tbuckley/cabot-search huggingface dataset:
Abstract 10555: Genetic Testing Underutilization in Patients with Cardiomyopathy: A Real-World Data Analysis
Authors: Ana Morales, Chad Moretz, Sheng Ren, Elizabeth Smith, Tom Callis, Joline Dalton, Taryn Hall, Kathryn Hatchell, Jaime Murillo, Robert L Nussbaum, Ellen Regalado, Susan Rojahn, Matteo Vatta, Edward D Esplin
Journal: Circulation (2021)

Introduction: Professional guidelines support genetic testing (GT) for dilated, hypertrophic, restrictive, arrhythmogenic, and peripartum cardiomyopathy to confirm a diagnosis, guide management, enable clinical trials, and/or allow more informed genetic counseling. Analysis of de-identified data from a commercial laboratory showed that 1 in 4 individuals who had cardiomyopathy GT billed to a national health insurer had a positive result; however, which patients undergo GT is largely unknown. Hypothesis: GT is underutilized in patients with genetic cardiomyopathy. Methods: A retrospective analysis was conducted using commercial and Medicare claims data from the UnitedHealth Group Clinical Discovery Database. The GT-cohort (index: GT dates 1/1/2017-12/31/2020) included patients with 12-months pre-index data including ≥1 ICD-10 codes associated with genetic or unspecified cardiomyopathy and GT Current Procedural Terminology (CPT) code(s). The non-GT cohort (index: outpatient visit dates 1/1/2017-12/31/2020 with 12-month pre-index data) had the same ICD codes, but no GT CPT code. Individuals with a personal and/or family history of cancer were excluded to avoid patients who had GT for cancer. Multivariable logistic regression analysis was performed to examine factors associated with GT. Results: Of 300,127 patients with cardiomyopathy, 3,287 (1.1%) had a GT CPT code. Factors that predicted a higher likelihood of GT (p &lt; 0.05) included being younger, living in an area with a higher education level, commercial insurance, no diagnosis of diabetes or myocardial infarction, diagnosis of mild liver disease, a higher number of outpatient medical and cardiology visits, cardiac-related hospitalizations (shorter length-of-stay), a higher number of 30-day all-cause readmissions, a higher number of cardiomyopathy diagnoses, and except for peripartum, all genetic cardiomyopathy types. Conclusions: Only 1.1% of patients with a cardiomyopathy ICD code had a GT claim. Considering a potential 25% testing yield, a larger portion could have benefited from a genetics guided diagnosis. More research is needed to investigate barriers related to GT and improve our ability to identify those who could benefit from cardiomyopathy genetic testing.
RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY
Authors: John Shumway, Marina Torras, Katherine Reeder-Hayes, Trevor Jolly, Elizabeth Dees, Emily Ray, Hyman Muss, Lisa Carey, Colette Shen
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had &amp;gt;1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.
TMOD-25. LATENT SOX9-POSITIVE CELLS BEHIND MYC-DRIVEN MEDULLOBLASTOMA RELAPSE
Authors: Anna Borgenvik, Sara Bolin, Vasil Savov, Karl O Holmberg, Miao Zhao, Gabriela Rosén, Sonja Hutter, Alexandra Garancher, Aldwin Suryo Rahmanto, Tobias Bergström, Oliver Mainwaring, Damiana Sattanino, Annemieke D Verbaan, Jessica Rusert, Anders Sundström, Yonglong Dang, Amelie Wenz, Stacey Richardson, Grammatiki Fotaki, Geraldine Giraud, Rebecca Hill, Adrian Dubuc, Antonia Kalushkova, Marc Remke, Matko Cancer, Helena Jernberg-Wiklund, xingqi Chen, Michael D Taylor, Olle Sangfelt, Steven Clifford, Ulrich Schüller, Robert Wechsler-Reya, Holger Weishaupt, Fredrik Swartling
Journal: Neuro-Oncology (2021)

Abstract Tumor recurrence developing from therapy resistance, immune escape and metastasis is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. Amplification of MYC genes is the most common genetic alteration in Group 3 and Group 4 subgroups that constitute two thirds of medulloblastoma. SOX9 is a transcription factor present in stem cells in the normal brain but is limited to rare, quiescent cells in medulloblastoma patients with MYC gene amplifications. By studying paired primary-recurrent patient samples and patient-derived xenografts we here identified significant accumulation of SOX9-positive cells in Group 3 and Group 4 relapses. To follow relapse at the single cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC was re-directed from the treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. In this model, distant recurrent tumors and spinal metastases developed. SOX9 promoted immune escape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we also showed how doxorubicin and MGMT inhibitors were specifically targeting recurrent cells that could be of potential use in future treatments for patients affected by these fatal relapses.
Abstract 14040: Hospital Volume-Outcome Relationship After Primary Percutaneous Coronary Intervention: A Contemporary Nationwide Analysis
Authors: Ayman Elbadawi, Islam Y Elgendy, Mohamed Omer, DAVID PANIAGUA, ALI E DENKTAS, Hani Jneid
Journal: Circulation (2021)

Introduction: There is paucity of data on the relationship between hospital procedural volume and outcomes of primary percutaneous coronary intervention (PCI) procedures in the past decade. Methods: We queried the National Inpatient Sample database (2010-2016) for hospitalizations undergoing primary PCI for STEMI. Hospitals were divided into 3 groups: low-volume (&lt;36 primary PCI/ year), moderate-volume (36-72 primary PCI/year) and high-volume (&gt;72 primary PCI/ year). The main outcome was in-hospital mortality. Results: The analysis included 694,505 hospitalizations for primary PCI. There were 329,878 (47.5%) primary PCI procedures performed at low-volume hospitals, 224,317 (32.3%) at moderate-volume, and 140,223 (20.2%) at high-volume hospitals. Compared with high-volume hospitals, low-volume hospitals were associated with higher in-hospital mortality in the unadjusted model (5.3% vs. 4.8%, odds ratio [OR] 1.10; 95% confidence interval-CI 1.02-1.18, p=0.01) and on multivariable analysis (adjusted-OR 1.15; 95%CI 1.04-1.27, p=0.01). There was no difference between moderate-volume and high-volume hospital in unadjusted analysis (5.1% vs. 4.8%, OR 1.07; 95%CI 0.99-1.15, p=0.11) and on multivariable analysis (adjusted-OR 1.08; 95%CI 0.97-1.20, p=0.17). Conclusions: This nationwide analysis showed that low-volume hospitals are associated with higher in-hospital mortality after primary PCI compared with high-volume hospitals even in recent years. The current threshold set by national guidelines for primary PCI hospitals remains valid in contemporary practice.
TAMI-01. BRAIN METASTASES: CURRENT LITERATURE REVIEW
Authors: Ruchi Raval, Aadi Pandya, Jaspreet Behl, Sumul Raval
Journal: Neuro-Oncology (2021)

Abstract PURPOSE As more information is gathered about brain metastases, it still remains that the current prognosis of brain metastases is very poor. Due to this, it is imperative that physicians are aware of the most important components regarding brain metastases. This literature review will encompass the most current literature in order to highlight the most crucial information. METHODS All mentioned studies and literature reviews cited in the paper were obtained through various sites, and were published between 1996 and 2017. The main components that were required from the papers reviewed included where in the body the brain metastases originated from, where in the brain they tended to spread to, what the signs and symptoms typical of patients with brain metastases are, and what the options are in terms of treatment. RESULTS Using the results from a variety of studies performed within the past three decades, it is apparent that brain metastases most commonly originate from, in order of increasing frequency, lung cancer, breast cancer, melanoma, and colorectal cancer. In addition, it is reaffirmed that the magnetic resonance imaging (MRI) is the best diagnostic tool to be used when dealing with brain metastases. The most frequent signs and symptoms of a brain metastases include cognitive changes, headaches, weakness, and seizures. Finally, supportive treatment includes use of corticosteroids, antiepileptic drugs (AEDs), and anticoagulation therapy. Definitive treatment for brain metastases varies based on size, location, and prevalence in the brain, but the most effective options include chemotherapy, radiation therapy, and surgery. CONCLUSIONS The study’s results confirm the need for more research to be done regarding brain metastases, and better options to increase the survival of patients.
Abstract 9465: Does Connectedness Matter: The Association Between Mutuality and Job Satisfaction Among Home Health Aides Caring for Adults with Heart Failure
Authors: Ariel Shalev, joanna Ringel, Monika M Safford, Barbara Riegel, Emily Franzosa, Ercole Vellone, Emma Tsui, Parag Goyal, Michael Stawnychy, Jennifer Reckrey, Madeline R Sterling
Journal: Circulation (2021)

Introduction: Adults with heart failure (HF) are increasingly aging in place and requiring help at home. However, due to poor compensation and the challenging nature of the work, home health aide (HHA) turnover rates are high. Identifying modifiable factors that can promote HHAs’ job satisfaction may help retain this workforce. We examined whether mutuality, or the connectedness between HHAs and their HF patients, is associated with HHAs’ job satisfaction. Methods: We conducted a cross-sectional survey of English-speaking agency-employed HHAs caring for an adult with HF in New York City. Mutuality was assessed with the Mutuality Scale, a validated 15-item scale measuring overall mutuality and its’ four domains (love, shared values, reciprocity, shared pleasurable activities). The overall scale and each domain score range from 0-4; higher scores indicate greater mutuality. Job satisfaction was assessed with one question; responses were categorized using a 4-point Likert scale. We used multivariable robust Poisson regression to examine the association between mutuality and job satisfaction, adjusting for HHAs’ demographics, employment, and HF caregiving history. Results: We studied 200 HHAs employed by 22 home care agencies; 94% (187 of 200) were female, 73% (145 of 200) were foreign-born, 43% (82 of 191) were non-Hispanic Black. They had a mean age of 48 years (SD 14), worked as a HHA for a median of 9 years (IQR 5-15), and spent a median of 24 hours/week (IQR 8-36) with a HF patient. The overall mean mutuality score was 2.92 (SD 0.79) and 80% (160 of 200) were satisfied with their job. Mean scores were lowest for reciprocity (2.62 [0.99]) and highest for shared pleasurable activities (3.16 [0.80]). In fully adjusted models, the overall mutuality score and each of the 4 domain scores were associated with increased job satisfaction. Only the shared activities domain was statistically significant (aPR: 1.17 [95% CI 1.04-1.32]). Conclusions: Greater mutuality, specifically the shared activities domain, between HHAs and HF patients was associated with higher job satisfaction. Our findings suggest that this modifiable domain of mutuality may be a possible target for interventions to promote mutuality between HHAs and patients as well as HHA job satisfaction.
DDRE-26. INHIBITION OF PRMT5 SENSITIZES GLIOBLASTOMA MODELS TO TRAMETINIB TREATMENT
Authors: Yesh Banasavadi, Sriya Namagiri, yoshihiro Otani, Shilpa Thammegowda, Hannah Sur, Sarah Rivas, Jean-Paul Bryant, Ashis Chowdhury, Cole Lewis, Toshihiko Shimizu, Stuart Walbridge, Tae Jin Lee, Dragan Maric, Ji Young Yoo, John Heiss, Balveen Kaur
Journal: Neuro-Oncology (2021)

Abstract With limited effective therapeutic strategies, the prognosis for glioblastoma (GBM) is very poor. Our previous study shows that the expression of Protein Arginine Methyltransferase 5 (PRMT5) is upregulated in GBM; its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. MEK inhibitors, including trametinib, are currently under investigation for GBM therapy. In this study, we tested whether inhibition of PRMT5 can enhance the anti-GBM efficacy of trametinib. Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot analysis were conducted. In vivo, PRMT5-intact and -depleted GBMNS were intracranially implanted in NSG mice and treated with trametinib by daily oral gavage, and tumor progression and mice survival rate were analyzed by MRI and Kaplan-Meier survival curve, respectively. Depletion of PRMT5 increased the cytotoxic effect of trametinib in GBMNS. Trametinib treatment increased the activity of ERBB3 and AKT; With PRMT5 knockdown, the activity of both AKT and ERBB3 decreased significantly. But, inhibition of ERBB3 alone failed to block the trametinib-induced AKT activity suggesting that even though PRMT5 regulates the activity of both ERBB3 and AKT, the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib treated GBMNS is because of AKT inhibition alone. In vivo, PRMT5-depletion extended the survival of the tumor-bearing mice that further increased in combination with trametinib treatment. Interestingly, trametinib treatment alone had no survival benefit.
Understanding risk and protective factors to UK railway workers' mental wellbeing during the COVID-19 pandemic: a cross-sectional survey
Authors: Nicola Cogan, Megan McGibbon, Amy Gardener, Liza Morton
Journal: The Lancet (2021)

BackgroundFrontline railway workers have provided an essential service throughout the COVID-19 pandemic. Although railway workers are known to be at risk of developing traumatic stress-related conditions, little is known about the effects of COVID-19 on the mental wellbeing of railway workers in the UK. We tested two hypotheses: (1) increased scores in COVID-19-related risk factors will predict decreased mental wellbeing and (2) protective factors will mediate the relationship between COVID-19-related risk factors and mental wellbeing.MethodsThe study consisted of a cross-sectional online survey exploring the effects of COVID-19 on the mental wellbeing of railway workers (n=906) in the UK, using data collected during third lockdown (between Dec 1, 2020, and March 24, 2021). The survey, advertised on social media and internal platforms of the Associated Society of Locomotive Engineers and Firemen, included measures of COVID-19-related risk factors (COVID-19 Perceived Risk Scale, COVID-19 Stress Measure, COVID-19 Burnout Scale, and PTSD Checklist–Civilian Version) and protective factors (brief resilience coping, team resilience, general help-seeking questionnaire) associated with mental wellbeing (Warwick Edinburgh Mental Wellbeing Scale–Short Form). We analysed responses via multiple regression and parallel mediation analyses. Open-ended questions, exploring railway workers' views of risks and protective factors for their mental wellbeing, were analysed using content analysis. The institutional ethics committee granted ethical approval and participants gave informed consent.FindingsCOVID-19 related risk factors negatively predicted wellbeing (r2=0·50, F=273·556 [3 variables, n=813], p<0·0001). Protective factors significantly mediated the relationship between wellbeing and burnout (indirect effect [IE] –0·0252, 95% CI –0·0364 to –0·0152), stress (IE –0·0252, –0·0364 to –0·0152), post-traumatic stress disorder (IE –0·0311, –0·0493 to –0·0145), and risk perception (IE –0·0244, –0·0411 to –0·0089). Content analysis found self-reported mental health decline throughout the COVID-19 pandemic, perceived loss of workplace supports, need for psychological support, and concerns for the future.InterpretationThese findings emphasise the importance of adaptive coping and team-based resilience in alleviating the negative impact that COVID-19 has on railway workers' mental wellbeing and in preventing burnout. Work-based supports and access to psychological input for railway workers who need it is highlighted. Building a resilient railway workforce moving forward requires attention to staff mental wellbeing and to ensuring that support systems are robust and accessible.FundingNone.
Abstract 11485: Left Ventricular Dimensions and Cardiovascular Outcomes in Systolic Heart Failure: The WARCEF Trial
Authors: Kazato Ito, Siyuan Li, Shunichi Homma, John L Thompson, Richard Buchsbaum, Kenji Matsumoto, Stefan D Anker, Min Qian, Marco Di Tullio
Journal: Circulation (2021)

Introduction: There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. Methods: We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial. Results: LV enlargement, whether by diameter (LV end-diastolic diameter index: LVEDDI, and LV end-systolic diameter index: LVESDI) or volume (LV end-diastolic volume index: LVEDVI, and LV end-systolic volume index: LVESVI), was independently associated with all-cause death [LVEDDI: hazard ratio (HR) per cm/m 2 1.53, LVESDI: HR per cm/m 2 1.65, LVEDVI: HR per 10 ml/m 2 1.07 and LVESVI: HR per 10 ml/m 2 1.10; all p-values &lt; 0.001], CV death (HR 1.68, 1.79, 1.09 and 1.12, respectively; all p-values &lt; 0.001) and HF hospitalization (HR 1.59, 1.79, 1.06 and 1.08, respectively; all p-values &lt; 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters. Conclusions: LV enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.
Abstract 13698: Prognostic Value of Left Atrial Volume and Reservoir Function at 3-months Post-Procedure in 792 Patients Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Songnan Wen, Sorin Pislaru, Grace Lin, Samuel Asirvatham, Garvan Kane, Cristina Pislaru
Journal: Circulation (2021)

Introduction: The predictive value of left atrial (LA) volume and reservoir function (ResF) post-atrial fibrillation (AF) ablation has been scarcely studied. Hypothesis: Abnormal LA volume and ResF post-ablation are associated with adverse cardiovascular events. Methods: We analyzed LA maximum (LAVImax) and minimum (LAVImin) volume index, and 2 measures of ResF, emptying fraction (LAEF) and expansion index (LAEI), prospectively measured at 3-month post-procedure in patients in sinus rhythm who underwent AF ablation between 2007-2016. Composite endpoint (CE) at follow up was all-cause mortality, cardiac hospitalization (heart failure or acute ischemic event) and stroke. Results: 792 patients were studied ( age 60±10 years, 25% women ; Table 1) . Over 7.5 years [IQR 3.0-9.7], 96 (12%) patients experienced CE, which was more prevalent in patients with enlarged LA and reduced ResF. Impaired LA volumes and ResF were each independently associated with CE ( Fig.1 ), even after adjustment for clinical, demographic and echo characteristics (Model A, Fig.2 ) (LAVImax ≥35 ml/m 2 : HR 2.15 [95% CI, 1.35-3.43], p=0.001; LAVImin≥20.5 ml/m 2 : HR 2.88 [1.77-4.69], p&lt;0.0001; LAEF&lt;39%: HR 2.00 [1.31-3.05], p=0.001; LAEI&lt;65%: HR 1.95 [1.27-3.01], p=0.003). ResF measures (LAEF and LAEI) were incremental to LAVImax (all p&lt;0.05), but not LAVImin (all p&gt;0.05; Fig.2 ). In patients with normal LA (LAVImax &lt;35 ml/m 2 ; n=408), increased LAVImin (≥20.5 ml/m 2 ) remained associated with CE (HR 3.11 [1.45-6.67], p=0.004) and cardiac hospitalization (HR 5.81 [1.87-18.01], p=0.002). These findings were independent of AF recurrence. Conclusions: In these patients, enlarged LA and impaired ResF at 3-month post-ablation were strongly associated with adverse cardiovascular outcomes, regardless of AF recurrence. Measures of LA ResF were incremental to LAVImax. Notably, LAVImin showed the strongest associations and even identified a high-risk subgroup among patients with non-dilated LA.
Sepsis guidance may change as result of deaths of two women from herpes infection after giving birth
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Clinical advice on how to treat new mothers with sepsis could change after two women died of a postpartum herpesvirus infection.

The Royal College of Obstetricians and Gynaecologists said viral infections must routinely be considered as a possible cause of postpartum infection. The advice came after it emerged that Kimberley Sampson, 29, and Samantha Mulcahy, 32, had died from HSV-1, an infection caused by the herpes virus, 44 days apart at East Kent Hospitals University NHS Foundation Trust in 2018. In both cases clinical staff thought the women had bacterial sepsis.

The college said it could …