tbuckley/cabot-search huggingface dataset:
Hypereosinophilic syndromes (HESs) variable clinical presentations and responses to treatment
Authors: S. Mitra, D. Power, P. D. Thornton, R. O Donnell, P. T. Murphy
Journal: Journal of Clinical Oncology (2007)

17529 Background: Hypereosinophilic syndromes (HESs) refers to a heterogenous group of disorders characterised by marked blood eosinophilia (&gt;1500/cu mm) and tissue eosinophilia (lasting for more than 6 months), in the absence of other eitiologies for eosinophilia, resulting in end organ damage. Eosinophilias may be reactive or due to a chronic myeloproliferative disorder (with evidence of clonal proliferation).Clonal eosinophilias are very often associated with the fusion gene FIP1L1-PDGFR alpha which causes the generation of a constitutively active Tyrosine Kinase. Treatment modalities for HES includes corticosteroids, chemotherapeutic agents, alpha- interferon, tyrosine kinase inhibitors (eg Imatinib mesylate) and the monoclonal anti-interleukin 5. Patients carrying FIP1L1-PDGFRalpha respond very well to Imatinib. Aim:Retrospective review of the variable response of 7 patients with HES (over a period of 6 months), to current treatment modalities. Methods: The 7 patients (6 Male, 1 Female; age range 37–80 yrs; mean age 56 yr) presented with eosinophilia in the range 2600–73,000 /cu mm.They were followed up for &gt;6 months. A response to treatment was defined as Eosinophil count&lt;1500 /cumm or Eosinophil count &lt; 5% of the total leucocyte count .Four of the 7 patients received Imatinib as initial treatment. Two patient initially had steroids followed by Imatinib and 1 patient (aged 80 yr) was treated with Hydroxyurea initially. Results: Four of the 6 patients receiving Imatinib responded to it. Of the 2 patients not responding to Imatinib,1 responded partially to Hydroxyurea and the other did not respond to monotherapy with steroid or alpha-interferon (but eventually responded to a combination of the two). The patient who had initial treatment with Hydroxyurea responded well. Of the 7 patients 1 was positive for the FIP1L1-PDGFRalpha fusion gene,1 result was equivocal, 3 were negative and 2 were not tested (not available at the time). Of the 2 that were negative,1 responded to Imatinib. Conclusions: Response of HES patients to the various treatment modalities, is variable and often unpredictable.The FIP1L1-PDGFR alpha fusion gene is not often present;however other Tyrosine Kinases may be dysregulated and hence a trial of Imatinib is worth considering in most cases. No significant financial relationships to disclose.
&lt;TITLE&gt;Quality of Life&lt;/TITLE&gt;
Authors: Sharon Parmet, Cassio Lynm, Richard M Glass
Journal: JAMA (2002)

Quality of LifeQ uality of life refers to a person' s perceived physical and mental well-being.Many factors can contribute to quality of life, including those that influence the "goodness" of life, a person' s happiness, and the ability to function independently and to enjoy life.Health-related quality of life (HRQOL) refers to those issues that can be affected by illnesses and their treatments.For example, pain associated with an illness and limitations in functioning that require being dependent on others to help with usual daily activities can decrease a person' s quality of life.The December 18, 2002, issue of JAMA includes an article about patient-physician communication regarding quality-of-life concerns and the use of questionnaires to monitor changes in HRQOL over time. MEASURING QUALITY OF LIFE FOR MORE INFORMATION
Origins and clonal convergence of gastrointestinal IgE <sup>+</sup> B cells in human peanut allergy
Authors: Ramona A. Hoh, Shilpa A. Joshi, Ji-Yeun Lee, Brock A. Martin, Sushama Varma, Shirley Kwok, Sandra C. A. Nielsen, Parastu Nejad, Emily Haraguchi, Priya S. Dixit, Swetha V. Shutthanandan, Krishna M. Roskin, Wenming Zhang, Dana Tupa, Bryan J. Bunning, Monali Manohar, Robert Tibshirani, Nielsen Q. Fernandez-Becker, Neeraja Kambham, Robert B. West, Robert G. Hamilton, Mindy Tsai, Stephen J. Galli, Rebecca S. Chinthrajah, Kari C. Nadeau, Scott D. Boyd
Journal: Science Immunology (2020)

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.
Covid-19: are we getting the communications right?
Authors: Andy Cowper
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: are we getting the communications right? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Determination of ER, PR and HER-2 status in primary breast tumors. A standardized unique method based on NASBA
Authors: Thibault Verjat, Pierre Jean Lamy, Anne C. Servanton, Jean Grenier, Alexander Krause, Philippe Leissner, Bruno Mougin
Journal: Cancer Research (2005)

2144  Background: The measurement of estrogen receptor (ER) and progesterone receptor (PR) amount is of considerable importance when evaluating the prognosis and the extent of the response to endocrine therapy in breast tumors. Assessment of HER-2 status is also becoming a standard for the management of breast cancer. Usually, ER, PR and HER-2 status are determined using different techniques (LBA, IHC, FISH) that require significant amount of material and that are not well standardized yet. We propose to determine the expression of these three clinically relevant markers at the mRNA level with a unique technique, the Nucleic Acid Sequence based Amplification (NASBA). The performance of this technique have been compared to existing methods measuring the status of ER, PR and HER-2, respectively. Methods: Tumor specimens from 102 patients with primary breast cancer collected at the CRLC of Montpellier were included in this study. The measurement of ESR1-, PGR- and HER-2 mRNA expression was performed by Real-Time NASBA as a combination of three duplex assays performed simultaneously using cyclophilin B (PPIB) as the normalizing gene. ESR1- and PGR mRNA expression was compared to cytosolic functional protein content as determined by Ligand Binding Assay while HER-2-mRNA expression was compared to quantitative-PCR and ELISA. Results: We found a statistically strong correlation between LBA and NASBA with respect to ER (Spearman rank correlation test r=0.77, p
Abstract P216: Co-ingestion of Dietary Nitrate and Caffeine Elevates Submaximal Oxygen Consumption and Oxygen-pulse Compared to Nitrate or Caffeine Alone
Authors: Phillip M Armentrout, James M Smoliga, Kennedy Marshall, Colin R Carriker
Journal: Circulation (2020)

Introduction: Previous studies have examined dietary nitrate's and caffeine’s combined effects on time-trial and peak power output with caffeine improving performance while nitrate exhibits no additive benefit with co-ingestion. However, less is known about their combined effect on submaximal intensity exercise. Dietary nitrate may reduce submaximal oxygen cost while caffeine may increase submaximal cost. Hypothesis: Co-ingestion of dietary nitrate may attenuate the rise in oxygen consumption following caffeine intake. Methods: Ten healthy individuals (4 males; 28 ± 10 years of age) and (6 females; 21 ± 3 years of age) participated in a double-blind, placebo controlled, crossover experiment. The first of five visits consisted of a maximal oxygen consumption (VO 2max ) treadmill test. Prior to visits 2 - 5, participants consumed either a dietary nitrate (~12.4 mmol, NIT) or placebo nitrate supplement (PLN) combined with either a caffeine (3 mg/kg, CAF) or placebo caffeine (PLC) dose for a total of 4 days. The final dose of NIT or PLN and CAF or PLC was consumed 2.5 and 1-hr pre-exercise, respectively. Visits 2 - 5 consisted of a 30-min treadmill run at ~65% VO 2max . During exercise, VO 2 and heart rate (HR) were measured continuously. A linear mixed effects model analysis was performed to determine how each supplementation influenced each dependent variable. Treatments (NIT+CAF, CAF+PLN, NIT+PLC, PLN+PLC) and exercise timepoints (10 and 30 min) served as fixed factors. If p&lt;0.05, p ost-hoc pairwise comparisons were performed. Results: Exercise VO 2 was significantly elevated for NIT+CAF at 10 and 30 minutes (36.2±4.1 and 37.7±5.0 ml/kg/min, respectively) compared to placebo (33.4±3.4 and 35.3±3.8 ml/kg/min, respectively) (p&lt;0.05). However, there was no difference in VO2 at either timepoint (10 or 30 minutes) for conditions CAF+PLN (34.3±3.9, 35.4±3.6, and 36.3±3.2 ml/kg/min, respectively) (p=0.07) and NIT+PLC (34.8±3.9, 36.0±4.2, and 36.6±4.4 ml/kg/min, respectively) (p=0.08) compared to PLN+PLC. No difference was observed for heart rate between conditions at any timepoint. However, oxygen-pulse (VO 2 /HR) at the end of exercise was elevated in NIT+CAF (15.1±2.5 ml/beat) compared to CAF+PLN, NIT+PLC, PLN+PLC (14.5±2.5, 14.2±2.5, 13.8±2.5 ml/beat, respectively). Conclusion: When consumed independently, a low-moderate dose of caffeine or dietary nitrate had no impact on oxygen consumption during 30 minutes of moderate intensity exercise. However, co-ingestion of dietary nitrate and caffeine elevated submaximal oxygen consumption compared to a placebo control; both overall (main effect) and at individual time points of 10 and 30 minutes. Additionally, oxygen-pulse was elevated with co-ingestion compared to all treatments perhaps due to enhanced tissue uptake or altered mitochondrial efficiency. Future work may examine such mechanisms.
Abstract P114: Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events (SEE) in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mengyuan Shi, Lin Yee Y Chen, Wobo Bekwelem, Faye L Norby, Elsayed Z Soliman, Aniqa Alam, Alvaro Alonso
Journal: Circulation (2020)

Objectives: Embolic stroke is a major complication of atrial fibrillation (AF). Mechanisms that lead to elevated stroke risk in AF are also likely to increase risk of extracranial systemic embolic events (SEE). However, little is known about the magnitude of the association of AF with SEE, needed to fully characterize the impact of AF on cardiovascular outcomes. We evaluated the association of AF with SEE and the prediction of SEE among persons with AF in a community-based cohort. Methods: We included 14,941 participants of the ARIC study (mean age, 54 ± 6, 55% women, 74% white) without AF at baseline (1987-89) and followed through 2017. AF was identified from study electrocardiograms, hospital discharges, and death certificates. SEE was defined as the presence of hospitalization discharge codes ICD-9-CM 444.xx or ICD-10-CM I74.x (Arterial embolism and thrombosis) in any position. CHA2DS2-VASc score, a predictor of stroke risk in AF, was calculated at the time of AF diagnosis. Cox models adjusting for fixed and time-varying covariates were used to estimate associations of incident AF with SEE risk and between CHA2DS2-VASc score and SEE risk in those with incident AF. Results: Among eligible participants, 3,114 developed AF and 270 had a SEE event. Incident AF was associated with increased risk of SEE [hazard ratio (HR) = 3.6, 95% confidence interval (CI) 2.6 - 5.0], after adjusting for baseline and time-dependent covariates (Table). The association of incident AF with SEE was stronger in women (HR 5.3, 95% CI 3.3 - 8.4) than in men (HR 2.7, 95% CI 1.7 - 4.3) (p for interaction = 0.002). In participants with incident AF, we identified 59 SEE events. Higher CHA 2 DS 2 -VASc score was associated with increased SEE risk (HR per 1-point increase = 1.2, 95% CI 1.1 - 1.5). Conclusions: AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA 2 DS 2 -VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict outcomes and guide treatments in persons with AF.
Comparison of Real-Time Fluorescence Confocal Digital Microscopy With Hematoxylin-Eosin–Stained Sections of Core-Needle Biopsy Specimens
Authors: Savitri Krishnamurthy, Sharjeel Sabir, Kechen Ban, Yun Wu, Rahul Sheth, Alda Tam, Funda Meric-Bernstam, Kenna Shaw, Gordon Mills, Roland Bassett, Stanley Hamilton, Marshall Hicks, Sanjay Gupta
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Strategies to procure high-quality core-needle biopsy (CNB) specimens are critical for making basic tissue diagnoses and for ancillary testing. <h3>Objectives</h3> To investigate acquisition of fluorescence confocal microscopy (FCM) images of interventional radiology (IR)–guided CNB in real time in the radiology suite and to compare the accuracy of FCM diagnoses with those of hematoxylin-eosin (H&amp;E)–stained CNB sections. <h3>Design, Setting, and Participants</h3> In this diagnostic study, FCM imaging of IR-guided CNBs was performed in the radiology suite at a major cancer center for patients with an imaging abnormality from August 1, 2016, to April 30, 2019. The time taken to acquire FCM images and the quality of FCM images based on percentage of interpretable tissue with optimal resolution was recorded. The FCM images were read by 2 pathologists and categorized as nondiagnostic, benign/atypical, or suspicious/malignant; these diagnoses were compared with those made using H&amp;E-stained tissue sections. Cases with discrepant diagnosis were reassessed by the pathologists together for a consensus diagnosis. Data were analyzed from June 3 to July 19, 2019. <h3>Interventions</h3> Each IR-guided CNB was stained with 0.6mM acridine orange, subjected to FCM imaging, and then processed to generate H&amp;E-stained sections. <h3>Main Outcomes and Measures</h3> Mean time taken for acquisition of FCM images, quality of FCM images based on interpretable percentage of the image, and accuracy of diagnostic categorization based on FCM images compared with H&amp;E-stained sections. <h3>Results</h3> A total of 105 patients (57 male [54.3%]; mean [SD] age, 63 [13] years) underwent IR-guided CNBs in a mean (SD) of 7 (2) minutes each. The FCM images showed at least 20% of the tissue with optimal quality in 101 CNB specimens (96.2%). The FCM images were accurately interpreted by the 2 pathologists in 100 of 105 cases (95.2%) (2 false-positive and 3 false-negative) and 90 of 105 cases (85.7%) (6 false-positive and 9 false-negative). A reassessment of 14 discordant diagnoses resulted in consensus diagnoses that were accurate in 101 of 105 cases (96.2%) (1 false-positive and 3 false-negative). <h3>Conclusions and Relevance</h3> The ease of acquisition of FCM images of acceptable quality and the high accuracy of the diagnoses suggest that FCM may be useful for rapid evaluation of IR-guided CNBs. This approach warrants further investigation.
Abstract 13642: Cell-Free HDL-Specific Phospholipid Efflux Predicts Plaque Burden and Coronary Artery Disease
Authors: Edward B Neufeld, Masaki Sato, Martin P Playford, Alexander V Sorokin, Angel Aponte, Scott M Gordon, Nehal N Mehta, Marcus Chen, Alan T Remaley
Journal: Circulation (2019)

Introduction: HDL functionality is thought to be a better predictor of CAD than HDL-C, but currently no suitable routine diagnostic test exists. Hypothesis: Cell-free fluorescent phospholipid efflu...
Adherence to surveillance guidelines following curative resection for stage II and III colorectal cancer
Authors: W. Y. Cheung, G. R. Pond, M. Rother, M. Krzyzanowska, J. Brierley, C. Swallow, L. Kaizer, J. Myers, S. Phillips, L. L. Siu
Journal: Journal of Clinical Oncology (2007)

4051 Background: The risk of disease recurrence in stage II and III colorectal cancer (CRC) patients (pts) following curative resection underscores the need for post-operative surveillance. However, there is continual controversy as to whether an intensive or conservative strategy is more appropriate. Our aims were to determine adherence in the ‘real world‘ to ASCO guidelines on CRC surveillance and to evaluate differences in practice patterns and outcomes between an academic instituation, Princess Margaret Hospital (PMH), and a community cancer center, Credit Valley Hospital (CVH). Methods: Stage II and III CRC pts diagnosed between 1999 and 2001 were identified from hospital cancer registries. Surveillance practices and outcomes in the first 5 years of follow-up were retrospectively reviewed. Results: A total of 244 and 97 pts were identified at PMH and CVH, respectively: 80 stage II and 119 stage III colon cancers (CC), and 66 stage II and 76 stage III rectal cancers (RC). Median age at diagnosis was 61.8 years. Surveillance patterns over a 5-year period, adherence to ASCO guidelines and comparisons between hospitals were tabulated (see table ). There were a total of 70 CRC recurrences: 53/244 (22%) at PMH and 17/97 (18%) at CVH. Among them, 53 (76%) were detected by surveillance (44 PMH, 9 CVH) and 17 (24%) by symptoms (9 PMH, 8 CVH). For recurrences detected by surveillance, 20/53 (38%) were resectable, whereas only 3/17 (18%) of those detected by symptoms were resectable. Of the 20 resectable recurrences detected by surveillance, 40% were CC and 60% were RC; CT scan was the method of detection in 55% of cases, and sites of recurrence included liver (7), lung (6), local (5), and nodes (2). Conclusions: CRC surveillance revealed significant departures from ASCO guidelines with a large academic institution employing a more intensive surveillance strategy with imaging than a community cancer center. Surveillance was associated with a higher proportion of resectable tumor recurrences than detection by symptoms. [Table: see text] No significant financial relationships to disclose.
Abstract P283: Where You Shop and Neighborhood Access to Fruit and Vegetables are Associated With Self-rated and Cardiometabolic Health
Authors: Gabrielle Corona, Wendy M Troxel, Tamara Dubowitz, Tiffany Gary-Webb
Journal: Circulation (2020)

Introduction: The food environment, including food retail venues, has been shown to be associated with diet, and many disadvantaged neighborhoods lack access to high quality and affordable healthy foods. Research has sought to understand whether and how the food retail environment influences diet, and it is possible that shopping at different types of stores (e.g. full-service vs discount grocery store) influences diet and self-reported health outcomes. There is limited understanding of whether factors of the food environment and primary shopping location impact cardiometabolic health (blood pressure, HbA1c, cholesterol) and self-rated health. Methods: We report on 459 individuals who participated in a blood draw in 2018 as part of the Pittsburgh Hill/Homewood Research on Eating, Shopping, and Health, a longitudinal natural-experiment study among African American adults from two socioeconomically similar neighborhoods. Participants reported their perceived access to fruit and vegetables within their neighborhood and where they did their primary food shopping. Outcomes include measured height, weight, blood pressure, cholesterol (HDL, Total), HbA1c, and participant’s self-rated health. We employed logistic regression to examine associations between 1) perceived fruit and vegetable availability, quality, and price and 2) primary food shopping store type and reason for shopping there, with cardiometabolic and self-rated health outcomes. Covariates were neighborhood, years lived in neighborhood, age, race, income, education, and marital status. Results: Participants were on average, 60.7 years old (SD=13.9); 81.7% (375 of 459) female; 80.4% (369 of 459) overweight/obese. After covariate adjustment, both more perceived accessibility of purchasing (OR: 0.47, 95% CI: 0.28, 0.79) and pricing of fruits and vegetables (OR: 0.59, 95% CI: 0.36, 0.96) within one’s neighborhood were associated with lower odds of high blood pressure. More accessible purchasing (OR: 0.59, 95% CI: 0.39, 0.90), pricing (OR: 0.62, 95% CI: 0.41, 0.94), and higher quality of fruits and vegetables (OR: 0.64, 95% CI: 0.42, 0.97) within one’s neighborhood were associated with lower odds of poor self-rated health. Doing one’s primary food shopping at a discount grocery store compared to a full-service grocery store was associated with lower odds of being overweight (OR: 0.51, 95% CI: 0.26, 0.99). Choosing a primary food store based on price rather than quality of food was associated with increased odds of high cholesterol (OR: 2.02, 95% CI: 1.19, 3.45). Conclusion: These results suggest that higher perceptions of access to fruits and vegetables in one’s neighborhood and choice of primary food shopping store are important correlates of cardiometabolic health. Further research should look towards understanding how direct food choices made at stores impact cardiometabolic outcomes within this population.