tbuckley/cabot-search huggingface dataset:
Slow-cycling (dormant) cancer cells in therapy resistance, cancer relapse and metastasis
Authors: Sukanya Basu, Yang Dong, Rahul Kumar, Collene Jeter, Dean G. Tang
Journal: Seminars in Cancer Biology (2021)

It is increasingly appreciated that cancer cell heterogeneity and plasticity constitute major barriers to effective clinical treatments and long-term therapeutic efficacy. Research in the past two decades suggest that virtually all treatment-naive human cancers harbor subsets of cancer cells that possess many of the cardinal features of normal stem cells. Such stem-like cancer cells, operationally defined as cancer stem cells (CSCs), are frequently quiescent and dynamically change and evolve during tumor progression and therapeutic interventions. Intrinsic tumor cell heterogeneity is reflected in a different aspect in that tumors also harbor a population of slow-cycling cells (SCCs) that are not in the proliferative cell cycle and thus are intrinsically refractory to anti-mitotic drugs. In this Perspective, we focus our discussions on SCCs in cancer and on various methodologies that can be employed to enrich and purify SCCs, compare the similarities and differences between SCCs, CSCs and cancer cells undergoing EMT, and present evidence for the involvement of SCCs in surviving anti-neoplastic treatments, mediating tumor relapse, maintaining tumor dormancy and mediating metastatic dissemination. Our discussions make it clear that an in-depth understanding of the biological properties of SCCs in cancer will be instrumental to developing new therapeutic strategies to prevent tumor relapse and distant metastasis.
Prevalence of High-Risk Nonvaccine Human Papillomavirus Types in Advanced Squamous Cell Carcinoma Among Individuals of African vs Non-African Ancestry
Authors: Erik A. Williams, Justin Newberg, Kevin Jon Williams, Meagan Montesion, Brian M. Alexander, Douglas I. Lin, Julia A. Elvin
Journal: JAMA Network Open (2021)

This cross-sectional study assesses the prevalence of high-risk human papillomavirus (hrHPV) types not covered by the 9-valent HPV vaccine among patients of African vs non-African ancestry with advanced squamous cell carcinoma.
Understanding the increased risk of infections in diabetes: innate and adaptive immune responses in type 1 diabetes
Authors: Anna W.M. Janssen, Rinke Stienstra, Martin Jaeger, Alain J. van Gool, Leo A.B. Joosten, Mihai G. Netea, Niels P. Riksen, Cees J. Tack
Journal: Metabolism (2021)
Endoscopic retrograde appendicitis therapy: a novel approach for peri-appendiceal abscess
Authors: Guangxing Cui, Wen Lv, Jiahui Wang, Xiaofeng Zhang
Journal: Endoscopy (2021)

A 66-year-old man presented with recurrent abdominal pain for half a month. He wrongly thought it was acute gastritis, without initially paying any attention to it; however, as the pain became aggravating, he came to our hospital. An abdominal computed tomography (CT) scan revealed a peri-appendiceal abscess ([Fig. 1]). Endoscopic retrograde appendicitis therapy (ERAT) was then performed.
The Glitter of the Simple
Authors: Andrea Fry
Journal: Annals of Internal Medicine (2021)

Ad LibitumMay 2021The Glitter of the SimpleAndrea Fry, NP, BA, BS, MSAndrea Fry, NP, BA, BS, MSMemorial Sloan Kettering Cancer CenterNew York, New YorkSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-4233 Audio Reading - “The Glitter of the Simple” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The Glitter of the Simple” by Andrea Fry, NP, BA, BS, MS Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Oh, I would divide the world into binaries,cast each earthly element to a pole—goodor bad—according to its flag:The stonefish with its ugly mug.Black-whiskered tarantula.Simply by appearancesI would judge.And likewise, disregardingconflicting evidence,I would crown the beautiful:The uncanny blues and goldof the poison dart frog.The sacred passion flowerringed by purple filaments,though its cool smiles nest in leavesof cyanide.Then I would round the numbers up or down,toss out their remainder,throw out the imperfect squares,too cumbersome to carry!I would ignore details:Castor oil is good[but the beans will kill youif you chew them].He stole the turnips[for he had nothing].The ... Author, Article, and Disclosure InformationAffiliations: Memorial Sloan Kettering Cancer CenterNew York, New YorkCurrent Author Address: Andrea Fry, NP, BA, BS, MS; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “The Glitter of the Simple” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The Glitter of the Simple” by Andrea Fry, NP, BA, BS, MS Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics May 2021Volume 174, Issue 5Page: 716 ePublished: 18 May 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy
Authors: Naveen Sharma, Oluwatomisin T. Atolagbe, Zhongqi Ge, James P. Allison
Journal: The Journal of Experimental Medicine (2021)

Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Human and murine LILRB4 have two extracellular domains but differ in the number of intracellular ITIMs (three versus two). We observed a high correlation in LILRB4 expression with other immune inhibitory receptors. After tumor challenge, LILRB4−/− mice and mice treated with anti-LILRB4 antibody showed reduced tumor burden and increased survival. LILRB4−/− genotype or LILRB4 blockade increased tumor immune infiltrates and the effector (Teff) to regulatory (Treg) T cell ratio and modulated phenotypes of TAMs toward less suppressive, CD4+ T cells to Th1 effector, and CD8+ T cells to less exhausted. These findings reveal that LILRB4 strongly suppresses tumor immunity in TME and that alleviating that suppression provides antitumor efficacy.
Abstract 13410: Patient and Family Perspectives of Early Mobilization in Acute Cardiovascular Care
Authors: Caroline Najjar, Michael Goldfarb
Journal: Circulation (2020)

Introduction: Early mobilization (EM) is safe, feasible, and associated with good outcomes in people with acute CV disease. While studies have explored the perspectives of care providers on mobilization, little is known about patient and family member perspectives and experience with mobilization. Methods: Patient and family member surveys were developed using previously validated surveys (Family Satisfaction with Care in the ICU and the Patient Mobilization Attitudes &amp; Beliefs survey). The survey assessed attitudes toward and knowledge of mobilization, the family member’s role in providing care and the mobilization care they received. Surveys were distributed to patients and their family members in an acute CV unit of a tertiary care centre in Montreal, Canada over a 4-month period. Results: 102 participants completed the survey (78 patients and 24 family members). Most patients (N=54; 69.2%) agreed or strongly agreed that EM should be routinely performed, although nearly half of the patients (N=37, 47.4%) felt that mobilization soon after admission was potentially dangerous. Out of 64 patients who underwent EM, 60 (93.8%) felt that mobilization helped their recovery (Figure). 35 patients (54.7%) felt that family member participation helped their mobilization. Family members included 12 (50.0%) spouses/partners, 10 (41.7%) children, 1 (4.2%) siblings, and 1 parent (4.2%). Most family members felt that mobilizing their relatives too soon after admission was potentially dangerous (N=17, 70.8%). However, family members were interested in being involved with mobilization (N=22; 91.7%) and only a few felt that mobilization should not be routinely performed (N=2; 8.3%). Conclusion: Patients felt that EM helped with their recovery process. Family members were interested in being involved in mobilizing their relatives. Our findings should inform efforts to overcome patient and family-related barriers to mobilization and design an EM program for acute CV care.
Abstract 15259: Breast Cancer and Heritable Pah Due to Bmpr2 Mutation: An Unexpected Discovery
Authors: Victoria Toro, Valerie Nadeau, Pierre Helie, Junichi Omura, Yann Grobs, Sandra Martineau, Roxane Paulin, Francois Potus, Olivier BOUCHERAT, Steeve Provencher, Sebastien Bonnet
Journal: Circulation (2020)

Introduction: BMPR2 mutation is reported in 80% of familial PAH and 20% of idiopathic cases. Recently, a rat model of hereditary Pulmonary Arterial Hypertension with a BMPR2 loss-of-function mutation has been generated. Similarly to human, only around 20% of the rats spontaneously developed mild PAH. Unexpectedly, we observed that 20% (95%CI:12-28) of the 82 Bmpr2+/Δ71 rats (93% of females) versus 4% (95%CI:0-9)of the 84 age-matched wild type littermates spontaneously developed mammary masses requiring euthanasia. Interestingly, rats with tumor had elevated PA and clearly exhibit PAH signs. Hypothesis: We hypothesized that mammary tumor exacerbates the penetrance of PAH in the BMPR2 mutated female rats. Methods/Results: BMPR2 mutated and wild-type female young rats were treated with the breast cancer inducer 7, 12- diméthylbenz(a)anthracene (DMBA) or Vehicle. DMBA causes on average more tumors development in BMPR2 mutated rats versus WT rats (6,2 vs. 4) P=0,0275. Compare to both vehicle-treated and DMBA rats (without tumor) BMPR2 mutated rats with DMBA-induced tumors had a significant increase in mean PA pressure (p&lt;0,0001); total pulmonary resistance (p&lt;0,0001) and a significant decrease in cardiac output (P=0,0293). Histologically, these changes were associated with an increase of pulmonary artery remodelling assessed by immunofluorescence. Mechanistically, development of PAH in the BMPR2 mutated rats with tumor was associated with a significant upregulation of BRD4 (western blot) (p=0,0149); IL-1β (P=0,0052), BRD3 (P=0,0791) and BIRC5 (P=0,0166) mRNA expression levels. Co-culture experiments with breast cancer cells and PASMC from both WT and BMPR2 mutated rats are ongoing to identify whether cancer cells are realising factors responsible for BRD4 activation and thus PASMC proliferation and resistance to apoptosis. Conclusions: We demonstrated for the first time that breast cancer exacerbates PAH development in BMPR2 mutated rats. Increased BRDs driven pro-inflammatory signalling is associated with PAH development in BMPR2 mutated rats. We are currently exploring whether BMPR2 mutated patients are more prone to breast cancer development or not and whether PAH development occurs more frequently in breast cancer patients.
104P Clinical characteristics of patients (pts) with complete response (CR) to abemaciclib-based endocrine therapy (ET) in MONARCH 2 (M2) and MONARCH 3 (M3)
Authors: J. Huober, E-M. Grischke, S. Guiu, N. Quenel Tueux, N. Chouaki, C. Stoffregen, A. Korfel, F. Lerebours
Journal: Annals of Oncology (2021)
Abstract P125: The Effects Of Vitamin D Supplementation On Orthostatic Hypotension: Results From STURDY
Authors: Stephen P Juraschek, Edgar R Miller, Lawrence J Appel
Journal: Circulation (2021)

Background: In some trials, vitamin D supplementation is associated with a lower risk of falls. Observational evidence has implicated orthostatic hypotension (OH) as a potential mechanism for this association. Objective: To determine if higher doses of vitamin D supplementation reduce the risk of OH. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 (200, 1000, 2000, and 4000 IU/day) on fall risk in adults age 70 years and older with low serum vitamin D levels (10-29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure. OH was defined as a drop in systolic or diastolic blood pressure of at least 20 or 10 mmHg, respectively, after 1 minute of standing. Participants were also asked about symptoms related to OH during the OH assessment and in the past month. Odds ratios were determined using generalized estimating equations to account for repeat measurements. Results: Among 387 participants with 924 OH assessments, mean age was 77 ± 5 years, 42% were women, and 17% black. Mean baseline systolic/diastolic blood pressure was 129 ± 19/67 ± 11 mm Hg; 2.3% had OH. Compared to 200 IU/day, 1000, 2000, and 4000 IU/day did not lower risk of OH during the trial ( Table ). Furthermore, vitamin D dose was not associated with orthostatic symptoms as participants stood up or after standing. In a subset with more detailed symptom assessments, there was no association between vitamin D dose and orthostatic symptoms or functional limitations in the preceding 30 days. Conclusions: Daily, higher dose vitamin D supplementation was not associated with OH or its symptoms. These findings do not support vitamin D as an intervention to prevent OH.
Abstract 15075: Exercise Stress Testing and Stress Cardiac Magnetic Resonance Imaging for Detection of Inducible Ischemia in a Large Cohort of Children With Anomalous Aortic Origin of a Coronary Artery
Authors: Amna Qasim, Tam Doan, Tam Dan Pham, Dana Reaves-O’Neal, Silvana M Molossi
Journal: Circulation (2020)

Introduction: The current AATS and AHA/ACC guidelines recommend maximal exercise stress test (mEST) to identify ischemia and direct decision-making in patients (pts) with anomalous aortic origin of a coronary artery (AAOCA). Stress cardiac magnetic resonance imaging (sCMR) has reliably identified myocardial perfusion abnormalities. Hypothesis: We hypothesize that EST and sCMR do not agree in the detection of inducible ischemia in AAOCA. Methods: AAOCA pts &lt;21 years old were prospectively enrolled and evaluated following a standardized approach from 12/2012-12/2019. mEST was performed in pts ≥6 years old, except those who presented with cardiac arrest or physical limitations. Demographic data, coronary anomaly type, EST (symptoms, ST changes, arrhythmias, metabolic parameters) and sCMR data were collected. A mEST was defined as max HR ≥85%ile with a subgroup defined as respiratory exchange ratio (RER) &gt;1.05. Abnormal mEST included: significant ST changes (≥1 mm horizontal or downsloping ST-depression, ≥2 mm upsloping ST depression, ST elevation), high-grade arrhythmia, abnormal peak VO2 (&lt;85% predicted). Continuous and categorical variables were compared using Wilcoxon-Rank sum and Fisher’s exact/χ2 respectively. McNemar’s test was used to determine the agreement between EST and sCMR. Results: Of 147 pts with AAOCA and both EST and sCMR, 140 achieved max HR ≥85%ile on EST. Table 1 compares demographics and EST parameters in pts with inducible ischemia on sCMR (+sCMR) vs without (-sCMR). Significant ST changes were seen in 2/26 (7.7%) pts with +sCMR compared to 8/114 (7%) pts with -sCMR. An abnormal mEST did not agree with sCMR in identifying inducible ischemia (McNemar p &lt; 0.001) in all AAOCA patients who achieved max HR, nor in the sub-group with RER &gt;1.05 (n = 88). Conclusions: mEST does not agree with sCMR in identifying inducible ischemia in patients with AAOCA. Our data suggest that mEST should not be used alone for the detection of inducible ischemia.
Abstract 12909: Usefulness of Sarcopenia Index for Predicting Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Francisco J Romeo, Ignacio M Seropian, Juan M Valle Raleigh, juan guido chiabrando, Cristian M Garmendia, Maximiliano Smietniansky, Mariela Cal, Carla R Agatiello, Daniel H Berrocal
Journal: Circulation (2020)

Introduction: Sarcopenia, a marker of biological senescence, is a robust prognostic indicator of outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI, serum creatinine value/cystatin C value x 100) and investigate its association with outcomes after TAVR. Methods: The study cohort comprised 100 patients ≥ 65 years of age (mean 83.9±5.7; 36% men) who underwent transfemoral TAVR at Hospital Italiano de Buenos Aires, Argentina from 2016 to 2018. The mean Society of Thoracic Surgeons (STS) score was 3.3±1.7. Sarcopenia was defined according to ROC curve for SI (AUC 0.731, CI 95% 0.599-0.863, p-value=0.001) for predicting the primary endpoint. Both all-cause mortality and/or readmissions for congestive heart failure (CHF) were defined as the primary endpoint within the first year after TAVR. Results: According to SI cutoff, half of the study population (SI ≤66) was sarcopenic before TAVR. The 30-day mortality increased significantly in the lowest SI tertile (sarcopenia+) group (12, 3, and 0%, p=.05, respectively). SI strongly correlated with timed-up and go and gait speed but not with body mass index and baseline C-reactive protein levels. Overall survival was worse (Log-rank test= p=0.02) and CHF readmissions were more prevalent in the lowest SI tertile (Log-rank test=p=0.01). On Cox regression analysis, a low SI (SI ≤66) had a significantly higher risk of the primary endpoint (adjusted hazard ratio: 4.01, 95% CI: 1.31-12.27, p=.015). Conclusions: SI, a novel-non-invasive method for assessing SMM was able to predict mid-term mortality and CHF readmissions. We suggest careful consideration of sarcopenia prior to TAVR in order to decide the best treatment approaches.
Abstract 16428: An On-Treatment Comparative Effectiveness Analysis of Ticagrelor vs Clopidogrel in US Real-world Setting
Authors: Tope Olufade, Nipun Atreja, Narinder Bhalla, John Venditto, Durgesh Bhandary, Naeem Khan, David Cobden
Journal: Circulation (2020)

Background: Current guidelines recommend ticagrelor over clopidogrel as part of DAPT regimen for ACS treatment. However, real-world head-to-head assessment of ticagrelor and clopidogrel has been methodologically challenging due to prescribing patterns and adherence. Thus, we conducted an on-treatment comparative analysis utilizing a large national payer data within US. Methods: A retrospective cohort study of ACS patients discharged on ticagrelor or clopidogrel between January 1, 2012 to September 30, 2019 was conducted utilizing the Optum TM Clinformatics TM data. Patients were required to have twelve months of continuous enrollment prior to the ACS event and a fill of their index prescription within 30 days of discharge. Hospitalization for MI and major bleeding were evaluated pre and post propensity score matching on demographic and clinical covariates (Table 1). Study outcomes were ascertained from day 31 until outcome of interest, switch from or discontinuation of index prescription or day 365. Results: Of 339,387 ACS patients, 14,110 ticagrelor and 57,482 clopidogrel treated patients met the study criteria. Prior to matching, MI hospitalization were significantly lower in the ticagrelor compared to the clopidogrel group (2.2 vs. 4.1 per 100 patient years; 47.3% RRR, p &lt; 0.001). Similarly, in the post-matching population (12,983 ticagrelor, 27,007 clopidogrel), the MI hospitalization rates were 2.2 vs. 3.3 per 100 patient years (33.5% RRR, p &lt;0.001). Hospitalization due to bleeding was 2.1 vs. 2.0 per 100 patient years (-2.7% RRR, p= 0.75 ) in the ticagrelor and clopidogrel patients respectively. Conclusion: In this real world on-treatment analysis, patients who were optimally adherent to ticagrelor post-ACS had significantly fewer MI hospitalization as compared to the clopidogrel cohort. Study findings highlight the importance of being adherent to guideline recommended treatment for better clinical outcomes without the added risk of bleeding.
Abstract 17332: Prognostic Impact of Right Ventricular Function and Tricuspid Regurgitation in Functional Mitral Regurgitation: A Meta-Analysis
Authors: Tam N Ngo, Vien T Truong, Hoang T Phan, Thuy T Pham, Tam T Quach, Thanh K Pham, Thu Q Nguyen, Khanh N Pham, Cassady Palmer, Tuan M Nguyen, Marwin Bannehr, Takayuki Gyoten, Christian Butter, Eugene Chung, Wojciech Mazur
Journal: Circulation (2020)

Introduction: Right ventricular dysfunction and tricuspid regurgitation grade are associated with cardiovascular mortality in the general population, primary MR, and other cardiovascular diseases. Hypothesis: The objective of this study was to investigate the prognostic importance of RVD, and TR in patients with functional mitral regurgitation (FMR) Methods: A systemic review and meta-analysis were performed using MEDLINE, Scopus, and Embase to assess the prognostic value of RVD and TR grade for mortality. RVD was defined as a TAPSE ≤ 16 mm or tissue Doppler-derived tricuspid lateral annular systolic velocity (S′TDI) &lt; 10 cm/s.Hazard ratios were extracted from multivariate models reporting on the association of RVD and TR with mortality and described as pooled estimates with 95% confidence intervals. Data were pooled across studies using the DerSimonian-Laird random-effects model. Results: A total of 9 nonrandomized studies met the inclusion criteria with eight studies having at least 12 months follow-up. Among the above studies, a total of 1325 patients (74.1% being male) were eligible for being included in our meta-analysis with an overall survival of 68.2% (n = 903). Of the enrolled patients, RVD was present in 39.1% and moderate-severe TR in 32.8%. RVD was significantly associated with mortality compared to normal RV function (HR, 1.89, 95% CI, 1.51-2.38, p &lt; 0.001, I2 =0). Additionally, patients with moderate-severe TR showed increased risk of mortality compared with those in the none-mild TR group (HR, 1.71. 95% CI, 1.36-2.15, p &lt; 0.001, I2 =0) Conclusions: This meta-analysis demonstrates the prognostic importance of RVD and TR grade in predicting all-cause mortality in patients with FMR. RV function and TR parameters may therefore be useful in the risk stratification of patients with FMR.