tbuckley/cabot-search huggingface dataset:
Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart
Authors: Elisa Avolio, Rajesh Katare, Anita C. Thomas, Andrea Caporali, Daryl Schwenke, Michele Carrabba, Marco Meloni, Massimo Caputo, Paolo Madeddu
Journal: Journal of Clinical Investigation (2022)

Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901. Differentiated PCs became more proangiogenic, more responsive to vasoactive agents, and insensitive to chemoattractants. RNA sequencing revealed transcripts marking the PD0325901-induced transition into proangiogenic, stationary VSMC-like cells, including the unique expression of 2 angiogenesis-related markers, aquaporin 1 (AQP1) and cellular retinoic acid-binding protein 2 (CRABP2), which were further verified at the protein level. This enabled us to trace PCs during in vivo studies. In mice, implantation of Matrigel plugs containing human PCs plus PD0325901 promoted the formation of αSMA+ neovessels compared with PC only. Two-week oral administration of PD0325901 to mice increased the heart arteriolar density, total vascular area, arteriole coverage by PDGFRβ+AQP1+CRABP2+ PCs, and myocardial perfusion. Short-duration PD0325901 treatment of mice after myocardial infarction enhanced the peri-infarct vascularization, reduced the scar, and improved systolic function. In conclusion, myocardial PCs have intrinsic plasticity that can be pharmacologically modulated to promote reparative vascularization of the ischemic heart.
Utility of external and internal magnets to facilitate bile duct cannulation by changing the position of the papilla
Authors: Yi Mou, Long He, Bing Hu
Journal: Endoscopy (2022)

A 75-year-old man attended the emergency department complaining of upper abdominal colic accompanied by nausea and cold sweating for 24 hours. Physical examination found that there was mild tenderness and tension in the upper region of his abdomen. Several of his liver function test and blood chemistry values were abnormal: neutrophil count 7710/µL (reference 2000–7000/µL), total bilirubin 2.1 mg/dL, direct bilirubin 1.3 mg/dL, pancreatic lipase 2085 IU/L. In addition, acute inflammatory markers, including procalcitonin (0.63 ng/mL), IL-6 (287 pg/mL), and C-reactive protein (59.1 mg/mL), were all elevated. A nonenhanced abdominal computed tomography scan indicated the presence of an 8-mm stone in the distal common bile duct ([Fig. 1]).
Abstract P2-08-22: Correlation of ER (ESR1), PR (PGR), and HER2 (ERBB2) at protein and mRNA levels in operable breast cancer
Authors: Lei Lei, Xiaojia Wang, Skye Hung-Chun Cheng
Journal: Cancer Research (2022)

Abstract Background:. We aimed to analyze the concordance between ER (ESR1), PR (PGR), and HER2 (ERBB2) levels and breast cancer subtyping results obtained by using the immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) methods and to assess recurrence-free survival (RFS) between subtypes as determined by the two methods. Patients and Methods:. We included a total of 441 operable breast cancer patients, consisting of the training (n = 116), testing (n = 56) and validation (n = 269) cohorts in this study. Protein levels of estrogen receptor (ER) and progesterone receptor (PR) were obtained by using the IHC and that of human epidermal growth factor receptor 2 (HER2) by the IHC/FISH methods. Expression (mRNA) levels of the corresponding genes, ESR1, PGR, and ERBB2, respectively, were determined by the RT-PCR method. We then compared the status of ER (ESR1), PR (PGR), and HER2 (ERBB2) in the training, testing and validation cohorts. We categorized all validation cases into luminal (ER/PR-positive and HER2-negative), HER2 (HER2-positive regardless of ER/PR status), and triple negative (TN: ER-, PR-, and HER2-negative) subtypes accordingly. The concordance of the two methods and RFS estimated by the Kaplan-Meier methods of the three different subtypes were revealed to evaluate the clinical performance. Results:. The concordance rates between the two methods in the validation cohort were 95.1% (Kappa = 0.74) for ER (ESR1), 91.1% (Kappa = 0.67) for PR (PGR), and 93.6% (Kappa = 0.59) for HER2 (ERBB2). Kappa statistic was 0.66 for the resulting luminal, HER2 and TN subtypes. The 5-year RFS was 83.3% for luminal vs. 73.9% for HER2 vs. 48.4% for TN subtypes as determined by the IHC (p = 0.019), and 84.3% vs. 66.3% vs. 54.4% by the RT-PCR method (p = 0.016). Conclusions:. Whereas discordance existed for some cases between the IHC and RT-PCR methods for determination of the ER (ESR1), PR (PGR), and HER2 (ERBB2) status and the resulting subtypes; both the methods showed values in RFS prognosis of the population studied. It is arguable that supplementing the conventional IHC with the molecular method for subtyping of breast cancer may have beneficial clinical implications. Citation Format: Lei Lei, Xiaojia Wang, Skye Hung-Chun Cheng. Correlation of ER (ESR1), PR (PGR), and HER2 (ERBB2) at protein and mRNA levels in operable breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-22.
53P Assessing the reporting quality of early phase dose-finding trials
Authors: C. Yap, O. Solovyeva, Z. Yin, J. Martin, T. Manickavasagar, C. Weir, S. Lee, M. Dimairo, R. Liu, A. Kightley, J.S. de Bono
Journal: Annals of Oncology (2022)
PREVALENCE OF LEFT ATRIAL SCAR IN PATIENTS WITH COEXISTENT ATRIAL FIBRILLATION AND OBSTRUCTIVE SLEEP APNEA
Authors: Sanghamitra Mohanty, Chintan Trivedi, Domenico Giovanni Della Rocca, SaiShishir Shetty, Angel Mayedo, Bryan MacDonald, John Burkhardt, Rodney P. Horton, Gerald Gallinghouse, Luigi Di Biase, Andrea Natale
Journal: Journal of the American College of Cardiology (2022)
FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation
Authors: Sandra J. Casak, Shan Pradhan, Lola A. Fashoyin-Aje, Yi Ren, Yuan-Li Shen, Yuan Xu, Edwin Chiu Yuen Chow, Ye Xiong, Jeanne Fourie Zirklelbach, Jiang Liu, Rosane Charlab, William F. Pierce, Nataliya Fesenko, Julia A. Beaver, Richard Pazdur, Paul G. Kluetz, Steven J. Lemery
Journal: Clinical Cancer Research (2022)

Abstract On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial that randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently assessed progression-free survival (PFS) was the primary endpoint. With a median follow-up of 6.9 months, the HR for PFS was 0.37 [95% confidence interval (CI), 0.25–0.54; P &amp;lt; 0.0001). Overall survival (OS) was the key secondary endpoint. At the final analysis of OS, with 70.5% of patients in the placebo arm receiving ivosidenib post disease progression, a non–statistically significant improvement in the ivosidenib arm with an HR = 0.79 (95% CI, 0.56–1.12) and median OS of 10.3 months (95% CI, 7.8–12.4) and 7.5 months (95% CI, 4.8–11.1) in the ivosidenib and placebo arms, respectively, were reported. Adverse reactions occurring in &amp;gt;20% of patients receiving ivosidenib were fatigue/asthenia, nausea, diarrhea, abdominal pain, ascites, vomiting, cough, and decreased appetite. Adverse reactions occurring in &amp;gt;20% of patients receiving placebo were fatigue/asthenia, nausea, abdominal pain, and vomiting. This is the first approval for the subset of patients with CCA harboring an IDH1 mutation.
24P Evidence for synergy between TNG908, an MTAPnull-selective PRMT5 inhibitor, and sotorasib in an MTAPnull/KRASG12C xenograft model
Authors: K. Briggs, G. Corriea, A. Tsai, M. Zhang, M.R. Tonini, E.W. Wilker, C.B. Davis, K.M. Cottrell, J.P. Maxwell, A. Huang
Journal: Annals of Oncology (2022)
Abstract P3-07-08: Germline mutational profiling in Indian TNBCs
Authors: C B Koppiker
Journal: Cancer Research (2022)

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of Indian breast cancer patients using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. Further analysis to investigate the association of tumor size, tumor grade, survival analysis with mutational profiles is in process. Similarly, we are also assessing. family history to underline the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: C B Koppiker. Germline mutational profiling in Indian TNBCs [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-08.
CARDIAC INJURY DESCRIBED BY CONTRAST-ENHANCED CARDIAC MAGNETIC RESONANCE IMAGING IN PATIENTS RECOVERED FROM COVID-19
Authors: Leonid Khokhlov, Roman Khokhlov, Svetlana Lipovka, Margarita Yarmonova, Ludmila Tribunzeva, Galina Prozorova, Mariya Dubrovina, Irina Lobas
Journal: Journal of the American College of Cardiology (2022)
On the perils of peeking into the future: comment on the article by Rosenthal et al
Authors: Melek Yalcin Mutlu, Koray Tascilar
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Per- and Polyfluoroalkyl Substances and Risk of Myocardial Infarction and Stroke: A Nested Case–Control Study in Sweden
Authors: Tessa Schillemans, Carolina Donat-Vargas, Christian H. Lindh, Ulf de Faire, Alicja Wolk, Karin Leander, Agneta Åkesson
Journal: Environmental Health Perspectives (2022)

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been associated with elevated cholesterol levels. However, data on incident cardiovascular disease (CVD) is lacking. Objectives: We investigated the association of exposure to PFAS with risk of myocardial infarction and stroke and, subsidiary, with baseline blood lipids. Methods: This population-based nested case–control study included first incident myocardial infarction and stroke cases with matched controls from two Swedish cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-year-olds (60YO). Baseline blood sampling occurred during 2003–2009 and 1997–1999 with follow-up through 2017 and 2014 for the SMC-C and the 60YO, respectively. Eight plasma PFAS concentrations were measured using targeted liquid chromatography–triple quadrupole mass spectrometry. Five of these were quantifiable in both cohorts; individual values and their standardized sum were categorized into tertiles based on the controls. First incident myocardial infarction (n=345) and ischemic stroke (n=354) cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Controls were randomly selected from each cohort after matching for age, sex, and sample date. Baseline blood lipids were measured in plasma or serum after overnight fasting. Results: Among the 1,528 case–control subjects, the mean (standard deviation) age was 66 (7.7) y and 67% of them were women. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher cholesterol and lower triglyceride levels among controls at baseline (n=631). The corresponding results were odds ratios=0.70 [95% confidence interval (CI): 0.53, 0.93] for CVD, 0.60 (95% CI: 0.39, 0.92) for myocardial infarction, and 0.83 (95% CI: 0.46, 1.50) for stroke. Discussion: This study indicated that exposure to PFAS, although associated with increased cholesterol levels, did not associate with an increased risk of myocardial infarction, stroke, or their composite end point. The findings improve our knowledge on potential health effects of environmental contaminants in the CVD context. https://doi.org/10.1289/EHP9791
Cancer risk among World Trade Center rescue and recovery workers: A review
Authors: Paolo Boffetta, Charles B. Hall, Andrew C. Todd, David G. Goldfarb, Maria J. Schymura, Jiehui Li, James E. Cone, Rachel Zeig‐Owens
Journal: CA A Cancer Journal for Clinicians (2022)

Abstract Twenty years after the September 11th, 2001 terrorist attacks, the association between exposures present at the World Trade Center (WTC) site and the risk of several specific types of cancer has been reported among rescue and recovery workers. The authors' objective was to conduct an updated review of these data. Most studies have found elevated rates of both prostate and thyroid cancers compared with rates in the general population, and some have reported statistically significant differences for the rates of all cancers as well. Studies including a larger combined cohort of WTC‐exposed rescue and recovery workers from 3 main cohorts have since replicated findings for these cancers, with additional years of follow‐up. Among this combined cohort, although a lower‐than‐expected standardized incidence ratio for all cancers was observed, WTC exposure was also related to an increased risk of cutaneous melanoma and tonsil cancer. Importantly, another study found that WTC‐exposed rescue and recovery workers who are enrolled in the federally funded medical monitoring and treatment program experienced improved survival post‐cancer diagnosis compared with New York state patients with cancer. On the basis of these combined cohort studies, the full effect of WTC exposure on cancer risk is becoming clearer. Consequently, the authors believe that surveillance of those with WTC exposure should be continued, and in‐depth analysis of epidemiologic, molecular, and clinical aspects of specific cancers in these workers should be pursued.
DURABLE POLYMER AND BIODEGRADABLE POLYMER DRUG-ELUTING STENTS AFTER COMPLEX CORONARY INTERVENTION IN ACUTE CORONARY SYNDROME: A POST HOC ANALYSIS FROM THE HOST-REDUCE-POLYTECH-ACS TRIAL
Authors: Doyeon Hwang, Kyung Woo Park, Jeehoon Kang, Jung-kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo, Keun-Ho Park, Seung-Woon Rha, Won-Yong Shin, Hong-Seok Lim, Kyungil Park, Yun-Kyeong Cho, Soon Jun Hong, Sanghyun Kim, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2022)
Assessment of Patient-Reported Naloxone Acquisition and Carrying With an Automated Text Messaging System After Emergency Department Discharge in Philadelphia
Authors: Anish K. Agarwal, Hareena K. Sangha, Anthony Spadaro, Rachel Gonzales, Jeanmarie Perrone, M. Kit Delgado, Margaret Lowenstein
Journal: JAMA Network Open (2022)

A central tenet of harm reduction and prevention of opioid overdose deaths is the distribution and use of naloxone. Patient-centered methods that investigate naloxone acquisition and carrying can guide opioid overdose education and naloxone distribution efforts.To assess patients' self-reported naloxone acquisition and carrying after an emergency department (ED) encounter using automated text messaging.This cohort study investigated self-reported patient behaviors involving naloxone after ED discharge in a large, urban academic health system in Philadelphia, Pennsylvania. Adult patients who were prescribed or dispensed naloxone and who had a mobile phone number listed in the electronic health record provided informed consent after ED discharge, and data were collected prospectively using text messaging from October 10, 2020, to March 19, 2021. Patients who did not respond to the survey or who opted out were excluded.Automated text message-based survey after ED discharge for patients who were prescribed or dispensed naloxone.The primary outcome was patient-reported naloxone acquisition, carrying, and use. Descriptive statistics were used to summarize patient demographic characteristics.Of 205 eligible patients, 41 (20.0%) completed the survey; of those patients, the mean (SD) age was 39.5 (13.7) years, and 21 (51.2%) were women. Fifteen (36.6%) had a personal history of being given naloxone after an overdose. As indicated by the ED record, 27 participants (65.9%) had naloxone dispensed in the ED, and 36 (87.8%) self-reported acquiring naloxone during or after their ED visit. Twenty-four participants (58.5%) were not carrying naloxone in the week before their ED visit. Twenty participants (48.8%) were carrying naloxone after the ED visit, and 27 (65.9%) reported planning to continue carrying naloxone in the future. Of the 24 individuals (58.5%) not carrying naloxone before their ED encounter, 13 (54.2%) reported planning to continue carrying naloxone in the future.In this cohort study of adult patients dispensed or prescribed naloxone from the ED, most reported acquiring naloxone on or after discharge. The ED remains a key point of access to naloxone for individuals at high risk of opioid use and overdose, and text messaging could be a method to engage and motivate patient-reported behaviors in enhancing naloxone acquisition and carrying.
How to Apply Translational Models to Probe Mechanisms of Cardiotoxicity
Authors: Carissa E. Livingston, Bonnie Ky, Kenneth B. Margulies
Journal: JACC CardioOncology (2022)

• Treatment-related cardiovascular disease is a leading cause of morbidity and mortality in cancer survivors. • For investigators, it is crucial that in vitro models are well-matched to the toxicity studied. • From simple to complex, we describe how in vitro models are used to model cardiotoxicity. • Integrating these models will provide opportunities to address growing challenges in cardio-oncology.
Effects of Intensive Lifestyle Intervention on All-Cause Mortality in Older Adults With Type 2 Diabetes and Overweight/Obesity: Results From the Look AHEAD Study
Authors: Rena R. Wing, George A. Bray, Maria Cassidy-Begay, Jeanne M. Clark, Mace Coday, Caitlin Egan, Mary Evans, John P. Foreyt, Stephen Glasser, Edward W. Gregg, Helen P. Hazuda, James O. Hill, Edward S. Horton, Juan Carlos Isaac, John M. Jakicic, Robert W. Jeffery, Karen C. Johnson, Steven E. Kahn, Stephen Kritchevsky, E. Lewis, Nisa M. Maruthur, Barbara J. Maschak-Carey, David M. Nathan, Jennifer Patricio, Anne Peters, Xavier Pi-Sunyer, David Reboussin, Donna H. Ryan, Valerie Ruelas, Helmut Steinburg, Katie Toledo, Thomas A. Wadden, Lynne E. Wagenknecht, Jacqueline Wesche-Thobaben, Holly Wyatt, Susan Z. Yanovski, Ping Zhang
Journal: Diabetes Care (2022)

OBJECTIVE Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5,145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 years of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE. RESEARCH DESIGN AND METHODS Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by subgroups (age, sex, race/ethnicity, and cardiovascular disease history), and an exploratory analysis by magnitude of weight loss in ILI versus DSE as reference. Analyses used proportional hazards regression and likelihood ratio. RESULTS The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants, respectively) (hazard ratio [HR] 0.91 [95% CI 0.81, 1.02]; P = 0.11). There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR 0.79 [95% CI 0.67, 0.94]; P = 0.007) relative to DSE. CONCLUSIONS ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE.
SOCIAL DETERMINANTS OF DIGITAL CARE ADOPTION IN SUBSPECIALIZED CARDIOVASCULAR MEDICINE: IMPACT OF RACE, ETHNICITY, INCOME, AND EDUCATION
Authors: Katherine Sauer, Amy Leigh Miller, David Chang, Thomas M. Tadros, Sunil Kapur, Paul Cameron Zei, Usha B. Tedrow, David T. Martin, Patrice Hoskins, Morgan Turner, Lindsay Harris, Julie B. Shea, Kenneth James Comeiro, Omar Kreidieh, William H. Sauer, Bruce A. Koplan
Journal: Journal of the American College of Cardiology (2022)