tbuckley/cabot-search huggingface dataset:
Transcatheter Aortic Valve Replacement in Low-risk Patients With Bicuspid Aortic Valve Stenosis
Authors: John K. Forrest, Basel Ramlawi, G. Michael Deeb, Firas Zahr, Howard K. Song, Neal S. Kleiman, Stanley J. Chetcuti, Hector I. Michelena, Abeel A. Mangi, Jeffrey A. Skiles, Jian Huang, Jeffrey J. Popma, Michael J. Reardon
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> The outcomes of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis have not been studied in a large scale, multicentered, prospective fashion. <h3>Objective</h3> To evaluate the procedural safety, efficacy, and 30-day outcomes of TAVR in patients with bicuspid aortic stenosis at low surgical risk. <h3>Design, Setting, and Participants</h3> The Low Risk Bicuspid Study is a prospective, single-arm trial study with inclusion/exclusion criteria developed from the Evolut Low Risk Randomized Trial. Follow-up is planned for 10 years. Patients underwent TAVR at 25 centers in the United States who were also participating in the Evolut Low Risk Randomized Trial from December 2018 to October 2019. Eligible patients had severe bicuspid aortic valve stenosis and met American Heart Association/American College of Cardiology guideline indications for aortic valve replacement. <h3>Interventions</h3> Patients underwent attempted implant of an Evolut or Evolut PRO transcatheter aortic valve, with valve size based on annular measurements. <h3>Main Outcomes and Measures</h3> The prespecified primary end point was the incidence of all-cause mortality or disabling stroke at 30 days. The prespecified primary efficacy end point was device success defined as the absence of procedural mortality, the correct position of 1 bioprosthetic heart valve in the proper anatomical location, and the absence of more than mild aortic regurgitation postprocedure. <h3>Results</h3> A total of 150 patients underwent an attempted implant. Baseline characteristics include mean age of 70.3 (5.5) years, 48.0% female (n = 72), and a mean Society of Thoracic Surgeons score of 1.4 (0.6%). Most patients (136; 90.7%) had Sievers type I valve morphology. The incidence of all-cause mortality or disabling stroke was 1.3% (95% CI, 0.3%-5.3%) at 30 days. The device success rate was 95.3% (95% CI, 90.5%-98.1%). At 30 days, the mean (SD) AV gradient was 7.6 (3.7) mm Hg and effective orifice area was 2.3 (0.7) cm<sup>2</sup>. A new permanent pacemaker was implanted in 22 patients (15.1%). No patients had greater than mild paravalvular leak. <h3>Conclusions and Relevance</h3> Transcatheter aortic valve replacement in low–surgical risk patients with bicuspid aortic valve stenosis achieved favorable 30-day results, with low rates of death and stroke and high device success rate. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03635424
Effect of exercise training for five years on all cause mortality in older adults—the Generation 100 study: randomised controlled trial
Authors: Dorthe Stensvold, Hallgeir Viken, Sigurd L Steinshamn, Håvard Dalen, Asbjørn Støylen, Jan P Loennechen, Line S Reitlo, Nina Zisko, Fredrik H Bækkerud, Atefe R Tari, Silvana B Sandbakk, Trude Carlsen, Jan E Ingebrigtsen, Stian Lydersen, Erney Mattsson, Sigmund A Anderssen, Maria A Fiatarone Singh, Jeff S Coombes, Eirik Skogvoll, Lars J Vatten, Jorunn L Helbostad, Øivind Rognmo, Ulrik Wisløff
Journal: BMJ (2020)

Abstract Objective To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). Design Randomised controlled trial. Setting General population of older adults in Trondheim, Norway. Participants 1567 of 6966 individuals born between 1936 and 1942. Intervention Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. Main outcome measure All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. Results Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. Conclusion This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. Trial registration ClinicalTrials.gov NCT01666340 .
Impact of curated data on electronic quality measure capture rates within CancerLinQ.
Authors: Katrina Caridad Rios, Arpitha Thakkalapally, Jacob Koskimaki, Mark Riffon, Robert S. Miller, George Anthony Komatsoulis, Danielle Potter
Journal: Journal of Clinical Oncology (2020)

307 Background: Accurate calculation of key quality measures is critical for informing high-quality, value-based cancer care that is consistent with clinical guidelines. The American Society of Clinical Oncology (ASCO)’s CancerLinQ enables oncology organizations around the US to view near-real time quality measure dashboards sourced from structured electronic medical record (EMR) data; however, use of structured data in key fields is highly variable. Unstructured content, such as progress notes, contains important clinical information on treatment and disease status, which can then undergo curation. This process involves trained data abstractors searching for key data elements through a combination of manual review and natural language processing (NLP) to extract structured data from unstructured content. We hypothesize inclusion of curated data substantially augments structured data alone by more accurately representing the patient journey, thus improving validity of quality measures across EMRs. Methods: A total of 96,399 records across 57,232 patients from 4 EMRs vendors were analyzed from 2018-2019 across structured EMR and curated data. Each record represents 1 of 7 key data elements used to calculate the Staging Documented within One Month of First Office Visit quality measure. Structured documentation of these data elements determines if a patient is concordant with the measure, meaning they were staged within 31 days of their first visit after diagnosis, or non-concordant, meaning they were not staged within the appropriate window. Results: More than a quarter of records from patients concordant or non-concordant with the measure (28.85%) had key data elements sourced from curation. In total, 33% of all records among concordant patients were sourced from curation. Relying on structured data alone would show only 67% concordance versus 97.5% concordance among curated records. This demonstrates that appropriate care may often be delivered but documentation may be missing in a significant fraction of structured EMR data, thus limiting accurate reporting capabilities. Conclusions: NLP-assisted curation can meaningfully supplement structured EMR data by providing a more accurate picture of care rendered, which can have substantial impacts on clinical care, quality reporting, and business operations. [Table: see text]
Ex vivo cultures and drug testing of primary acute myeloid leukemia samples: Current techniques and implications for experimental design and outcome
Authors: D.G.J. Cucchi, R.W.J. Groen, J.J.W.M. Janssen, J. Cloos
Journal: Drug Resistance Updates (2020)

New treatment options of acute myeloid leukemia (AML) are rapidly emerging. Pre-clinical models such as ex vivo cultures are extensively used towards the development of novel drugs and to study synergistic drug combinations, as well as to discover biomarkers for both drug response and anti-cancer drug resistance. Although these approaches empower efficient investigation of multiple drugs in a multitude of primary AML samples, their translational value and reproducibility are hampered by the lack of standardized methodologies and by culture system-specific behavior of AML cells and chemotherapeutic drugs. Moreover, distinct research questions require specific methods which rely on specific technical knowledge and skills. To address these aspects, we herein review commonly used culture techniques in light of diverse research questions. In addition, culture-dependent effects on drug resistance towards commonly used drugs in the treatment of AML are summarized including several pitfalls that may arise because of culture technique artifacts. The primary aim of the current review is to provide practical guidelines for ex vivo primary AML culture experimental design.
A skeleton muscle model using GelMA-based cell-aligned bioink processed with an electric-field assisted 3D/4D bioprinting
Authors: Gi Hoon Yang, Wonjin Kim, Juyeon Kim, GeunHyung Kim
Journal: Theranostics (2020)

The most important requirements of biomedical substitutes used in muscle tissue regeneration are appropriate topographical cues and bioactive components for the induction of myogenic differentiation/maturation. Here, we developed an electric field-assisted 3D cell-printing process to fabricate cell-laden fibers with a cell-alignment cue. Methods: We used gelatin methacryloyl (GelMA) laden with C2C12 cells. The cells in the GelMA fiber were exposed to electrical stimulation, which induced cell alignment. Various cellular activities, such as cell viability, cell guidance, and proliferation/myogenic differentiation of the microfibrous cells in GelMA, were investigated in response to parameters (applied electric fields, viscosity of the bioink, and encapsulated cell density). In addition, a cell-laden fibrous bundle mimicking the structure of the perimysium was designed using gelatin hydrogel in conjunction with a 4D bioprinting technique. Results: Cell-laden microfibers were fabricated using optimized process parameters (electric field intensity = 0.8 kV cm-1, applying time = 12 s, and cell number = 15 × 106 cells mL-1). The cell alignment induced by the electric field promoted significantly greater myotube formation, formation of highly ordered myotubes, and enhanced maturation, compared to the normally printed cell-laden structure. The shape change mechanism that involved the swelling properties and folding abilities of gelatin was successfully evaluated, and we bundled the GelMA microfibers using a 4D-conceptualized gelatin film. Conclusion: The C2C12-laden GelMA structure demonstrated effective myotube formation/maturation in response to stimulation with an electric field. Based on these results, we propose that our cell-laden fibrous bundles can be employed as in vitro drug testing models for obtaining insights into the various myogenic responses.
An open-label study evaluating the efficacy of abatacept in alopecia areata
Authors: Julian Mackay-Wiggan, Brigitte N Sallee, Eddy Hsi Chun Wang, Freda Sansaricq, Nhan Nguyen, Carey Kim, James C Chen, Angela M Christiano, Raphael Clynes
Journal: Journal of the American Academy of Dermatology (2020)
Disparities in Adverse Maternal Outcomes Among Asian Women in the US Delivering at Term
Authors: Stephen M. Wagner, Matthew J. Bicocca, Megha Gupta, Suneet P. Chauhan, Hector Mendez-Figueroa, Jacqueline G. Parchem
Journal: JAMA Network Open (2020)

Disparities in maternal outcomes are representative of racial/ethnic health inequities in the US.
Correction: Primary therapy and relative survival among elderly patients with chronic myeloid leukemia: a population-based study in the Netherlands, 1989–2017
Authors: Geneviève I. C. G. Ector, Otto Visser, Peter E. Westerweel, Jeroen J. W. M. Janssen, Nicole M. A. Blijlevens, Avinash G. Dinmohamed
Journal: Leukemia (2020)
The early life education of the immune system: Moms, microbes and (missed) opportunities
Authors: Nitya Jain
Journal: Gut Microbes (2020)

The early life immune system is characterized by unique developmental milestones. Functionally diverse immune cells arise from distinct waves of hematopoietic stem cells, a phenomenon referred to as 'layered' immunity. This stratified development of immune cells extends to lineages of both innate and adaptive cells. The defined time window for the development of these immune cells lends itself to the influence of specific exposures typical of the early life period. The perinatal immune system develops in a relatively sterile fetal environment but emerges into one filled with a multitude of antigenic encounters. A major burden of this comes in the form of the microbiota that is being newly established at mucosal surfaces of the newborn. Accumulating evidence suggests that early life microbial exposures, including those arising in utero, can imprint long-lasting changes in the offspring's immune system and determine disease risk throughout life. In this review, I highlight unique features of early life immunity and explore the role of intestinal bacteria in educating the developing immune system.
Antisense Drugs Make Sense for Neurological Diseases
Authors: C. Frank Bennett, Holly B. Kordasiewicz, Don W. Cleveland
Journal: The Annual Review of Pharmacology and Toxicology (2020)

The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs—antisense oligonucleotides (ASOs)—show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Intrathecal injection into the cerebral spinal fluid results in broad distribution of antisense drugs and long-term effects. Approval of nusinersen in 2016 demonstrated that effective treatments for neurodegenerative diseases can be identified and that treatments not only slow disease progression but also improve some symptoms. Antisense drugs are currently in development for amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, and Angelman syndrome, and several drugs are in late-stage research for additional neurological diseases. This review highlights the advances in antisense technology as potential treatments for neurological diseases.
Prevalence and Outcome of COVID-19 Infection in Cancer Patients: A National Veterans Affairs Study
Authors: Nathanael R Fillmore, Jennifer La, Raphael E Szalat, David P Tuck, Vinh Nguyen, Cenk Yildirim, Nhan V Do, Mary T Brophy, Nikhil C Munshi
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Emerging data suggest variability in susceptibility and outcome to coronavirus disease 2019 (COVID-19) infection. Identifying risk factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations. Methods We analyzed electronic health records of the US Veterans Affairs Healthcare System and assessed the prevalence of COVID-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for COVID-19 who were positive, as well as outcome attributable to COVID-19, and stratified by clinical characteristics including demographics, comorbidities, cancer treatment, and cancer type. All statistical tests are 2-sided. Results Of 22 914 cancer patients tested for COVID-19, 1794 (7.8%) were positive. The prevalence of COVID-19 was similar across age. Higher prevalence was observed in African American (15.0%) compared with White (5.5%; P &amp;lt; .001) and in patients with hematologic malignancy compared with those with solid tumors (10.9% vs 7.8%; P &amp;lt; .001). Conversely, prevalence was lower in current smokers and patients who recently received cancer therapy (&amp;lt;6 months). The COVID-19–attributable mortality was 10.9%. Higher attributable mortality rates were observed in older patients, those with higher Charlson comorbidity score, and in certain cancer types. Recent (&amp;lt;6 months) or past treatment did not influence attributable mortality. Importantly, African American patients had 3.5-fold higher COVID-19–attributable hospitalization; however, they had similar attributable mortality as White patients. Conclusion Preexistence of cancer affects both susceptibility to COVID-19 infection and eventual outcome. The overall COVID-19–attributable mortality in cancer patients is affected by age, comorbidity, and specific cancer types; however, race or recent treatment including immunotherapy do not impact outcome.
Evaluation of a centralized toxicity view in the electronic health record (EHR) for physician-recorded Common Terminology Criteria for Adverse Events (CTCAE).
Authors: Rebecca Levin-Epstein, Martin Ma, Naomi Y. Jiang, Luca Faustino Valle, Stephanie Yoon, David Jablonsky, Michael L. Steinberg, Amar Upadhyaya Kishan, Allan D. Wu, Ann C. Raldow
Journal: Journal of Clinical Oncology (2020)

296 Background: Patients’ treatment-related acute and late toxicities are essential clinical data, yet this information is widely dispersed among notes in the EHR. This lack of structure impedes clinician ability to efficiently and comprehensively integrate toxicity information into clinical management. We aimed to consolidate toxicity data to improve clinician efficiency in accessing this information, and to evaluate the utility of this tool in radiation oncology. Methods: We developed an auto-updating flowsheet view (“Synopsis”) in the Epic EHR that longitudinally integrates physician-graded CTCAE toxicity selected using a SmartForm embedded in EHR notes. Physicians timed themselves performing 4 tasks to assess acute and post-treatment toxicity information for patients seen in follow-up, alternating with vs. without use of Synopsis. Wilcoxon Rank-Sum testing compared recorded task times with and without Synopsis. A survey was sent to physicians regarding qualitative utility of Synopsis. Results: Six physicians reviewed 98 patients seen in follow-up (49 with Synopsis, 49 without Synopsis) at median 8.1 months (Synopsis) and 6.5 months (no Synopsis) since completion of radiation (p = 0.88). Use of Synopsis was associated with significantly faster assessment of: overall toxicity history (median 50 vs. 93 seconds, p = 0.0007), highest acute toxicity during treatment (median 19 vs. 40 seconds, p = 0.0002), highest post-treatment toxicity (11 vs. 65 seconds, p &lt; 0.0001), and longitudinal review of a single symptom (8 vs. 61 seconds, p &lt; 0.0001). Among 10 physician survey respondents, 100% reported that Synopsis improved efficiency and 30% reported it led to a change in management. All physicians felt it was important to understand a patient’s toxicity history, but 80% reported that time required with the note-based EHR structure was prohibitive; with use of Synopsis, 90% reported that this task was now feasible. Specific domains most improved included ability to: identify high-grade toxicities (100%), contextualize new symptoms (80%), summarize treatment-related toxicity (80%), navigate in the EHR to a time of high-grade toxicity (60%), evaluate the success of an intervention (30%), and decide whether to discuss a reported new symptom (30%). Conclusions: A centralized toxicity view in the EHR improves clinician efficiency in evaluating longitudinal toxicity data and enhances clinician ability to comprehensively integrate toxicity information into patient care.
Evaluation of outpatient cancer rehabilitation for upper extremity functioning for individuals with breast cancer.
Authors: Mackenzi Pergolotti, Kelley Renee Covington, Michael Dean Stubblefield, Tiffany Kendig
Journal: Journal of Clinical Oncology (2020)

287 Background: Specialized cancer rehabilitation is recommended for individuals with breast cancer from diagnosis throughout survivorship to mitigate the negative acute, late and lasting effects of cancer and cancer treatment on upper extremity functioning. However, evidence supporting the impact of community-based outpatient rehabilitation services is lacking, especially for older adults. Methods: Individuals with breast cancer attended cancer-specialized outpatient physical or occupational therapy provided by a single institution with multiple locations across the US in 2019, and completed the Quick DASH (Disabilities of the Arm, Shoulder and Hand). From de-identified rehabilitation records, we abstracted patient and therapy characteristics, Quick DASH scores and therapy satisfaction scores (0-10 point scale) for individuals with a history of breast cancer (identified by ICD code). We used descriptive statistics to summarize characteristics, paired samples t-tests to evaluate Quick DASH scores from initial evaluation (pre) and discharge (post) therapy, and independent samples t-test to compare mean pre-post difference for individuals younger than 65 ( &lt; 65) versus 65 and older (≥ 65). Results: Patients ( N= 556) were 60.56 ± 12.24 (range = 31.52-89.95) years old and predominantly female ( n= 551, 99.1%). They attended cancer rehabilitation (Physical: n= 477, 85.8%, Occupational: n = 79 (14.2%)) for a median of 8 ( IQR= 5.0 – 13.0) sessions over 8.97 ± 7.57 (range = 0.71-47.7) weeks. Average pre-post change in Quick DASH score (-13.51) was significant (p &lt; .01) and exceeded the validated minimal clinically important difference (-11.20). There was no significant difference between average pre-post change for Quick Dash scores between &lt; 65 (n = 334, 60.1%) and ≥ 65 (n = 222, 39.9%) groups (-15.84 vs. -10.01, p = .07). Therapy satisfaction was rated high (median = 10.0, IQR = 10.0-10.0). Conclusions: Specialized rehabilitation for individuals with breast cancer was associated with statistically and clinically significant improvement in upper extremity function and high rates of satisfaction. Older adults demonstrated benefits similar to younger adults. These findings add to the growing evidence for specialized outpatient cancer rehabilitation.