tbuckley/cabot-search huggingface dataset:
Weighing Evidence from Mendelian Randomization—Early-Life Obesity as a Causal Factor in Multiple Sclerosis?
Authors: Alberto Ascherio, Kassandra L. Munger
Journal: PLoS Medicine (2016)

In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis.
Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study
Authors: Joann G Elmore, Anna NA Tosteson, Margaret S Pepe, Gary M Longton, Heidi D Nelson, Berta Geller, Patricia A Carney, Tracy Onega, Kimberly H Allison, Sara L Jackson, Donald L Weaver
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To evaluate the potential effect of second opinions on improving the accuracy of diagnostic interpretation of breast histopathology. <b>Design</b>&nbsp;Simulation study. <b>Setting</b>&nbsp;12 different strategies for acquiring independent second opinions. <b>Participants</b>&nbsp;Interpretations of 240 breast biopsy specimens by 115 pathologists, one slide for each case, compared with reference diagnoses derived by expert consensus. <b>Main outcome measures</b>&nbsp;Misclassification rates for individual pathologists and for 12 simulated strategies for second opinions. Simulations compared accuracy of diagnoses from single pathologists with that of diagnoses based on pairing interpretations from first and second independent pathologists, where resolution of disagreements was by an independent third pathologist. 12 strategies were evaluated in which acquisition of second opinions depended on initial diagnoses, assessment of case difficulty or borderline characteristics, pathologists' clinical volumes, or whether a second opinion was required by policy or desired by the pathologists. The 240 cases included benign without atypia (10% non-proliferative, 20% proliferative without atypia), atypia (30%), ductal carcinoma in situ (DCIS, 30%), and invasive cancer (10%). Overall misclassification rates and agreement statistics depended on the composition of the test set, which included a higher prevalence of difficult cases than in typical practice. <b>Results</b>&nbsp;Misclassification rates significantly decreased (P&lt;0.001) with all second opinion strategies except for the strategy limiting second opinions only to cases of invasive cancer. The overall misclassification rate decreased from 24.7% to 18.1% when all cases received second opinions (P&lt;0.001). Obtaining both first and second opinions from pathologists with a high volume (≥10 breast biopsy specimens weekly) resulted in the lowest misclassification rate in this test set (14.3%, 95% confidence interval 10.9% to 18.0%). Obtaining second opinions only for cases with initial interpretations of atypia, DCIS, or invasive cancer decreased the over-interpretation of benign cases without atypia from 12.9% to 6.0%. Atypia cases had the highest misclassification rate after single interpretation (52.2%), remaining at more than 34% in all second opinion scenarios. <b>Conclusion</b>&nbsp;Second opinions can statistically significantly improve diagnostic agreement for pathologists' interpretations of breast biopsy specimens; however, variability in diagnosis will not be completely eliminated, especially for breast specimens with atypia.
<sup>68</sup>Ga-HBED-CC-PSMA PET/CT Versus Histopathology In Primary Localized Prostate Cancer: A Voxel-Wise Comparison
Authors: Constantinos Zamboglou, Florian Schiller, Tobias Fechter, Gesche Wieser, Cordula Annette Jilg, Alin Chirindel, Nasr Salman, Vanessa Drendel, Martin Werner, Michael Mix, Philipp Tobias Meyer, Anca Ligia Grosu
Journal: Theranostics (2016)

Purpose:We performed a voxel-wise comparison of 68 Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of 68 Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa).Methodology: Nine patients with histopathological proven primary PCa underwent 68 Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy.Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared.Histopathological information was matched to ex-vivo CT.PCa volume (PCa-histo) and non-PCa tissue in the prostate (NPCa-histo) were processed to obtain a PCa-model, which was adjusted to PET-resolution (histo-PET).Each histo-PET was coregistered to in-vivo PSMA-PET/CT data.Results: Analysis of spatial overlap between histo-PET and PSMA PET revealed highly significant correlations (p < 10 -5 ) in nine patients and moderate to high coefficients of determination (R²) from 42 to 82 % with an average of 60 ± 14 % in eight patients (in one patient R 2 = 7 %).Mean SUVmean in PCa-histo and NPCa-histo was 5.6 ± 6.1 and 3.3 ± 2.5 (p = 0.012).Voxel-wise receiver-operating characteristic (ROC) analyses comparing the prediction by PSMA-PET with the non-smoothed tumor distribution from histopathology yielded an average area under the curve of 0.83 ± 0.12.Absolute and relative SUV (normalized to SUVmax) thresholds for achieving at least 90 % sensitivity were 3.19 ± 3.35 and 0.28 ± 0.09, respectively.Conclusions: Voxel-wise analyses revealed good correlations of 68 Ga-HBED-CC-PSMA PET/CT and histopathology in eight out of nine patients.Thus, PSMA-PET allows a reliable detection and delineation of PCa as basis for PET-guided focal therapies.
Abstract 17383: Exploratory Study of Emergency Cardiopulmonary Bypass for Resuscitation and Long-term Survival From Prolonged Ventricular Fibrillation Cardiac Arrest in Rats
Authors: Ingrid A Magnet, Florian Ettl, Wolfgang Weihs, Alexandra Warenits, Daniel Grassmann, Michael Wagner, Ursula Teubenbacher, Johann Sipötz, Fritz Sterz, Andreas Janata
Journal: Circulation (2013)

BACKGROUND: Emergency cardiopulmonary bypass (ECPB) may achieve successful resuscitation after prolonged cardiac arrest (CA) when conventional cardiopulmonary resuscitation (CPR) fails. A rodent model of ventricular fibrillation (VF) CA would allow optimizing ECPB use. In this study, we assessed the feasibility of a 10 min ventricular fibrillation (VF) CA model with ECPB resuscitation in rats in terms of return of spontaneous circulation (ROSC) rate and long-term survival with neurologic and histologic outcome.

METHODS: The ECPB setup consisted of an open reservoir, a roller pump, a capillary membrane oxygenator, primed with 15 mL of heparinized crystalloid solution, connected by silicone tubing to a draining catheter in the right jugular vein and an inflow catheter in the right femoral artery, and a circulating water bath. VF was initiated in adult male Sprague-Dawley rats (450 g, anesthetized) endocardially. After 10 min of CA, rats were resuscitated with ECPB at a flow rate of 50 mL/min, mechanical ventilations and drugs (epinephrine, bicarbonate, heparin). With start of ECPB, rats were cooled to mild therapeutic hypothermia. After defibrillation and ROSC, rats were weaned from CPB and maintained at 33°C for 5 hours. Outcome parameters included resuscitability, survival to 1 month with neurologic deficit score (NDS; 0% = normal, 100% = dead), overall performance category (OPC; 1 = normal, 5 = dead) and a histologic damage score (HDS, pending). All data is presented as mean±SD.

RESULTS: ROSC was achieved in 14 / 14 animals within 3.3±0.9 min on bypass, 10 / 14 animals survived to 1 month (7 OPC 1, 3 OPC 2). NDS was 1.9±2.5. All animals experienced marked neurologic (motoric, sensory and cognitive) and overall improvement over the long observation period. The deficits that persisted were motoric on the lower extremities.

CONCLUSION: In a rat model of prolonged VF CA, ECPB resuscitation with mild hypothermia leads to 100% resuscitability and favorable functional outcome and long-term survival after 10 min of VF.
Longitudinal Body Composition Changes in Diffuse Large B-cell Lymphoma Survivors: A Retrospective Cohort Study of United States Veterans
Authors: Daphne Y. Xiao, Suhong Luo, Katiuscia O’Brian, Kristen M. Sanfilippo, Arun Ganti, Peter Riedell, Ryan C. Lynch, Weijian Liu, Brad S. Kahl, Amanda F. Cashen, Todd A. Fehniger, Kenneth R. Carson
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Body composition parameters are associated with long-term health outcomes. We assessed longitudinal body composition changes in diffuse large B-cell lymphoma (DLBCL) survivors and identified clinical variables associated with the long-term development of sarcopenia and visceral obesity. Methods: A retrospective cohort of United States veterans with DLBCL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab, was assembled. Muscle, subcutaneous fat, and visceral fat areas were measured with computed tomography analysis. Data were analyzed with repeated-measures analysis of variance and logistic regression. All statistical tests were two-sided. Results: Three hundred forty-two patients were included. Muscle area initially decreased during treatment, then returned to baseline by 24 months after treatment. Subcutaneous fat area increased from baseline by 6.5% (95% confidence interval [CI] = 2.6% to 10.5%) during treatment and by 21.4% (95% CI = 15.7% to 27.2%) by 24 months after treatment. Visceral fat area increased from baseline by 4.5% (95% CI = -0.9% to 9.9%) during treatment and by 21.6% (95% CI = 14.8% to 28.4%) by 24 months after treatment. Variables associated with long-term development of sarcopenia included: baseline sarcopenia (adjusted odds ratio [aOR] = 17.21, 95% CI = 8.48 to 34.94), older than age 60 years (aOR = 2.93, 95% CI = 1.46 to 5.88), and weight loss greater than 5% during treatment (aOR = 2.40, 95% CI = 1.12 to 5.14). Variables associated with long-term visceral fat gain included: weight gain greater than 5% during treatment (aOR = 4.60, 95% CI = 2.42 to 8.74). Conclusions: DLBCL survivors undergo unfavorable long-term body composition changes. Patients at risk for the long-term development of sarcopenia or visceral obesity can be identified based on clinical risk factors and targeted for lifestyle interventions.
Bone marrow lesions and synovitis on MRI associate with radiographic progression after 2 years in hand osteoarthritis
Authors: W Damman, R Liu, JL Bloem, FR Rosendaal, M Reijnierse, M Kloppenburg
Journal: Annals of the Rheumatic Diseases (2016)

To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years.Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded.Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1)).BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy.
P1334 : A multicentre, randomised, open-label study comparing the efficacy and safety of two doses of Doxorubicin TransdrugTM to best standard of care in patients with advanced Hepatocellular Carcinoma (HCC) after sorafenib. The relive study
Authors: P. Merle, G. Pelletier, F. Habersetzer, G. Luca Frassineti, G.-P. Pageaux, I. Borbath, R. Gérolami, G. Sánchez Antolín, J.-P. Bronowicki, Z. Horváth, Y. Touchefeu, A. Maieron, H. Wege, V. Breder, N. Gabrail, B. Vasseur, P. Attali, J.-F. Blanc
Journal: Journal of Hepatology (2015)
T Cells From CLL Patients Recognize Spontaneously Peptides Derived of the Receptor Tyrosine Kinase Ror1
Authors: Mohammad Hojjat -Farsangi, Amir Hossein Daneshmanesh, Mahmood Jeddi-Tehrani, Anders Osterborg, Fazel Shokri, Håkan Mellstedt, Hodjattallah Rabbani
Journal: Blood (2010)
Comparing an apple to a fruit salad.
Authors: N Spector, W Pulcheri, M Nucci, A Maiolino
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.8.3021 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9256146 Comparing an apple to a fruit salad. N SpectorxN SpectorSearch for articles by this author , W PulcherixW PulcheriSearch for articles by this author , M NuccixM NucciSearch for articles by this author , A MaiolinoxA MaiolinoSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.8.3021 PDF "Comparing an apple to a fruit salad.." Journal of Clinical Oncology, 15(8), pp. 3021–3022© 1997 by American Society of Clinical Oncology
The Effects of Glutamine Supplementation on Markers of Autophagy and Apoptosis in Peripheral Blood Mononuclear Cells from Patients with Sickle Cell Disease
Authors: Patrick B Walter, Leah Hohman, Andrew Rokeby, Julian Lum, Robert Hagar, Melinee Stewart, Lisa Lavrisha, Elliott Vichinsky, Claudia R. Morris
Journal: Blood (2015)
Binding of Drugs to Serum Albumin
Authors: Jan Koch-Weser, Edward M. Sellers
Journal: New England Journal of Medicine (1976)

Competition between Drugs for Albumin BindingConcomitantly administered drugs can influence one another's binding to serum albumin, other serum proteins or tissue proteins. Interaction at the tissue level is difficult to study, and its clinical importance remains unknown. Since some drugs are extensively localized in tissues (e.g., tricyclic antidepressants, diazepam, quinidine, phenothiazines) their displacement from these sites by other drugs could be quantitatively very important.Drug binding to serum albumin can be decreased or enhanced by other drugs, but no clinically important examples of the latter are known. In contrast, there are many drugs that partially displace one another from . . .
Clinical validation of real-time PCR and SNaPshot methods in comparison to NGS for KRAS and NRAS Mutation Detection in colorectal cancer at Genia Laboratories (Uruguay).
Authors: Juan Martin Marques, Leticia Repetto, Lucia Guggeri, Santiago Lamuedra, Valentina Russo, Alejandra Torres, Rosina Fossati, Carlos Azambuja, Astrid Agorio
Journal: Journal of Clinical Oncology (2015)

e22121 Background: Companion Tests are essential to predict whether drugs will work in targeted therapies for colorectal cancer (CRC). Hence, genetic tests are needed to perform accurate and sensitive diagnosis of mutations on tumor samples. At Genia Laboratories we set up and validated two methods to detect mutations in KRAS and NRAS genes, used as Companion Test in Uruguay and Argentine. Methods: 1- Mutation detection in codon 12 and 13 of KRAS gene by Real Time PCR. This method was based on an Allele-Specific Real Time PCR with the use of blockers. We validated this method and compared its performance to a Qiagen test approved by FDA (KRAS RGQ PCR Kit) and ion torrent NGS. 2- Mutation detection in codon 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes by SNaPshot. This method detected the most prevalent mutations in exons 2, 3 and 4 of KRAS and NRAS, and was validated at Genia Laboratories. On an overall study we compared results obtained for a set of 85 clinical samples using our SNaPshot method, our Real Time PCR method, and NGS. For each method we evaluated accuracy, precision, analytical sensitivity, and analytical specificity. Results: The accuracy of our Real Time PCR method showed 100% of concordance when compared to Qiagen reference method. We were able to detect mutations present at 2.5 to 5% in CRC tumor samples with our Real Time assay. With SNaPshot assay we were able to detect mutations at 3 to 12.5%. With NGS analysis of samples we detected mutations present at 3-5%. Conclusions: At Genia Laboratories we validated two methods for CRC Companion Tests: 1) our Real Time PCR method shows advantages in processing time of the samples and high sensibility for diagnosing the most prevalent mutations in KRAS; 2) our SNaPshot method serves to diagnose the most prevalent KRAS and NRAS mutations. With our results using NGS, we can envisage a promising future for CRC mutations diagnosis, as it is highly accurate and sensitive. Both NGS and Sanger work with direct detection of mutation, but NGS is much more sensitive. The experience we acquired in CRC genetic diagnosis and validation of methods is of high value for clinical diagnosis in our region.
From bones to blood pressure, developing novel biologic approaches targeting the osteoprotegein pathway for pulmonary vascular disease
Authors: Sarah Dawson, Allan Lawrie
Journal: Pharmacology & Therapeutics (2016)

Osteoprotegerin (tnfsf11b, OPG) is a soluble member of the TNF superfamily originally described as an important regulator of osteoclastogenesis almost 20years ago. OPG is a heparin-binding secreted glycoprotein that exists as a 55-62kDa monomer or a 110-120kDa disulphide-linked homodimer. Acting as a soluble decoy receptor for RANKL, OPG actively regulates RANK signalling, and thereby osteoclastogenesis. OPG has subsequently been shown to also be a decoy receptor TNF related apoptosis inducing-ligand (tnfsf10, TRAIL, Apo2L). TRAIL is a type II transmembrane protein that is widely expressed in a variety of human tissues, including the spleen, lung, and prostate. Through binding to TRAIL, OPG can inhibit TRAIL-induced apoptosis of cancer cells. More recently, OPG has been demonstrated to be secreted by, and influence, vascular smooth muscle cells phenotype particularly related to vascular calcification and pulmonary vascular remodelling. In pulmonary artery smooth muscle cell (PASMC) suppression of BMP, induction of 5-HT and IL-1 signalling have been shown to stimulate the release of OPG in vitro, which causes cell migration and proliferation. Patients with idiopathic PAH (IPAH) demonstrate increased circulating and tissue levels of OPG, and circulating serum levels predict survival. In pre-clinical models, OPG levels correlate with disease severity. Since OPG is a naturally circulating protein, we are investigating the potential of novel biologic antibody therapies to rescue PAH phenotype in disease models. Further pre-clinical and mechanistic data are forthcoming, but we believe current published data identify OPG as an exciting and novel therapeutic target in PAH.
Correlation of anti-tumor adaptive immunity with clinical response in a phase II “Window” trial of neoadjuvant cetuximab in patients with resectable stage III-IV head and neck squamous carcinoma (HNSCC).
Authors: Robert L. Ferris, Seungwon Kim, Sumita Trivedi, Raghvendra Mohan Srivastava, Fernando Concha-Benavente, Dwight Earl Heron, David Andrew Clump, Umamaheswar Duvvuri, William E. Gooding, Jonas Talmadge Johnson, James Ohr, Julie E. Bauman
Journal: Journal of Clinical Oncology (2016)

6060 Background: Despite near universal EGFR expression in HNSCC, the anti-EGFR antibody, cetuximab, improves survival in only 15% of patients. Activation of immune cell subsets might contribute to anti-tumor responses. We investigated the association of cetuximab response with FcγR polymorphism, hypothesized to influence the potency of cetuximab-FcγR binding and NK cell-mediated cytotoxicity, and peripheral EGFR-specific T cells, markers of tumor-antigen specific cellular immunity. Methods: We conducted a prospective phase II “window” trial in patients with previously untreated, resectable stage III-IVA HNSCC (n = 40) using cetuximab (400 mg/m2 then 250mg/m2/week) for 3-4 weeks preoperatively, followed by adjuvant chemoradiation with or without cetuximab. Biomarkers in peripheral blood (PBL) and tumor infiltrating lymphocytes (TIL) were correlated with clinical response and acneiform rash. In the brief window setting,, response was measured using changes in pre/post tumor diameter on CT scans as a continuous variable ( ≥ 10% decrease). Results: Median follow up for progression free survival (PFS) was 24 mo (range 1–54 mo). 3-year PFS was 84% (95% CI = 71%-98%). Objective response was observed in 11 of 33 (33%) evaluable patients. Adjusted for baseline size, response was associated with improved PFS (p = 0.058). Response was also associated with higher circulating EGFR-specific T cells after neoadjuvant cetuximab (p < 0.04). FcγRIIIa VV/VF genotypes on natural killer cells were favorable; tumors shrank by median 10% vs +3.8% growth in FF expressors. Rash during window exposure was not associated with response, however was associated with FcγR genotype (FF > VF > VV; p = 0.077). Conclusions: In previously untreated HNSCC patients, response to neoadjuvant cetuximab was associated with enhanced cellular immunity against EGFR and improved PFS. Response modestly correlated with FcγRIIIa genotype but not rash. EGFR-specific T cells frequency is a novel immune biomarker of cetuximab response, warranting validation in larger cohorts. Clinical trial information: NCT01218048.
Disciplinary Action in the Medical Profession
Authors: W P MULVANEY, C W BECK, M A QURESHI
Journal: JAMA (1964)

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
癌における拡散強調画像: Restriction Spectrum Imagingの物理学的基礎および適用
Authors: S White Nathan, R Mcdonald Carrie, Farid Niky, Kuperman Josh, Karow David, M Schenker-Ahmed Natalie, Bartsch Hauke, Rakow-Penner Rebecca, Holland Dominic, Shabaik Ahmed, Bjornerud Atle, Hope Tuva, Hattangadi-Gluth Jona, Liss Michael, Parsons J. Kellogg, C Chen Clark, Raman Steve, Margolis Daniel, E Reiter Robert, Marks Leonard, Kesari Santosh, J Mundt Arno, J Kane Christopher, S Carter Bob, G Bradley William, M Dale Anders
Journal: Cancer Research (2014)
Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma
Authors: Ana L. Gomes, Ana Teijeiro, Stefan Burén, Krishna S. Tummala, Mahmut Yilmaz, Ari Waisman, Jean-Philippe Theurillat, Cristian Perna, Nabil Djouder
Journal: Cancer Cell (2016)
Endoscopic bridge to radiology: a sequential life-saving hemostatic approach
Authors: Antonino Granata, Roberto Miraglia, Gabriele Curcio, Mario Traina
Journal: Endoscopy (2015)

A 17-year-old girl known to have portal vein cavernoma presented at our institute with massive upper gastrointestinal bleeding, which was causing hypovolemic shock. The girl required multiple blood transfusions and maximal medical support.