tbuckley/cabot-search huggingface dataset:
177P Clinicopathologic characteristics in large cell neuroendocrine carcinomas of the lung (LCNCL): The experience of one center
Authors: M. Vaslamatzis, A. Laskarakis, T. Tegos, M. Pavlakis, T. Argyrakos, N. Alevizopoulos, C. Zoublios, E. Vasili, E. Gioti, K. Athanasiadi
Journal: Journal of Thoracic Oncology (2018)
Expression of MICA/b, a ligand for natural killer (NK) cell recognition, on human pancreatic adenocarcinoma and potential for NK intervention.
Authors: Julie Djeu, Danielle Gilvary, Thu Le Trinh, Nhan Tu, Domenico Coppola
Journal: Journal of Clinical Oncology (2017)

129 Background: Pancreatic cancer remains a leading cause of cancer-related mortality because of lack of means for early detection and notable refractoriness to standard chemotherapy in advanced stages of disease. Mobilization of the immune system is therefore an important option to explore. Natural Killer (NK) cells are potent effector cells in immune surveillance against cancer and offer a unique advantage because of expression of a C-type, lectin-like, type II transmembrane glycoprotein, NKG2D, on the cell surface. NKG2D is a receptor that specifically recognizes common stress-induced proteins such as MICA/B on tumor cells, targeting them for perforin/granzyme B-mediated destruction. The goal of this study is to examine if MICA/B is expressed on human pancreatic cancer cells, allowing the potential to direct immunotherapy against pancreatic cancer via NK cell therapy. Methods: This study was conducted under an IRB approved protocol. Pancreatic samples were taken from 121 patients with pancreatic ductal adenocarcinoma (PDA) and 103 cases of normal adjacent pancreatic tissues (NP) were included for comparison in a tissue microarray developed in the Tissue Core. All cases were stained for MICA/B AB using the Ventana automated immunostainer Discovery XT (Ventana,Tucson, AZ). Human pancreatic cell lines were also immunostained for MICA/B expression and tested for sensitivity to NK cell lysis in vitro. Results: A significant increase in MICA/B expression was observed during the progression from NP to PDA (p value &lt; 0.0001) in pancreatic tumor tissues. Additionally, all pancreatic cell lines, including MiaPaca, Panc-1, and PCSC, express MICA/B and were readily lysed by NK cells. Conclusions: We report an increase in MICA/B expression during the progression of pancreatic ductal adenocarcinoma and MICA/B may represent a new immunotherapeutic target in pancreatic gastric carcinogenesis.
Abstract 19654: Cardiac Epigenetic and Transcriptional Responses to In Utero Diesel Exposure
Authors: Jamie M Goodson, James W MacDonald, Theo K Bammler, Yonggang Liu, Michael T Chin
Journal: Circulation (2016)

Introduction:  We have previously shown, in a mouse model, that gestational exposure to diesel exhaust causes placental inflammation, as well as increased cardiac hypertrophy, fibrosis and susceptibility to heart failure in the adult offspring following transverse aortic constriction (TAC). We have also found that the hearts of the in utero diesel exhaust (DE) exposed mice show an increased rate of apoptosis following TAC, and that neonatal cardiomyocytes from in utero exposed mice are more susceptible to apoptosis to hydrogen peroxide, suggesting an alteration of the cardiomyocytes that increases sensitivity to apoptotic triggers. The basis for this susceptibility is unknown.   Hypothesis:  We hypothesize that in utero exposure to DE alters DNA methylation at specific loci in cardiomyocytes and also alters transcriptional profiles to promote susceptibility to injury.   Methods:  We performed reduced representation bisulfite sequencing and RNA sequencing on neonatal cardiomyocytes isolated from p0 pups exposed to DE or filtered air (FA) in utero.   Results:  Analysis of CpG-enriched DNA from exposed neonatal cardiomyocytes showed not only global hypomethylation in DE exposed animals, but also 63 specific differentially methylated regions (DRMs). Ingenuity pathway analysis indicates hypomethylation of DRMs associated with genes involved in pathways important for cardiac hypertrophy, beta-adrenergic and GPCR signaling. RNA sequencing showed signficantly dysregulated transcription of 300 genes involved in pathways such as mitochondrial carnitine shuttling, fatty acid oxidation, AMPK signaling, and cell cycle regulation.   Conclusions:  In utero exposure to diesel exhaust leads to profound changes in cardiomyocyte DNA methylation and RNA transcription that likely alter beta-adrenergic signaling, cellular energetics and cell cycle regulation. These alterations likely have downstream effects that promote susceptibility to adult injury. Understanding how exposure changes gene expression through dysregulation of DNA methylation or other mechanisms will be vital for identifying therapeutic interventions for air pollution-related heart failure.
What is the minimal clinically important difference for helium-3 magnetic resonance imaging ventilation defects?
Authors: Rachel L. Eddy, Sarah Svenningsen, David G. McCormack, Grace Parraga
Journal: European Respiratory Journal (2018)

<b>In asthmatics, the estimated MCID for <sup>3</sup>He MRI ventilation defect volume is 110 mL and that for ventilation defect percentage is 2%, which are similar to FEV</b><sub><b>1</b></sub><b>, suggesting that these biomarkers are suitable for use in clinical trials</b>http://ow.ly/yQ8K30jAFnX
The Corticotropin-Releasing Factor Stimulation Test
Authors: George P. Chrousos, Heinrich M. Schulte, Edward H. Oldfield, Philip W. Gold, Gordon B. Cutler, D. Lynn Loriaux
Journal: New England Journal of Medicine (1984)

We investigated the effect of exogenous corticotropin-releasing factor on plasma levels of ACTH and cortisol in 13 patients with ACTH-secreting pituitary adenomas (Cushing's disease) and in 9 patients with other forms of Cushing's syndrome. In all patients with Cushing's disease, ovine corticotropin-releasing factor, given intravenously as a bolus injection (1 microgram per kilogram of body weight), caused a further increase in the already elevated levels of ACTH and cortisol. Successful transphenoidal adenomectomy was followed as early as one week after surgery by normalization or near-normalization of the ACTH and cortisol responses to corticotropin-releasing factor. On the other hand, patients with the ectopic ACTH syndrome, who also had high basal plasma concentrations of ACTH and cortisol, had no ACTH or cortisol responses to corticotropin-releasing factor. This difference in responsiveness between these two patient groups cannot be explained on the basis of different metabolic clearance rates of exogenous corticotropin-releasing factor, as shown by similar disappearance curves of immunoreactive corticotropin-releasing factor from plasma. Patients with Cushing's syndrome of adrenal origin who were hypercortisolemic during testing had undetectable plasma levels of ACTH and no ACTH or cortisol responses to corticotropin-releasing factor. We conclude that stimulation of the pituitary-adrenal axis with corticotropin-releasing factor may be useful in differentiating pituitary from ectopic causes of Cushing's syndrome.
Effect of dose-optimized imatinib (IM) 800 mg on deep molecular responses (CMR 4.5) and prediction of survival: Results from the randomized CML-study IV.
Authors: Rüdiger Hehlmann, Michael Lauseker, Benjamin Hanfstein, Martin C. Müller, Annette Schreiber, Ulrike Proetel, Markus Pfirrmann, Susanne Schnittger, Jolanta Dengler, Christiane Falge, Andreas Neubauer, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Gabriela M. Baerlocher, Stefan W. Krause, Andreas Hochhaus, Joerg Hasford, Susanne Saussele
Journal: Journal of Clinical Oncology (2013)

7051 Background: Since complete molecular remission (CMR 4.5) defines a subgroup of patients who may stay in remission even after discontinuation of treatment, we analysed whether CMR 4.5 is reached faster with dose optimized IM 800 mg and whether the achievement of CMR 4.5 at specified points in time results in better survival than the achievement of less deep remissions. Methods: Confirmed CMR 4 and CMR 4.5 are defined as ≤ 0.01% BCR-ABL IS or ≥ 4 log reduction and ≤ 0.0032% BCR-ABL IS or ≥ 4.5 log reduction, respectively, from standardized baseline as determined by real-time PCR in 2 independent analyses. Details on CML-Study IV have been published (Hehlmann et al., JCO 2011). Cumulative incidences were estimated under consideration of competing risks. Landmark analyses were performed to evaluate the prognostic impact of different remissions at 4 years on survival. Results: Of 1551 randomized patients with newly diagnosed chronic phase CML 1525 were evaluable. Median age was 52 years, 88% were EUTOS low risk, 12% high risk. 113 patients were transplanted (73 in first chronic phase), 246 received 2nd generation TKI. 152 patients have died. After a median observation time of 67.5 months, 6-year OS was 88.2%.CMR 4.5 was reached after a median of about 76.1 months with IM 800 and 107.3 months with IM 400. EUTOS low-risk patients reached all remissions faster than high-risk patients. Independent of treatment approach CMR 4.5 at 4 years predicted OS significantly better than complete cytogenetic remission (p=0.043), but not significantly better than major molecular remission (MMR) or CMR4. After a median observation of 3.9 years 1 of 626 patients with CMR 4 has progressed. Only six of the 394 patients with CMR 4.5 have died after a median observation time of 3.0 years, no patient has progressed. An additional finding was that achieving MMR at 3 and at 6 months predicts faster achievement of CMR 4.5. Conclusions: We conclude that dose optimized IM 800 induces CMR 4.5 faster than IM 400 and that CMR 4.5 at 4 years is associated with a survival advantage. Dose optimized IM 800 may provide an improved therapeutic basis for treatment discontinuation in patients with CML. Clinical trial information: NCT00055874.
Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure
Authors: Markus Reichold, Enriko D. Klootwijk, Joerg Reinders, Edgar A. Otto, Mario Milani, Carsten Broeker, Chris Laing, Julia Wiesner, Sulochana Devi, Weibin Zhou, Roland Schmitt, Ines Tegtmeier, Christina Sterner, Hannes Doellerer, Kathrin Renner, Peter J. Oefner, Katja Dettmer, Johann M. Simbuerger, Ralph Witzgall, Horia C. Stanescu, Simona Dumitriu, Daniela Iancu, Vaksha Patel, Monika Mozere, Mehmet Tekman, Graciana Jaureguiberry, Naomi Issler, Anne Kesselheim, Stephen B. Walsh, Daniel P. Gale, Alexander J. Howie, Joana R. Martins, Andrew M. Hall, Michael Kasgharian, Kevin O’Brien, Carlos R. Ferreira, Paldeep S. Atwal, Mahim Jain, Alexander Hammers, Geoffrey Charles-Edwards, Chi-Un Choe, Dirk Isbrandt, Alberto Cebrian-Serrano, Ben Davies, Richard N. Sandford, Christopher Pugh, David S. Konecki, Sue Povey, Detlef Bockenhauer, Uta Lichter-Konecki, William A. Gahl, Robert J. Unwin, Richard Warth, Robert Kleta
Journal: Journal of the American Society of Nephrology (2018)

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.
Potential role of extracellular vesicle–mediated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy
Authors: Takamasa Ito, Takashi Shiromizu, Shunsuke Ohnishi, Shotaro Suzuki, Katsuhiro Mabe, Akito Hasegawa, Hideyuki Ujiie, Yasuyuki Fujita, Yuichi Sato, Shuji Terai, Mototsugu Kato, Masahiro Asaka, Takeshi Tomonaga, Hiroshi Shimizu, Riichiro Abe
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 12141: ApoE-HDL Cholesterol Predicts Incident Cardiovascular Events: Aric Study
Authors: Anandita Agarwala, Wensheng Sun, Vijay Nambi, Cameron Guild, Josef Coresh, Christie M Ballantyne, Ron Hoogeveen
Journal: Circulation (2016)

Background: ApoE-HDL-C, a subfraction of HDL-C that contains ApoE, is thought to be cardioprotective via its inhibition of arterial stiffening and its role in reverse cholesterol transport. Objective: We examined the relationship between ApoE- HDL-C and incident cardiovascular events in the biracial Atherosclerosis Risk in Communities (ARIC) study. Methods: ApoE-HDL-C was measured in 9,258 ARIC participants using a novel automated homogeneous assay (Denka Seiken). The association between ApoE-HDL-C and HDL-C with incident cardiovascular events was assessed using Cox proportional hazard regression models. Covariates included age, race, gender, race, BMI, systolic blood pressure, use of anti-hypertensive medications, diabetes, smoking status, total cholesterol and triglycerides. Results: Mean ApoE-HDL-C and HDL-C levels were 5.06 ± 1.79 mg/dL and 51.10 ± 16.74 mg/dL, respectively. ApoE-HDL-C comprised roughly 10% of total HDL-C levels. ApoE-HDL-C levels were higher in non-diabetics, women and African Americans and showed strong positive correlations with HDL-C and total cholesterol levels. Both apoE-HDL-C and HDL-C were associated with incident CVD, driven mainly by CHD (Table 1). Each 10 mg/dL increase in HDL-C levels was associated with a decreased risk of incident CVD after multivariate adjustment (HR 0.89, 95% CI 0.85, 0.93, p&lt;0.001). A 1 mg/dL increase in ApoE-HDL-C was associated with a decreased risk of incident CVD after similar multivariate adjustment (HR 0.91, 95% CI 0.88, 0.95, p&lt;0.001). Conclusion: ApoE-HDL-C predicts incident CVD similarly to HDL-C in the biracial ARIC cohort.
Preliminary results from a single-arm, phase II study assessing the efficacy of pembrolizumab plus radiotherapy in metastatic triple negative breast cancer.
Authors: Alice Ho, Christopher Andrew Barker, Ayca Gucalp, Lizza Lebron-Zapata, Yong Hannah Wen, Anh Phung, Molly Wilgucki, Micaela Henrich, Brittany Arnold, Sujata Patil, Heather L. McArthur
Journal: Journal of Clinical Oncology (2017)

95 Background: Two trials have demonstrated overall response rates of 19% with immune checkpoint inhibitors alone in chemotherapy-resistant triple negative breast cancer (TNBC). Radiation therapy (RT) is frequently used to enhance local control in TNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. We evaluate the safety and efficacy of the combination of RT and pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, in a single-arm, two-stage, phase II study in metastatic TNBC. Results from the first stage are reported. Methods: Eligibility criteria includes women with biopsy-proven TNBC, ECOG performance status 0-2, ≥ 2 measurable sites of metastatic disease with at least one site requiring RT. A total RT dose of 3000 cGy is delivered in one week in 5 fractions. Pembrolizumab is given intravenously at 200 mg/kg D1+/- 3 days and then every 3 weeks until disease progression as defined by RECIST v 1.1. The primary endpoint is overall response rate at week 13 in the non-targeted, non-irradiated lesions. Secondary endpoints include safety and overall survival. Tumor biopsies are obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: Nine patients were enrolled in the first phase and assessed for antitumor activity and safety. Median age was 52 years (range 37-73). Three patients died secondary to disease-related complications (at weeks 2, 6 and 8) and 1 came off study due to disease progression prior to week 13. Of the 5 patients evaluable at week 13, 2 had a partial response, 1 had stable disease and 2 had disease progression. Common toxicities were mild and included fatigue, myalgia and nausea. One grade 3 event was reported - hyperbilirubinemia not attributable to study therapy after one dose of pembrolizumab. Conclusions: The combination of pembrolizumab and RT was well-tolerated in the first stage of a phase II study. Responses were observed outside of the RT fields in 2 of 5 patients who were evaluable at 13 weeks. The contribution of RT to pembrolizumab is unknown and will be investigated in the second stage of the study, which is ongoing. Correlative studies are planned. Clinical trial information: NCT02730130.
Abstract 12105: Temperature Variability During Targeted Temperature Management is not Associated With Neurological Outcomes following Cardiac Arrest
Authors: Arash Nayeri, Nirmanmoh Bhatia, Benjamin Holmes, Nyal Borges, William Armstrong, Meng Xu, Eric Farber-Eger, Quinn Wells, John McPherson
Journal: Circulation (2016)

Introduction: Recent studies on comatose survivors of cardiac arrest undergoing targeted temperature management (TTM) have reported similar outcomes at multiple target temperatures. However, details regarding core temperature variability during TTM and its prognostic implications remain unknown. Hypothesis: Increasing core temperature variability during TTM will predict poor neurological outcomes. Methods: We analyzed a prospectively collected cohort of 242 consecutive comatose survivors of cardiac arrest treated with TTM at a tertiary care hospital between 2007 and 2014. Core temperature variability was defined as the statistical variance (i.e. standard deviation squared) amongst all core temperature recordings during the maintenance phase of TTM. Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score &gt;2, was the primary outcome. Death prior to hospital discharge was assessed as the secondary outcome. Results: Baseline patient characteristics are reported in Table 1. A poor neurological outcome was observed in 147 (61%) patients and 136 (56%) patients died prior to hospital discharge. In multivariable logistic regression, increased core temperature variability was not associated with increased odds of poor neurological outcomes (OR 0.38, 95% CI 0.11-1.38, p=0.142) or death (OR 0.43, 95% CI 0.12-1.53, p=0.193) at hospital discharge. Conclusions: In this study, individual core temperature variability during TTM was not associated with poor neurological outcomes or death at hospital discharge. Table 1. Baseline characteristics and clinical features. Data are presented as median (IQR) for continuous variables and number (percentage) of patients for categorical variables. N represents the number of non-missing values. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation; TTM, targeted temperature management.
Deaths in Epilepsy
Authors: Orrin Devinsky, Anuradha Singh, Daniel Friedman
Journal: JAMA Neurology (2018)

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Unprocessed and Processed Meat Consumption and Blood Pressure: The INTERMAP Study
Authors: L.M. Oude Griep, P. Seferidi, J. Stamler, Q. Chan, L. van Horn, L.M. Steffen, K. Miura, H. Ueshima, N. Okuda, L. Zhao, S.S. Soedamah-Muthu, M.L. Daviglus, P. Elliott
Journal: Circulation (2015)
Management of Ventricular Arrhythmias and Sudden Cardiac Death Risk Related to Ischemic and Nonischemic Cardiomyopathy
Authors: Sana M. Al-Khatib, William G. Stevenson
Journal: JAMA Cardiology (2018)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Cardiology journal