tbuckley/cabot-search huggingface dataset:
Abstract 16903: Predictors of Major Bleeding Risk: Insights from the Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)
Authors: Shaun G Goodman, Daniel M Wojdyla, Harvey D White, Jonathan P Piccini, John F Paolini, Christopher C Nessel, Kenneth W Mahaffey, Manesh R Patel, Richard C Becker, Jonathan L Halperin, Werner Hacke, Daniel E Singer, Graeme J Hankey, Gunter Breithardt, Keith A Fox, Robert M Califf
Journal: Circulation (2011)

Background: AF is associated with increased ischemic stroke risk. Oral anticoagulation reduces this risk, but there is often suboptimal use of stroke prophylaxis among AF patients, which may be due to challenges in risk stratification for bleeding. Methods: We investigated factors associated with bleeding in 14,264 pts with nonvalvular AF randomized to rivaroxaban or dose-adjusted warfarin in ROCKET AF. Endpoints of interest were ISTH-defined major bleeding events, intracranial and fatal bleeding. Cox proportional hazards modeling was used to identify factors associated with major bleeding. Results: Over a median follow-up of 1.94 yrs, a major bleed occurred in 395 (5.55%; 3.60 per 100-pt yrs) pts assigned rivaroxaban and 386 (5.42%; 3.45 per 100-pt yrs) assigned warfarin (HR 1.04, 95% CI 0.90, 1.20). Intracranial (0.49% vs. 0.74% per yr; p=0.019) and fatal bleeding (0.24% vs. 0.48% per yr; p=0.003) were lower with rivaroxaban. Pts (n=781) with a major bleed were more likely to be older (median 75 vs. 73 yrs), smokers (40 vs. 33%), and with lower baseline calculated CrCl (median 63 vs. 68 mL/min); less likely to be female (34 vs. 40%) and have a prior stroke/TIA (46 vs. 53%) (all p&lt;0.002) compared with those without a major bleed (n=13,455). Increased age, male sex, BMI, history of diabetes and COPD, and decreased calculated CrCl were independent predictors of increased risk for major bleeding (C-index=0.62). No significant interaction was identified between predictors of bleeding and components of major bleeding. Conclusions: Major bleeding rates were similar with rivaroxaban or warfarin; however, intracranial and fatal bleeding was significantly lower with rivaroxaban. Older age, male sex, prior diabetes, increased BMI, lower diastolic BP, and reduced renal function at baseline were independently associated with major bleeding. Careful assessment of bleeding risk in patients with AF is required to support clinical decision making for stroke prevention therapy.
Evolution and long‐term outcomes of combined immunodeficiency due to CARMIL2 deficiency
Authors: Burcu Kolukisa, Dilek Baser, Bengu Akcam, Jeffrey Danielson, Sevgi Bilgic Eltan, Yesim Haliloglu, Asena Pinar Sefer, Royale Babayeva, Gamze Akgun, Louis‐Marie Charbonnier, Klaus Schmitz‐Abe, Yasemin Kendir Demirkol, Yu Zhang, Claudia Gonzaga‐Jauregui, Raul Jimenez Heredia, Nurhan Kasap, Ayca Kiykim, Esra Ozek Yucel, Veysel Gok, Ekrem Unal, Aysenur Pac Kisaarslan, Serdar Nepesov, Gokhan Baysoy, Zerrin Onal, Gozde Yesil, Tulin Tiraje Celkan, Haluk Cokugras, Yildiz Camcioglu, Ahmet Eken, Kaan Boztug, Bernice Lo, Elif Karakoc‐Aydiner, Helen C. Su, Ahmet Ozen, Talal A. Chatila, Safa Baris
Journal: Allergy (2021)

Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations.The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape.Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years).This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.
Epidemiology and co-infection patterns in patients with respiratory tract infections in southern China between 2018 and 2020
Authors: Jingyi Liang, Zhufeng Wang, Yong Liu, Linxiu Zeng, Zhengtu Li, Jiamin Liang, Hanwen Liang, Mei Jiang, Zifeng Yang
Journal: Journal of Infection (2021)

We read with interest the recent report by Liang and colleagues in this Journal, who compared the detection rate of 20 respiratory Viruses and bacteria by Influenza-Like Illness Surveillance in Beijing, China, 2016–2018 (REF).1
Determinants to establish non-self terminated ventricular fibrillation of Brugada syndrome comparing with heart disease by time-domain frequency analysis
Authors: K Uno, Seiichiro Sakurai, Daigo Nagahara, Kenjiro Miyamoto, Kimio Nishisato, Takuji Yoshioka, Nobuaki Kokubu, Satoshi Yuda, Akiyoshi Hashimoto, Kazufumi Tsuchihashi, Yoshito Wakao
Journal: Circulation (2005)
Direct reprogramming induces vascular regeneration post muscle ischemic injury
Authors: Keerat Kaur, Yoav Hadas, Ann Anu Kurian, Magdalena M. Żak, Jimeen Yoo, Asharee Mahmood, Hanna Girard, Rinat Komargodski, Toshiro Io, Maria Paola Santini, Nishat Sultana, Mohammad Tofael Kabir Sharkar, Ajit Magadum, Anthony Fargnoli, Seonghun Yoon, Elena Chepurko, Vadim Chepurko, Efrat Eliyahu, Dalila Pinto, Djamel Lebeche, Jason C. Kovacic, Roger J. Hajjar, Shahin Rafii, Lior Zangi
Journal: Molecular Therapy (2021)

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFβ, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.
P51-1 A case of recurrent breast cancer with liver metastasis successfully treated with multi-disciplinary
Authors: Yuko Nakayama, Shingo Inoue, Masato Ohmori, Ayako Kimura, Katsutoshi Shoda, Shinji Furuya, Naohiro Hosomura, Hidenori Akaike, Hidetake Amemiya, Makoto Sudo, Yoshihiko Kawaguchi, Hiromiti Kawaida, Hiroshi Kono, Daisuke Ichikawa
Journal: Annals of Oncology (2021)
Comments on Computed Tomography for Evaluating Appendicitis
Authors: Andrew Hu, Timothy B. Lautz, Mehul V. Raval
Journal: JAMA Surgery (2021)

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 Surgery 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 Surgery journal
Fructose‐1,6‐Bisphosphate Aldolase B Depletion Promotes Hepatocellular Carcinogenesis Through Activating Insulin Receptor Signaling and Lipogenesis
Authors: Guijun Liu, Ningning Wang, Cunzhen Zhang, Min Li, Xuxiao He, Chunzhao Yin, Qiaochu Tu, Xia Shen, Lili Zhang, Jingwen Lv, Yongqiang Wang, Huimin Jiang, Shiting Chen, Nan Li, Yongzhen Tao, Huiyong Yin
Journal: Hepatology (2021)

Background and Aims Insulin receptor (IR) transduces cell surface signal through phosphoinositide 3-kinase (PI3K)–AKT pathways or translocates to the nucleus and binds to the promoters to regulate genes associated with insulin actions, including de novo lipogenesis (DNL). Chronic activation of IR signaling drives malignant transformation, but the underlying mechanisms remain poorly defined. Down-regulation of fructose-1,6-bisphosphate aldolase (ALDO) B in hepatocellular carcinoma (HCC) is correlated with poor prognosis. We aim to study whether and how ALDOB is involved in IR signaling in HCC. Approach and Results Global or liver-specific ALDOB knockout (L-ALDOB−/−) mice were used in N-diethylnitrosamine (DEN)–induced HCC models, whereas restoration of ALDOB expression was achieved in L-ALDOB−/− mice by adeno-associated virus (AAV). 13C6-glucose was employed in metabolic flux analysis to track the de novo fatty acid synthesis from glucose, and nontargeted lipidomics and targeted fatty acid analysis using mass spectrometry were performed. We found that ALDOB physically interacts with IR and attenuates IR signaling through down-regulating PI3K–AKT pathways and suppressing IR nuclear translocation. ALDOB depletion or disruption of IR/ALDOB interaction in ALDOB mutants promotes DNL and tumorigenesis, which is significantly attenuated with ALDOB restoration in L-ALDOB−/− mice. Notably, attenuated IR/ALDOB interaction in ALDOB-R46A mutant exhibits more significant tumorigenesis than releasing ALDOB/AKT interaction in ALDOB-R43A, whereas knockdown IR sufficiently diminishes tumor-promoting effects in both mutants. Furthermore, inhibiting phosphorylated AKT or fatty acid synthase significantly attenuates HCC in L-ALDOB−/− mice. Consistently, ALDOB down-regulation is correlated with up-regulation of IR signaling and DNL in human HCC tumor tissues. Conclusions Our study reports a mechanism by which loss of ALDOB activates IR signaling primarily through releasing IR/ALDOB interaction to promote DNL and HCC, highlighting a potential therapeutic strategy in HCC.
The role of non‐coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential
Authors: Xiang Meng, Qiu‐Yue Lou, Wen‐Ying Yang, Yue‐Rong Wang, Ran Chen, Lu Wang, Tao Xu, Lei Zhang
Journal: Cancer Communications (2021)

Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in the world, arises from the interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5-fluorouracil, and paclitaxel have now become the first-line options for OSCC patients. Nevertheless, most OSCC patients eventually acquire drug resistance, leading to poor prognosis. With the discovery and identification of non-coding RNAs (ncRNAs), the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized. The mechanisms of drug resistance of OSCC are intricate and involve drug efflux, epithelial-mesenchymal transition, DNA damage repair, and autophagy. At present, strategies to explore the reversal of drug resistance of OSCC need to be urgently developed. Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting, controlled release, and consistent pharmacokinetic profiles. In particular, the combined application of new technologies (including CRISPR systems) opened up new horizons for the treatment of drug resistance of OSCC. Hence, this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC, elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC, and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC.
Longitudinal metabolomics of human plasma reveals prognostic markers of COVID-19 disease severity
Authors: Miriam Sindelar, Ethan Stancliffe, Michaela Schwaiger-Haber, Dhanalakshmi S. Anbukumar, Kayla Adkins-Travis, Charles W. Goss, Jane A. O’Halloran, Philip A. Mudd, Wen-Chun Liu, Randy A. Albrecht, Adolfo García-Sastre, Leah P. Shriver, Gary J. Patti
Journal: Cell Reports Medicine (2021)

There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determines disease severity. Through analysis of longitudinal samples, we confirm that most of these markers are directly related to disease progression and that their levels return to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19.
Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities
Authors: Lisa K. Stamp, Hamish Farquhar, Huai Leng Pisaniello, Ana B. Vargas-Santos, Mark Fisher, David B. Mount, Hyon K. Choi, Robert Terkeltaub, Catherine L. Hill, Angelo L. Gaffo
Journal: Nature Reviews Rheumatology (2021)

Abstract Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.
VP7-2021: KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC
Authors: P. Schmid, J. Cortes, R. Dent, L. Pusztai, H. McArthur, S. Kümmel, J. Bergh, C. Denkert, Y.H. Park, R. Hui, N. Harbeck, M. Takahashi, M. Untch, P.A. Fasching, F. Cardoso, Y. Ding, K. Tryfonidis, G. Aktan, V. Karantza, J. O’Shaughnessy
Journal: Annals of Oncology (2021)
The size of apolipoprotein (a) is an independent determinant of the reduction in lipoprotein (a) induced by PCSK9 inhibitors
Authors: Valentin Blanchard, Kévin Chemello, Tim Hollstein, Clément Chong Hong-Fong, Friederike Schumann, Thomas Grenkowitz, Brice Nativel, Stefan Coassin, Mikaël Croyal, Ursula Kassner, Claudia Lamina, Elisabeth Steinhagen-Thiessen, Gilles Lambert
Journal: Cardiovascular Research (2021)

Abstract Aims Lipoprotein (a) [Lp(a)] is a lipoprotein species causatively associated with atherosclerosis. Unlike statins, PCSK9 inhibitors (PCSK9i) reduce Lp(a), but this reduction is highly variable. Levels of Lp(a) are chiefly governed by the size of its signature protein, apolipoprotein (a) [apo(a)]. Whether this parameter determines some of the reduction in Lp(a) induced by PCSK9i remains unknown. We aimed to investigate if the Lp(a) lowering efficacy of PCSK9i is modulated by the size of apo(a), which is genetically determined by the variable number of KIV domains present on that protein. Methods and results The levels of Lp(a) and the size of apo(a) were assessed in plasma samples from 268 patients before and after treatment with PCSK9i. Patients were recruited at the Outpatient Lipid Clinic of the Charité Hospital (Berlin) between 2015 and 2020. They were hypercholesterolaemic at very high cardiovascular disease risk with low-density lipoprotein (LDL)-cholesterol levels above therapeutic targets despite maximally tolerated lipid-lowering therapy. Patients received either Alirocumab (75 or 150 mg) or Evolocumab (140 mg) every 2 weeks. Apo(a), apoB100, and apoE concentrations as well as apoE major isoforms were determined by liquid chromatography high-resolution mass spectrometry. Apo(a) isoforms sizes were determined by western blot. PCSK9i sharply reduced LDL-cholesterol (−57%), apoB100 (−47%), and Lp(a) (−36%). There was a positive correlation between the size of apo(a) and the relative reduction in Lp(a) induced by PCSK9i (r = 0.363, P = 0.0001). The strength of this association remained unaltered after adjustment for baseline Lp(a) levels and all other potential confounding factors. In patients with two detectable apo(a) isoforms, there was also a positive correlation between the size of apo(a) and the reduction in Lp(a), separately for the smaller (r = 0.350, P = 0.0001) and larger (r = 0.324, P = 0.0003) isoforms. The relative contribution of the larger isoform to the total concentration of apo(a) was reduced from 29% to 15% (P &amp;lt; 0.0001). Conclusions The size of apo(a) is an independent determinant of the response to PCSK9i. Each additional kringle domain is associated with a 3% additional reduction in Lp(a). This explains in part the variable efficacy of PCSK9i and allows to identify patients who will benefit most from these therapies in terms of Lp(a) lowering.
Exercise Capacity in Young Adults Born Small for Gestational Age
Authors: Fàtima Crispi, Mérida Rodríguez-López, Gabriel Bernardino, Álvaro Sepúlveda-Martínez, Susanna Prat-González, Carolina Pajuelo, Rosario J. Perea, Maria T. Caralt, Giulia Casu, Kilian Vellvé, Francesca Crovetto, Felip Burgos, Mathieu De Craene, Constantine Butakoff, Miguel Á. González Ballester, Isabel Blanco, Marta Sitges, Bart Bijnens, Eduard Gratacós
Journal: JAMA Cardiology (2021)

Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood.To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA.This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected.Being born SGA.Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing.This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P < .001).This cohort of young adults born SGA had markedly reduced exercise capacity. These results support further research to clarify the causes of impaired exercise capacity and the potential association with increased cardiovascular mortality among adults born SGA.
P4-10 The impact of neutrophil/lymphocyte ratio (NLR) on overall survival for patients with metastatic colorectal cancer
Authors: Kazuaki Harada, Takeshi Kawakami, Toshiki Masuishi, Yasuyuki Kawamoto, Hirohumi Go, Kyoko Kato, Ryosuke Kumanishi, Satoshi Yuki, Kouji Yamamoto, Hirofumi Yasui, Yoshito Komatsu, Kei Muro, Takeharu Yamanaka, Kentaro Yamazaki
Journal: Annals of Oncology (2021)
Abstract 10888: Impact of Sodium Bicarbonate on Survival in Patients With Prolonged Out-of-Hospital Cardiac Arrest; SOS-KANTO study 2002 & 2012
Authors: Koichiro Shinozaki, Tomoko Ogasawara, Shigeto Oda, Atsushi Sakurai, Yoshio Tahara, Naohiro Yohemoto, Ken Nagao, Arino Yaguchi, Naoto Morimura
Journal: Circulation (2015)

Introduction: The impact of sodium bicarbonate (SB) usage on survival outcomes in patients who have prolonged cardiac arrest (CA) remains unclear. A change in the overall use of SB has occurred ove...