tbuckley/cabot-search huggingface dataset:
Air Pollution and Progression of Atherosclerosis in Different Vessel Beds—Results from a Prospective Cohort Study in the Ruhr Area, Germany
Authors: Frauke Hennig, Marie Henrike Geisel, Hagen Kälsch, Sarah Lucht, Amir Abbas Mahabadi, Susanne Moebus, Raimund Erbel, Nils Lehmann, Karl-Heinz Jöckel, André Scherag, Barbara Hoffmann
Journal: Environmental Health Perspectives (2020)

OBJECTIVES: Due to inconsistent epidemiological evidence on health effects of air pollution on progression of atherosclerosis, we investigated several air pollutants and their effects on progression of atherosclerosis, using carotid intima media thickness (cIMT), coronary calcification (CAC), and thoracic aortic calcification (TAC).METHODS: We used baseline (2000)(2001)(2002)(2003) and 5-y follow-up (2006)(2007)(2008) data from the German Heinz Nixdorf Recall cohort study, including 4,814 middle-aged adults.Residence-based long-term air pollution exposure, including particulate matter (PM) with aerodynamic diameter ≤2:5 lm (PM 2:5 ), (PM 10 ), and nitrogen dioxide (NO 2 ) was assessed using chemistry transport and land use regression (LUR) models.cIMT was quantified as side-specific median IMT assessed from standardized ultrasound images.CAC and TAC were quantified by computed tomography using the Agatston score.Development (yes/no) and progression of atherosclerosis (change in cIMT and annual growth rate for CAC/TAC) were analyzed with logistic and linear regression models, adjusting for age, sex, lifestyle variables, socioeconomic status, and traffic noise.RESULTS: While no clear associations were observed in the full study sample (mean age 59.1 ( ± 7:6) y; 53% female), most air pollutants were marginally associated with progression of atherosclerosis in participants with no or low baseline atherosclerotic burden.Most consistently for CAC, e.g., a 1:5 lg=m 3 higher exposure to PM 2:5 (LUR) yielded an estimated odds ratio of 1.19 [95% confidence interval (CI): 1.03, 1.39] for progression of CAC and an increased annual growth rate of 2% (95% CI: 1%, 4%).CONCLUSION: Our study suggests that development and progression of subclinical atherosclerosis is associated with long-term air pollution in middle-aged participants with no or minor atherosclerotic burden at baseline, while overall no consistent associations are observed.
Migration-induced cell shattering due to DOCK8 deficiency causes a type 2–biased helper T cell response
Authors: Caitlin Schneider, Connie Shen, Angelica A. Gopal, Todd Douglas, Benjamin Forestell, Keith D. Kauffman, Dakota Rogers, Patricio Artusa, Qian Zhang, Huie Jing, Alexandra F. Freeman, Daniel L. Barber, Irah L. King, Maya Saleh, Paul W. Wiseman, Helen C. Su, Judith N. Mandl
Journal: Nature Immunology (2020)
Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma
Authors: Nadine Abdallah, Linda B. Baughn, S. Vincent Rajkumar, Prashant Kapoor, Morie A. Gertz, Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Ronald S. Go, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Yi Lin, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Mustaqeem Siddiqui, John Lust, Robert A. Kyle, Rhett Ketterling, Leif Bergsagel, Patricia Greipp, Shaji K. Kumar
Journal: Clinical Cancer Research (2020)

Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma.This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1).A rearrangement involving MYC was found in 8% of patients and was associated with elevated β2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI + IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P = 0.007).MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.
Race, Ethnicity, and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer in the Randomized TAILORx Trial
Authors: Kathy S Albain, Robert J Gray, Della F Makower, Amir Faghih, Daniel F Hayes, Charles E Geyer, Elizabeth C Dees, Matthew P Goetz, John A Olson, Tracy Lively, Sunil S Badve, Thomas J Saphner, Lynne I Wagner, Timothy J Whelan, Matthew J Ellis, William C Wood, Maccon M Keane, Henry L Gomez, Pavan S Reddy, Timothy F Goggins, Ingrid A Mayer, Adam M Brufsky, Deborah L Toppmeyer, Virginia G Kaklamani, Jeffrey L Berenberg, Jeffrey Abrams, George W Sledge, Joseph A Sparano
Journal: JNCI Journal of the National Cancer Institute (2020)

Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment.The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided.Of 9719 eligible women with hormone receptor-positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25.Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.
Natural medicine in neuroprotection for ischemic stroke: Challenges and prospective
Authors: Tao Tao, Maozhu Liu, Mengyuan Chen, Ying Luo, Cheng Wang, Tongtong Xu, Yixu Jiang, Yiyan Guo, John H. Zhang
Journal: Pharmacology & Therapeutics (2020)

There is a growing interest in using natural medicines to treat stroke as the leading cause of disability worldwide. Especially plant-derived natural medicines have multiple beneficial effects, including antioxidative, anti-inflammatory, antiapoptotic, suggesting their potential for stroke treatment. However, failure in clinical translation has created a substantial challenge for their use as stroke treatment. This review summarises the status of using natural medicinal formulations in stroke treatment, as well as the challenges. Although natural medicines have excellent prospects for ischaemic stroke treatment, several concerns need to be addressed for translating the success in animal research to humans. Specifically, there should be more considerations for investigating the precise mechanisms of natural medicines mediating the neuroprotective effects on stroke. Moreover, to further improve the prospects of clinical translation, further studies should be performed in aged animals rather than young adult animals.
Frailty Triage: Is Rationing Intensive Medical Treatment on the Grounds of Frailty Ethical?
Authors: Dominic J. C. Wilkinson
Journal: The American Journal of Bioethics (2020)

In early 2020, a number of countries developed and published intensive care triage guidelines for the pandemic. Several of those guidelines, especially in the UK, encouraged the explicit assessment of clinical frailty as part of triage. Frailty is relevant to resource allocation in at least three separate ways, through its impact on probability of survival, longevity and quality of life (though not a fourth—length of intensive care stay). I review and reject claims that frailty-based triage would represent unjust discrimination on the grounds of age or disability. I outline three important steps to improve the ethical incorporation of frailty into triage. Triage criteria (ie frailty) should be assessed consistently in all patients referred to the intensive care unit. Guidelines must make explicit the ethical basis for the triage decision. This can then be applied, using the concept of triage equivalence, to other (non-frail) patients referred to intensive care.
Cotrimoxazole reduces systemic inflammation in HIV infection by modulating the gut microbiota and blunting immune cell activation
Authors: C Bourke, E Gough, G Pimundu, A Shonhai, C Berejena, L Terry, L Baumard, N Choudhry, Y Karmali, M Bwarkura-Dangarembizi, V Musiime, J Lutaakome, A Kekitiinwa, K Mutasa, A J Szubert, M J Spyer, J Deayton, M Glass, H M Geum, C Pardieu, D M Gibb, N Klein, T Edens, A S Walker, A Manges, A J Prendergast
Journal: Science Translational Medicine (2019)
Abstract A18: Ccn1 expression by fibroblasts is required for melanoma metastasis
Authors: James Hutchenreuther, Katherine Quensel, Krista Vincent, Lynne-Marie Posrovit, Andrew Leask
Journal: Cancer Research (2020)

Abstract Metastatic melanoma is highly fatal. Within the tumor microenvironment, the role of cancer-associated fibroblasts (CAFs) in melanoma metastasis and progression is relatively understudied. Matricellular proteins of the CCN family are emerging targets for cancer therapy. Anti-CCN2 (CTGF) strategies are under clinical development; however, the role of CCN1 (cyr61) in cancers is unclear. Herein, we use bioinformatic analyses to report that the CCN1 is overexpressed, in a fashion independent of BRAF mutational status, in melanoma. In human melanoma patients, CCN1 expression negatively correlates with overall survival, disease-free, and metastasis-free survival (p&amp;lt;0.03). CCN1 expression positively correlates with expression of stroma and neovascularization markers. To assess the role of CAFs in melanoma progression, we used C57BL/6 mice expressing a tamoxifen-dependent cre recombinase expressed under the control of a fibroblast-specific promoter/enhancer (COL1A2) to delete CCN1 postnatally in fibroblasts. Mice deleted or not for CCN1 in fibroblasts were injected subcutaneously with B16-F10 melanoma cells. Loss of CCN1 in CAFs did not result in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, but resulted in reduced extracellular matrix surrounding tumors, as detected by trichrome stain, and reduced tumor-induced neovascularization, as detected by staining with anti-CD31 antibodies. CCN1-deficient skin showed reduced expression of mRNAs encoding collagen crosslinking enzymes (PLOD2 and LOX) and impaired formation of collagen fibers, as determined by electron microscopy. Tumor growth was not affected by loss of CCN1 from tumor stroma; however, micrometastasis to the lung was severely impaired (p&amp;lt;0.001). Our results provide new insights into the crosstalk among different cell types in the tumor microenvironment and confirm the essential role of CAFs in metastasis and tumor neovascularization. Our data are consistent with the hypothesis that CAFs are essential for melanoma metastasis and that CCN1 is a therapeutic target for melanoma. Citation Format: James Hutchenreuther, Katherine Quensel, Krista Vincent, Lynne-Marie Posrovit, Andrew Leask. Ccn1 expression by fibroblasts is required for melanoma metastasis [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A18.
Abstract A09: Characteristics of uveal melanoma patients with central nervous system metastases
Authors: Sapna P. Patel, Patrick Hwu, Michael Davies, Michael Wong, Hussein Tawbi, Rodabe Amaria, Adi Diab, Dan Gombos, Isabella C. Glitza
Journal: Cancer Research (2020)

Abstract In contrast to cutaneous melanoma, central nervous system (CNS) metastasis from uveal melanoma are uncommon, occurring in less than 5% of uveal patients. There is no published literature describing the features or survival of this unique population. Here we describe the clinical characteristics and outcomes of uveal melanoma CNS metastasis patients. We performed an MD Anderson Cancer Center institutional database review from 1999–2017 for consecutive uveal melanoma patients with CNS metastasis. Excluding dural-based metastases, 19 patients were identified. Ethnic makeup was 84% White, 11% Hispanic, 5% other, and median age at diagnosis was 52.4 years. The gender distribution was 12 (63%) female and 7 (37%) male. Primary tumor location in the uveal tract was 26% choroid, 11% iridociliary, 5% chiliochoroidal, and 58% not otherwise specified. Seven of 19 (37%) patients were treated with enucleation; 63% received radiation therapy for primary uveal melanoma. Median interval from diagnosis of uveal melanoma to diagnosis of CNS metastasis was 5 years. Only 7 patients had molecular testing for mutations. Of these, all had G-alpha mutations: 4 (57%) with GNAQ, and 3 (43%) with GNA11 hotspot mutations in Q209. At the time of data cutoff, 14 of 19 (74%) patients were deceased. Additional clinical information regarding treatment for CNS metastasis, histopathologic evaluation, and overall survival will be presented at the meeting. Citation Format: Sapna P. Patel, Patrick Hwu, Michael Davies, Michael Wong, Hussein Tawbi, Rodabe Amaria, Adi Diab, Dan Gombos, Isabella C. Glitza. Characteristics of uveal melanoma patients with central nervous system metastases [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A09.
Frequency and Outcomes of Preoperative Stress Testing in Total Hip and Knee Arthroplasty from 2004 to 2017
Authors: Daniel S. Rubin, Robert Hughey, Rebecca M. Gerlach, Sandra A. Ham, R. Parker Ward, Peter Nagele
Journal: JAMA Cardiology (2020)

Cardiac stress testing is often performed prior to noncardiac surgery, although trends in use of preoperative stress testing and the effect of testing on cardiovascular outcomes are currently unknown.To describe temporal trends and outcomes of preoperative cardiac stress testing from 2004 to 2017.Cross-sectional study of patients undergoing elective total hip or total knee arthroplasty from 2004 to 2017. Trend analysis was conducted using Joinpoint and generalized estimating equation regression. The study searched IBM MarketScan Research Databases inpatient and outpatient health care claims for private insurers including supplemental Medicare coverage and included patients with a claim indicating an elective total hip or total knee arthroplasty from January 1, 2004, to December 31, 2017.Elective total hip or knee arthroplasty.Trend in yearly frequency of preoperative cardiac stress testing.The study cohort consisted of 801 396 elective total hip (27.9%; n = 246 168 of 801 396) and total knee (72.1%; 555 228 of 801 396) arthroplasty procedures, with a median age of 62 years (interquartile range, 57-70 years) and 58.1% women (n = 465 545 of 801 396). The overall rate of stress testing during the study period was 10.4% (n = 83 307 of 801 396). The rate of stress tests increased 0.65% (95% CI, 0.09-1.21; P = .03) annually from quarter (Q) 1 of 2004 until Q2 of 2006. A joinpoint was identified at Q3 of 2006 (95% CI, 2005 Q4 to 2007 Q4) when preoperative stress test use decreased by -0.71% (95% CI, -0.79% to 0.63%; P < .001) annually. A second joinpoint was identified at the Q4 of 2013 (95% CI, 2011 Q3 to 2015 Q3), when the decline in stress testing rates slowed to -0.40% (95% CI, -0.57% to -0.24%; P < .001) annually. The overall rate of myocardial infarction and cardiac arrest was 0.24% (n = 1677 of 686 067). Rates of myocardial infraction and cardiac arrest were not different in patients with at least 1 Revised Cardiac Risk Index condition who received a preoperative stress test and those who did not (0.60%; n = 221 of 36 554 vs 0.57%; n = 694 of 122 466; P = .51).The frequency of preoperative stress testing declined annually from 2006 through 2017. Among patients with at least 1 Revised Cardiac Risk Index condition, no difference was observed in cardiovascular outcomes between patients who did and did not undergo preoperative testing.
Effect of Avoiding Cow's Milk Formula at Birth on Prevention of Asthma or Recurrent Wheeze Among Young Children
Authors: Hiroshi Tachimoto, Eiji Imanari, Hidetoshi Mezawa, Mai Okuyama, Takashi Urashima, Daishi Hirano, Noriko Gocho, Mitsuyoshi Urashima
Journal: JAMA Network Open (2020)

Children with food allergies may develop asthma or recurrent wheeze.To evaluate whether asthma or recurrent wheeze among children were changed by avoiding supplementing breastfeeding (BF) with cow's milk formula (CMF) in the first 3 days of life.This randomized, unmasked, clinical trial was conducted at 1 university hospital in Japan beginning October 2013 with follow-up examinations occurring until January 2020. A total of 312 newborns at risk for atopy were randomized and assigned to either BF with or without amino acid-based elemental formula (EF) or BF with CMF, with follow-up examinations for participants showing signs of atopy conducted at 24 months. Follow-up examinations ran through January 2020.Immediately after birth, newborns were randomly assigned (1:1 ratio) to either breastfeeding with or without amino acid-based elemental formula for at least the first 3 days of life (no CMF group) or breastfeeding supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (CMF group).Asthma or recurrent wheeze diagnosed by the pediatric allergy specialists of this trial; subgroups were stratified by serum levels of 25-hydroxyvitamin D and IgE.Of 312 infants (156 [50.0%] randomized to the no CMF group), 302 (96.8%) were followed up at their second birthday: 77 of 151 (51.0%) in the no CMF group and 81 of 151 (53.6%) in the CMF group underwent extended follow-up because of having atopic conditions. Asthma or recurrent wheeze developed in 15 (9.9%) of the children in the no CMF group, significantly less than the children in the CMF group (27 [17.9%]; risk difference, -0.079; 95% CI, -0.157 to -0.002). In participants with vitamin D levels above the median at 5 months of age, asthma or recurrent wheeze developled in 5 (6.4%) children in the no CMF group, significantly less than in the children in the CMF group (17 [24.6%]; risk difference, -0.182; 95% CI, -0.298 to -0.067; P for interaction = .04). In the highest quartile group of total IgE at age 24 months, asthma or recurrent wheeze developed in 2 children (5.3%) in the no CMF group, significantly less than the children in the CMF group (14 [43.8%]; risk difference, -0.385; 95% CI, -0.571 to -0.199; P for interaction = .004).The findings of this study suggest that avoiding CMF supplementation in the first 3 days of life has the potential to reduce the risk of asthma or recurrent wheeze in young children, especially among those with high vitamin D or high IgE levels.umin.ac.jp/ctr Identifier: UMIN000011577.
Annals Graphic Medicine - Dr. Mom: Places to Find When You Start a New Job at a Hospital
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2020)

Web Exclusives6 October 2020Annals Graphic Medicine - Dr. Mom: Places to Find When You Start a New Job at a HospitalFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0088 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 October 2020Volume 173, Issue 7Page: W125-W126 ePublished: 6 October 2020 Issue Published: 6 October 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Health in Aging — Past, Present, and Future
Authors: Linda P. Fried, John W. Rowe
Journal: New England Journal of Medicine (2020)

Interview with Dr. Linda Fried on advances in research on aging and ongoing efforts to provide older Americans with high-quality prevention and care. (12:33)Download Increases in life expectancy necessitate new scientific understanding of how to both extend and enhance health over the course of our longer lives. Accumulated evidence has laid the groundwork for a new era of prevention and health promotion for an extended health span.