tbuckley/cabot-search huggingface dataset:
Abstract 19443: Predictors of Wound Healing in Patients With Critical Limb Ischemia With Tissue Loss following Successful Endovascular Therapy
Authors: Norihiro Kobayashi, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano
Journal: Circulation (2013)

Background: Sometimes we can’t achieve wound healing in patients with critical limb ischemia (CLI) with tissue loss even after successful endovascular therapy (EVT). Multiple factors including patient background, intervention outcomes, and also wound characteristics are associated with wound healing. Therefore we evaluated predictors of wound healing in CLI after successful EVT. Methods: Between April 2007 and April 2012, 179 patients (217 limbs) with CLI classified to Rutherford 5 or 6 were treated with EVT in our institute. Of these, 128 patients (146 limbs) were successfully treated. Successful EVT was defined as revascularization of achievement of direct blood flow to the wounds evaluated by digital subtraction angiography just after EVT. Each variables were analyzed using the univariate Cox proportional hazards model for wound healing. All variables tested in univariate analysis with p &lt; 0.25 were included in multivariate Cox hazards model. Results: The mean follow-up period was 21±17 months. Wound healing rates were 41%, 58%, 71%, and 72%, at 3, 6, 12, and 18 months, respectively. Multivariate Cox proportional hazard analysis revealed that insulin use (HR 0.47, 95%CI 0.30-0.73, p=0.001), dependence on hemodialysis (HR 0.35, 95%CI 0.23-0.53, p&lt;0.001), wounds located only at toes (HR 2.79, 95%CI 1.78-4.38, p&lt;0.001), gangrene (HR 0.66, 95%CI 0.44-0.97, p=0.037), and revascularization basing on angiosome concept (HR 1.53, 95%CI 1.16-2.02, p=0.002) were independent predictors of wound healing following successful EVT. Conclusions: Achievement of direct blood flow to the wounds is important factor for wound healing, but that is not enough. Insulin use, dependence on hemodialysis, and gangrene can be predictors of wound healing failure. Furthermore, wounds located only at toes and revascularization basing on angiosome concept can be predictors of wound healing.
TCT-23 Management and Outcome of Failed Percutaneous Edge-to-Edge Mitral Valve Plasty: Insight From an International Registry
Authors: Antonio Mangieri, Francesco Melillo, Claudio Montalto, Paolo Denti, Fabien Praz, Alessandra Sala, Mirjam Winkel, Maurizio Taramasso, Ana Paula Tagliari, Antonio Popolo Rubbio, Federico De Marco, Francesco Bedogni, Stefan Toggweiler, Joachim Schofer, Christina Brinkmann, Horst Sievert, Nicolas Van Mieghem, Joris Ooms, Jean-Michel Paradis, Eric Brochet, Dominique Himbert, Leor Perl, Ran Kornowski, Alfonso Ielasi, Damiano Regazzoli, Luca Baldetti, Giulia Masiero, Giuseppe Tarantini, Azeem Latib, Alessandra Laricchia, Gattas Angie, Didier Tchetche, Nicolas Dumonteil, Francesco Giannini, Eustachio Agricola, Matteo Montorfano, Philipp Lurz, Gabriele Crimi, Francesco Maisano, Antonio Colombo
Journal: Journal of the American College of Cardiology (2021)
Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study
Authors: Ya Wang, Long Qiao, Jie Yang, Xiong Li, Yaqi Duan, Jiahao Liu, Shaoqi Chen, Huayi Li, Dan Liu, Tian Fang, Jingjing Ma, Xiaoting Li, Fei Ye, Junxiang Wan, Juncheng Wei, Qin Xu, Ensong Guo, Ping Jin, Mingfu Wu, Lin Zhang, Yun Xia, Yaqun Wu, Jun Shao, Yaojun Feng, Qing Zhang, Zongyuan Yang, Gang Chen, Qinghua Zhang, Xingrui Li, Shixuan Wang, Junbo Hu, Xiaoyun Wang, Mona P. Tan, Kazuaki Takabe, Beihua Kong, Qifeng Yang, Ding Ma, Qinglei Gao
Journal: Cancer Communications (2021)

Abstract Background To date, there is no approved blood‐based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. Methods We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan‐cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre‐treatment serum SEMA4C levels, measured using optimized in‐house enzyme‐linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post‐surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. Results We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls ( P &lt; 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900–0.941) and 0.932 (95%CI: 0.911–0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early‐stage breast cancer ( n = 366) and ductal carcinoma in situ ( n = 85) were 0.931 (95%CI: 0.916–0.946) and 0.879 (95%CI: 0.832–0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision ( P &lt; 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. Conclusions Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.
DPP inhibition alters the CXCR3 axis and enhances NK and CD8+ T cell infiltration to improve anti-PD1 efficacy in murine models of pancreatic ductal adenocarcinoma
Authors: Allison A Fitzgerald, Shangzi Wang, Veena Agarwal, Emily F Marcisak, Annie Zuo, Sandra A Jablonski, Melanie Loth, Elana J Fertig, John MacDougall, Eugene Zhukovsky, Shubhendu Trivedi, Dimple Bhatia, Vince O'Neill, Louis M Weiner
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer death in the USA by 2030. Immune checkpoint inhibitors fail to control most PDAC tumors because of PDAC’s extensive immunosuppressive microenvironment and poor immune infiltration, a phenotype also seen in other non-inflamed (ie, ‘cold’) tumors. Identifying novel ways to enhance immunotherapy efficacy in PDAC is critical. Dipeptidyl peptidase (DPP) inhibition can enhance immunotherapy efficacy in other cancer types; however, the impact of DPP inhibition on PDAC tumors remains unexplored. Methods We examined the effects of an oral small molecule DPP inhibitor (BXCL701) on PDAC tumor growth using mT3-2D and Pan02 subcutaneous syngeneic murine models in C57BL/6 mice. We explored the effects of DPP inhibition on the tumor immune landscape using RNAseq, immunohistochemistry, cytokine evaluation and flow cytometry. We then tested if BXCL701 enhanced anti-programmed cell death protein 1 (anti-PD1) efficacy and performed immune cell depletion and rechallenged studies to explore the relevance of cytotoxic immune cells to combination treatment efficacy. Results In both murine models of PDAC, DPP inhibition enhanced NK and T cell immune infiltration and reduced tumor growth. DPP inhibition also enhanced the efficacy of anti-PD1. The efficacy of dual anti-PD1 and BXCL701 therapy was dependent on both CD8+ T cells and NK cells. Mice treated with this combination therapy developed antitumor immune memory that cleared some tumors after re-exposure. Lastly, we used The Cancer Genome Atlas (TCGA) to demonstrate that increased NK cell content, but not T cell content, in human PDAC tumors is correlated with longer overall survival. We propose that broad DPP inhibition enhances antitumor immune response via two mechanisms: (1) DPP4 inhibition increases tumor content of CXCL9/10, which recruits CXCR3+ NK and T cells, and (2) DPP8/9 inhibition activates the inflammasome, resulting in proinflammatory cytokine release and Th1 response, further enhancing the CXCL9/10-CXCR3 axis. Conclusions These findings show that DPP inhibition with BXCL701 represents a pharmacologic strategy to increase the tumor microenvironment immune cell content to improve anti-PD1 efficacy in PDAC, suggesting BXCL701 can enhance immunotherapy efficacy in ‘cold’ tumor types. These findings also highlight the potential importance of NK cells along with T cells in regulating PDAC tumor growth.
Association of White Matter Hyperintensities With Pathology and Progression of Parkinsonism in Aging
Authors: Shahram Oveisgharan, Lei Yu, Victoria N. Poole, Arnold M. Evia, Lisa L. Barnes, Julie A. Schneider, Konstantinos Arfanakis, David A. Bennett, Aron S. Buchman
Journal: JAMA Neurology (2021)

Progressive parkinsonism is common in older adults without a diagnosis of Parkinson disease and is associated with adverse health outcomes, but its pathologic basis is controversial.To examine if the burden of cerebral white matter hyperintensity (WMH), a common manifestation of cerebrovascular disease pathologies, is associated with the rate of progressive parkinsonism.This community-based cohort study included participants recruited in 3 ongoing cohorts that began enrollment in 1994, 1997, and 2004. Prior to death, participants were observed for a mean of 7.5 years, with annual clinical assessments. From 4427 participants enrolled in the 3 cohorts, 2134 died. Postmortem autopsy was performed in 1725 decedents, and 598 also had ex vivo brain magnetic resonance imaging. Participants were excluded if they were missing any of the 9 postmortem pathology indices (n = 22) or repeated parkinsonism assessment (n = 41) or had received a clinical diagnosis of Parkinson disease at any point before or during the study (n = 19). Data were analyzed from April 2020 to August 2021.WMH burden was assessed using a modified Fazekas rating scale.Parkinsonism was assessed annually using 26 items of a modified motor portion of the Unified Parkinson's Disease Rating Scale. A summary score was developed from the item scores, with higher scores indicating more severe parkinsonism.Of 516 included decedents, 364 (70.5%) were female, and the mean (SD) age at death was 90.2 (6.4) years. Higher WMH was associated with faster progressive parkinsonism (estimate, 0.024; SE, 0.008; P = .002). The attenuation of this association was greater when controlling for indices of cerebrovascular disease pathologies than when controlling for neurodegenerative pathologies (cerebrovascular disease: estimate, 0.019; SE, 0.008; P = .02; neurodegenerative: estimate, 0.022; SE, 0.008; P = .003), but both remained significant.In this cohort study, higher levels of both WMH and indices of cerebrovascular disease pathologies in aging brains were associated with more rapid progressive parkinsonism. Further studies are needed to determine if in vivo brain imaging of older adults for evidence of WMH and aggressive medical treatment of vascular risk factors and diseases can reduce the occurrence or severity of late-life parkinsonism.
HIF-αs promote mitochondrial cardiolipin synthesis and respiration efficiency
Authors: Duyen Dang, Sang Chun, Kyunghee Burkitt, Marcia Cruz-Correa, Xianlin Han, Long Dang
Journal: Cancer Research (2008)

4109  The hypoxia-inducible transcription factors, HIF-1 and HIF-2, have been strongly associated with cancer cell growth and survival. HIF-1 is composed of the HIF-1α and HIF-1β subunits; and HIF-2 is composed of the HIF-2α and HIF-1β subunits. Whereas HIF-1β is constitutively expressed, HIF-1α and HIF-2α protein stability and synthesis are regulated by intratumoral hypoxia and genetic alterations in oncogenes and tumor suppressor genes. Cancer cells balance glycolysis and aerobic respiration in metabolizing glucose. The role of HIF-1α in mediating glycolysis is well-described. Recently, HIF-1α has been implicated in regulating mitochondrial respiration. The role of HIF-2α in glucose metabolism remains unclear. We hypothesized that HIF-1α and HIF-2α (HIF-αs) cooperate to promote cancer glucose metabolism. To examine the roles of HIF-αs, we disrupted the HIF-1α and HIF-2α genes, alone and in combination, in two human colon cancer cell lines: HCT116 and RKO. Expression of both HIF-αs led to a 5-fold increase in in vitro and in vivo tumor growth. Consistent with the literature, HIF-1α, but not HIF-2α, mediated aerobic glycolysis, as measured by cellular ATP and lactate levels. In addition, both HIF-αs were required to promote mitochondrial respiration efficiency. Specifically, loss of both HIF-αs led to a 3-fold increase in mitochondrial and cellular ROS (as measured by MitoSOX Red and DCFDA), a 2-fold increase in mitochondrial hyperpolarization (as measured by the ratio of MitoTracker Red CMXRos to MitoTracker Green FM), and a 4-fold decrease in oxygen consumption (as measured by the oxygen-sensing fluorescent dye (Ru(DPP)3)). We next determined the mechanisms by which HIF-αs promote mitochondrial respiration efficiency. Cardiolipin is a mitochondrial phospholipid that interacts with electron transport chain proteins to optimize mitochondrial respiration. Global lipidome analyses on isolated mitochondria revealed that the presence of both HIF-αs induced the synthesis of mitochondrial cardiolipin species by 3-6-fold. Microarray analyses identified a novel set of HIF-αs target genes. Two of these genes were PCK2 and ACSL5, which encode for mitochondrial enzymes that catalyze essential steps in cardiolipin synthesis. Subsequent analyses in multiple cell lines confirmed that HIF-αs induce mitochondrial PCK2 and ACSL5 expression by ~4-fold. In addition, mitochondrial PCK2 and ACSL5 expression were ~3-fold increased in human colorectal cancer cancers compared to their adjacent normal mucosa. Together, these data elucidate a novel growth-promoting bioenergetic pathway, in which both HIF-αs induce the expression of genes important for mitochondrial cardiolipin synthesis (PCK2 and ACSL5). This results in increased levels of cardiolipin, an important component of the inner mitochondrial membrane. The consequent increase in mitochondrial respiration efficiency contributes to tumor growth.
The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial
Authors: Michael E. Nassif, Sheryl L. Windsor, Barry A. Borlaug, Dalane W. Kitzman, Sanjiv J. Shah, Fengming Tang, Yevgeniy Khariton, Ali O. Malik, Taiyeb Khumri, Guillermo Umpierrez, Sumant Lamba, Kavita Sharma, Sadiya S. Khan, Lokesh Chandra, Robert A. Gordon, John J. Ryan, Sunit-Preet Chaudhry, Susan M. Joseph, Chen H. Chow, Manreet K. Kanwar, Michael Pursley, Elias S. Siraj, Gregory D. Lewis, Barry S. Clemson, Michael Fong, Mikhail N. Kosiborod
Journal: Nature Medicine (2021)

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.
Loneliness is strongly linked to depression among older adults, a long term study suggests
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyLee SL, Pearce E, Ajnakina O, et al. The association between loneliness and depressive symptoms among adults aged 50 years and older: a 12-year population-based cohort study. Lancet Psychiatry 2021;8:1.To read the full NIHR Alert go to https://evidence.nihr.ac.uk/alert/loneliness-strongly-linked-depression-older-adults/.
TCT-31 Frailty Adjusted Risk Score for Outcomes in Type 2 Myocardial Infarction
Authors: Jayakumar Sreenivasan, Aaqib H. Malik, Katerina Jurkoshek, Muhammad Khan, Sreema Puthiya Parambath, Ziad Ali, Srihari Naidu, Erin Michos, Howard Cooper
Journal: Journal of the American College of Cardiology (2021)
Management of Abdominal Aortic Aneurysms
Authors: Andres Schanzer, Gustavo S. Oderich
Journal: New England Journal of Medicine (2021)

Repair of abdominal aortic aneurysm is recommended in men with an aneurysm of 5.5 cm or more and in women with an aneurysm of 5.0 cm or more. In randomized trials, endovascular aortic aneurysm repair was associated with a lower risk of perioperative complications and death than open surgical repair, but mortality was similar after approximately 2 years. After endovascular repair, long-term imaging surveillance is recommended.
A Molecular Inquiry into the Role of Antibody-Drug Conjugates in Bacillus Calmette-Guérin-exposed Non–muscle-invasive Bladder Cancer
Authors: Woonyoung Choi, Kara Lombardo, Sunil Patel, Gabriel Epstein, Mingxiao Feng, Andrew Gabrielson, Noah M. Hahn, Jean Hoffman-Censits, David McConkey, Trinity J. Bivalacqua, Andres Matoso, Max Kates
Journal: European Urology (2021)
爪乾癬のためのアダリムマブ:第3相,無作為化,プラセボ対照試験の最初の26週間の有効性と安全性【Powered by NICT】
Authors: E Elewski Boni, M Okun Martin, Papp Kim, S Baker Christopher, J Crowley Jeffrey, Guillet Gerard, Sundaram Murali, Poulin Yves, Gu Yihua, Geng Ziqian, A Williams David, A Rich Phoebe
Journal: Journal of the American Academy of Dermatology (2018)
TCT-307 Intraoperative Optical Coherence Tomography of the Saphenous Vein Conduit in Patients Undergoing Coronary Artery Bypass Surgery
Authors: Edward Lundy, Evan Shlofmitz, Allen Jeremias, Georges Abou-Eid, Craig Porter, Susan Thomas, Akiko Maehara, Thomas Pappas, Nelson Mei, Jonathan Scheiner, Newell Robinson, Ziad Ali, Richard Shlofmitz
Journal: Journal of the American College of Cardiology (2021)
ST-Segment Depression in V<sub>2</sub> With Precordial Hyperacute T-Waves Is an Anterior ST-Segment Elevation Myocardial Infarction (STEMI) Equivalent
Authors: Phillip Rubin, Paul C. Montana
Journal: JAMA Internal Medicine (2021)

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TCT-56 Long-Term Clinical Outcome and Performance of Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Replacement
Authors: Andrea Scotti, Luca Nai Fovino, Mauro Massussi, Francesco Cardaioli, Giulio Rodinò, Carolina Montonati, Saverio Continisio, Mauro Boiago, Alessandro Diliberti, Alice Benedetti, Giulia Lorenzoni, Dario Gregori, Yuji Matsuda, Luisa Cacciavillani, Andrea Pavei, Giulia Masiero, Massimo Napodano, Chiara Fraccaro, Tommaso Fabris, Sabino Iliceto, Giuseppe Tarantini
Journal: Journal of the American College of Cardiology (2021)
A good 10 minutes of GP time can save hours in the emergency department
Authors: Graeme M Mackenzie
Journal: BMJ (2021)

Stressed teams, as Oliver illustrates, always seek to blame.1

The myth of the lazy, golf playing GP, amazingly, endures. Lunch for many GPs is a fond memory. Many work into the evening. Hospital doctors are similar. Most GP time is spent looking at information and making countless small decisions. One holistic consultation might involve scores of decisions. Key information is often hidden …
Multifunctional Hybrid Hydrogel Enhanced Antitumor Therapy through Multiple Destroying DNA Functions by a Triple‐Combination Synergistic Therapy (Adv. Healthcare Mater. 21/2021)
Authors: Jiamin Zhang, Lijun Yang, Fan Huang, Cuicui Zhao, Jinjian Liu, Yumin Zhang, Jianfeng Liu
Journal: Advanced Healthcare Materials (2021)

Gold Nanoparticle Aggregates In article number 2101190, Jinjian Liu, Yumin Zhang, Jianfeng Liu and co-workers report a multifunctional hybrid hydrogel for triple-synergistic destruction of tumor DNA functions. The sustained release of DOX can prevent DNA replication; meanwhile, gold nanoparticle aggregates can exacerbate DNA damage and inhibit DNA self-repair via dual-sensitization, i.e., radiosensitization and photo-sensitization. This triple-synergistic strategy achieves a highly efficient antitumor efficacy.