tbuckley/cabot-search huggingface dataset:
Is extensive lymphadenectomy necessary for regional control of stage III cutaneous melanoma?
Authors: Manabu Fujita, Myung-Shin Sim, Mark B. Faries
Journal: Journal of Clinical Oncology (2014)

9064 Background: The extent of regional lymphadenectomy in stage III melanoma is still controversial because most recommendations are not based on statistical analysis of the minimum number of excised nodes necessary to minimize regional recurrence. Methods: We used our center’s melanoma database to identify all patients diagnosed with stage III neck, axillary or inguinal regional metastasis of cutaneous melanoma between 1971 and 2010. We then excluded cases with multiple tumor-involved nodal basins, multiple primaries, <4 removed nodes, or local/ in-transit recurrence. Univariate and multivariate analyses assessed the prognostic significance of demographic and tumor-related variables, including basin site and number of excised nodes, with respect to rates of 5-year regional recurrence-free survival (RRFS) and 10-year melanoma-specific survival (MSS). Results: Of 2,748 patients, 785 with regional neck (N=152), axillary (N=387) or inguinal (N=246) metastasis were eligible for study. These patients underwent removal of 4-79 neck nodes (mean 28.8), 4-65 axillary nodes (mean 18.6), or 4-64 inguinal nodes (mean 16.4). Neck, axillary and inguinal regional recurrence rates were 11.8% (18/152), 6.5% (25/387), and 9.8% (24/246), respectively. By multivariate analysis, 5-year RRFS was significantly improved when 20 or more nodes were removed (p=0.02) in neck basins, when 10 or more nodes were removed in inguinal basins (p=0.01), or when nodes were not palpable in neck (p=0.05) or axillary basins (p=0.02). The most significant prognostic factor for 10-year MSS was regional recurrence in any of the three sites (p<0.01). Conclusions: Removal of at least 10 nodes from groin basins and at least 20 nodes from neck basins should minimize regional recurrence in patients with stage III cutaneous melanoma. Comparable recommendations for the axillary basin will likely require meta-analyses that incorporate extracapsular extension and genomic biomarkers.
Abstract 9718: Risk Factors for the Development and Progression of Thoracic Aorta Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: George Youssef, Mengye Guo, Richard Kronmal, Robyn L McClelland, David M Shavelle, Khurram Nasir, Juan Rivera, J. Jeffrey Carr, Nathan D Wong, Matthew Budoff
Journal: Circulation (2012)

Objective: To evaluate risk factors for the incidence and progression of thoracic aorta calcification (TAC) Introduction : Vascular calcification independently predicts cardiovascular disease (CVD) and computed tomography (CT) is a useful tool to evaluate and quantify TAC. Previous TAC progression reports were limited to dialysis and renal transplant patients, This is the first study to evaluate TAC progression in a large multi-ethnic cohort without clinically evident CVD at entry Methods: Non-contrast enhanced cardiac CT (EBCT or MSCT) were obtained in 5886 of the 6814 MESA participants (mean age 62 yrs; 48% male; 40% white, 27% African American (AA), 21% Hispanic, 12% Chinese. Baseline (BL) and follow up (FU) TAC scores were derived Results: 4308 (73%) subjects had no detectable BL TAC. Mean FU duration was 2.4±0.8 yrs, during which 12% developed TAC. The overall incidence rate was 4.8%/yr and was greater with age across gender and ethnic groups,TAC incidence was significantly lower in AA than whites. Regression analyses showed FU time, age, systolic BP, antihypertensives, and smoking were predictors of incident TAC. 1578 (27%) subjects had prevalent TAC at BL scan with a positive association between the averaged annual TAC change and BL age. While the overall median (25 th , 75 th %tiles) change was 32.9 (-1.4,112.2) Agatston units, 38% of study population showed an annual Agatston score progression change of 10-99 and AA showed the lowest median across all ethnic groups; 22.7 (-3,86.8). Regression analyses showed MSCT use, FU time, age, systolic BP, lipid-lowering medication, DM and current smoking were predictors of TAC progression (Tab1) Conclusion: In the MESA cohort, both TAC incidence and progression were significantly associated with traditional CV risk factors. AA had the lowest incidence and median change across ethnic groups, consistent with previous findings for coronary calcification. Further studies are needed to correlate progression with outcome data
Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis
Authors: Claire Rempenault, Bernard Combe, Thomas Barnetche, Cécile Gaujoux-Viala, Cédric Lukas, Jacques Morel, Charlotte Hua
Journal: Annals of the Rheumatic Diseases (2017)

Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has been shown to improve survival rates in other inflammatory diseases. We aimed to assess the available literature on the cardiovascular impact of HCQ in patients with RA.We systematically searched for studies evaluating the effects of HCQ on cardiovascular outcomes of known risk factors for CVD in patients with RA. Databases searched were MEDLINE (via PubMed), EMBase, Cochrane Library and the American College of Rheumatology and European League Against Rheumatism annual meetings. A meta-analysis was performed with a random-effects model, estimating mean differences (MDs), HRs and 95% CIs. Data were extracted by one investigator and independently checked by another.The literature search revealed 185 articles and abstracts of interest; further examination resulted in 16 studies fulfilling the criteria. The MDs between HCQ users and non-users in levels of total, low-density and high-density cholesterol and triglycerides were -9.8 (95% CI -14.0 to -5.6), -10.6 (95% CI -14.2 to -7.0), +4.1 (95% CI 2.2 to 6.0) and -19.2 (95% CI -27.2 to -11.1), respectively. Diabetes incidence was lower for HCQ ever users than never users (HR 0.59 (95% CI 0.49 to 0.70)). HCQ seemed to decrease insulin resistance and incidence of CVD, but data were too few for meta-analysis.Besides its limited efficacy for disease activity and progression, HCQ may benefit the metabolic profile and to a lesser extent cardiovascular events in patients with RA, which suggests its usefulness combined with other conventional synthetic disease-modifying antirheumatic drugs.
Patient Selection for Cardiac Resynchronization Therapy
Authors: S. Adam Strickberger, Jamie Conti, Emile G. Daoud, Edward Havranek, Mandeep R. Mehra, Ileana L. Piña, James Young
Journal: Circulation (2005)

Cardiac resynchronization therapy (CRT) is a relatively new therapy for patients with symptomatic heart failure resulting from systolic dysfunction. CRT is achieved by simultaneously pacing both the left and right ventricles. Biventricular pacing resynchronizes the timing of global left ventricular depolarization and improves mechanical contractility and mitral regurgitation. Published clinical trials have demonstrated that CRT results in improved clinical status and lower mortality rate when selected patients with systolic ventricular dysfunction and heart failure are treated with CRT. This advisory identifies appropriate candidates for CRT on the basis of the inclusion criteria and results from the published clinical trials.
Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives
Authors: Silke Ryan
Journal: European Respiratory Journal (2017)

I thank D. Monneret and J-P. Bastard for their interest in our manuscript [1] and I could not agree more with their comment that the role of soluble CD163 (sCD163) in obstructive sleep apnoea (OSA) requires further detailed evaluation. As outlined in our article, the measurement of sCD163 in our patient cohort followed our results from the in vitro and in vivo studies demonstrating M1 polarisation of adipose tissue macrophages in response to intermittent hypoxia and thus, was not an a priori hypothesis of our study. Nonetheless, the detected independent association of sCD163 with OSA severity is intriguing. sCD163 in sleep apnoea requires further evaluation <http://ow.ly/o3R130d82YZ>
In nonvalvular AF, DOAC-related risk for GI bleeding was lower with apixaban than dabigatran or rivaroxaban
Authors: Ronald L. Koretz
Journal: Annals of Internal Medicine (2017)

Source Citation Abraham NS, Noseworthy PA, Yao X, Sangaralingham LR, Shah ND. Gastrointestinal safety of direct oral anticoagulants: a large population-based study. Gastroenterology. 2017;152:1014-22.e1 28043907
Abstract 13080: Transition Readiness in Adolescents With Heart Disease as Perceived by Their Parents: Do Parents and Teens Agree?
Authors: Karen Uzark, Sunkyung Yu, Ray Lowery, Katherine Afton, Angela Yetman, Jonathan W Cramer, Nancy Rudd, Scott Cohen, Russell Gongwer, Michelle Gurvitz
Journal: Circulation (2016)

Introduction: Transition is defined as “the process by which adolescents and young adults with chronic childhood illnesses are prepared to take charge of their lives and their health in adulthood”. Knowledge deficits and lack of transition readiness (TR) in 13-25 year olds with congenital or acquired heart disease have been previously reported. The aim of this multicenter study was to examine agreement between parental perceptions of their adolescent’s TR (knowledge, self-efficacy, self-management behaviors) and adolescent self-reported TR. Methods: Adolescents (n=175), age 13-18 yrs, and their parents completed the TR Assessment utilizing an e-tablet, web-based format at a routine clinic visit. Parent responses to the survey were compared to the teens’ self-reported responses and items of greatest disagreement identified. Results: Median patient age was 15.7 yrs. Parents perceived knowledge deficit scores (% of items with no reported knowledge) were significantly higher than self-reported by teens, 29.2% vs 25.9% p=.01. On a 100-point scale (higher = better), the mean score for self-efficacy was significantly lower as perceived by parents than by teens, 58.6 ± 21.1 vs 68.2 ± 18.3 (p&lt;.0001), but parent and teen reports of self-management were not significantly different, 39.5 ± 15.2 vs 41.0 ± 15.8 (p=.27). For specific knowledge deficits, overall agreement ranged from poor to fair (kappa 0.07-0.41), highest for name of heart condition/surgery (0.41), poor for exercise/sports allowed (0.10) and follow-up needs (0.10). In patients on medications (n=94), agreement was moderate for medication purpose (0.42) and refill (0.46), but poor for name (0.17). For self-efficacy and self-management, agreement also ranged from poor to fair (kappa =0.16-0.29); parents more often perceived that their teen understood what the doctor said, but overestimated how difficult it was for the teen to talk to the doctor/nurse. Teens tended to request information more often than their parents (79% vs 65%, p=.06) and information requested varied (pregnancy/contraception, communication, insurance). Conclusion: Parents and teens differ in their perceptions regarding TR. Routine TR assessment is important to identify transition needs for both patients and their parents.
Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging
Authors: Petra Füger, Jasmin K Hefendehl, Karthik Veeraraghavalu, Ann-Christin Wendeln, Christine Schlosser, Ulrike Obermüller, Bettina M Wegenast-Braun, Jonas J Neher, Peter Martus, Shinichi Kohsaka, Martin Thunemann, Robert Feil, Sangram S Sisodia, Angelos Skodras, Mathias Jucker
Journal: Nature Neuroscience (2017)
C/EBPβ is required for survival of Ly6C− monocytes
Authors: Akihiro Tamura, Hideyo Hirai, Asumi Yokota, Naoka Kamio, Atsushi Sato, Tsukimi Shoji, Takahiro Kashiwagi, Yusuke Torikoshi, Yasuo Miura, Daniel G. Tenen, Taira Maekawa
Journal: Blood (2017)
Impact of antibiotic exposure on the risk of colorectal cancer.
Authors: Shimon Ben Boursi, Kevin Haynes, Ronac Mamtani, Yu-Xiao Yang
Journal: Journal of Clinical Oncology (2014)

1599 Background: Previous reports revealed colonic dysbiosis in tumor tissue from cases with colorectal cancer (CRC) showing lower levels of microbial diversity and an enrichment of certain bacterial strains. It was suggested that the composition of the microbiota might serve, among other genetic and environmental factors, as a significant promoter of the multistep process of CRC formation. Antibiotic therapy reduces the overall bacterial diversity, with substantial consequences for the resultant functional stability of the colonic microbiota. Aim: To evaluate the association between the type and cumulative dose of antibiotic exposure and CRC risk. Methods: We conducted a nested case-control study using The Health Improvement Network (THIN), a large population-based medical records database from the United Kingdom (UK) that contains information on 11.7 million patients with follow up of up to 18 years. Study cases were defined as those with any medical code of CRC. Subjects with known familial colorectal cancer syndromes or IBD were excluded from the study. For every case, 4 eligible controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was defined as any antibiotic therapy at least 6 month before index date. The OR and 95%CI were estimated using conditional logistic regression analysis adjusted for BMI, alcoholism, smoking history, Diabetes mellitus and chronic NSAIDs use. Results: 22,023 CRC patients and 85,981 controls were identified with a mean follow up time of 6 years (SD 3.53). The adjusted OR for CRC among user of penicillins, quinolones and metronidazole was 1.08 (95%CI 1.04-1.12), 1.08 (95%CI 1.03-1.14) and 1.11 (95%CI 1.05-1.18) respectively with p<0.0001 for all. The modest risk increase remained statistically significant only for remote exposure to penicillins (OR 1.05, 95%CI 1.001-1.09, for exposure 10 years before index date). There was no statistically significant effect with other antibiotic classes, anti-viral or anti-fungal therapy. Conclusions: Past exposure to Penicillins is related to a modest elevation in CRC risk, possibly through effects on the colonic microbiota.
The Problem of Gastric Cancer&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: William A. Cooper
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article The Problem of Gastric Cancer Get access William A. Cooper William A. Cooper research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 1, August 1941, Pages 85–94, https://doi.org/10.1093/jnci/2.1.85 Published: 01 August 1941
Clinical impact of microsatellite instability in patients with stage II and III gastric cancer: Results from the CLASSIC trial.
Authors: Yoon Young Choi, Hyunki Kim, Han-Kwang Yang, Woo Ho Kim, Young Woo Kim, Myeong-Cherl Kook, Young-Kyu Park, Hyung-Ho Kim, Hye-Seung Lee, Kyung Hee Lee, Mi Jin Gu, Seung Ho Choi, Soon Won Hong, Jong Won Kim, Sung Hoon Noh, Jae-Ho Cheong
Journal: Journal of Clinical Oncology (2017)

4022 Background: The clinical implications of microsatellite instability (MSI) in gastric cancer are unclear. We investigated the usefulness of MSI status as a predictor of prognosis and responsiveness to adjuvant chemotherapy in patients with stage II and III gastric cancer. Methods: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five mononucleotide markers were used to assess tumor MSI status. Results: Of 592 specimens, 36 (6.1%) were MSI-high (MSI-H), whereas others were MSI-low or microsatellite-stable (MSS). Among 286 patients not treated with adjuvant therapy, those with MSI-H tumors had a better 5-year disease-free survival rate than did those with MSI-low/MSS tumors (hazard ratio adjusted by age, sex, tumor grade, disease stage, tumor location: 0.244 [95% confidence interval, 0.069–0.867]; p = 0.0292). Among 306 patients who received adjuvant chemotherapy, MSI-H status did not correlate with better disease-free survival (adjusted hazard ratio: 0.561 [95% confidence interval, 0.190–1.654]; p = 0.2946). Benefits from adjuvant chemotherapy differed by MSI status; although adjuvant chemotherapy improved disease-free survival among patients with MSI-low/MSS (adjusted hazard ratio: 0.634 [95% confidence interval, 0.485–0.828]; p = 0.0008), no benefit was observed in the MSI-H group (adjusted hazard ratio: 1.877 [95% confidence interval, 0.284–12.390]; p = 0.5130). Conclusions: Among patients with stage II and III gastric cancer, a MSI-H status correlated with a favorable prognosis, and adjuvant chemotherapy benefited those with MSI-L/MSS tumors but not those with MSI-H tumors.
Abstract 247: Expression and Activity of K <sub>ATP</sub> Channel in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells of Nondiabetic and Type II Diabetic Patients
Authors: Scott Canfield, Zeljko J Bosnjak, Anna Stadnicka
Journal: Circulation Research (2012)

Pharmacological preconditioning with volatile anesthetics (APC) protects the myocardium against ischemia/reperfusion injury via multiple pathways that include the cardiac sarcolemmal (sarc) KATP channel. However, APC is altered or absent in metabolic diseases such as diabetes. To investigate the underlying mechanisms we evaluated the expression and activity of cardiac sarcKATP channel in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells of non-diabetic (N-iPSCs) and type II diabetic (DM-iPSCs) patients. Differentiation of human iPSCs into CMs was confirmed by positive immunostaining for cardiac-specific markers and expression of green fluorescent protein under transcriptional control of cardiac promoter myosin light chain-2v that was delivered by lentiviral vector. Immunocytochemical analysis of cardiac sarcKATP channel subunits was carried out with Anti-Kir6.2 and Anti-SUR2A antibodies. Images were captured using a laser-scanning confocal microscope. Single KATP channel activity was monitored from excised inside-out patches at membrane potentials +80 mV to -80 mV, in symmetrical 140 mM K+. The channel was closed by 1 µM glibenclamide and 2 mM ATP. Immunocytochemical analysis showed the presence and colocalization of Kir6.2 and SUR2A proteins in CMs derived from both N-iPSCs and DM-iPSCs. Interestingly, sarcolemmal expression of these subunits appeared lower in DM-iPSCs. Electrophysiological recordings demonstrated that at 5 µM ATP internal single sarcKATP channels were open more frequently in N-iPSCs (7 of 16 cultures) than in DM-iPSCs (3 of 16 cultures). When measured at +40 mV, the single channel current amplitude (2.2 pA) and conductance (55 pS) were typical for the cardiac sarcKATP channel in N-iPSCs. By contrast, the DM-iPSC channels flickered between the open and closed state, resulting in higher noise level and decreased current amplitude (1.6 pA). This is the first report of sarcKATP channel expression and activity in CMs differentiated from human N-iPSCs and DM-iPSCs. The study suggests that compromised APC in human diabetic heart may in part result from altered expression of sarcKATP channel subunits and altered channel kinetics.
Abstract 442: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis via Mir122 Induction
Authors: Jingyuan Li, Negar Motayagheni, Neusha Barakati, Mansoureh Eghbali
Journal: Circulation Research (2016)

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.
植物ウイルスナノ粒子ベースHER2ワクチン:微粒子担体の微分輸送,局在化および細胞間相互作用に影響された免疫応答【Powered by NICT】
Authors: Shukla Sourabh, T Myers Jay, E Woods Sarah, Gong Xingjian, E Czapar Anna, Commandeur Ulrich, Y Huang Alex, D Levine Alan, F Steinmetz Nicole
Journal: Biomaterials (2017)