tbuckley/cabot-search huggingface dataset:
Lung Cancer Screening Considerations During Respiratory Infection Outbreaks, Epidemics or Pandemics: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report
Authors: Rudolf M. Huber, Milena Cavic, Anna Kerpel-Fronius, Lucia Viola, John Field, Long Jiang, Ella A. Kazerooni, Coenraad F.N. Koegelenberg, Anant Mohan, Ricardo Sales dos Santos, Luigi Ventura, Murry Wynes, Dawei Yang, Javier Zulueta, Choon-Taek Lee, Martin C. Tammemägi, Claudia I. Henschke, Stephen Lam
Journal: Journal of Thoracic Oncology (2021)
Abstract 13927: Sustained Maximal Inspiratory Pressure: A Novel Measure of Inspiratory Muscle Performance and Its Relationship to Physiology and Function in Heart Failure
Authors: Rohan V Shah, Lawrence P Cahalin, Jacob M Haus, Kelly Allsup, Amanda Delligatti, James Kostra, Daniel J Gottlieb, Cody Wolf, Thomas Byard, Daniel E Forman
Journal: Circulation (2021)

Introduction: The sustained maximal inspiratory pressure (SMIP) is a novel measure of inspiratory muscle performance that reflects the ability of the inspiratory muscles to maintain force over time from residual volume (RV) to total lung capacity (TLC) and has been described as single-breath work capacity. In chronic obstructive pulmonary disease SMIP has been found to be more highly correlated to a greater number of physiologic and functional measures than maximal inspiratory pressure (MIP). This study examined the relationship of SMIP and MIP to a variety of physiologic and functional measures in patients with heart failure (HF). Methods: Fifty male Veterans (mean±SD age, BMI, LVEF = 69.9±8.0 years, 33.6±7.2 kg/m 2 , 40.1±14.4%, respectively) with HF underwent measurement of MIP and SMIP with the PrO2 device (Smithfield, RI) which were measured from RV during initial inhalation and to TLC, respectively. Pulmonary function and maximal expiratory pressure (MEP) were also assessed. Exercise capacity was assessed via cardiopulmonary exercise testing (CPET) and leg strength testing. Physical function was assessed with grip strength, 6-minute walk distance (6MWD), and sit-to-stand test (STS). Results: The mean±SD MIP and SMIP were 66.3±24.8 cmH 2 O and 351.3±151.4 PTU, respectively. Both MIP and SMIP were significantly (p&lt;0.05) correlated to many physiologic (r=.33-.48) and functional measures (r=.38-.62) with the greatest correlate to MIP being MEP (r=.58) and the greatest correlate to SMIP being FEV 1 (r=.62). The greatest physiologic correlate to MIP and SMIP was CPET peak tidal volume with identical r-values (.48). Absolute and relative peak oxygen consumption (pVO 2 ) were correlated to both MIP and SMIP with identical r-values for absolute pVO 2 (.33) and slightly higher r-values between MIP and relative pVO 2 (.37 vs .34). The greatest functional correlate to MIP and SMIP was leg strength/endurance (r=.53 and .46, respectively) followed by STS (r=.52 and .45, respectively) and 6MWD (r=.49 and .45, respectively). Conclusions: MIP and SMIP are significantly correlated in a positive direction to many physiologic and functional measures supporting the role of inspiratory muscle training and further study of SMIP and MIP in HF.
High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma (MM) and Relationship with Disease Status/Line of Therapy
Authors: Katia Mancuso, Elena Zamagni, Vincenza Solli, Liliana Gabrielli, Lucia Pantani, Serena Rocchi, Ilaria Rizzello, Paola Tacchetti, Alessio Fusco, Gabriella De Cicco, Margherita Ursi, Marco Talarico, Emanuele Favero, Giuliana Nepoti, Barbara Ruffini, Carolina Terragna, Tiziana Lazzarotto, Pier Luigi Zinzani, Michele Cavo
Journal: Blood (2021)
Alan Martin Driscoll
Authors: Frank Schweitzer
Journal: BMJ (2021)

Alan Martin Driscoll was born in Plymouth. His father was chief pharmacist to the navy at the Royal Naval Hospital Haslar and his mother a piano teacher. From them he inherited his interest in medicine and art. He qualified at St George’s Hospital (University of London), taking both the conjoint board exams (MRCS, LRCP) and the University of London finals (MBBS) in 1961. After house appointments Alan decided to specialise in obstetrics and gynaecology, receiving most of his training at St Thomas’ Hospital, London. He achieved the …
Abstract 12246: Significant Improvement In Atherosclerotic Risk Factors From Intensive Cardiac Rehabilitation Is Lost After Program Discontinuation
Authors: Rohan Vuppala, Samuel A Miller, Ghaith Al Tibi, Samuel J Medina, Sadie K Webb, Huimin Hu, Xianyan Chen, Nicolas Chronos
Journal: Circulation (2021)

Introduction: Intensive Cardiac Rehabilitation [ICR: Dr. Dean Ornish Program] is proven to reduce risk factors associated with CVD by facilitating stress management education, plant-based nutrition, and structured exercise. The present study aimed to determine if ICR programs can show sustained improvement in high-risk (elderly and rural) populations. Hypothesis: We assessed the hypothesis that ICR participants would not show sustained atherosclerotic risk factor improvement in a 7-14-month timeframe after program completion. Methods: Participants (n=65, mean age 75 +/- 6.5 (56% Male)) with a prior diagnosis of stable angina pectoris, secondary to CVD, completed a nine-week ICR program. Patients’ biomarker data was tracked in the range of 7-14 months following program completion. Eight biomarkers were evaluated including LDL, HDL, and Hb-A1c. The analysis utilized either parametric or nonparametric paired tests, with an adjusted P -value of 0.00625 as eight variables were tested. Serum labs were drawn at least five months before program commencement and at most one week following program completion. BMI was recorded at a separate date, with the P- value set at 0.05. Results: The sample size was n=62. From baseline, patients’ LDL (11.8% decrease, 95% CI) and Hb-A1c (3.2% decrease, 95% CI) showed significant change ( P &lt;0.00625) using the paired Wilcoxon signed-rank test. During the follow-up period, the same methods were applied to a smaller sample size (n=30). This resulted in a significant change ( P &lt; 0.00625) for LDL (increased 13.4%) and HDL (increased 7.3%). With n=55, BMI showed significant change (3.9% decrease, 95% CI, P&lt; 0.05) using the paired Wilcoxon signed-ranked test directly after program completion. In the follow-up period, n=36 and BMI showed significant change (1.5% increase, 95% CI, P &lt; 0.05) with the same method. Conclusion: Patients with atherosclerotic coronary disease optimized on medical therapy prior to enrollment in the ICR still showed improvement in biomarker levels with rehabilitation. However, these programmatic benefits were lost in the subsequent months due to a lack of structured supervision. In conclusion, we suggest long-term maintenance of ICR protocols and structured supervision in high-risk populations.
Abstract 14191: New Approaches to Factual and Counterfactual Risk Prediction for Cardiovascular Disease Using the Parametric G-formula
Authors: Christopher B Boyer, Goodarz Danaei
Journal: Circulation (2021)

Introduction: Over the last few decades, clinical prediction models of the risk of cardiovascular disease have proliferated and are now used extensively in research and clinical care. However, most models have several limitations: (1) they often use only the baseline examination cycle despite the fact that the underlying data sources often include longitudinal assessments of risk factors over time, (2) they make predictions under the "natural course" for the population from which they were derived without making explicit how risk factors varied over time, and (3) they are not appropriate for predictions under alternative counterfactual scenarios such as if an individual were to initiate treatment or adopt healthy lifestyle changes. In this study, we consider an alternative approach based on the parametric g-formula which resolves these limitations. Methods: We compare a g-formula-based model to standard approaches to prediction modeling via Monte Carlo simulation as well as in empirical data. For the latter, we use data from 14,222 longitudinal assessments of 2,771 participants in the Framingham Offspring Study (FOS) to predict 10-year risk of ASCVD. Model discrimination and calibration are assessed via C statistic and calibration slope. We also investigate improvements in risk estimates from our g-formula model as compared to those from the Pooled Cohort Equations (PCE) using the integrated discrimination index and net reclassification index. Results: In simulations, the g-formula model performs better than standard approaches when longitudinal observations are added and makes correct counterfactual predictions when assumptions are met. When applied to FOS data, the g-formula model had better discrimination (C statistic, 0.77 vs. 0.73) and better calibration (slope, 1.07 vs. 0.83) than the PCE. Improvements in the net re-classification index at the 7.5% risk threshold (0.14; 95% CI: 0.05 - 0.26) as well as the integrated discrimination index (2.6%; 95% CI: 1.5% - 3.7%) were significant, suggesting the g-formula better classifies those at increased risk of ASCVD. Conclusion: A longitudinal model based on the g-formula could better use available data from cohort studies and provides a principled framework for predicting risk under interventions.
Abstract 11697: Associations of Soluble Urokinase-Type Plasminogen Activator Receptor and Doxorubicin-Related Cardiotoxicity at Standard Treatment Doses for Breast Cancer
Authors: Jian H Chu, Lillian Tung, melody cobleigh, Ruta Rao, Steven B Feinstein, Lydia Usha, April Swoboda, Jochen Reiser, Tochi M Okwuosa
Journal: Circulation (2021)

Introduction: Elevated soluble urokinase type plasminogen activator (suPAR) is a risk factor for renal and cardiovascular (CV) diseases in the general population. Hypothesis: We evaluated associations between suPAR and markers of subclinical cardiotoxicity in breast cancer (BCa) patients receiving standard (std) dose doxorubicin (DOX) therapy. Methods: We conducted a prospective study of patients at Rush University Medical Center who received std (≤240 mg/m2, 4 cycles) DOX-based chemotherapy for BCa between January 2017 and May 2019. We used mixed effects linear regression models to evaluate associations between suPAR and global longitudinal strain (GLS), NT-proBNP, troponin-I, and hsCRP at baseline, cycle 2 and 4 of DOX, and 3, 6, and 12 months post-DOX treatment with adjustment for baseline demographics, CV risk factors, and CV medications. Results: Of the 37 women in our study (age 47±9.3 years, 60% White, 60% left-sided BCa, and 86% adjuvant radiation therapy), the median baseline suPAR was normal at 1.83 (1.31, 3.68) ng/dL. No woman experienced clinically significant cardiotoxicity during treatment (&gt;10% decrease in LVEF to &lt;50%). Baseline GLS was normal (-20.2±2.3%) and the mean change in GLS following DOX therapy was +1.1%. Neither baseline suPAR nor suPAR levels during treatment were associated with GLS, NT-proBNP, hsCRP, and troponin-I (all p&lt;0.05). Surrogate biomarkers of cardiotoxicity such as troponin-I and hsCRP were not associated with GLS (p&lt;0.05) while NT-proBNP was negatively associated with GLS with marginal significance (p=0.04). Conclusions: In patients receiving std DOX treatment for BCa ± radiation therapy, there was minimal subclinical cardiotoxicity as evidenced by minimal changes in GLS and lack of associations between cardiac biomarkers and GLS. Furthermore, suPAR was not associated with any of these markers at this std DOX dose for BCa. A normal baseline suPAR level may be associated with low risk for DOX-associated cardiotoxicity.
Abstract 10800: Pituitary Apoplexy Induced Takotsubo Cardiomyopathy
Authors: Amandeep S Saini, Kourosh Shargani, Caleb V Wutawunashe, Steve Guo
Journal: Circulation (2021)

Introduction: Takotsubo Cardiomyopathy (TTC), defined by transient myocardial dysfunction with patterns of regional hyperkinesis, commonly arises after an emotional or physical stressor and hypokinesis. Here, we report a TTC case in the setting of pituitary apoplexy. Case: An 82-year-old Male with a history of hypertension, hyperlipidemia, pituitary adenoma, and complete heart block (status post permanent pacemaker) was admitted to the ED after one week of malaise, nausea, and vomiting. The day prior, he developed a severe frontal pressure headache and intermittent blurry vision. He had no chest pain and initially stable vitals, but later became lethargic and febrile to 101.6F with nonsustained ventricular tachyarrhythmias. EKG showed deep T-wave inversions in V2-V4 concerning for pathologic central nervous system T-waves (Fig. 1A). An echocardiogram revealed reduced left ventricular ejection fraction (LVEF) of 20% and akinesis of all mid-myocardial apical segments (Fig. 1B-D). Labs included flat troponin trend, lactate 5 mmol/L, and electrolyte derangements of magnesium 1.5 mEq/L, phosphorous 1.0 mEq/L, and potassium 3.2 mEq/L. In the cardiac care unit, his pacemaker settings were increased from 60 to 80 bpm due to QT prolongation and torsades de pointes on telemetry (Fig. 1E). Given his history of pituitary adenoma, an MRI Sella was performed and was notable for pituitary apoplexy and interval gland enlargement (Fig. 1F). Further labs revealed low cortisol, TSH, and testosterone. Stress dose steroids and levothyroxine were initiated and he underwent transphenoidal resection. Following these interventions, he was afebrile and no longer experienced his chief complaints. Repeat EKG and echocardiogram showed T-wave resolution in V2-V4 (Fig. 1G) and LVEF 50-55%, respectively. Conclusion: Neuroendocrine disorders should be considered as possible stressors in TTC. Early recognition and treatment can ensure favorable outcomes with pituitary apoplexy.
Abstract 12201: Dissecting the Protective Effect of Phosphodiesterase 3A Hyperactivity on the Heart Using Single Nuclei Sequencing and Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Michael B Mücke, Tamara Pallien, Philip Dierks, Ryan Walker-Gray, Anastasiia Sholokh, Duncan C Miller, Sebastian Diecke, Norbert Hubner, Enno Klussmann
Journal: Circulation (2021)

Mutations causing hyperactivity of phosphodiesterase 3A (PDE3A) lead to autosomal dominant hypertension with brachydactyly type E. Affected patients suffer from profoundly increased blood pressure and, if untreated, die from stroke at the age of 50 years. Surprisingly, the hearts of affected individuals show little signs of hypertrophic responses to these conditions, indicating a beneficial effect of PDE3A hyperactivity on the damaging mechanisms of the heart. PDE3A inhibition was previously tested as a treatment for heart failure. While PDE3A inhibitors lead to short term positive inotropy, treatment with these drugs decreases overall survival of heart failure patients, underlining the importance of PDE3A in the heart. As arterial hypertension is a major risk factor for cardiovascular disease and proves to be a major burden on the healthcare system, dissecting the mechanisms underlying the protective effect of PDE3A can open new paths to preventing and treating heart failure. We hypothesize that PDE3A activation protects the heart from the detrimental effects of high blood pressure via spatially distinct regulation of cAMP levels through its different isoforms, leading to an altered calcium handling of cardiomyocytes. We are focusing on two mutations causing PDE3A hyperactivity, one in a regulatory hotspot the other in the catalytic domain. Using single nuclei sequencing of left ventricles of rats, genetically engineered to recapitulate the human mutations, we are dissecting the differences in the cell type-specific gene regulatory response to high blood pressure compared to the wildtype. To follow up in a human model system, we used genome editing to introduce the mutations of interest into human induced pluripotent stem cells (hiPSC). hiPSC lines containing PDE3A mutations as well as isogenic matched control hiPSCs were differentiated to generate hiPSC-derived cardiomyocytes (hiPSC-CMs). Preliminary data from a well-established 2D system show significantly altered calcium handling of PDE3A-mutant hiPSC-CMs. Performing RNA-sequencing, calcium imaging and cAMP measurements in isogenic hiPSC-CMs, we are functionally characterizing the effect of PDE3A activity on cardiomyocyte profile and physiology to a high resolution.
Pre-Transplant M Protein Level Predicts Minimal Residual Disease Status after Autologous Stem Cell Transplantation in Multiple Myeloma
Authors: Zachary S Meyer, Mohamed Manaa, Yan Han, Magdalena Czader, Attaya Suvannasankha, Rafat Abonour, Sherif S Farag, Melissa Stanley, Mohammad Issam Abu Zaid
Journal: Blood (2021)
Association between greenspace and time spent in nature with subjective wellbeing: a cross-sectional data linkage study
Authors: Joanne Garrett, Benedict Wheeler, Ashley Akbari, Richard Fry, Rebecca Geary, Rebecca Lovell, Ronan A Lyons, Amy Mizen, Mark Nieuwenhuijsen, Francis Rowney, Gareth Stratton, Daniel Thompson, Alan Watkins, Mathew White, James White, Sue Williams, Sarah E Rodgers
Journal: The Lancet (2021)
Abstract 13744: Carotid Sinus Syndrome With Symptomatic Bradycardia Due to Papillary Thyroid Cancer
Authors: Todd Nagamine, Jihun Yeo, Horyun Choi, Jason Huynh, Kanitsoraphan Chanavuth
Journal: Circulation (2021)

The patient is a 45-year-old male with no significant past medical history who presents to the hospital for an elective surgical neck mass biopsy. The patient started noticing a slow-growing neck mass six years ago, although he did not seek medical attention. While he was monitored in preoperative room, he developed symptomatic bradycardia. Telemetry showed a complete heart block rhythm. Upon further questioning, he had been having increasing episodes of near syncope for the past two months. Physical examination was significant for bradycardia without an audible murmur. A neck exam revealed a fixed right neck mass palpable across the midline to the left with a prominent thyroid isthmus. Carotid pulses were palpable bilaterally with no bruits. A temporary transvenous pacemaker was placed and the patient was admitted to the hospital for observation. Upon further workups, CT images 1 and 2 in supplemental section. A cervical lymph node biopsy eventually revealed metastatic papillary thyroid carcinoma. The patient was diagnosed with carotid sinus syndrome secondary to papillary thyroid cancer with a vasovagal component. He was discharged with a plan for radiation and close follow-up with an electrophysiologist to evaluate permanent pacemaker eligibility after receiving treatment for thyroid cancer.
Abstract 13850: Proteomic Profiling to Identify Pre-Transplant Biomarkers of Renal Failure After Heart Transplantation
Authors: Lauren K Truby, Lydia Kwee, Brian Shaw, Richa Agarwal, Adam D Devore, Stuart Knechtle, Xunrong Luo, Chetan B Patel, Dongfeng Chen, Dawn E Bowles, Carmelo A Milano, Christopher L Holley, Svati H Shah
Journal: Circulation (2021)

Introduction: In patients being considered for heart transplantation (HT), differentiating reversible kidney injury due to cardiorenal syndrome from irreversible renal disease that will necessitate simultaneous heart-kidney transplant (sHK) remains a clinical challenge. Hypothesis: We hypothesized that pre-transplant proteomic profiling could identify novel biomarkers of post-transplant renal failure in HT recipients and, in so doing, identify those patients who may derive benefit from sHK evaluation. Methods: We performed targeted proteomic profiling of serum samples collected within the 24 hours prior to HT or sHK. Using a multivariable logistic regression including relative protein expression, age, and sex with adjustment for batch effect, we identified those pre-transplant proteins that were differentially expressed between patients who received HT and sHK. Proteins that met FDR significance in this multivariable model were then tested for association with post-transplant RRT in isolated HT recipients. Patients with known intraoperative hemodynamic insult as a result of primary graft dysfunction were excluded from this analysis. This model was adjusted for age, sex, and MDRD eGFR. ROC analysis was performed to test the performance of the final protein model. Results: Pre-transplant expression of 97 proteins was noted to be significantly different at the FDR p &lt;0.05 level in sHK recipients (n=12) when compared to HT (n=231) recipients in the multivariable model. We identified 205 isolated HT recipients, among whom 33 required post-HT RRT. Among these 97 candidate We identified a total of 15 proteins, many of which have previously been associated with acute and chronic kidney injury, including KIM1, FABP4, PAR-1, VSIG2, and GDF-15, that were significantly associated with post-HT RRT after adjustment for age, sex, and pre-transplant eGFR. In ROC analysis in our cohort, the AUC of the 15-protein model was 0.82. Conclusions: Proteomic profiling of pre-transplant serum of HT recipients may identify HT candidates at high risk for post-transplant RRT. Individually and in aggregate, these 17 proteins warrant additional investigation as novel biomarkers that may identify patients who would benefit from sHK evaluation.
Elder abuse in the UK: out of the shadows and on to the agenda
Authors: Carolyn Stephens, Nicolas Mays, Rita Issa, Lesley Perkins, Rebecca Scott
Journal: BMJ (2021)

Elder abuse is a major public health problem, facing one in six older people globally (defined as aged 60 and older). 1 2 Older people with dementia are at much higher risk, 3 and the disease is predicted to affect over a million people in the UK by 2025.
Abstract 11984: Impact of Underlying Pulmonary Hypertension on In-Hospital Outcomes Among Patients With Septic Shock
Authors: Rhythm Vasudeva, Mohinder Vindhyal, Suveen Krishna Pothuru, Zubair Shah, Kamal gupta
Journal: Circulation (2021)

Background: Pulmonary Hypertension (PHTN) patients typically have chronic multiple comorbidities and are more vulnerable to acute clinical conditions leading to decreased survival. The impact of pulmonary hypertension on outcomes in patients with septic shock remains unknown. Methods: Adult patients with a diagnosis of septic shock were identified in the National Readmissions Database (NRD) between the years 2016-2017. Propensity matched retrospective cross sectional clinical outcomes were compared between patients with and without non-cardiac PHTN using appropriate statistical methods after nearest matching on a 2:1 ratio for several demographic, social and clinical variables. Patients with cardiogenic shock, aortic and mitral valvular heart disease, underlying systolic and combined heart failure (HF), and PHTN due to left heart disease were excluded from the primary analysis. Appropriate ICD-10 codes were used. Results: A total of 13,676 patients diagnosed with non-cardiac PHTN and septic shock were identified with a mean age of 68 years and 58.6% identified as females. Patients with PHTN had higher comorbidities, including hypertension, chronic pulmonary disease, renal failure, diabetes, CAD, and obesity. After matching, patients with septic shock and non-cardiac PHTN were noted to have a higher mortality (33.2% vs 31.3%, p &lt; 0.001), greater vasopressor use (7.9% vs 6.6%, p &lt; 0.001), higher rates of acute heart failure (1.1% vs 0.6%, p &lt; 0.001), longer hospital stay (14.0 days vs 12.7 days, p &lt; 0.001), and higher hospital costs ($196,411 vs $171,537), when compared to patients with septic shock and without PHTN. Rates of AKI were noted to be lower in patients with PHTN. Amongst stroke outcomes, minimal differences in ischemic strokes were noted. There were no MI outcomes observed. Discussion: PHTN is associated with worse mortality, morbidity, and resource utilization outcomes in patients admitted with septic shock, except AKI. These findings should be interpreted carefully given the administrative nature of the database, and the population cohort restricted to readmissions.