tbuckley/cabot-search huggingface dataset:
Use of a four gene panel of epigenetic markers to classify serrated colonic adenomas with CpG island methylator phenotype.
Authors: J. Jenab-Wolcott, Y. Yao, W. Yan, S. Schulte, S. Harada, C. Brensinger, B. J. Giantonio, A. Rustgi, A. Sepulveda
Journal: Journal of Clinical Oncology (2010)

3600 Background: Colonic sessile serrated adenomas (SSA) have distinct pathologic features and may progress to carcinoma. The CpG island methylation phenotype (CIMP) is thought to be a pivotal mechanism in the serrated-carcinoma molecular pathway. The goal of this study is to define a panel of epigenetic markers for molecular classification of colonic SSA. Methods: 232 patients with colonic SSA were identified in the pathology database of the University of Pennsylvania. A total of 21 SSA and 16 controls (normal colonic mucosa from surgical specimens for colonic carcinoma) were used for the characterization of CpG methylation status of four epigenetic loci (MLH1, MGMT, p16INK4a, and MINT31). Selected areas of SSA or normal colonic mucosa were microdissected from paraffin sections and DNA was extracted. Bisulfite modified DNA was used for Quantitative SYBR green methylation specific PCR (QMSP). The levels of methylation at each CpG locus were measured relative to the internal reference gene (ACTB) and reported as a % of ACTB. Wilcoxon rank sum tests, Chi-square or Fisher's exact tests were used for statistical analyses. Results: Of the 232 patients, 137 were female and 95 were male with average age of 63 years. There were 159 SSA in the right and 66 in the left colon. In the panel selected for molecular analysis there was no significant difference between the SSA and controls by gender, anatomic location, or age. Positive methylation was scored at ≥ 2%. All non-neoplastic control cases showed negative methylation. The SSA group had significantly higher methylation levels of MGMT, MINT31, as well as a higher average methylation of the 4 markers (17.0% ± 13.3) and a higher number of methylated sites (1.8 ± 0.9) as compared to normal controls (0.2% ± 0.1) and (0.0 ± 0.0), respectively, p < 0.0001. Conclusions: In this study, all the colonic SSA were identified by positive methylation on either MINT31, MGMT or both, using a quantitative cut-off value for methylation of four markers, while none of the control samples showed methylation at these loci. Our data suggests that a limited panel of epigenetic markers maybe sufficient for molecular classification of colonic serrated adenomas. No significant financial relationships to disclose.
In Vivo Treatment with Prostaglandin E2 (PGE2) Selectively Expands Short-Term Hematopoietic Stem Cells.
Authors: Benjamin J. Frisch, Jonathan M. Weber, Rebecca L. Porter, Benjamin J. Gigliotti, Julianne N. Smith, Adam J. Olm-Shipman, Regis J. O’Keefe, Craig T. Jordan, Laura M. Calvi
Journal: Blood (2007)
Asthma phenotypes in inner-city children
Authors: Edward M. Zoratti, Rebecca Z. Krouse, Denise C. Babineau, Jacqueline A. Pongracic, George T. O'Connor, Robert A. Wood, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Steven M. Sigelman, Peter J. Gergen, Alkis Togias, Cynthia M. Visness, William W. Busse, Andrew H. Liu
Journal: Journal of Allergy and Clinical Immunology (2016)
Comparison of FDG-PET and tumor markers for the diagnosis of lung carcinoma.
Authors: H. Terai, K. Soejima, K. Naoki, H. Yasuda, S. Yoda, R. Satomi, S. Nakayama, S. Ikemura, T. Satou, A. Ishizaka
Journal: Journal of Clinical Oncology (2010)

e21067 Background: Serum tumor markers (TMs) have been long used to distinguish malignant from benign lung tumors. While 18F-fluoro-2-deoxy-D-glucose (FDG)-PET is currently widely used and considered as a useful imaging method for the diagnosis of lung carcinoma. Although the diagnostic accuracy of FDG-PET was initially reported to be quite high, it has been revealed that its accuracy is not as high as expected. The purpose of this study is to reevaluate and compare the accuracy of FDG-PET and TMs for the diagnosis of lung carcinoma. Methods: We evaluated 386 cases underwent PET/CT scan from April 2003 to March 2008 in our institution, retrospectively. We selected 146 cases of primary lung carcinoma and 55 cases of benign pulmonary diseases including tuberculosis, cryptococcosis, etc. whose diagnosis was finally confirmed. The study was approved by the IRB of Keio University. We also evaluated clinical parameters including age, gender, smoking history and nodule diameter as well as TMs (CEA, CYFRA and ProGRP). We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) by FDG-PET and TMs or in combination with other parameters using multiple logistic regression analysis. Results: The PET positive rate in the primary lung carcinomas and the benign diseases was 84.9% (124/146) and 48.1% (26/55), respectively. The PET possessed higher sensitivity but lower specificity compared to TM for all stages, especially in early stages (I + II) (Table). Additionally, the multiple logistic regression analysis revealed that the nodule diameter and the FDG uptake were identified as significant predicting factors (p<0.05) and these factors had predictive value for the early stage lung carcinoma as a sensitivity of 77.3%. Combination with tumor markers and FDG uptake were not able to lead better prediction formula. Conclusions: The FDG-PET is useful to diagnose lung carcinoma, especially in the early stage compared to TMs. Parameters All stages Stage I + II Stage III + IV Sensitivity (%) FDG-PET 84.9 71.6 96.2 TM 62.1 43.9 77.2 Specificity (%) FDG-PET 52.7 52.7 52.7 TM 90.4 90.4 90.4 PPV (%) FDG-PET 82.7 64.9 74.5 TM 94.1 85.3 92.4 NPV (%) FDG-PET 56.9 60.4 93.5 TM 43.6 56.0 75.8 No significant financial relationships to disclose.
Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis
Authors: Adriana Stamm, Stéphanie Saxer, Mona Lichtblau, Elisabeth D. Hasler, Suzana Jordan, Lars C. Huber, Konrad E. Bloch, Oliver Distler, Silvia Ulrich
Journal: European Respiratory Journal (2016)

The aim of the present study was to investigate the prognostic value of exercise haemodynamics measured during right heart catheterisation (RHC) in patients with systemic sclerosis (SSc) referred for evaluation of pulmonary hypertension. SSc patients undergoing RHC at rest and during maximal supine incremental cycle exercise were grouped into resting precapillary pulmonary hypertension (PH rest ) (mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure &lt;15 mmHg), exercise-induced pulmonary hypertension (PH ex ) (mPAP ≥30 mmHg and mPAP/cardiac output &gt;3 mmHg·L −1 ·min −1 at maximal exercise), and without pulmonary hypertension (PH none ). Patients' characteristics, haemodynamics and follow up data were compared between groups. 72 SSc patients were followed for median (interquartile range) 33 (15–55) months. Mean (95% CI) survival without transplantation estimated by Kaplan-Meyer analysis was 4.4 (0.8–2.9) years in PH rest (n=17), 5.2 (4.4–6.1) years in PH ex (n=28) and 9.5(8.4–10.6) years in PH none (n=27; p&lt;0.05 versus others). In Cox regression models, the exercise-induced increase in mPAP (hazard ratio (HR) 1.097, 95% CI 1.002–1.200) and the coefficient of pulmonary vascular distensibility alpha (HR 0.100, 95% CI 0.012–0.871) controlled for age, but not resting haemodynamics predicted transplant-free survival. Among SSc patients with normal mPAP at rest, an excessive increase in mPAP during exercise and an impaired vascular distensibility may indicate an early stage of pulmonary vasculopathy, associated with reduced survival similar to resting pulmonary hypertension patients.
Frequency and predictors of a high clinical response in patients with psoriasis on biological therapy in daily practice: results from the prospective, multicenter BioCAPTURE cohort
Authors: J. Zweegers, B. Roosenboom, P.C.M. van de Kerkhof, J.M.P.A. van den Reek, M.E. Otero, S. Atalay, A.L.A. Kuijpers, M.I.A. Koetsier, W.P. Arnold, M.A. Berends, L. Weppner-Parren, M. Bijen, M.D. Njoo, J.M. Mommers, P.P.M. van Lümig, R.J.B. Driessen, W. Kievit, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2016)

It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni‐ and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.
Clinical outcomes of resected biliary tract cancer: A cohort study.
Authors: Anne Meier, Federico Aucejo, Bijan Eghtesad, David Vogt, Charles Miller, Matthew Walsh, Robert James Pelley, Alok A. Khorana, Davendra Sohal
Journal: Journal of Clinical Oncology (2016)

e15594 Background: Clinical outcomes of biliary tract cancer (BTC) remain suboptimal, even when surgical resection is performed. A better understanding of predictive factors can lead to improved management strategies. Methods: We conducted a retrospective cohort study of consecutive patients undergoing resection of BTC at the Cleveland Clinic from 1/1/06 to 6/30/2014. Clinical, laboratory, pathologic, and survival data were extracted from medical records, and potential predictors of overall survival (OS) were evaluated. Hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study comprised 142 patients. Median age was 63; 54% were female, 92% were Caucasian. Six (4%) had ulcerative colitis; 5 (4%) had primary sclerosing cholangitis. Location: intrahepatic (n = 64, 45%), extrahepatic (n = 42, 30%), gallbladder (n = 36, 25%). pT: 0/1 (32, 23%), 2 (49, 35%), 3 (51, 36%), 4 (10, 7%). Grade (N = 138): 0/1 (14, 10%), 2 (76, 55%), 3/4 (48, 35%). Positive margins (N = 137): 52 (38%) cases. Adjuvant chemotherapy (n = 66) and radiation (n = 31) were used in several cases. There were 89 (63%) deaths; median OS was 25.7 (95% CI: 20.3-33.7) months. Adjusted multivariable analyses showed that pT, tumor grade, and tumor location were associated with OS (Table). Conclusions: Pathologic features can help identify patients at higher risk of mortality after resected BTC. Prospective studies should evaluate strategies focusing on improving outcomes in these patients. Adjusted multivariable analysis of predictors of OS*. Variable Category Median OS (months) HR (95% CI) p pT 0/1 (ref) 75.6 2 24.6 2.24 (1.14-4.40) 0.02 3 29.1 1.29 (0.62-2.66) 0.49 4 9.0 8.41 (3.48- 20.37) < 0.001 Grade 0/1 (ref) 31.3 2 27.9 1.74 (0.73-4.14) 0.21 3/4 19.3 2.43 (1.00-5.90) 0.05 Location Intrahepatic (ref) 31.3 Extrahepatic 22.3 1.75 (1.02-3.01) 0.04 Gallbladder 17.8 2.26 (1.28-4.00) 0.005 *ref: reference category
Prognostic Impact Of Serum Free Light Chain (sFLC) Assay In Newly Diagnosed Multiple Myeloma (MM) Treated With Bortezomib
Authors: Paola Tacchetti, Serena Rocchi, Annalisa Pezzi, Elena Zamagni, Lucia Pantani, Beatrice Anna Zannetti, Katia Mancuso, Annamaria Brioli, Giovanni Martinelli, Michele Cavo
Journal: Blood (2013)
Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma
Authors: Weimin Liu, Sucai Liu, Mukesh Verma, Iram Zafar, James T. Good, Donald Rollins, Stephen Groshong, Magdalena M. Gorska, Richard J. Martin, Rafeul Alam
Journal: Journal of Allergy and Clinical Immunology (2016)
Surveillance de la grippe dans les pays membres du réseau européen EISS d'octobre 2000 à avril 2001
Authors: K Mantey, A Mosnier, W J Paget
Journal: Eurosurveillance (2001)

Dans les pays couverts par le systeme EISS (European Influenza Surveillance Scheme), l’hiver 2000-2001 a ete principalement marque par la circulation du virus grippal de type A (H1N1). Le virus de type B, qui globalement representait une minorite de cas, s'est repandu plus tard dans la saison et etait predominant en Grande-Bretagne, Irlande et Portugal. L’activite grippale a atteint son maximum durant la periode de janvier a fevrier/mars 2001, avec peu de decalage entre les pays (4 semaines maximum). Dans l’ensemble, les taux d’incidence rapportes ont ete inferieurs a ceux de la saison precedente, ce qui illustre une faible activite de la grippe.
Caffeic Acid Phenyl Ester, a Component of the Chinese Herb Propolis, Inhibits Platelet Aggregation Via Competition with Fibrinogen for Binding to aIIbb3
Authors: Ya Ping Wu, Albert Huisman, Cees Weeterings, Philip G. de Groot, Yun Xiang Zhang, Shao Dong PAN, Ran Wei, Jia Fu Wang
Journal: Blood (2008)
Biomaterials in siRNA Delivery: A Comprehensive Review
Authors: William Ho, Xue‐Qing Zhang, Xiaoyang Xu
Journal: Advanced Healthcare Materials (2016)

With the dearth of effective treatment options for prominent diseases including Ebola and cancer, RNA interference (RNAi), a sequence‐specific mechanism for genetic regulation that can silence nearly any gene, holds the promise of unlimited potential in treating illness ever since its discovery in 1999. Given the large size, unstable tertiary structure in physiological conditions and negative charge of small interfering RNAs (siRNAs), the development of safe and effective delivery vehicles is of critical importance in order to drive the widespread use of RNAi therapeutics into clinical settings. Immense amounts of time and billions of dollars have been devoted into the design of novel and diverse delivery strategies, and there are a handful of delivery systems that have been successfully translated into clinic. This review provides an introduction to the in vivo barriers that need to be addressed by siRNA delivery systems. We also discuss the progress up to the most effective and clinically advanced siRNA delivery systems including liposomal, polymeric and siRNA conjugate delivery systems, as well as their design to overcome the challenges.
Ability of unsuccessful high-dose IL-2 therapy followed immediately by low-dose metronomic temozolomide to induce complete and near-complete remissions in metastatic melanoma.
Authors: S. A. Fateh, T. Schell, R. Gingrich, R. Neves, J. J. Drabick
Journal: Journal of Clinical Oncology (2010)

e19001 Background: Metastatic melanoma is a disease with a very poor prognosis. High-dose interleukin-2 (HD IL-2) and temozolomide (TMZ) are both approved treatments for this malignancy but response rates to each are poor. HD IL-2 is the only therapy to date that has been shown to induce durable complete responses but only in a very small percentage of patients. TMZ is an oral atypical alkylating agent with known cytotoxic activity against melanoma. The combination of TMZ followed by HD IL-2 has been studied but did not improve responses over what had been observed for HD IL-2 alone. In our clinical practice, we noted rapid and dramatic responses to TMZ when given immediately after a full course of HD IL-2. Methods: We administered TMZ immediately as continuous low dose metronomic therapy to 6 sequentially treated patients with metastatic melanoma who had just completed a full course of HD IL-2 and either had failed to respond or progressed. Results: All of these patients had complete or near complete responses (CR and nearCR). The response rate has been 100% to date and occurs within 1 or 2 cycles of TMZ. Two pts are alive and disease free off TMZ, 2 are doing well in active treatment, one died from progressive disease, and one died from an acute myocardial infarction. Interestingly 3 of the 6 patients exhibited polyarthralgias on TMZ. Conclusions: These responses were much better than what is typically observed for single agent TMZ, which has been shown to decrease the T regulatory population of lymphocytes (T-regs). We hypothesize the TMZ may be synergic with HD IL-2 in a sequence-specific fashion by allowing the immune activation induced by the HD IL-2 to proceed without the brakes applied by the T-reg population of cells whose major function is to inhibit an exuberant immune response. This postulated mechanism would result in the sequence-specific activity noted in our patients that would occur early and be associated with autoimmune manifestations. A prospective phase II trial to test this sequence but given repeatedly has been initiated with correlative studies to test the hypothesis that T-regs inhibition by TMZ is the mechanism of action. No significant financial relationships to disclose.
The usefulness of a BP180NC16a-domain ELISA in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy
Authors: A M Powell, Y Sakuma-Oyama, N Oyama, S Albert, B S Bhogal, Martin Black
Journal: British Journal of Dermatology (2003)
Poly(GR) in C9ORF72 -Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons
Authors: Rodrigo Lopez-Gonzalez, Yubing Lu, Tania F. Gendron, Anna Karydas, Helene Tran, Dejun Yang, Leonard Petrucelli, Bruce L. Miller, Sandra Almeida, Fen-Biao Gao
Journal: Neuron (2016)
Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury
Authors: Zhicheng Wang, Jia Nong, Robert B. Shultz, Zhiling Zhang, Taegyo Kim, Veronica J. Tom, Ravi K. Ponnappan, Yinghui Zhong
Journal: Biomaterials (2016)
Who will operate on you?
Authors: Daniel Sokol
Journal: BMJ (2016)

A late change of surgeon may invalidate a patient’s consent



Kathleen Jones had terrible back pain. Following the advice of Daniel Chan, a highly regarded and experienced spinal surgeon, in 2010 she agreed to undergo decompression surgery. She believed that Chan would perform the operation and had waited for his return from leave so that he could undertake it.

Six days before the operation Mr Sundaram, a fellow in trauma and orthopaedics, asked for her consent to the procedure. She signed the consent form, which included the statement, “I understand that you cannot give me a guarantee that a particular person will perform the procedure. The person will, however, have appropriate experience.”

On the morning of the operation a nurse told Jones that Chan was …
An “all 5 mm ports” technique for laparoscopic day-case anti-reflux surgery: A consecutive case series of 205 patients
Authors: L.M. Almond, V. Charalampakis, P. Mistry, M. Naqvi, J. Hodson, G. Lafaurie, J. Matthews, R. Singhal, P. Super
Journal: International Journal of Surgery (2016)
Detection of BCR-ABL Mutation by High Resolution Melting Analysis Is Affected by the Sequence Content, Position and Type of Nucleotide Change and DNA Dye Together with Salt Composition of PCR Mixes.
Authors: Sylvie Nadvornikova, Vaclava Polivkova, Gouse M Shaik, Petr Draber, Jana Moravcova, Katerina Machova Polakova
Journal: Blood (2009)
Evolution of Rituximab as “Standard” Therapy in Patients (pts) with Newly Diagnosed Follicular (FL), Mantle Cell (MCL), and Diffuse Large B Cell (DLCL) Non-Hodgkin’s Lymphoma (NHL) in 5 United States Comprehensive Cancer Centers: An Analysis from the National Comprehensive Cancer Network (NCCN) NHL Outcomes Project.
Authors: Jonathan W. Friedberg, Michelle E. Kho, Eva M. Lepisto, M. Alma Rodriguez, Anna TerVeer, Ann S. LaCasce, Auyporn P. Nademanee, Michael Millenson, Myron Czuczman, Joyce Niland, Andrew D. Zelenetz, Jane C. Weeks
Journal: Blood (2004)
P0784 : Sofosbuvir in combination with peginterferon and ribavirin for patients chronically infected with hepatitis C virus genotype 4: “Real-Life” experience of two large viral hepatitis centers in Northern Germany
Authors: M.H. Wehmeyer, S. Jordan, C. Eißing, J. Hartl, A. Stöhr, J. Petersen, A.W. Lohse, S. Lüth, P. Buggisch, J. Schulze zur Wiesch
Journal: Journal of Hepatology (2015)
Diffuse atrophic papules and plaques, intermittent abdominal pain, paresthesias, and cardiac abnormalities in a 55-year-old woman
Authors: Brittany Oliver, Manfred Boehm, Douglas R. Rosing, Lee S. Shapiro, Daniel T. Dempsey, Peter A. Merkel, Chyi-Chia Richard Lee, Edward W. Cowen
Journal: Journal of the American Academy of Dermatology (2016)
First line trastuzumab-based therapy in her2-positive metastatic breast cancer patients presenting with de novo or recurrent disease
Authors: A. D'Alonzo, M. Lambertini, A. Ferreira, F. Poggia, F. Puglisi, F. Sottotetti, E. Poletto, E. Pozzi, E. Risi, A. Lai, C. Dellepiane, V. Sini, S. Ziliani, G. Minuti, S. Mura, D. Grasso, S. Fancelli, P. Pronzato, L. Del Mastro
Journal: Annals of Oncology (2015)