tbuckley/cabot-search huggingface dataset:
Abstract 17120: Metabolic Syndrome Induces Long Lasting Phenotype in Bone Marrow-Derived Macrophages and Their Progenitor Cells Through Oxidative Stress and Histone H3-Lysine 4 Methylation State
Authors: Muthusamy Thiruppathi, Pijus Barman, Milie Fang, Giamila Fantuzzi, Elizabetta Benevolenskaya, Timothy Koh, Norifumi Urao
Journal: Circulation (2018)

Metabolic syndrome is associated with low-grade inflammation and accumulation of inflammatory macrophages with largely unknown mechanisms. Here we report that bone marrow-derived macrophages (BMM) and their progenitor cells develop long lasting pro-inflammatory phenotype in metabolic syndrome. Using mice fed a high-fat diet (HFD) or a normal diet (ND), we found that BMM generated from HFD mice (BMM-HFD) exhibit higher transcription activities of pro-inflammatory genes than BMM generated from ND mice (BMM-ND). This is associated with increased oxidative stress (2.7-fold) and histone H3-lysine 4 tri-methylation (H3K4me3)( %), along with increased Set7 H3K4 methyltransferase (41%), in BMM-HFD. KDM5A H3K4 demethylase, however, is not changed in its levels but in its subcellular localization—increased extranuclear localization—in BMM-HFD. In addition, lower nuclear KDM5 enzymic activity was found in their BM progenitor cells (40%), and it was reversed by reduction of oxidative stress, resulting in reduction in H3K4me3 levels in those cells (33%). ChIP-PCR analysis revealed that H3K4me3 is increased at promoter lesions of potential KDM5A-targeted genes such as Tnf , Il6 and Cdkn2a . Moreover, adoptive transfer experiment in hindlimb ischemia, BM progenitor cells from HFD mice induce accumulation of pro-inflammatory macrophages, establishing a link between BM progenitor cells and macrophages in vivo. In summary, our result suggest that metabolic syndrome induces oxidative stress at the BM progenitor level, which causes long lasting inflammatory phenotype of their derived macrophages in vitro and in vivo. This causal effect may be mediated by oxidative stress and enzymes regulating H3K4me3.
Abstract 17054: Sex-Related Differences in Atherosclerosis Burden and Composition Evaluated by Magnetic Resonance: A Complex Interaction Between Visceral Adiposity and Atherogenic Lipoproteins
Authors: Stéphanie LeBlanc, François Coulombe, Karine Bibeau, Olivier F Bertrand, Philippe Pibarot, Jean-Pierre Després, Eric Larose
Journal: Circulation (2018)

Introduction: Visceral adiposity increases the level of atherogenic lipoproteins and is linked to sex-related differences in cardiovascular risk. Hypothesis. Atherogenic lipoproteins could mediate the relationship between visceral fat and sex-related differences in atherosclerosis burden and composition, including the lipid-rich necrotic core (LRNC). Methods: This study included 294 women (39.4 ± 15.0 years) and 324 men (39.5 ± 13.8 years), matched for age and risk factors (hypertension, dyslipidemia, obesity, diabetes, smoking). Carotid atherosclerosis, visceral abdominal fat (VAT) and cardiac fat (CAT) were studied by magnetic resonance imaging. Results: For similar age and risk profile, women had less VAT ( p &lt;0.001) and CAT ( p &lt;0.001) than men. Carotid atherosclerosis prevalence ( p &lt;0.001) and carotid wall volume ( p &lt;0.001) were higher in men. Although LRNC prevalence was similar in women and men ( p =0.23), men had a greater LRNC volume ( p &lt;0.001). An interaction was observed between waist-to-hip ratio (WHR) and sex on LRNC volume ( p =0.025). There was also an interaction between sex, VAT, and total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C) on LRNC volume ( p =0.012), beyond age and risk factors ( p =0.011). Only 8.6% of men and none of the women were classified at high risk (presence of LRNC) by the Framingham Risk Score while 35.4% of men and 14.0% of women were classified at high risk by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score (risk of advanced atherosclerosis). Elevated TC/HDL-C (≥3) and/or WHR (≥0.8 in women, ≥0.9 in men) were superior to the PDAY risk score, identifying 62.2% of women (Net Reclassification Improvement [NRI]=1.85, p &lt;0.001) and 79.3% of men (NRI=0.26, p &lt;0.001) with LRNC. Conclusions: Women had less visceral adiposity, carotid atherosclerosis burden and LRNC volume, independently of age and risk profile. Carotid LRNC volume varied with sex, VAT, and atherogenic lipoproteins. WHR and TC/HDL-C improved the identification of high-risk carotid atherosclerosis features in women as well as men. This evidence supports the clinical potential of the atherogenic lipoprotein profile and of adiposity distribution in atherosclerosis risk evaluation of both women and men.
Evaluation of drug-drug interactions among patients with metastatic prostate cancer in routine care.
Authors: Noemie Gassian, Anne-Laure Clairet, Morgan Goujon, Alexandre Frontczak, Fabien Calcagno, Hamadi Almotlak, Guillaume Mouillet, Tristan Maurina, Ulrich Stein, Thierry Nguyen, Marie Jeannin, Antoine Thiery-Vuillemin
Journal: Journal of Clinical Oncology (2022)

111 Background: Prostate cancer often occurs in an elderly population, at higher risk of drug-drug interactions (DDIs). There is a medical need to increase the knowledge of DDI prevalence and their severity among patients coming from routine care. This study used a prospective approach with the aim to quantify and describe DDIs in medical prescription of prostate cancer treatments. Methods: DDIs were assessed from two perspectives: 1) “real DDI” between the patient’s comedications and the actual anti-cancer agent prescribed; 2) “modelized DDI” between the patient’s comedications and drugs that have proven activity in metastatic endocrine sensitive prostate cancer (MESPC) or castrate resistant prostate cancer (CRPC) settings with positive phase 3 trial and gained EMA approval. French national thesaurus, Micromedex software and complementary manual analysis by pharmacist were used to identified DDIs. Clinical relevance of DDIs was scored using the validated scale of Hatoum. Results: A total of 91 patients were included, 15% of whom were participating in a clinical trial. Some imbalances were observed between patients from clinical trial and routine care (age, ECOG, MESPC/MCRPC). The median number of comedications used per patient was 6 [1-16]. Among real DDI, Enzalutamide was the anticancer agent with the higher risk of interaction (18-54% of patients). In modelized DDI, Enzalutamide and Apalutamide were the two most risky drugs (35-76% and 22-73% depending on Micromedex or Thesaurus analyze). Not all DDIs discovered were clinically significant according to Hatoum scale. Conclusions: DDIs are frequents, according to Micromedex and National Thesaurus tools but pharmacist and physician advices are essentials to determine their potential impacts.
Sunscreens, photocarcinogenesis, melanogenesis, and psoralens.
Journal: BMJ (1981)

Sunscreens, photocarcinogenesis, melanogenesis, and psoralensMost years in Britain, and regularly in sunnier countries, exposure to ultraviolet radiation takes its toll in terms of acute burns, photodermatoses, aging skin, and skin cancers.The high risk of skin cancers from exposure to the sun does not hit the headlines because almost all such lesions are completely curable.Nevertheless, the general public should be better informed about the harmful effects of actinic exposure as increasing leisure and a fashion for tanned skin are putting more and more people at risk.The pale Celtic skin tans poorly and is much more susceptible to damage than intrinsi- cally darker skins, which tan more readily; melanin seems to be protective to a greater or less extent against all the adverse effects of ultraviolet radiation.So how far can skin protection be helped by provoking melanogenesis ?The most damaging part of the ultraviolet spectrum is in the waveband from 280 to 315 nm-the UV-B range.The spectrum of terrestrial sunlight extends down to about 290 nm, well into the UV-B and up into the UV-A range (315 to 400 nm).Most suntan preparations include in their formulation substances which act as barriers to UV-B.People with normal skins generally use such preparations, if at all, only during their summer holidays, but patients with photodermatoses need to use sun barriers throughout much of the year.The "sun-protection factor" has been widely used in Europe and the United States, but rather less in Britain, as a measure of sunbarrier efficiency.The sun-protection factor is the ratio of the ultraviolet radiation exposure required to produce minimal sunburn erythema with the sunbarrier preparation in place to that required in the case of untreated skin.Sunbarrier prepara- tions with a low sun-protection factor of, say, 2 would allow exposure to be doubled before sunburn occurred.These are suitable for people who tan readily and wish to avoid the more acute discomforts of sunburn.A sunbarrier preparation with a sun-protection factor as high as 15 should, in theory, afford protection all day long or at least for extended periods; these, which are the standby of preventive treatment for patients with abnormal photosensitivity, were recently accepted for NHS prescription as "borderline substances."The active ingredients, including cinnamates, aminobenzoates, salicylates, and benzimidazoles, act by absorbing ultraviolet radiation in the UV-B range.The more powerful sunbarrier preparations could, if widely used, largely prevent the epidemic of skin cancer that plagues the so-called "Celts of Australia."They
Regulation of factor Xa in vitro in human and mouse plasma and in vivo in mouse. Role of the endothelium and plasma proteinase inhibitors.
Authors: H E Fuchs, S V Pizzo
Journal: Journal of Clinical Investigation (1983)

The regulation of human Factor Xa was studied in vitro in human and mouse plasma, and in vivo in mouse. In human plasma, 125I-Factor Xa bound to alpha 1-proteinase inhibitor, antithrombin III, and alpha 2-macroglobulin in a ratio of 4.9:1.9:1 as determined by gel electrophoresis and by adsorption to IgG-(antiproteinase inhibitor)-Sepharose beads. The distribution of Factor Xa in mouse plasma was similar. The clearance of Factor Xa in mice was rapid (50% clearance in 3 min) and biphasic. alpha 1-Proteinase inhibitor-trypsin, even at a 2,000-fold molar excess, failed to inhibit the clearance of Factor Xa, while alpha 2-macroglobulin-trypsin inhibited only the later phase of clearance. The plasma clearance of diisopropylphosphoryl-Factor Xa was more rapid than native Factor Xa (50% clearance in 2.5 min), and the clearance was blocked by diisopropylphosphoryl-thrombin. Electrophoresis experiments confirmed that by 2 min after injection into the murine circulation, 90% of the bound Factor Xa was on alpha 2-macroglobulin, in marked contrast to the in vitro results. Organ distribution studies at 3 and 15 min with 125I-Factor Xa demonstrated that the majority of radioactivity was in the liver, with significant radioactivity also present in lung and kidney. Autopsies performed 30 s after injection of 125I-Factor Xa also demonstrated significant binding to the aorta and vena cava. These studies indicate that Factor Xa binds to specific thrombin-binding sites on endothelial cells, and that this binding alters its proteinase inhibitor specificity. Factor Xa binds to alpha 2-macroglobulin in vivo, whereas the predominant in vitro inhibitor of Factor Xa is alpha 1-proteinase inhibitor.
Submucosal tunneling cecetomy in a dog: is it applicable for appendectomy in human?
Authors: Xin-Yang Liu, Wei-Feng Chen, Jian-Wei Hu, Ping-Hong Zhou, Quan-Lin Li
Journal: Endoscopy (2022)

We hereby present the successful application of submucosal tunneling cecetomy on a 12-kg female Beagle dog to mimic appendectomy in human. The steps were as follows ([Fig. 1], [Video 1]). Step 1: mucosal incision – the colonic cavity was intensively washed with normal saline to avoid leakage of fecal contents; the mucosa opposite the ileocecal valve was chosen for mucosal incision; a 2-cm horizontal or oblique mucosal incision was created. Step 2: submucosal tunneling – a submucosal tunnel was created until intentional perforation of the muscularis propria, about 3 cm from the appendix; the distance of 3 cm provided critical working space and better visualization of the appendix. Step 3: dissection of the appendix – the appendix was then dissected from the mesoappendix with electrocoagulation of mesentery vessels. Step 4: ligation of the appendix – the bottom of the appendix was ligated with an endoloop. Step 5: resection of the appendix – the appendix was resected using a snare; to prevent leakage, the stump was then secured with another endoloop. Step 6: retrieval and mucosal closure – the appendix was retrieved by a snare; after careful hemostasis, the mucosal incision site was closed using hemostatic clips. The procedure took 50 minutes, and the dog was sacrificed after the operation.
TROPiCS-04: Study of sacituzumab govitecan (SG) in patients (pts) with locally advanced (LA) unresectable or metastatic urothelial cancer (mUC) that has progressed after prior platinum (PLT) and checkpoint inhibitor (CPI) therapy.
Authors: Christof Vulsteke, Petros Grivas, Scott T. Tagawa, Joaquim Bellmunt, Maria De Santis, Ignacio Duran, Peter-Juergen Goebell, Andrea Necchi, Srikala S. Sridhar, Cora N. Sternberg, Mitchell Robert Sierecki, Usman Aziz, Trishna Goswami, Yohann Loriot
Journal: Journal of Clinical Oncology (2022)

TPS582 Background: Treatment options are limited for pts with LA unresectable or mUC who progress after prior PLT-based and CPI therapies. SG is an antibody-drug conjugate (ADC) composed of an anti-trophopblast cell surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) via a proprietary hydrolyzable linker. In the phase 2 registrational study TROPHY-U-01 (NCT03547973), SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.9 months in pts with mUC who progressed after prior PLT-based and CPI therapies (n = 113; median, 3 prior lines of therapy; 84% with ≥1 Bellmunt risk factors; Tagawa et al, J Clin Oncol. 2021). These results compared favorably with historic data for single-agent chemotherapy (ORR, ̃18%; OS, 9 months; Powles et al. J Clin Oncol. 2021) and led to accelerated approval of SG by the US Food and Drug Administration for pts with LA or mUC who previously received a PLT-containing chemotherapy and CPI. The phase 3 TROPiCS-04 trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in pts with LA unresectable or mUC who progressed after prior PLT-based and CPI therapies. Key eligibility requirements include Eastern Cooperative Oncology Group performance status 0-1; no prior CPI or ADC therapy within 4 weeks of study drug initiation; no history of active interstitial lung disease or noninfectious pneumonitis; and adequate hematologic, hepatic, and renal function. Pts will be randomly assigned 1:1 to receive SG 10 mg/kg intravenously (IV) on days 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m 2 , docetaxel 75 mg/m 2 , or vinflunine 320 mg/m 2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in pts deemed to be receiving clinical benefit per investigator assessment. Approximately 600 pts will be enrolled across ̃280 sites in 3 regions (North America, Europe, and Asia-Pacific) to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review and investigator assessment), safety, and quality of life. Study enrollment started in January 2021 and is ongoing with pts currently enrolled at 30 sites across all 3 regions. Clinical trial information: NCT04527991.
Preemptive clipping for post-ampullectomy bleeding: the jury is still out
Authors: Lars Aabakken
Journal: Endoscopy (2022)

Endoscopic resection of nonmalignant ampullary tumors is among the significant utilities of endoscopic retrograde cholangiopancreatography (ERCP). Even in lesions that are borderline resectable based on computed tomography or endosonography, an endoscopic ampullary resection offers vital histology sampling to inform further treatment and follow-up.
<i>Notes from the Field:</i> Outbreak of COVID-19 Among a Highly Vaccinated Population Aboard a U.S. Navy Ship After a Port Visit — Reykjavik, Iceland, July 2021
Authors: Tammy E. Servies, Eric C. Larsen, Rodney C. Lindsay, Jonathan S. Jones, Regina Z. Cer, Logan J. Voegtly, Matthew R. Lueder, Francisco Malagon, Kimberly A. Bishop-Lilly, Asha J. Riegodedios
Journal: MMWR Morbidity and Mortality Weekly Report (2022)
American Rheumatism Association. Experience with Cortisone in the Management of Rheumatoid Arthritis : Report of a Co-Operative Study Conducted by a Committee of the American Rheumatism Association
Authors: Joseph Bunim, Gideon Deforest, Richard Freyberg, William Kammerer, Donald Mainland, Currier Mcewen, Felix Moore, Charles Ragan, William Robinson, Edward Rosenberg, Charles Short, Charles Slocumb, Charley Smyth, Arthur Bagnall, Claire Lingg, Walter Bauer, Theodore Bayles, Paul Bilka, Ephraim Engleman, Dwight Ensign, Wallace Graham, Edward Hartung, Philip Hench, Mayo Clinic, W Holbrook, Joseph Hollander, John Lansbury, Melvin Levin, James Lightbody, L Lockie, Morris Ziff, Faulkner Clinic, Michael Reese, Richard Smith, Benjamin Clinic, Robert Stecher, Anita Ausenbachs
Journal: Annals of the Rheumatic Diseases (1955)

a pre- liminary report was presented of the co-operative clinical trial of ACTH, cortisone, and aspirin in the treatment of rheumatic fever, sponsored by the Medical Research Council of Great Britain and the Council on Rheumatic Fever and Congenital Heart Disease of the American Heart Association (Joint Report, 1955).This report aroused such interest that it was decided to consider undertaking a similar study of cortisone in the treatment of rheumatoid arthritis.The feasibility of such a study was dis- cussed by an ad hoc committee consisting of Drs
Response-Adapted Treatment Following Radiotherapy in Patients With Resectable Locally Advanced Hypopharyngeal Carcinoma
Authors: Xi Luo, Xiaodong Huang, Shaoyan Liu, Xiaolei Wang, Jingwei Luo, Jianping Xiao, Kai Wang, Yuan Qu, Xuesong Chen, Ye Zhang, Jingbo Wang, Jianghu Zhang, Guozhen Xu, Li Gao, Runye Wu, Junlin Yi
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear. <h3>Objective</h3> To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC. <h3>Design, Setting, and Participants</h3> This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded. <h3>Exposures</h3> Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT. <h3>Main Outcomes and Measures</h3> Five-year overall survival and survival with a functional larynx. <h3>Results</h3> Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively;<i>P</i> &lt; .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39;<i>P</i> = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84,<i>P</i> = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%. <h3>Conclusions and Relevance</h3> In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.
Solvent abuse.
Authors: C H Ashton
Journal: BMJ (1990)

OBJECTIVE:To identify health insurance disparities in the population undergoing continuous EEG monitoring for epilepsy. DESIGN/METHODS:We reviewed the healthcare Cost and Utilization Project9s Nationwide Inpatient Sample (NIS) database from 2000 to 2011 for hospitalizations encoding epilepsy or convulsions as a primary diagnosis (ICD 9-CM codes 345.xx or 780.39).Continuous EEG (cEEG) monitoring was identified by procedure code 89.19. Multivariate regression model were generated after adjusting with confounders to evaluate association between payment type and cEEG utilization. RESULTS:Out of 2795525 hospitalizations for epilepsy or convulsions, 275814 (8.8[percnt]) had continuous EEG monitoring coded. In multivariate analysis, the odds of utilizing cEEG monitoring were lower in Medicare/Medicaid (Adjusted Odds Ratio [OR] 0.65; 95[percnt] Confidence Interval [CI] 0.60-0.71; Beta value [b]: -0.4293; p&lt;0.001) and self/no/other (OR 0.49; 95[percnt] CI 0.42-0.58; b: -0.6508; p&lt;0.001) as compared to private insurance. This effect does not vary over the year (p: 0.10 and P: 0.92 respectively for Medicare/Medicaid and self/no/other), between teaching or non teaching hospitals (p: 0.16 and P: 0.07) and between urban or rural hospitals (p: 0.99 and P: 0.97). Additionally, male gender, black and Hispanic ethnicity as compare to white and lowest quartile of median household income as compare to highest were each independently associated with lower utilization. CONCLUSION: In patients who were admitted with primary diagnosis of epilepsy or convulsions, rates of cEEG monitoring is associated with payment disparity. Further studies are needed to identify the factors leading to these disparities. <b>Disclosure:</b> Dr. dave has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Savani has nothing to disclose. Dr. Bhatia has nothing to disclose. Dr. Eccher has nothing to disclose.