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Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation.
Shoemaker MB, Husser D, Roselli C, Al Jazairi M, Chrispin J, Kühne M, Neumann B, Knight S, Sun H, Mohanty S, Shaffer C, Thériault S, Rinke LL, Siland JE, Crawford DM, Ueberham L, Zardkoohi O, Büttner P, Geelhoed B, Blum S, Aeschbacher S, Smith JD, Van Wagoner DR, Freudling R, Müller-Nurasyid M, Montgomery J, Yoneda Z, Wells Q, Issa T, Weeke P, Jacobs V, Van Gelder IC, Hindricks G, Barnard J, Calkins H, Darbar D, Michaud G, Kääb S, Ellinor P, Natale A, Chung M, Nazarian S, Cutler MJ, Sinner MF, Conen D, Rienstra M, Bollmann A, Roden DM, Lubitz S
(2020) Circ Arrhythm Electrophysiol 13: e007676
MeSH Terms: Aged, Atrial Fibrillation, Body Surface Potential Mapping, Catheter Ablation, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Preoperative Period, Prognosis, Prospective Studies, Recurrence
Show Abstract · Added March 24, 2020
BACKGROUND - Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.
METHODS - Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.
RESULTS - Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (<0.001) and had fewer clinical risk factors for AF (=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; <0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; <0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; =0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; =0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; =0.13).
CONCLUSIONS - Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.
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16 MeSH Terms
Mindfulness-Based Blood Pressure Reduction (MB-BP): Stage 1 single-arm clinical trial.
Loucks EB, Nardi WR, Gutman R, Kronish IM, Saadeh FB, Li Y, Wentz AE, Webb J, Vago DR, Harrison A, Britton WB
(2019) PLoS One 14: e0223095
MeSH Terms: Blood Pressure, Blood Pressure Determination, Feasibility Studies, Female, Focus Groups, Follow-Up Studies, Humans, Hypertension, Interviews as Topic, Male, Middle Aged, Mindfulness, Patient Acceptance of Health Care, Qualitative Research, Treatment Outcome
Show Abstract · Added January 4, 2020
BACKGROUND AND OBJECTIVES - Impacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP).
METHODS - This was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure.
RESULTS - Acceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, p<0.001), emotion regulation (Difficulties in Emotion Regulation Score, p = 0.02), and self-awareness (Multidimensional Assessment of Interoceptive Awareness, p<0.001). Several determinants of hypertension were improved in participants not adhering to American Heart Association guidelines at baseline, including physical activity (p = 0.02), Dietary Approaches to Stop Hypertension-consistent diet (p<0.001), and alcohol consumption (p<0.001). Findings demonstrated mean 6.1 mmHg reduction in SBP (p = 0.008) at one year follow-up; effects were most pronounced in Stage 2 uncontrolled hypertensives (SBP≥140 mmHg), showing 15.1 mmHg reduction (p<0.001).
CONCLUSION - MB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.
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The impact of social determinants of health on laryngotracheal stenosis development and outcomes.
Dang S, Shinn JR, Campbell BR, Garrett G, Wootten C, Gelbard A
(2020) Laryngoscope 130: 1000-1006
MeSH Terms: Adult, Aged, Aged, 80 and over, Critical Care, Female, Follow-Up Studies, Humans, Laryngoscopy, Laryngostenosis, Male, Middle Aged, Retrospective Studies, Risk Factors, Social Determinants of Health, Time Factors, Tracheal Stenosis, Treatment Outcome, Young Adult
Show Abstract · Added July 30, 2020
OBJECTIVES - The social determinants of health affect a wide range of health outcomes and risks. To date, there have been no studies evaluating the impact of social determinants of health on laryngotracheal stenosis (LTS). We sought to describe the social determinants in a cohort of LTS patients and explore their association with treatment outcome.
METHODS - Subjects diagnosed with LTS undergoing surgical procedures between 2013 and 2018 were identified. Matched controls were identified from intensive care unit (ICU) patients who underwent intubation for greater than 24 hours. Medical comorbidities, stenosis characteristics, and patient demographics were abstracted from the clinical record. Tracheostomy at last follow-up was recorded from the medical record and phone calls. Socioeconomic data was obtained from the American Community Survey.
RESULTS - One hundred twenty-two cases met inclusion criteria. Cases had significantly lower education compared to Tennessee (P = .009) but similar education rates as ICU controls. Cases had significantly higher body mass index (odds ratio [OR]: 1.04, P = .035), duration of intubation (OR: 1.21, P < .001), and tobacco use (OR: 1.21, P = .006) in adjusted analysis when compared to controls. Tracheostomy dependence within the case cohort was significantly associated with public insurance (OR: 1.33, P = .016) and chronic obstructive pulmonary disease (OR: 1.34, P = .018) in adjusted analysis.
CONCLUSION - Intubation practices, medical comorbidities and social determinants of health may influence the development of LTS and tracheostomy dependence after treatment. Identification of at-risk populations in ICUs may allow for prevention of tracheostomy dependence through the use of early tracheostomy and specialized follow-up.
LEVEL OF EVIDENCE - Level 3, retrospective review comparing cases and controls Laryngoscope, 130:1000-1006, 2020.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.
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High prevalence of antibiotic allergies in cladribine-treated patients with hairy cell leukemia - lessons for immunopathogenesis and prescribing.
Meher-Homji Z, Tam CS, Siderov J, Seymour JF, Holmes NE, Chua KYL, Phillips EJ, Slavin MA, Trubiano JA
(2019) Leuk Lymphoma 60: 3455-3460
MeSH Terms: Adult, Aged, Anti-Bacterial Agents, Antineoplastic Combined Chemotherapy Protocols, Australia, Case-Control Studies, Cladribine, Drug Hypersensitivity, Female, Follow-Up Studies, Humans, Leukemia, Hairy Cell, Male, Middle Aged, Prevalence, Prognosis, Retrospective Studies, Survival Rate, Vidarabine
Show Abstract · Added March 30, 2020
The relationship between hematological malignancy and chemotherapy on the prevalence of antibiotic allergy label (AAL) is ill-defined. We performed a multicenter retrospective case-control study comparing AAL rates among cladribine-treated hairy cell leukemia (C-HCL) cases, non-HCL cladribine-treated controls (control-1), and fludarabine-treated controls (control-2). The prevalence of AALs in C-HCL patients was 60%, compared with control-1 (14%,  < .01) and control-2 patients (25%,  < .01). The predominant phenotype was maculopapular exanthem (92%). The drugs implicated in AAL causality in C-HCL patients included beta-lactams (81%), trimethoprim-sulfamethoxazole (58%), and allopurinol (69%). C-HCL patients demonstrate high rates of AAL, potentially due to immune dysregulation, impacting beta-lactam utilization.
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19 MeSH Terms
Multicenter Validation of the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) Score.
Mikati AG, Flahive J, Khan MW, Vedantam A, Gopinath S, Nordness MF, Robertson C, Patel MB, Sheth KN, Muehlschlegel S
(2019) Neurosurgery 85: E872-E879
MeSH Terms: Adolescent, Adult, Aged, Brain Injuries, Cohort Studies, Female, Follow-Up Studies, Glasgow Coma Scale, Head Injuries, Penetrating, Humans, Injury Severity Score, Male, Middle Aged, Registries, Retrospective Studies, Young Adult
Show Abstract · Added June 6, 2019
BACKGROUND - Civilian penetrating traumatic brain injury (pTBI) is a serious public health problem in the United States, but predictors of outcome remain largely understudied. We previously developed the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) score, a logistic, regression-based risk stratification scale for estimating in-hospital and 6-mo survival after civilian pTBI with excellent discrimination (area under the receiver operating curve [AUC-ROC = 0.96]) and calibration, but it has not been validated.
OBJECTIVE - To validate the SPIN score in a multicenter cohort.
METHODS - We identified pTBI patients from 3 United States level-1 trauma centers. The SPIN score variables (motor Glasgow Coma Scale [mGCS], sex, admission pupillary reactivity, self-inflicted pTBI, transfer status, injury severity score, and admission international normalized ratio [INR]) were retrospectively collected from local trauma registries and chart review. Using the original SPIN score multivariable logistic regression model, AUC-ROC analysis and Hosmer-Lemeshow goodness of fit testing were performed to determine discrimination and calibration.
RESULTS - Of 362 pTBI patients available for analysis, 105 patients were lacking INR, leaving 257 patients for the full SPIN model validation. Discrimination (AUC-ROC = 0.88) and calibration (Hosmer-Lemeshow goodness of fit, P value = .58) were excellent. In a post hoc sensitivity analysis, we removed INR from the SPIN model to include all 362 patients (SPINNo-INR), still resulting in very good discrimination (AUC-ROC = 0.82), but reduced calibration (Hosmer-Lemeshow goodness of fit, P value = .04).
CONCLUSION - This multicenter pTBI study confirmed that the full SPIN score predicts survival after civilian pTBI with excellent discrimination and calibration. Admission INR significantly adds to the prediction model discrimination and should be routinely measured in pTBI patients.
Copyright © 2019 by the Congress of Neurological Surgeons.
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16 MeSH Terms
Papillary thyroid carcinoma behavior: clues in the tumor microenvironment.
Bergdorf K, Ferguson DC, Mehrad M, Ely K, Stricker T, Weiss VL
(2019) Endocr Relat Cancer 26: 601-614
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Female, Follow-Up Studies, Humans, Lymphocytes, Tumor-Infiltrating, Male, Middle Aged, Mutation, Prognosis, Thyroid Cancer, Papillary, Thyroid Neoplasms, Tumor Microenvironment, Young Adult
Show Abstract · Added April 15, 2019
The prevalence of thyroid carcinoma is increasing and represents the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most frequent subtype. The genetic alterations identified in PTCs fail to distinguish tumors with different clinical behaviors, such as extra-thyroidal extension and lymph node metastasis. We hypothesize that the immune microenvironment may play a critical role in tumor invasion and metastasis. Computational immunogenomic analysis was performed on 568 PTC samples in The Cancer Genome Atlas using CIBERSORT, TIMER and TIDE deconvolution analytic tools for characterizing immune cell composition. Immune cell infiltrates were correlated with histologic type, mutational type, tumor pathologic T stage and lymph node N stage. Dendritic cells (DCs) are highly associated with more locally advanced tumor T stage (T3/T4, odds ratio (OR) = 2.6, CI = 1.4-4.5, P = 5.4 × 10-4). Increased dendritic cells (OR = 3.4, CI = 1.9-6.3, P = 5.5 × 10-5) and neutrophils (OR = 10.5, CI = 2.7-44, P = 8.7 × 10-4) significantly correlate with lymph node metastasis. In addition, dendritic cells positively correlate with tall cell morphology (OR = 4.5, CI = 1.6-13, P = 4.9 × 10-3) and neutrophils negatively correlate with follicular morphology (OR = 1.3 × 10-3, CI = 5.3 × 10-5-0.031, P = 4.1 × 10-5). TIDE analysis indicates an immune-exclusive phenotype that may be mediated by increased galectin-3 found in PTCs. Thus, characterization of the PTC immune microenvironment using three computational platforms shows that specific immune cells correlate with mutational type, histologic type, local tumor extent and lymph node metastasis. Immunologic evaluation of PTCs may provide a better indication of biologic behavior, resulting in the improved diagnosis and treatment of thyroid cancer.
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Stroke Recurrence in Nigerian Children With Sickle Cell Disease: Evidence for a Secondary Stroke Prevention Trial.
Abdullahi SU, DeBaun MR, Jordan LC, Rodeghier M, Galadanci NA
(2019) Pediatr Neurol 95: 73-78
MeSH Terms: Adolescent, Anemia, Sickle Cell, Antisickling Agents, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Hydroxyurea, Infant, Male, Nigeria, Prospective Studies, Recurrence, Secondary Prevention, Stroke
Show Abstract · Added March 24, 2020
BACKGROUND - To improve the quality of care for children with sickle cell anemia in Kano, Nigeria, we initiated a standard care protocol in 2014 to manage children with strokes at Aminu Kano Teaching Hospital.
METHODS - The standard care protocol requires that children with acute strokes be treated with hydroxyurea at a fixed dose of 20 mg/kg/day within two months of the stroke.
RESULTS - Twenty-nine children with sickle cell anemia and initial stroke were identified based on clinical World Health Organization criteria from 2014 to 2017. Follow-up was a median of 1.04 years (interquartile range 0.43 to 1.83 years) to either July 2017 or a second stroke, corresponding to an initial stroke incidence rate of 0.88 per 100 patient-years. Eight children had a recurrent stroke, six of whom were prescribed hydroxyurea 20 mg/kg/day by two months after initial stroke. Two children died. Six of the recurrent strokes occurred within six months of the initial stroke, two before hydroxyurea prescription. The stroke recurrence rate was 17.4 events per 100 patient-years. Adherence was approximately 60%, partly because families had to pay for hydroxyurea. Stroke incidence is probably underestimated because despite formal training for stroke detection during the quality improvement period, no participant had assessment using a standardized pediatric stroke scale and neuroimaging was not available.
CONCLUSIONS - In children with sickle cell anemia, a high rate of initial and recurrent strokes exists in a low-resource setting. Ongoing needs include training to detect strokes with an objective stroke assessment and government-supported free access to hydroxyurea for stroke prevention.
Copyright © 2019 Elsevier Inc. All rights reserved.
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16 MeSH Terms
Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis.
Limketkai BN, Shah SC, Hirano I, Bellaguarda E, Colombel JF
(2019) Gut 68: 2152-2160
MeSH Terms: Adolescent, Adult, Aged, Child, Child, Preschool, Comorbidity, Eosinophilic Esophagitis, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Inflammatory Bowel Diseases, Male, Middle Aged, Population Surveillance, Prevalence, Prospective Studies, Risk Assessment, Risk Factors, United States, Young Adult
Show Abstract · Added March 3, 2020
OBJECTIVE - Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses.
DESIGN - We conducted a prospective cohort analysis using the Truven MarketScan database (2009-2016) to estimate the incidence and prevalence of EoO in patients with Crohn's disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses.
RESULTS - Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p<0.01; prevalence ratio (PR) 7.8, p<0.01) or UC (IRR 3.5, p<0.01; PR 5.0, p<0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p<0.01; PR 7.6, p<0.01; UC: IRR 3.4, p<0.01; PR 4.9, p<0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p<0.01).
CONCLUSION - Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
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Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease.
Scoville EA, Allaman MM, Adams DW, Motley AK, Peyton SC, Ferguson SL, Horst SN, Williams CS, Beaulieu DB, Schwartz DA, Wilson KT, Coburn LA
(2019) Sci Rep 9: 2882
MeSH Terms: Adipokines, Adult, Biomarkers, Case-Control Studies, Crohn Disease, Cytokines, Fatty Acids, Unsaturated, Female, Follow-Up Studies, Humans, Inflammation Mediators, Male, Middle Aged, Prognosis, Prospective Studies, Severity of Illness Index
Show Abstract · Added March 16, 2019
Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.
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16 MeSH Terms
Associations of Unhealthy Food Environment With the Development of Coronary Artery Calcification: The CARDIA Study.
Kelman J, Pool LR, Gordon-Larsen P, Carr JJ, Terry JG, Rana JS, Kershaw KN
(2019) J Am Heart Assoc 8: e010586
MeSH Terms: Adolescent, Adult, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Disease Progression, Female, Follow-Up Studies, Food Supply, Forecasting, Humans, Incidence, Male, Prospective Studies, Restaurants, Risk Assessment, Risk Factors, United States, Vascular Calcification, Young Adult
Show Abstract · Added April 3, 2019
Background While prior studies have linked the neighborhood environment and development of subclinical atherosclerosis, it is unknown whether living in neighborhoods with greater availability of "unhealthy" food outlets (fast-food chain restaurants and convenience stores) is associated with risk of developing coronary artery calcification ( CAC ). Methods and Results We included 2706 CARDIA study (Coronary Artery Risk Development in Young Adults) participants who underwent CAC measurement during follow-up years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011). Neighborhood features examined included percentage of all food outlets that were convenience stores and fast-food chain restaurants within a 3-km Euclidean buffer distance from each participant's residence. Econometric fixed effects models, which by design control for all time-invariant covariates, were used to model the longitudinal association between simultaneous within-person change in percentage food outlet and change in CAC . At baseline (year 15), 9.7% of participants had prevalent CAC . During 10 years of follow-up, 21.1% of participants developed CAC . Each 1-SD increase in percentage of convenience stores was associated with a 1.34 higher odds of developing CAC (95% CI : 1.04, 1.72) after adjusting for individual- and neighborhood-level covariates; however, there was no significant association between increased percentage of fast-food chain restaurants and developing CAC (odds ratio=1.15; 95% CI : 0.96, 1.38). There were no significant associations between increases in either food outlet percentage and progression of CAC . Conclusions Our findings suggest that increases in the relative availability of convenience stores in participants' neighborhoods is related to the development of CAC over time.
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20 MeSH Terms