tbuckley/cabot-search huggingface dataset:
Risk Factors and Biomarkers of Poor Outcomes
Authors: Justin T. Tretter, Andrew N. Redington
Journal: Circulation (2018)

In many ways, the surgical management in tetralogy of Fallot (TOF) is the poster child for the development of congenital cardiac surgery, with progressive evolution leading to the current era when early complete repair carries an exceptionally low mortality.Consequently, there are more adults with the diagnosis than children. 1 However, these triumphs have been tarnished by the realization that our patients have a continuous late hazard of impaired functional status, heart failure, arrhythmias, and death, at least in part related to the consequences of residual right ventricular (RV) outflow tract dysfunction. 2e have come a long way in the past 3 decades, from initially considering residual pulmonary incompetence as a benign aftermath of repair to the understanding of its central role in the pathogenesis of many late adverse consequences.As a result, pulmonary valve replacement (PVR), once rarely performed, is considered inevitable for many patients.It is now, of course, all about timing. 2,3If there were no adverse consequences to PVR, the timing question would be irrelevant, but although the clock is inevitably ticking for many with postoperative RV outflow tract dysfunction, a different clock starts ticking after PVR.How, then, should we decide when to intervene?Because of the relatively low incidence of adverse outcomes to support statistically significant associations in small groups of patients with repaired TOF, current guidelines for timing of surgical PVR in the asymptomatic patient have depended on preoperative markers of poor ventricular remodeling after surgery, heavily focusing on thresholds of RV size and systolic function. 2,3Although largely addressing a different patient population and with a different inherent risk/benefit profile, timing for transcatheter PVR is often inferred from surgical PVR guidelines. 3Such recommendations have been based on the not unreasonable assumption that reverse remodeling of the RV to normal is desirable, and by defining a threshold of irreversibility, we might prevent the later adverse consequences of chronic pulmonary incompetence.][4] Geva and colleagues 5 are to be commended for their current multicenter IN-DICATOR cohort observational study (International Multicenter TOF Registry) of patients with repaired TOF, describing preoperative risk factors for postoperative occurrence of death or sustained ventricular tachycardia after PVR, as well as associations with the secondary outcomes of significant heart failure and sustained atrial tachyarrhythmias.This is the first study to meticulously investigate post-PVR outcomes in a relatively large cohort. 5Primary outcome predictors included pre-
A randomized controlled proof‐of‐concept trial of digoxin and furosemide in adults with cutaneous warts
Authors: M. Rijsbergen, T. Niemeyer‐van der Kolk, G. Hogendoorn, S. Kouwenhoven, C. Lemoine, E.S. Klaassen, M. de Koning, S. Beck, J.N. Bouwes Bavinck, G. Feiss, J. Burggraaf, R. Rissmann
Journal: British Journal of Dermatology (2018)

Topical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts.To assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT.Treatment with ICVT was assessed for efficacy, safety and tolerability in a single- centre, randomized, double-blind, placebo-controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed-model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643.Wart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (-3·0 mm, 95% confidence interval -4·9 to -1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (-94%, 95% confidence interval -100 to -19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts.This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.
Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23
Authors: Rubén Martínez-Barricarte, Janet G. Markle, Cindy S. Ma, Elissa K. Deenick, Noé Ramírez-Alejo, Federico Mele, Daniela Latorre, Seyed Alireza Mahdaviani, Caner Aytekin, Davood Mansouri, Vanessa L. Bryant, Fabienne Jabot-Hanin, Caroline Deswarte, Alejandro Nieto-Patlán, Laura Surace, Gaspard Kerner, Yuval Itan, Sandra Jovic, Danielle T. Avery, Natalie Wong, Geetha Rao, Etienne Patin, Satoshi Okada, Benedetta Bigio, Bertrand Boisson, Franck Rapaport, Yoann Seeleuthner, Monika Schmidt, Aydan Ikinciogullari, Figen Dogu, Gonul Tanir, Payam Tabarsi, Mohammed Reza Bloursaz, Julia K. Joseph, Avneet Heer, Xiao-Fei Kong, Mélanie Migaud, Tomi Lazarov, Frédéric Geissmann, Bernhard Fleckenstein, Cecilia Lindestam Arlehamn, Alessandro Sette, Anne Puel, Jean-François Emile, Esther van de Vosse, Lluis Quintana-Murci, James P. Di Santo, Laurent Abel, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Stuart G. Tangye, Federica Sallusto, Jean-Laurent Casanova
Journal: Science Immunology (2018)

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rβ1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL-12Rβ2 or IL-23R deficiency, lacking responses to IL-12 or IL-23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that αβ T, γδ T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-γ in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-γ in response to IL-23. We also show that the development of IFN-γ-producing CD4
Human nectin-like 3 is a prostate associated trans-membrane protein regulated by methylation
Authors: Guimin Chang, Shuping Xu, Norman M. Greenberg, Jeffrey R. Gingrich
Journal: Cancer Research (2005)

925  Nectin-like 3 (Necl-3) was cloned and identified utilizing differential display PCR analysis and rapid amplification of cDNA ends (RACE) from human prostate cancer and normal brain. Full-length Necl-3 cDNA has a 1311bp open reading frame encoding 437 amino acids. Necl-3 is a novel member of the immunoglobulin superfamily with three extracellular Ig-like domains, a transmembrane region and an intracellular domain. The intracellular domain contains a protein 4.1 binding domain and C-terminal PDZ binding domain (PDZBD). Chromosomal mapping showed that this gene is located at human chromosome 3p12.1. RT-PCR results have demonstrated that mRNA expression in some prostate cancer cell lines was reduced compared with expression in normal prostate epithelial cell lines and normal prostate tissue. There was higher expression of Necl-3 at the protein level in normal prostate cell lines than in all prostate cancer cell lines tested. A PDZBD protein array assay was performed demonstrating that the Necl-3 PDZBD can strongly bind to the hDlg (human discs large) family tumor suppressor gene family, including Dlg-2/MPP-2, DLG1-D3, DLG4-D3 et al. To determine the mechanism of down-regulation of Necl-3 in prostate cancer, we examined whether methylation of the Necl-3 promoters was involved in regulation of Necl-3 gene expression. Promoter sequence analysis revealed two CpG islands. Bisulfite genomic sequencing revealed that the Necl-3 gene promoter exhibits distinct methylation patterns. The promoter was unmethylated in normal prostate epithelial cell lines RWPE-1and primary prostate cancer cell line PPC-1, but extensively methylated in prostate cancer cell lines such as DU145, TSU and partially methylated in LNCaP, PC-3, and RWPE-2 (transformed by Ki-Ras from RWPE-1). We demonstrated a significant correlation between promoter hypermethylation and loss of Necl-3 mRNA expression in prostate cancer cell lines. Treatment of prostate cancer cells with demethylating agents effectively reactivated the expression of Necl-3 mRNA. Thus, expression of Necl-3 mRNA in prostate tumors was found to be inversely associated with the degree of promoter methylation. These results are consistent with the hypothesis that Necl-3 may be an important tumor suppressor gene involved in the progression of prostate cancer through gene silencing by promoter DNA methylation.
Abstract 14030: The Impact of Arterial Stiffness on Long-term Clinical Outcomes in Patients at Low Risk of Cardiovascular Disease
Authors: Naoyuki Abe, Takashi Miura
Journal: Circulation (2016)

Background: Brachial-ankle pulse wave velocity (PWV) is a simple method for assessing arterial stiffness. This study aimed to investigate the implication of PWV for predicting long-term clinical outcomes in patients at low risk of cardiovascular disease (CVD) Methods: To evaluate the impact of arterial stiffness on long-term clinical outcomes in patients at low risk of CVD, we excluded patients having a history of cardiac and cerebrovascular disease, undergoing hemodialysis and showing abnormal ABI. We retrospectively evaluated the association between PWV and long-term clinical outcomes in 1886 patients, who underwent arterial plethysmography at admission. The endpoint of this study was major cardiovascular events (MACE) - a composite of cardiovascular death, myocardial infarction and ischemic stroke. Results: During a median follow-up of 4.9 years, 119 patients had MACE. Patients with MACE exhibited significantly higher PWV values compared to those without MACE. Receiver operating characteristic (ROC) an...
Histologic subtype of treatment failures after noninvasive therapy for superficial basal cell carcinoma: An observational study
Authors: Lieke C.J. van Delft, Patty J. Nelemans, Maud H.E. Jansen, Aimee H.M.M. Arits, Marieke H. Roozeboom, Myrurgia A. Hamid, Klara Mosterd, Nicole W.J. Kelleners-Smeets
Journal: Journal of the American Academy of Dermatology (2018)
A Glimmer of Hope for Pancreatic Cancer
Authors: Hedy L. Kindler
Journal: New England Journal of Medicine (2018)

Recent advances in precision medicine and immunotherapy have transformed the once bleak outlook for many patients with solid tumors, including melanoma and non–small-cell lung cancer. Unfortunately, these newer approaches have not affected the dismal outcomes for patients with pancreatic adenocarcinoma. Only 8% of patients with this disease are cured, the lowest rate among any solid tumors.1 Within the next decade, pancreatic cancer is projected to become the second leading cause of death from cancer in the United States,2 which reflects the inadequacy of our current treatment options. Surgery is the only potential cure, but fewer than 20% of patients are . . .
Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma
Authors: Hung Huynh, Liek Yeow Lee, Kah Yong Goh, Richard Ong, Huai‐Xiang Hao, Alan Huang, Youzhen Wang, Diana Graus Porta, Pierce Chow, Alexander Chung
Journal: Hepatology (2018)

The fibroblast growth factor (FGF) signaling cascade is a key signaling pathway in hepatocarcinogenesis. We report high FGF receptor (FGFR) expression in 17.7% (11 of 62) of hepatocellular carcinoma (HCC) models. Infigratinib, a pan-FGFR inhibitor, potently suppresses the growth of high-FGFR-expressing and sorafenib-resistant HCCs. Infigratinib inhibits FGFR signaling and its downstream targets, cell proliferation, the angiogenic rescue program, hypoxia, invasion, and metastasis. Infigratinib also induces apoptosis and vessel normalization and improves the overall survival of mice bearing FGFR-driven HCCs. Infigratinib acts in synergy with the microtubule-depolymerizing drug vinorelbine to promote apoptosis, suppress tumor growth, and improve the overall survival of mice. Increased expression levels of FGFR-2 and FGFR-3 through gene amplification correlate with treatment response and may serve as potential biomarkers for patient selection. Conclusion: Treatments with Infigratinib alone or in combination with vinorelbine may be effective in a subset of patients with HCC with FGFR-driven tumors.
Isotretinoin's paradoxical effects in immortalized sebocytes
Authors: B.C. Melnik, S.M. John, N.F. Agamia, W. Chen, V. De Vita, A.S. Karadag, G. Plewig, G. Schmitz
Journal: British Journal of Dermatology (2018)

Linked Article: Burney et al. Br J Dermatol 2018; 179:1201–2.
Abstract 219: Impact of Combination Therapy on Cardiovascular Outcomes in Patients with Symptomatic Subclavian Artery Stenosis
Authors: Fan Ye, Narendranath Epperla, Hong Liang, Po-Huang Chyou, Richard Dart, Joseph Mazza, Amr Idris, Adeeb Sakkalaek, Steven Yale
Journal: Circulation Research (2017)

Background: Subclavian artery stenosis (SAS) is narrowing of the subclavian artery most commonly caused by atherosclerosis. It serves as a marker for cerebrovascular and myocardial ischemic events. Methods: A retrospective cohort study was conducted to determine the association of treatment via combination therapy (antiplatelet drug plus either by-pass surgery or percutaneous transluminal angioplasty (PTA) with or without stent implantation) versus antiplatelet drug therapy alone on cardiovascular events and all-cause mortality in Marshfield Clinic patients diagnosed with symptomatic SAS from January 1, 1995 to December 31, 2009. Results: Of the total 2153 cases, 100 patients were identified as eligible to be included in the study. Of these 100 patients that meet inclusion criteria, 30 underwent combination therapy while 70 were managed only with pharmacological drug treatment. Adverse cardiovascular events occurred in 5/30 (17%) of combination therapy patients compared to 28/70 (40%) of antiplatelet drug therapy only patients (p = 0.0355). Accordingly, all-cause mortality was higher (47%) in the antiplatelet drug therapy only group than the combination therapy group (13%) [hazard ratio = 3.45, p = 0.0218]. Conclusions: Preliminary findings in this pilot data set suggest that combination therapy (medications plus either surgical or interventional repair) of subclavian artery stenosis is associated with less cardiovascular adverse events and higher survival rates, benefits that extend beyond the target vessel. Prospective randomized studies with larger number of patients are needed to validate these findings.
Abstract 13752: Percutaneous Mitral Commissurotomy versus Mitral Valve Replacement for Extremely Severe Mitral Stenosis
Authors: Duk-Hyun Kang, Jung Ae Hong, Ran Heo, Sahmin Lee, Jong-Min Song, Kee-Joon Choi, Jae-Kwan Song, Jae-Won Lee, Joo-Hee Zo
Journal: Circulation (2017)

Introduction: Even after percutaneous mitral commissurotomy (PMC) is successfully performed, post-PMC mitral valve area (MVA) is often ≤ 1.5 cm2 in patients with very small MVA. Because smaller pos...
Consanguinity and Double Recessive Gene Pathology
Authors: Alexandros Onoufriadis, Arti Nanda, Adam Sheriff, Kenji Tomita, Nesrin S. Gomaa, Michael A. Simpson, John A. McGrath
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Abstract 21: Associations of Nonalcoholic Fatty Liver Disease with Measures of Early Brain Health
Authors: Lisa B VanWagner, James G Terry, Lisa Chow, Amy Alman, Hakmook Kang, Katherine Ingram, Christina Shay, Cora E Lewis, Robert N Bryan, Lenore Launer, J. J Carr
Journal: Circulation (2016)

Background: Subclinical liver disease may be a risk factor for cognitive impairment. Obesity is related to metabolic processes that affect brain structures underlying cognitive decline. Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular disease (CVD) morbidity. In a population-based cross-sectional sample of black and white adults free from prevalent liver or cerebrovascular disease, we tested the hypothesis that NAFLD is associated with early measures of brain health independent of BMI or visceral adipose tissue (VAT). Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and brain magnetic resonance (MR) images were included. NAFLD was defined after exclusion of other causes of liver fat. 3T brain MR images provided estimates of normal tissue volume (NTV) and total (CBF-tot) and gray matter (CBF-GM) cerebral blood flow. NTV was adjusted for intracranial volume (ICV, brain plus cerebral spinal fluid). CBF was adjusted for total tissue volume (TTV, total brain tissue perfused). Linear regression models tested associations. Results: Mean liver attenuation (LA) was 56.9 HU (range 16.6-81.3). NAFLD prevalence was 11%. Lower LA (higher liver fat) was associated with reduced NTV, CBF-tot and CBF-GM after adjusting for ICV, demographics, and health behaviors (p&lt;0.05). LA remained associated with CBF-tot and CBF-GM after adjustment for CVD factors (p&lt;0.05). Only NTV was significant after adjustment for CVD factors and BMI (p=0.02). After adjusting for VAT, the relationship between LA and NTV was attenuated (p=0.06). Findings were similar when using a clinical cutpoint of ≤51 HU for NAFLD (Table 1). Conclusion: Increased liver fat and CT-defined NAFLD are negatively associated with early brain health, reflected in MR measures of structure and perfusion. BMI and VAT attenuate the relationship providing insight into the potential role of obesity in brain health and disease.
Abstract 20037: Optimal Two Stent Strategies Applied to Non Left Main Trunk Coronary Bifurcation Lesions Differ According to the Lesion Locations
Authors: Tomohiko Sato
Journal: Circulation (2017)

Introduction: Optimal two stent strategy for treating coronary bifurcation lesion is still controversial. T stenting and protrusion (TAP) technique had been generally thought to be favorable, but r...
Abstract 12593: Improvement in Aortic Vascular Inflammation by 18-FDG PET/CT Associates With Reduction in Aortic Wall Thickness by MRI
Authors: Mohammad T Kabbany, Amit K Dey, Parag Shukla, Abhishek Chaturvedi, Joseph B Lerman, Tsion M Aberra, Aditya A Joshi, Joanna I Silverman, Qimin Ng, Heather L Teague, Asha Dahiya, Justin A Rodante, Mark A Ahlman, Martin P Playford, Nehal N Mehta
Journal: Circulation (2016)

Introduction: The presence of aortic vascular inflammation (VI) by 18-FDG PET/CT predicts future cardiovascular (CV) events. Furthermore, aortic wall thickness by MRI has been shown to be an important marker of early subclinical atherosclerosis. Whether improvement in aortic vascular inflammation by FDG PET/CT is associated with improvement in aortic wall thickness by MRI is not known. Hypothesis: We hypothesized that an improvement in VI by FDG PET/CT will associate with an improvement in aortic wall thickness by MRI in a well characterized cohort of Psoriasis (PSO) patients. Methods: Consecutively recruited PSO patients (N=64) underwent whole-body PET/CT and MRI exams at baseline and 1-year follow-up. VI was assessed as target-to-background ratio (TBR) [Excellence Brilliant Workstation]. To measure aortic wall thickness, wall boundaries of the thoracic descending aorta were traced on each MRI slice [Qplaque, Medis]. The longitudinal change in wall thickness of the thoracic descending aorta was analyzed using unadjusted and adjusted multivariable regression (STATA 12). Results: The cohort was middle-aged (mean±SEM 50.67±1.80) and had a low cardiovascular risk by Framingham risk score [median-3, IQR- (1-7)]. Overall the cohort had an average TBR of 1.74±0.02 consistent with moderate vascular inflammation. At follow-up, the total cohort had a mean improvement in TBR of 7.47% (p&lt;0.001) with use of topical therapy (64%), biological therapy (59%) and UVB (13%). Improvement in TBR of the aorta was associated with reduction in mean wall thickness of the descending thoracic aorta beyond adjustment for traditional risk factors, statin use, &amp; systemic/biologic PSO therapy (β=0.30, p = 0.03). Conclusions: Improvement in aortic VI by FDG PET/CT was associated with reduction in aortic wall thickness by MRI at one year, suggesting a reduction in VI may improve early atherosclerosis. Our findings suggest that an improvement in vascular inflammation may mitigate structural abnormalities of the aorta. Randomized controlled studies are needed to confirm these findings.
Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma
Authors: Xi Cao, Ying Hu, Shi Luo, Yuejing Wang, Tao Gong, Xun Sun, Yao Fu, Zhirong Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma via naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membrane-coated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery in vivo. Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models, celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.