Citations

AbstractCeliac disease is a global disease requiring genetic susceptibility and gluten exposure to trigger immune‐mediated enteropathy. The effect of the degree of gluten‐containing grain availability on celiac disease prevalence is unknown. Our objective was to compare country‐based gluten availability to celiac prevalence using a systematic literature review. We searched MEDLINE, Embase, Cochrane, and Scopus until May 2021. We included population‐based serum screening with confirmatory testing (second serological study or small intestine biopsy) and excluded specific, high‐risk, or referral populations. We determined country‐specific gluten availability using the United Nations food balance for wheat, barley, and rye. Human leukocyte antigen (HLA) frequencies were obtained from allelefrequencies.net. The primary outcome was association between gluten‐containing grain availability and celiac disease prevalence. Generalized linear mixed models method with Poisson's link was used for analysis. We identified 5641 articles and included 120 studies on 427 146 subjects from 41 countries. Celiac disease prevalence was 0–3.1%, median 0.75% (interquartile range 0.35, 1.22). Median wheat supply was 246 g/capita/day (interquartile range 214.8, 360.7). The risk ratio (RR) for wheat availability on celiac disease was 1.002 (95% confidence interval [CI]: 1.0001, 1.004, P = 0.036). A protective association was seen with barley, RR 0.973 (95% CI: 0.956, 0.99, P = 0.003), and rye, RR 0.989 (95% CI: 0.982, 0.997, P = 0.006). The RR for gross domestic product on celiac disease prevalence was 1.009 (95% CI: 1.005, 1.014, P < 0.001). The RR for HLA‐DQ2 was 0.982 (95% CI: 0.979, 0.986, P < 0.001), and that for HLA‐DQ8 was 0.957 (95% CI: 0.950, 0.964, P < 0.001). In this geo‐epidemiologic study, gluten‐containing grain availability showed mixed associations with celiac disease prevalence.

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on its incidence, risk factors, and clinical outcomes are scarce. Objective We aimed to study the incidence, risk factors and clinical significance of AFMR, defined as &gt;mild functional MR in the absence of more than mild left ventricle enlargement or dysfunction, in AF and sinus rhythm (SR). Methods Adults with a new diagnosis of AF between 2010–2021 who had a transthoracic echocardiogram (TTE) were identified (n=57,109). Similarly, adults with no diagnosis of AF who had a TTE between 2010–2021 were identified for comparison (n= 364,767). Patients with &gt;mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, or with no follow up TTE ≥6 months from baseline were excluded. Furthermore, patients with AF had to have a TTE within 1 month of AF diagnosis. The presence of ≥2 of 4 abnormal diastolic function parameters [mitral septal e’ &lt;0.07 m/sec, mitral septal E/e’ &gt;15 in SR and &gt;11 in AF, TR velocity &gt;2.80 m/sec, left atrial volume index &gt;34 ml/m2] was determined. Cox proportional hazards regression was used to determine risk factors associated with incident AFMR and all-cause death. Patients without the event of interest were censored at last follow up. Patients who developed &gt;mild MR of other types (primary or functional ventricular) were censored at that time. Results Overall, 1,747 (median age 67 years; 34% females) patients with AF and 29,623 (median age 59; 51% females) in SR were included. Incident AFMR occurred in 167 patients with AF over median 3.1 (IQR 1.6–5.1) years [incidence rate of 2.6 per 100-person year] and in 780 patients in SR over median 3.1 (IQR 1.5–5.8) years [incidence rate 0.7 per 100-person year] (Figure 1). AF remained associated with AFMR after adjusting to confounding factors [age ≥65, female sex, ≥2 abnormal diastolic function parameters, and low hemoglobin; adjusted HR 3.23 (2.71–3.85)]. Independent risk factors associated with incident AFMR in AF were age ≥65, female sex, persistent AF, and ≥2 abnormal diastolic function parameters, whereas successful rhythm control without recurrence was a protective factor (Figure 2a). Risk factors for AFMR in SR were age ≥65 years, female sex, presence of ≥2 abnormal diastolic function parameters, and low hemoglobin (Figure 2a). Incident AFMR was independently associated with all-cause death in both AF and SR (Figure 2b). Conclusions AF confers more than 3-fold increase in the risk of AFMR. Diastolic dysfunction, older age, and female sex were independent risk factors for incident AFMR in both SR and AF. Paroxysmal AF and successful rhythm control were protective factors against AFMR in AF. AFMR is universally associated with worse mortality.

Abstract Funding Acknowledgements Type of funding sources: None. Background Severe aortic-stenosis (AS) is the guideline-based indication for aortic-valve-replacement (AVR) performance, which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory, uncertain and lacking quantitative Doppler-Echocardiographic ascertainment. Thus, population-based trends in presentation, treatment and outcome are unknown. Methods All adults residents our County (MN,USA) diagnosed with incident (first-diagnosis) severe AS based on quantitative Doppler-Echocardiography (aortic-valve-area≤1cm2, aortic-valve-area-index≤0.6cm2/m2, mean-gradient≥40mmHg, peak-velocity≥4m/s, Doppler-velocity-index≤0.25) between 1997–2016, were accounted for and trends for incidence, presentation, treatment and outcome analysed. Results Incident severe-AS was diagnosed in 1069 community-residents over 20-years. Incidence-rate was 52.5[49.4–55.8] per 100.000 patient/year, slightly higher in male vs. female and was almost unchanged after age and sex adjustment for the US population 53.8[50.6–57.0] per-100000 residents/year. Over 20-years severe AS-incidence remained stable (p = 0.20) but absolute-burden of incident-cases markedly increased (p = 0.0004) due to population growth. Incidence-trend differed by sex, stable in men (incidence-rate-ratio 0.99, p = 0.72) but declining in women: (incidence-rate-ratio 0.93, p = 0.024). AS clinical-presentation, age, symptoms, comorbidity, ventricular size/function, valve-area-index, low-flow or low-ejection-fraction AS, remained stable. Over the study 20 years, AVR performance grew (1997–2001 to 2012–2016, at 3-month:14% to 21%, p = 0.02; at 1-year 19% to 33%,p&lt;0.0001), and was more prompt (from 1.3[0.11–3.3]years in 1997–2001 to 0.48[0.15–2.11]years in 2013–2016, p = 0.001) but severe AS undertreatment remained prominent (&gt;40%). Early-AVR (within 3-months) was associated with survival benefit (adjusted-hazard-ratio 0.55[0.42–0.71], p&lt;0.0001) stable throughout the 20-years. Despite these improvements, overall mortality, 8.3% within 3-months, 17.8% within 1-year, 36% within 3-years, was swift, considerable and unabated (all p≥0.44) throughout the 20-year study. Conclusion Over 20 years, the population incidence of severe-AS remained stable with increased absolute case-burden purely related to population growth. Despite stable severe-AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease-lethality did not decline. These findings have important population-health management implications.

Abstract Funding Acknowledgements Type of funding sources: None. Background Aortic valve stenosis (AS) and heart failure with preserved ejection fraction (HFpEF) present with similar cardiac alterations, but their overlap is poorly understood.(1–3). Purpose To study left ventricular (LV) hypertrophy, diastolic dysfunction, left atrial (LA) dysfunction, hemodynamics, and exercise capacity according to HFpEF status versus AS severity. Methods Patients (n=206) with at least moderate AS (aortic valve area ≤0.85 cm2/m2) and discordant symptoms underwent cardiopulmonary exercise testing with simultaneous echocardiography. The population was stratified according to the probability of underlying HFpEF by the H2FPEF score [0–5 (AS/HFpEF-) vs. 6–9 points (AS/HFpEF+)] and AS severity (Moderate vs. Severe). Results Mean age was 73±10 years with 40% women. Stratification yielded 41 AS/HFpEF+ (20%) versus 165 AS/HFpEF- (80%) and 139 Severe (67%) versus 67 Moderate (33%) AS patients. AS/HFpEF+ patients had a lower LV global longitudinal strain, impaired diastolic function, reduced LV compliance, and more pronounced LA dysfunction compared to AS/HFpEF- patients. The mean pulmonary arterial pressure-cardiac output (mPAP/CO) slope was significantly higher in AS/HFpEF+ versus AS/HFpEF- (5.4±3.1 vs. 3.9±2.2 mmHg/L/min, respectively; p = 0.003), mainly driven by impaired cardiac output (CO) reserve and chronotropic incompetence, with signs of right ventricular-pulmonary arterial (RV-PA) uncoupling. AS/HFpEF+ versus AS/HFpEF- was associated with a lower peak aerobic capacity (11.5±3.7 vs. 15.9±5.9 mL/min/kg, respectively; p&lt;0.0001), but did not differ between Moderate and Severe AS (14.7±5.5 vs. 15.2±5.9mL/min/kg, respectively; p = 0.6). Conclusions A high H2FPEF score is associated with a reduced exercise capacity and adverse hemodynamics in patients with moderate to severe AS. Both exercise performance and hemodynamics correspond better with intrinsic cardiac dysfunction than AS severity itself.

Abstract Funding Acknowledgements Type of funding sources: None. Background The impact of capacitance and blood volume redistribution on outcomes of patients with chronic heart failure is incompletely understood. Quantitative plasma volume (PV) measurements together with echocardiographic evaluation allow a comprehensive assessment of the interplay between volumetric overload, cardiac chamber remodelling and myocardial function. Purpose We hypothesize that PV expansion is associated with myocardial and renal dysfunction, right ventricular-pulmonary arterial uncoupling and unfavorable outcomes in HF patients with reduced ejection fraction (HFrEF). Methods Patients hospitalized at Mayo Clinic with decompensated HF and who had PV by the indicator-dilution nuclear methodology (Daxor BVA100) were included. Patients were considered hypervolemic if BV was ≥25% over expected. The primary endpoint was the composite of all-cause mortality or heart transplantation. The closest TTE to the time of PV was used to measure various indexes of myocardial performance (standard echo parameters and global chamber-specific strain parameters). Event-free survival was estimated using the Kaplan-Meier method. The relationship between PV and various parameters was evaluated with correlation coefficient (r²). Results A total of 65 patients were enrolled in the study. Reduced LVEF was present in 53 (81.6%) patients. There were 44 events (32 deaths, 12 heart transplants) after a median follow-up of 43 months (IQR 14–65). Results in patients with HFrEF are presented in the Table. Our main findings were: 1) PV expansion was associated with an increased risk of adverse events (Figure 1); 2) Volume redistribution correlated with various indexes of cardiac chamber function, suggesting that volume overload and associated cardiac remodeling may be responsible for altered myocardial mechanics in patients with HFrEF (Figure 2); 3) right ventricular-pulmonary arterial uncoupling was triggered by the plasma volume expansion, that causes postcapillary pulmonary hypertension; 4) PV redistribution was also associated with renal dysfunction and increasing the level of the protein catabolism (Table 1). Conclusion Expansion of plasma volume in HFrEF patients is associated with left atrium dilatation, abnormal filling of both atria and right ventricular dilatation / dysfunction. Plasma volume redistributions apparently became a trigger of right ventricular-pulmonary arterial uncoupling and stimulated postcapillary pulmonary hypertension, renal dysfunction with increasing the level of protein catabolism and unfavorable outcomes.

OBJECTIVE Tectal plate gliomas are rare, slow-growing tumors of the midbrain that are discovered predominantly in the pediatric population. Because of their indolent nature, treatment mainly consists of observation and management of hydrocephalus. Unfortunately, a subset of tectal gliomas may exhibit tumor enlargement and disease progression. Currently, there are no established guidelines for predicting future progression of tectal gliomas or the need for tumor-directed treatment. In this paper, the authors present a large case series of tectal plate gliomas with the aim of determining early indicators of tumor progression and the need for tumor-directed treatment in a pediatric population, along with providing their experience in treating progressive tumors. METHODS A retrospective chart review of 170 patients diagnosed with tectal plate glioma from a single institution, of whom 67 were pediatric patients (≤ 18 years of age), was performed. Univariate analysis was used to determine statistically significant predictors of symptomatic disease progression requiring eventual tumor-directed therapy. RESULTS The median patient age of the full cohort was 24 years (range 0–73 years). Compared with the pediatric population, the adult population had more instances of incidental lesions (p < 0.001) and lower rates of hydrocephalus (50% vs 84%, p < 0.001). Of the pediatric patients who had ≥ 5 years of follow-up (n = 51), 12 (24%) experienced radiological progression and 13 (25%) required treatment for their tumor. The 1-year, 5-year, and 10-year radiographic progression-free survival (PFS) rates were 98%, 90%, and 86%, respectively. In univariate analysis, lesion involvement of the pons, moderate T1 hypointensity, and moderate contrast enhancement on baseline radiology were significantly associated with worse radiographic PFS. Alternatively, significant predictors of requiring tumor-directed treatment included extraocular eye movement abnormalities at presentation, involvement of the lesion beyond the tectum on baseline radiology, moderate T1 hypointensity, moderate contrast enhancement, and an increase in total lesion size during progression. At the most recent follow-up, 94% of the patients had stable/nonprogressive disease, 2% had progressive disease, and 4% died of tumor progression. CONCLUSIONS Patients who demonstrate radiographic progression may not necessarily experience clinical/symptomatic progression or require tumor-directed treatment. Certain patient presentation characteristics and baseline radiographic features may be predictive of worse radiographic PFS or the need for future tumor-directed treatment in the pediatric population. Typically, the natural history of these lesions lends to excellent long-term survival, even in patients who experience clinical progression, should appropriate treatment be initiated.

Abstract Objective Textual radiology reports contain a wealth of information that may help understand associations among diseases and imaging observations. This study evaluated the ability to detect causal associations among diseases and imaging findings from their co-occurrence in radiology reports. Materials and Methods This IRB-approved and HIPAA-compliant study analyzed 1 702 462 consecutive reports of 1 396 293 patients; patient consent was waived. Reports were analyzed for positive mention of 16 839 entities (disorders and imaging findings) of the Radiology Gamuts Ontology (RGO). Entities that occurred in fewer than 25 patients were excluded. A Bayesian network structure-learning algorithm was applied at P &lt; 0.05 threshold: edges were evaluated as possible causal relationships. RGO and/or physician consensus served as ground truth. Results 2742 of 16 839 RGO entities were included, 53 849 patients (3.9%) had at least one included entity. The algorithm identified 725 pairs of entities as causally related; 634 were confirmed by reference to RGO or physician review (87% precision). As shown by its positive likelihood ratio, the algorithm increased detection of causally associated entities 6876-fold. Discussion Causal relationships among diseases and imaging findings can be detected with high precision from textual radiology reports. Conclusion This approach finds causal relationships among diseases and imaging findings with high precision from textual radiology reports, despite the fact that causally related entities represent only 0.039% of all pairs of entities. Applying this approach to larger report text corpora may help detect unspecified or heretofore unrecognized associations.

Abstract Objective To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). Methods Information sources : Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. Eligibility criteria : Systematic reviews and meta‐analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. Data : Target diseases, model components used ( n = 11), and six outcomes (disease‐specific, generic health‐related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). Synthesis : Narrative synthesis, including proportion of reviews documenting outcome benefits. Results More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes ( n = 22), depression ( n = 16), heart disease ( n = 12), aging ( n = 11), and kidney disease ( n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease‐specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. Conclusions Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.