patients with asthma.The ADAM33 protein was identified in the bronchoalveolar lavage (BAL) fluids of patients with asthma and normal control subjects using Western blotting antibody against the catalytic domain. ADAM33 expression was analyzed using immunohistochemical staining of mucosal biopsy specimens. The levels of ADAM33 protein in the BAL fluids were measured by dot blotting, and were correlated with the FEV1 values of the patients with asthma.Western blot analysis revealed the presence of the ADAM33 protein, with a molecular mass of approximately 55 kD in the BAL fluids. ADAM33 was expressed in the smooth muscles and basement membranes of almost all the patients with asthma, but was absent in the normal control subjects. The ADAM33 levels were increased significantly in patients with moderate to severe asthma and in patients with mild asthma, as compared with normal control subjects (p = 0.001 and p = 0.016, respectively). The ADAM33 protein levels correlated inversely with the FEV(1)% predicted in the patients with asthma (r = -0.486, p = 0.018).ADAM33 is associated with asthma development, and the levels of ADAM protein are related to asthma severity.
Abstract 544: ERK 1/2 is Essential for the Augmentation of Akt and eNOS phosphorylation by Atorvastatin
Authors: Yumei Ye, Ramanna Merla, Saraswathy Manickavasagam, Yu Lin, Regino J Perez-Polo, Ming-He Huang, Yochai Birnbaum
Journal: Circulation (2007)
Development of Olaparib for BRCA-Deficient Recurrent Epithelial Ovarian Cancer
Authors: Krishnansu S. Tewari, Ramez N. Eskander, Bradley J. Monk
Journal: Clinical Cancer Research (2015)

The FDA approval of the PARP inhibitor olaparib for fourth-line therapy of germline BRCA1/2-mutated ovarian cancer represents the first registered indication for this class of drugs in any disease. PARP is a family of proteins involved in the repair of single-strand DNA breaks. High-grade serous ovarian carcinomas with BRCA deficiencies may be particularly vulnerable to both direct and indirect effects of PARP inhibition. This phenotype frequently arises as a consequence of defects in the repair of damaged DNA, rendering cancer cells susceptible to DNA-damaging platinum compounds and targeted therapies affecting homologous recombination repair (HRR). When cells already deficient in HRR are exposed to PARP inhibitors, apoptosis occurs by way of synthetic lethality. In this review, we trace the clinical development of olaparib for women with recurrent epithelial ovarian carcinoma harboring germline BRCA mutations, a biomarker for HRR deficiency present in 15% to 20% of cases. Clinical trials highlighted include not only those pivotal studies that have led to regulatory approval in the United States and in Europe, but also those in which olaparib was studied in novel combinations, including chemotherapy and antiangiogenesis agents.
Cadaver Studies of the Anatomy of Arterial Supply to the Inferior Turbinates
Authors: Nigel Padgham, Richard Vaughan-Jones
Journal: Journal of the Royal Society of Medicine (1991)

The anatomy of the arterial supply of the inferior turbinate was studied by dissection and serial histological sections. The arrangement was found to be constant, with a single main descending branch of the sphenopalatine artery entering its substance from above, 1-1.5 cm from its posterior border. This artery branches as it passes forwards within the turbinate, remaining close to the bone. As these pass anteriorly they give rise to arterial arcades which remain close to or within the bone, with the main artery increasing in diameter. The implications of these findings are discussed in a surgical context.
&lt;emph type="ital"&gt;DICER1&lt;/emph&gt; Mutations in Familial Multinodular Goiter With and Without Ovarian Sertoli-Leydig Cell Tumors
Authors: Thomas Rio Frio, Amin Bahubeshi, Chryssa Kanellopoulou, Nancy Hamel, Marek Niedziela, Nelly Sabbaghian, Carly Pouchet, Lucy Gilbert, Paul K. O’Brien, Kim Serfas, Peter Broderick, Richard S. Houlston, Fabienne Lesueur, Elena Bonora, Stefan Muljo, R. Neil Schimke, Dorothée Bouron-Dal Soglio, Jocelyne Arseneau, Kris Ann Schultz, John R. Priest, Van-Hung Nguyen, H. Rubén Harach, David M. Livingston, William D. Foulkes, Marc Tischkowitz
Journal: JAMA (2011)

Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs.To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1.From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation.Detection of germline DICER1 gene mutations in familial MNG with and without SLCT.We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in in-frame deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers.DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.
Moving Beyond “Lumpology”: PET/CT Imaging of Pheochromocytoma and Paraganglioma
Authors: Michael S. Hofman, Rodney J. Hicks
Journal: Clinical Cancer Research (2015)

High somatostatin receptor expression on the cell membrane of succinate dehydrogenase mutation-related pheochromocytoma and paraganglioma provides a potential target for imaging and therapy. (68)Ga-DOTATATE positron emission PET/CT may represent a new gold standard for staging pheochromocytoma/paraganglioma and have future therapeutic implications.