tbuckley/cabot-search huggingface dataset:
DEVELOPMENT AND PROGRESSION OF TRICUSPID REGURGITATION FOLLOWING PERMANENT PACEMAKER IMPLANTATION AFTER TAVR
Authors: Mohanad Hamandi, Johanna Van Zyl, Russana Thomas, Necole Kell, Anna Sannino, Karim Al-Azizi, Molly Szerlip, Srinivasa Potluri, Zuyue Wang, Katherine Harrington, Justin Schaffer, J. Michael DiMaio, Michael Mack, Paul A. Grayburn
Journal: Journal of the American College of Cardiology (2020)
VISIT-TO-VISIT VARIABILITY IN BLOOD PRESSURE AND CARDIAC STRUCTURE AND FUNCTION: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY
Authors: Chike Nwabuo, Yuichiro Yano, Henrique Moreira, Duke Appiah, Henrique Vasconcellos, Queen Aghaji, Anthony Viera, Jamal S. Rana, Ravi V. Shah, Venkatesh Murthy, Mercedes Carnethon, Norrina Allen, Pamela Schreiner, Donald M. Lloyd-Jones, Joao A.C. Lima
Journal: Journal of the American College of Cardiology (2020)
Comorbidity and outcomes in elderly women treated with breast-conserving therapy
Authors: E. E. Harris, S. L. Urtishak, W. Hwang, B. Kinosian, L. J. Solin
Journal: Journal of Clinical Oncology (2006)

599 Background: Breast cancer incidence increases with age and is a major cause of morbidity and mortality among elderly women. Co-morbidities are often considered in treatment management of elderly women. Methods: Between 1979 and 2002, 238 women age 70 or older with unilateral stage I or II invasive breast cancer underwent conventional breast conservation treatment with radiation. The age distribution was 122 women (51%) age 70–74 years, 71 women (30%) age 75–79 years, and 45 women (19%) age ≥80 years. Surgical axillary staging was performed in 73% (n= 173) of patients, of which 73% (n=126) were N0, and 27% (n=47) were N1. Co-morbidities were scored using the Charlson Comorbidity Index and Cumulative Illness Rating Scale (CIRS). Median follow-up was 6.2 years. Results: On analysis by age groups, the 10-year cancer specific outcomes were not significantly different (see Table ). However, distant metastases were the most common site of first failure in all age groups: 9% for age 70–74; 12% for age 75–79 and 11% for age &gt;/= 80. Second malignancies were the second most common cause of first failure in all age groups. Death from intercurrent disease was significantly more likely in the older age groups. In this cohort, moderate and severe co-morbidities were not significantly more common in the older age groups, and CIRS score did not correlate with overall survival. Conclusions: Breast conserving surgery and definitive breast irradiation provide excellent outcomes in appropriately selected elderly women. Older age itself is not a contraindication to breast conserving therapy. Women of any age with lower co-morbidity indices should be offered standard treatment. [Table: see text] No significant financial relationships to disclose.
The New Age of Cell-Free Biology
Authors: Vincent Noireaux, Allen P. Liu
Journal: Annual Review of Biomedical Engineering (2020)

The cell-free molecular synthesis of biochemical systems is a rapidly growing field of research. Advances in the Human Genome Project, DNA synthesis, and other technologies have allowed the in vitro construction of biochemical systems, termed cell-free biology, to emerge as an exciting domain of bioengineering. Cell-free biology ranges from the molecular to the cell-population scales, using an ever-expanding variety of experimental platforms and toolboxes. In this review, we discuss the ongoing efforts undertaken in the three major classes of cell-free biology methodologies, namely protein-based, nucleic acids-based, and cell-free transcription-translation systems, and provide our perspectives on the current challenges as well as the major goals in each of the subfields.
Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma
Authors: Ioana Agache, Yang Song, Claudio Rocha, Jessica Beltran, Margarita Posso, Corinna Steiner, Pablo Alonso‐Coello, Cezmi Akdis, Mubeccel Akdis, Giorgio Walter Canonica, Thomas Casale, Tomas Chivato, Jonathan Corren, Stefano del Giacco, Thomas Eiwegger, Davide Firinu, James E. Gern, Eckard Hamelmann, Nicola Hanania, Mika Mäkelä, Irene Hernández Martín, Parameswaran Nair, Liam O'Mahony, Nikolaos G. Papadopoulos, Alberto Papi, Hae‐Sim Park, Luis Pérez de Llano, Santiago Quirce, Joaquin Sastre, Mohamed Shamji, Jurgen Schwarze, Carlos Canelo‐Aybar, Oscar Palomares, Marek Jutel
Journal: Allergy (2020)

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV1 increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.
Performance of High-Sensitivity Cardiac Troponin Assays to Reflect Comorbidity Burden and Improve Mortality Risk Stratification in Older Adults With Diabetes
Authors: Olive Tang, Natalie Daya, Kunihiro Matsushita, Josef Coresh, A. Richey Sharrett, Ron Hoogeveen, Xiaoming Jia, B. Gwen Windham, Christie Ballantyne, Elizabeth Selvin
Journal: Diabetes Care (2020)

OBJECTIVE Incorporation of comorbidity burden to inform diabetes management in older adults remains challenging. High-sensitivity cardiac troponins are objective, quantifiable biomarkers that may improve risk monitoring in older adults. We assessed the associations of elevations in high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) with comorbidities and improvements in mortality risk stratification. RESEARCH DESIGN AND METHODS We used logistic regression to examine associations of comorbidities with elevations in either troponin (≥85th percentile) among 1,835 participants in the Atherosclerosis Risk in Communities (ARIC) Study with diabetes (ages 67–89 years, 43% male, 31% black) at visit 5 (2011–2013). We used Cox models to compare associations of high cardiac troponins with mortality across comorbidity levels. RESULTS Elevations in either troponin (≥9.4 ng/L for hs-cTnI, ≥25 ng/L for hs-cTnT) were associated with prevalent coronary heart disease, heart failure, chronic kidney disease, pulmonary disease, hypoglycemia, hypertension, dementia, and frailty. Over a median follow-up of 6.2 years (418 deaths), both high hs-cTnI and high hs-cTnT further stratified mortality risk beyond comorbidity levels; those with a high hs-cTnI or hs-cTnT and high comorbidity were at highest mortality risk. Even among those with low comorbidity, a high hs-cTnI (hazard ratio 3.0 [95% CI 1.7, 5.4]) or hs-cTnT (hazard ratio 3.3 [95% CI 1.8, 6.2]) was associated with elevated mortality. CONCLUSIONS Many comorbidities were reflected by both hs-cTnI and hs-cTnT; elevations in either of the troponins were associated with higher mortality risk beyond comorbidity burden. High-sensitivity cardiac troponins may identify older adults at high mortality risk and be useful in guiding clinical care of older adults with diabetes.
Samarium-153 effectiveness in the quality of life of bone metastatic cancer patients.
Authors: Grecory Tsoukalas, Alexandros Tzovaras, Nikolaos Tsoukalas, Sofia Stamatopoulou, George Gatsos, Pantelis Kountourakis, Nikos Mpaziotis, Kuriaki Mystakidou
Journal: Journal of Clinical Oncology (2013)

e20635 Background: Osseous metastases in patients suffering from cancer, is a multifactor symptom which affects quality of life. Methods: The Samarium group (SG) n=53 patients received a single bolus infusion of (153)Sm (37 MBq/kg), and we compared with a Control group(CG) n=37. Both groups of patients who had metastatic bone cancer requiring analgesia answered the following questionnaires: Greek Brief Pain Inventory (GBPI), Brief Multidimensional Life Satisfaction Scale (BMLSS), Hospital Anxiety Depression Scale (HADS), ECOG/WHO/Zubrod score and Hospital Satisfaction Scale (HSS),day 0 and 30±3 days after the intervention start.There was no statistically significant(SS) difference for the variables(V-) sex, age, pain’s localization and lodging. Results: Pain severity and pain interference change over time was the same for both groups P= 0.0005. For the V- HADS-anxiety, SG showed no SS improvementP= 0.397, something which was achieved for the CG,P= 0.031. The V- HADS improved SS for both groups P= 0.031 and P= 0.003 respectively which changed over time with the same way. This may show the strong relation between pain and depression. The V- ECOG also changed over time in the same way for both SG(P=0.005) and CG (P=0.014). The percentage of patients who changed scale towards improvement for their quality of life was 24,3% for the CG and 15,1% for the SG. The V-BMLSS change over time was similar for both groups. There was no SS difference for the V-HSS towards medical and nursing personnel for both groups (P=1.000). Myelotoxicity for the SG was moderate and reversible, as well as the side effects for the CG. Finally an equivalence test between the two groups, showing that both treatment regimens were equivalent for all variables: Pain severity=0.034, Pain interference=0.009, HAD-anxiety P=0.048, HAD-depression=0.033, BMLSS=0.016, ECOG=0.0005. During our study among the patients of the SG in some cases the stabilization of bone lesions was observed, and in one case partial and/or complete remission. Conclusions: Administration of (153)Sm is another equivalent option for those patients who are intolerant or resistant to medication treatment having a better cost-effectiveness result.
EICOSAPENTAENOIC ACID AMELIORATES VASCULAR INFLAMMATION: A MECHANISTIC RATIONALE FOR ITS ATHEROPROTECTIVE EFFECTS
Authors: Anthony David Pisaniello, Belinda A. Di Bartolo, Ge Liu, Peta M. King, Robert A. Gibson, Joanne T.M. Tan, Stephen J. Nicholls
Journal: Journal of the American College of Cardiology (2020)
Validation of the supplementary quality of life questionnaire for mouth/throat and hand/foot soreness.
Authors: Jennifer L Beaumont, Jose Diaz, Sadya Khan, David Cella
Journal: Journal of Clinical Oncology (2013)

9574 Background: PISCES is a randomized crossover trial evaluating patient preference of pazopanib versus sunitinib in advanced/ metastatic renal cell carcinoma. The Supplementary Quality of Life Questionnaire (SQLQ) was developed for this trial to assess hand/foot soreness and mouth/throat soreness (MTS). The objective of this project is to validate the SQLQ. Methods: SQLQ was administered at baseline and every two weeks thereafter. EQ-5D was administered at baseline, during the washout period, and end of second treatment period. Treatment arms were collapsed for validation. SQLQ assesses severity of MTS (1 item), limitations due to MTS (5 items), severity of hand soreness (1 item), severity of foot soreness (1 item), limitations due to foot soreness (5 items) and ability to work (1 item). Cronbach’s coefficient alpha was used to evaluate the internal consistency reliability of the multi-item subscales.T-tests compared scores between groups defined by performance status (0 versus 1) and number of metastatic sites (0/1 versus 2+) at baseline. Effect sizes (ES = mean difference / pooled standard deviation) were calculated. Results: Of 169 patients randomized, data was available on 168. Over 80% of on-study patients completed the SQLQ at each assessment. Cronbach’s coefficient alpha was ≥ 0.80 for both limitations subscales at all assessments except baseline (limitations due to MTS). Both scores differentiated between performance status groups at baseline with ES &gt; 0.40 (p&lt;0.05). Scores significantly differed by severity of soreness with large ES of 0.9-2.1. Moderate correlations with EQ-5D were observed for limitations scores; correlations were smaller for soreness ratings. MTS and limitations due to MTS worsened after baseline with moderate – large ES; moderate ES was observed for changes in other scores. Limitation change scores were minimal in groups with no change in soreness rating; patients with worsened soreness reported similarly worsened limitations due to soreness with moderate – large ES. Conclusions: SQLQ is a valid and responsive measure of MTS, hand/foot soreness, and limitations due to soreness. Use of the SQLQ in future clinical trials will provide further external validation.
Whole-Neuron Synaptic Mapping Reveals Spatially Precise Excitatory/Inhibitory Balance Limiting Dendritic and Somatic Spiking
Authors: Daniel Maxim Iascone, Yujie Li, Uygar Sümbül, Michael Doron, Hanbo Chen, Valentine Andreu, Finola Goudy, Heike Blockus, Larry F. Abbott, Idan Segev, Hanchuan Peng, Franck Polleux
Journal: Neuron (2020)
THE SYNERGISTIC EFFECT OF NIRS-DETECTED LIPID-RICH PLAQUE AND WALL SHEAR STRESS ON HUMAN CORONARY PLAQUE GROWTH
Authors: Jolanda Wentzel, Eline M. Hartman, Giuseppe De Nisco, Ayla Hoogendoorn, Annette Kok, Frank Gijsen, Ton van der Steen, Joost Daemen
Journal: Journal of the American College of Cardiology (2020)
CLO20-051: LYMPHA: Eliminating the Burden of Lymphedema in Cancer Patients Requiring Nodal Dissections. A Pilot Study
Authors: Maria Cassandre Medor, Sylia Mohand-Said, Andrea Ibrahim, Laura Baker, Audrey Litvak, Moein Momtazi, Carolyn Nessim
Journal: Journal of the National Comprehensive Cancer Network (2020)
PTH/PTHrP Receptor Signaling Restricts Arterial Fibrosis in Diabetic LDLR <sup>−/−</sup> Mice by Inhibiting Myocardin-Related Transcription Factor Relays
Authors: Abraham Behrmann, Dalian Zhong, Li Li, Su-Li Cheng, Megan Mead, Bindu Ramachandran, Parastoo Sabaeifard, Mohammad Goodarzi, Andrew Lemoff, Henry M. Kronenberg, Dwight A. Towler
Journal: Circulation Research (2020)

Rationale: The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR −/− mice. Objective: To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR −/− mice (PTH1R-VKO) and Cre-negative controls. Methods and Results: Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. PTH1R-VKO cohorts exhibited increased aortic collagen accumulation in vivo, and VSM cultures from PTH1R-VKO mice elaborated more collagen (2.5-fold; P =0.01) with elevated Col3a1 and Col1a1 expression. To better understand these profibrotic responses, we performed mass spectrometry on nuclear proteins extracted from Cre-negative controls and PTH1R-VKO VSM. PTH1R deficiency reduced Gata6 but upregulated the MADS (MCM1, Agamous, Deficiens, and Srf DNA-binding domain)-box transcriptional co-regulator, Mkl-1 (megakaryoblastic leukemia [translocation] 1). Co-transfection assays ( Col3a1 promoter-luciferase reporter) confirmed PTH1R-mediated inhibition and Mkl-1-mediated activation of Col3a1 transcription. Regulation mapped to a conserved hybrid CT(A/T) 6 GG MADS-box cognate in the Col3a1 promoter. Mutations of C/G in this motif markedly reduced Col3a1 transcriptional regulation by PTH1R and Mkl-1. Upregulation of Col3a1 and Col1a1 in PTH1R-VKO VSM was inhibited by small interfering RNA targeting Mkl1 and by treatment with the Mkl-1 antagonist CCG1423 or the Rock (Rho-associated coiled-coil containing protein kinase)-2 inhibitor KD025. Chromatin precipitation demonstrated that VSM PTH1R deficiency increased Mkl-1 binding to Col3a1 and Col1a1 , but not TNF , promoters. Proteomic studies of plasma extracellular vesicles and VSM from PTH1R-VKO mice identified C1r (complement component 1, r) and C1s (complement component 1, s), complement proteins involved in vascular collagen metabolism, as potential biomarkers. VSM C1r protein and C1r message were increased with PTH1R deficiency, mediated by Mkl-1-dependent transcription and inhibited by CCG1423 or KD025. Conclusions: PTH1R signaling restricts collagen production in the VSM lineage, in part, via Mkl-1 regulatory circuits that control collagen gene transcription. Strategies that maintain homeostatic VSM PTH1R signaling, as reflected in extracellular vesicle biomarkers of VSM PTH1R/Mkl-1 action, may help mitigate arteriosclerosis and vascular fibrosis.
Options and limitations using <sup>11</sup>c-acetate PET/CT imaging for detection of recurrent disease following radical prostatectomy in patients with prostate cancer.
Authors: Volker Mueller-Mattheis, Melanie Fahlbusch, Hubertus Hautzel, Peter Albers
Journal: Journal of Clinical Oncology (2013)

e16003 Background: Patients with rising PSA levels after definitive local therapy of prostate carcinoma often present a diagnostic dilemma . A local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. In this prospective study the effectiveness of 11 C-acetate PET (AC-PET) matched with corresponding CT scans in patients with PSA relapse were evaluated. Methods: 103 patients (mean age 70.87 years; range 56 – 90 years) with histologically confirmed adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following RP (n = 97) or radiotherapy (n=6). Whole-body PET images were obtained after iv - administration of 1,000 MBq of 11 C-acetate. A CT scan from the neck to the pelvic floor was performed additionally. An image overlay of corresponding CT and PET scans was done. By using attenuation corrected PET data, standardized uptake value (SUV) was calculated, cut-off 2. Results: Out of 103 patients n=42 were AC-PET positive. PSA level in 16 of this subset was between 0.5 and 1.45 ng/mL (mean value 1.14 ng/mL), in 16 patients between 2.7 and 9.01 ng/mL, and 7 patients had a PSA distribution between 13.4 and 30.5 ng/mL, respectively. Analysing the AC-PET positive patients, in 16/42 AC-PET demonstrated hypermetabolic lymphnode lesions, in 10/16 metastatic lesions were histopathologically confirmed, in the remaining 6 unspecific inflammatory tissue alterations were identified. In 9 patients with corresponding AC-PET and CT scans radiotherapy of proven lymphnode metastases was performed followed by decreasing PSA level. 23/42 patients were treated with hormone manipulation (21/23) or chemotherapy (2/23). Combining the patients having undergone surgery and radiotherapy (n=25) there were 19/25 true positive in terms of AC-PET, in 13 / 25 PSA level was &lt; 2.0 ng/mL. Conclusions: Although AC-PET seems to be a promising tool in the detection of recurrent prostate cancer even with PSA levels &lt; 2 ng/ml, false positive patients with a different metabolism marked by 11 C-acetate decrease the specificity of the approach. Thus there is still a need for a more specific tracer development.
COPD: How can evidence from randomised controlled trials apply to patients treated in everyday clinical practice?
Authors: Ant..nio Duarte-de-Ara..jo, Pedro Teixeira, Venceslau Hespanhol, Jaime Correia-de-Sousa
Journal: Pulmonology (2020)

To evaluate the degree to which evidence from large clinical trials can be applied to patients treated in a local hospital cohort of COPD outpatients. The authors selected seventeen RCTs identified in a systematic way from GOLD 2019 consensus document, and applied their inclusion and exclusion criteria to a real-world cohort of a previous cross-sectional study of 303 COPD outpatients included consecutively. When the inclusion criteria of the 17 RCTs were applied to a real-world cohort of COPD outpatients, only a small portion of them were eligible to participate in the referred trials, from 4.29% to 60.07%. However, when both the inclusion and the exclusion criteria were applied, only as little as 3.63% to as much as 40.59% of patients were eligible to participate. Hence, only a small fraction of patients from this cohort could benefit from the findings of these RCTs. There is a need to complement the efficacy evidence provided by large RCTs according to the extent to which their results, designed to target significant patient populations, can be applied to typical patients treated in routine clinical practice.
EFFICACY AND SAFETY OF A 52 WEEK OPEN LABEL PHASE 2B EXTENSION TRIAL WITH MONTHLY DOSING OF AN ANTI-PCSK9 SMALL BINDING PROTEIN
Authors: Evan A. Stein, Traci Turner, Bain Butcher, Padma Mangu, Dean Kereiakes, Rong Zhou, Ran Fu, Tracy Mitchell, Tracy Mitchell
Journal: Journal of the American College of Cardiology (2020)
Early post-transplantation factors predict survival outcomes in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis
Authors: Tania Jain, Katie L. Kunze, Luke Mountjoy, Daniel K. Partain, Heidi Kosiorek, Nandita Khera, William J. Hogan, Vivek Roy, James L. Slack, Pierre Noel, Veena D. S. Fauble, Jose F. Leis, Lisa Sproat, Ayalew Tefferi, Mrinal M. Patnaik, Ruben A. Mesa, Jeanne Palmer
Journal: Blood Cancer Journal (2020)

Factors predicting allogeneic hematopoietic cell transplantation (HCT) outcomes in myelofibrosis in the early post-HCT period have not been defined thus far. We attempt to study such factors that can help identify patients at a higher risk of relapse or death. This retrospective study included 79 patients who underwent first HCT for myelofibrosis at three centers between 2005 and 2016. Univariate analysis showed that red blood cell (RBC) transfusion dependence (HR 9.02, 95% CI 4.0-20.35), platelet transfusion dependence (HR 8.17, 95%CI 3.83-17.37), 100% donor chimerism in CD33 + cells (HR 0.21, 95%CI 0.07-0.62), unfavorable molecular status (HR 4.41, 95%CI 1.87-10.39), normal spleen size (HR 0.42, 95%CI 0.19-0.94), grade ≥ 2 bone marrow fibrosis (vs. grade ≤ 1; HR 2.7, 95%CI 1.1-6.93) and poor graft function (HR 2.6, 95%CI 1.22-5.53) at day +100 were statistically significantly associated with relapse-free survival (RFS). RBC transfusion dependence and unfavorable molecular status were also statistically significant in the multivariate analysis. Patients in whom both of these factors were present had a significantly worse RFS when compared to those with one or none. While limited by a small sample size, we demonstrate the significance of transfusion dependence and molecular status at day +100 in predicting outcomes.