Genetically Modified Porcine-to-Human Cardiac Xenotransplantation.

A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).

Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial.

BACKGROUND: Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics. METHODS: We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213). RESULTS: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples. CONCLUSIONS: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

Immunogenicity of COVID-19 Vaccination in Patients With End-Stage Renal Disease Undergoing Maintenance Hemodialysis: The Efficacy of a Mix-and-Match Strategy.

BACKGROUND: The objective of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with end-stage renal disease (ESRD) on hemodialysis. METHODS: ESRD patients at the hemodialysis center of a tertiary-care university-affiliated hospital and healthy employees at the clinical laboratory center were prospectively recruited between March and June 2021. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody analysis, blood samples were collected serially on days 0, 14, 28, and 56 after the first vaccine dose, and on days 7 and 50 after the second dose. Antibodies against the SARS-CoV-2 spike protein were quantified, and SARS-CoV-2 neutralizing antibodies were measured in the serum and plasma. RESULTS: Thirty-one ESRD patients and 55 healthy employees were regularly monitored. Twenty-five (80.6%) ESRD patients on hemodialysis received a mix-and-match strategy with ChAdOx1-BNT162b2 (AZ-Pf group) and six (19.4%) received two doses of ChAdOx1 (AZ-AZ group). ESRD patients on hemodialysis showed lower binding antibody titers and neutralizing antibody activities compared to healthy participants following the first vaccination with ChAdOx1. After the second dose, AZ-Pf group had higher immunogenicity than healthy people on days 7 and 50. The binding antibody titer and neutralizing antibody activities on days 7 and 50 were significantly higher in the AZ-Pf group than in the AZ-AZ group. CONCLUSION: ESRD patients on hemodialysis receiving the mix-and-match strategy (ChAdOx1-BNT162b2) have COVID-19 vaccine immunogenicity comparable to healthy individuals receiving two doses of ChAdOx1. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04871945.

Left ventricular hypertrophy in a contemporary cohort of autosomal dominant polycystic kidney disease patients.

BACKGROUND: Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) often develop hypertension in childhood or early adulthood. Although this could result in left ventricular hypertrophy (LVH), a major risk factor for cardiovascular morbidity and mortality, prior studies of LVH in ADPKD have yielded conflicting results. We estimated the prevalence of LVH using consensus echocardiography criteria and examined the independent association of ADPKD severity with LV mass in a contemporary cohort of ADPKD patients. METHODS: Adults with ADPKD and eGFR> 15 ml/min/1.73m2 were enrolled in a single-center study. Left Ventricular Mass (LVM) was quantified using 2D echocardiography, and LVH was defined using gender-specific cut-points of LVM and LVM indexed to body surface area (LVMI) from consensus guidelines. Total Kidney Volume (TKV) was quantified using Magnetic Resonance Imaging, and GFR was estimated from serum creatinine using the CKD-Epi equation. Multiple linear regression was used to estimate the association of TKV and eGFR with LVM and LVMI, adjusting for potential confounders. RESULTS: Among 126 participants (78% with hypertension), median age was 46 years, median eGFR 63 ml/min/1.73 m2, and median [IQR] systolic blood pressure was 125 [116-133] mmHg. Prevalence of LVH was 21.4% as defined by LVMI and was not significantly different (p = 0.8) between those with and without HTN, and was similar (21.4%) after excluding those (N = 21) with known cardiac disease. Greater TKV and lower eGFR were directly correlated with greater LVMI (p = .016 and p < .001, respectively). In multiple linear regression models accounting for potential confounders including blood pressure, greater TKV was positively associated with LVM ([Formula: see text] =0.19, p = 0.04). CONCLUSIONS: In a contemporary cohort of ADPKD patients with well-controlled blood pressure, the prevalence of LVH is high, and ADPKD severity as reflected by TKV is independently associated with greater LV mass. These results may suggest a relationship between ADPKD pathophysiology and increased LV mass.

Cardiac function assessed by myocardial deformation in adult polycystic kidney disease patients.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease. METHODS: A total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (- 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group. RESULTS: There was a significantly worse GLS in the ADPKD patients (mean: - 17.8 ± 2.5%) compared to the healthy controls (mean: - 21.9 ± 1.9%), p < 0.001. The same was true for E/SRe (mean: 10.0 ± 0.3 cm) compared to the control group (mean: 6.5 ± 0.3 cm), p < 0.001. In simple logistic regression, male gender (OR: 4.74 [2.10-10.71], p < 0.001), fasting glucose (odds ratio (OR) 1.05 [1.01-1.10], p = 0.024), htTKV (OR: 1.07 [1.01-1.13], p = 0.013), HDL cholesterol (OR: 0.97 [0.94, 0.996], p = 0.025), triglycerides (OR: 1.01 [1.00-1.02], p = 0.039), hemoglobin (OR: 1.50 [1.11-2.04], p = 0.009), and ß-blocker use (OR: 1.07 [1.01, 1.13], p = 0.013) were all associated with higher GLS. After multivariate logistic regression with backward model selection, only male gender (OR: 5.78 [2.27-14.71], p < 0.001) and ß-blocker use (OR: 14.00 [1.60, 122.51], p = 0.017) remained significant. In simple logistic regression models, BMI (OR: 1.11 [1.02-1.20], p = 0.015), systolic blood pressure (OR: 1.03 [1.00-1.06], p = 0.027) and ß-blocker use (OR: 17.12 [2.15-136.20], p = 0.007) were associated with higher E/SRe - a novel measure of left ventricular filling pressure. After backward elimination, only ß-blocker use (OR: 17.22 [2.16, 137.14], p = 0.007) remained significant. CONCLUSION: Higher GLS and E/SRe are common in ADPKD patients, even in patients with preserved eGFR and normal left ventricular EF. GLS and E/SRe may aid in cardiovascular risk stratification in patients with ADPKD as they represent early markers of cardiac dysfunction.

High-Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure: MESA (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Although small elevations of high-sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy. METHODS: We measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models. RESULTS: Late gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus 12% (highest category versus

Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. METHODS AND RESULTS: We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). CONCLUSIONS: Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

Compressed sensing reconstruction for undersampled breath-hold radial cine imaging with auxiliary free-breathing data.

PURPOSE: To improve compressed sensing (CS) reconstruction of accelerated breath-hold (BH) radial cine magnetic resonance imaging (MRI) by exploiting auxiliary data acquired between different BHs. MATERIALS AND METHODS: Cardiac function is usually assessed using segmented cine acquisitions over multiple BHs to cover the entire left ventricle (LV). Subjects are given a resting period between adjacent BHs, when conventionally no data are acquired and subjects rest in the scanner. In this study the resting periods between BHs were used to acquire additional free-breathing (FB) data, which are subsequently used to generate a sparsity constraint for each cardiac phase. Images reconstructed using the proposed sparsity constraint were compared with conventional CS using a composite image generated by averaging different cardiac phases. The efficacy of the proposed reconstruction was compared using indices of LV function and blood-myocardium sharpness. RESULTS: The proposed method provided accurate LV ejection fraction measurements for 33% and 20% sampled datasets compared with fully sampled reference images, and showed 14% and 11% higher blood-myocardium border sharpness scores compared to the conventional CS. CONCLUSION: The FB data acquired during resting periods can be efficiently used to improve the image quality of the undersampled BH data without increasing the total scan time.

Free-breathing 3D cardiac MRI using iterative image-based respiratory motion correction.

Respiratory motion compensation using diaphragmatic navigator gating with a 5 mm gating window is conventionally used for free-breathing cardiac MRI. Because of the narrow gating window, scan efficiency is low resulting in long scan times, especially for patients with irregular breathing patterns. In this work, a new retrospective motion compensation algorithm is presented to reduce the scan time for free-breathing cardiac MRI that increasing the gating window to 15 mm without compromising image quality. The proposed algorithm iteratively corrects for respiratory-induced cardiac motion by optimizing the sharpness of the heart. To evaluate this technique, two coronary MRI datasets with 1.3 mm(3) resolution were acquired from 11 healthy subjects (seven females, 25 ± 9 years); one using a navigator with a 5 mm gating window acquired in 12.0 ± 2.0 min and one with a 15 mm gating window acquired in 7.1 ± 1.0 min. The images acquired with a 15 mm gating window were corrected using the proposed algorithm and compared to the uncorrected images acquired with the 5 and 15 mm gating windows. The image quality score, sharpness, and length of the three major coronary arteries were equivalent between the corrected images and the images acquired with a 5 mm gating window (P-value > 0.05), while the scan time was reduced by a factor of 1.7.

Scar heterogeneity on cardiovascular magnetic resonance as a predictor of appropriate implantable cardioverter defibrillator therapy.

BACKGROUND: Despite the survival benefit of implantable-cardioverter-defibrillators (ICDs), the vast majority of patients receiving an ICD for primary prevention do not receive ICD therapy. We sought to assess the role of heterogeneous scar area (HSA) identified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) in predicting appropriate ICD therapy for primary prevention of sudden cardiac death (SCD). METHODS: From September 2003 to March 2011, all patients who underwent primary prevention ICD implantation and had a pre-implantation LGE-CMR were identified. Scar size was determined using thresholds of 4 and 6 standard deviations (SD) above remote normal myocardium; HSA was defined using 3 different criteria; as the region between 2 SD and 4 SD (HSA2-4SD), between 2SD and 6SD (HSA2-6SD), and between 4SD and 6SD (HSA4-6SD). The end-point was appropriate ICD therapy. RESULTS: Out of 40 total patients followed for 25 ± 24 months, 7 had appropriate ICD therapy. Scar size measured by different thresholds was similar in ICD therapy and non-ICD therapy groups (P = NS for all). However, HSA2-4SD and HSA4-6SD were significantly larger in the ICD therapy group (P = 0.001 and P = 0.03, respectively). In multivariable model HSA2-4SD was the only significant independent predictor of ICD therapy (HR = 1.08, 95%CI: 1.00-1.16, P = 0.04). Kaplan-Meier analysis showed that patients with greater HSA2-4SD had a lower survival free of appropriate ICD therapy (P = 0.026). CONCLUSIONS: In primary prevention ICD implantation, LGE-CMR HSA identifies patients with appropriate ICD therapy. If confirmed in larger series, HSA can be used for risk stratification in primary prevention of SCD.

The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors.

OBJECTIVE: Genetically engineered pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit growth and diastolic heart failure within 1 month after transplantation. Grafts function for up to 6 months, but only after administration of temsirolimus and afterload-reducing agents to reduce this growth. In this study we investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts, without the use of adjuncts to prevent intrinsic graft growth after transplantation. METHODS: Genetically engineered pig hearts were transplanted orthotopically into weight-matched baboons between 15 and 30 kg, using continuous perfusion preservation before implantation (n = 5). Xenografts included knockout of carbohydrate antigens and knockin of human transgenes for thromboregulation, complement regulation, and inflammation reduction (grafts with intact growth hormone, n = 2). Three grafts contained the additional knockout of GHR (GHR knockout grafts; n = 3). Transthoracic echocardiograms were obtained twice monthly and comprehensively analyzed by a blinded cardiologist. Hemodynamics were measured longitudinally after transplantation. RESULTS: All xenografts demonstrated life-supporting function after transplantation. There was no difference in intrinsic growth, measured using septal and posterior wall thickness and left ventricular mass, on transthoracic echocardiogram out to 1 month in either GHR knockout or GHR intact grafts. However, hypertrophy of the septal and posterior wall was markedly elevated by 2 months post transplantation. There was minimal hypertrophy out to 6 months in GHR knockout grafts. Physiologic mismatch was present in all grafts after transplantation, which is largely independent of growth. CONCLUSIONS: Xenografts with GHR knockout show reduced post-transplantation xenograft growth using echocardiography >6 months after transplantation, without the need for other adjuncts.

Left ventricular systolic dysfunction during acute pulmonary embolism.

BACKGROUND: Heart failure increases the risk of death in acute pulmonary embolism (PE). The role of the left ventricle (LV) in acute PE is not well defined. OBJECTIVE: To identify the prevalence of LV systolic dysfunction, morphology, and prognosis of the LV during an acute PE. METHODS: Retrospective study (26-months) of patients diagnosed with an acute PE presenting with LV systolic dysfunction at the University of Maryland. RESULTS: Among 769 acute PE patients, 78 (10.5 %) had LV systolic dysfunction and 42 (53.8 %) had history of cardiac disease. Patients without history of cardiac disease were younger (mean age [SD] 54.9 [16.8] vs. 62.6 [16.6]; p = 0.04), had a higher BMI (31.2 [12.2] vs. 29.2 [7.7]; p = 0.005), and less hypertension (20 [34.5 %] vs. 38 [65.5 %]; p = 0.0005). A massive PE was most common in patients without history of cardiac disease (8[22.2 %] vs. 2[4.7 %], p = 0.02). There was no difference in clot burden, but right ventricular strain was more frequently seen in patients without history cardiac disease in the initial CT (p = 0.001). The median troponin and lactate were similar in both groups. In 41 patients with follow-up echocardiograms, improvement in LVEF% was observed in patients without cardiac history (median Δ LVEF% [IQR]; 20 [6.2-25.0]). While patients with cardiac disease did not demonstrate similar changes (median Δ LVEF% [IQR]; 0 [-5-17.5]; p = 0.01). In hospital mortality was 12.8 % with no difference between both groups (p = 0.17). CONCLUSION: Pulmonary embolism can be associated with LV systolic dysfunction, even in patients without history of cardiac disease.

Accelerated late gadolinium enhancement cardiac MR imaging with isotropic spatial resolution using compressed sensing: initial experience.

PURPOSE: To evaluate the use of low-dimensional-structure self-learning and thresholding (LOST) compressed sensing acquisition and reconstruction in the assessment of left atrial (LA) and left ventricular (LV) scar by using late gadolinium enhancement (LGE) magnetic resonance (MR) imaging with isotropic spatial resolution. MATERIALS AND METHODS: The study was approved by the local institutional review board and was compliant with HIPAA. All subjects provided written informed consent. Twenty-eight patients (eight women; mean age, 58.0 years ± 10.1) with a history of atrial fibrillation were recruited for the LA LGE study, and 14 patients (five women; mean age, 54.2 years ± 18.6) were recruited for assessment of LV myocardial infarction. With use of a pseudorandom k-space undersampling pattern, threefold accelerated three-dimensional (3D) LGE data were acquired with isotropic spatial resolution and reconstructed off-line by using LOST. For comparison, subjects were also imaged by using standard 3D LGE protocols with nonisotropic spatial resolution. Images were compared qualitatively by three cardiologists with regard to diagnostic value, presence of enhancement, and image quality. The signed rank test and Wilcoxon unpaired two-sample test were used to test the hypothesis that there would be no significant difference in image quality ratings with different resolutions. RESULTS: Interpretable images were obtained in 26 of the 28 patients (93%) in the LA LGE study. LGE was seen in 17 of 30 cases (57%) with nonisotropic resolution and in 18 cases (60%) with isotropic resolution. Diagnostic quality scores of isotropic images were significantly higher than those of nonisotropic images with coronal views (median, 3 vs 2, respectively [25th and 75th percentiles: 3, 3 vs 2, 3]; P < .001) and sagittal views (median, 3 vs 2 [25th and 75th percentiles: 3, 4 vs 2, 3]; P < .001) but lower with axial views (median, 4 vs 3 [25th and 75th percentiles: 3, 4 vs 3, 3]; P < .001). For the LV LGE study, all patients had interpretable images. LGE was seen in six of 14 patients (43%), with 100% agreement between both data sets. Diagnostic quality scores of high-isotropic-resolution LV images were higher than those of nonisotropic images with short-axis views (median, 4 vs 3 [25th and 75th percentiles: 3, 4 vs 2, 3]; P = .014) and two-chamber views (median, 4 vs 3 [25th and 75th percentiles: 3, 4 vs 2, 3]; P = .001). CONCLUSION: An accelerated LGE acquisition with LOST enables imaging with high isotropic spatial resolution for improved assessment of LV, LA, and pulmonary vein scar.

Free-breathing cardiac MR with a fixed navigator efficiency using adaptive gating window size.

A respiratory navigator with a fixed acceptance gating window is commonly used to reduce respiratory motion artifacts in cardiac MR. This approach prolongs the scan time and occasionally yields an incomplete dataset due to respiratory drifts. To address this issue, we propose an adaptive gating window approach in which the size and position of the gating window are changed adaptively during the acquisition based on the individual's breathing pattern. The adaptive gating window tracks the breathing pattern of the subject throughout the scan and adapts the size and position of the gating window such that the gating efficiency is always fixed at a constant value. To investigate the image quality and acquisition time, free breathing cardiac MRI, including both targeted coronary MRI and late gadolinium enhancement imaging, was performed in 67 subjects using the proposed navigator technique. Targeted coronary MRI was acquired from eleven healthy adult subjects using both the conventional and proposed adaptive gating window techniques. Fifty-six patients referred for cardiac MRI were also imaged using late gadolinium enhancement with the proposed adaptive gating window technique. Subjective and objective image assessments were used to evaluate the proposed method. The results demonstrate that the proposed technique allows free-breathing cardiac MRI in a relatively fixed time without compromising imaging quality due to respiratory motion artifacts.

The association between dietary sodium intake and osteoporosis.

The association of inadequate dietary sodium intake with bone mineral density (BMD) and the risk of osteoporosis is controversial. To find the association between low sodium diet and the risk of incipient osteoporosis, we performed a population-based cross-sectional analysis using Tanaka method for estimation 24-h urinary sodium excretion (e24hUNaETanaka) as a candidate indicator of sodium intake. We identified 3869 participants without osteoporosis and classified them into quartiles according to their value of e24hUNaETanaka. BMD was measured to find participants at risk of osteoporosis. Lower e24hUNaETanaka was related to decreasing BMD of the distal radius. Multiple Cox-proportional hazard models demonstrated that e24hUNaETanaka had an inverse association with the risk of osteoporosis (adjusted HR = 0.859, 95% CI = 0.751-0.982) and survival analysis revealed that the lowest quartile group had poor osteoporosis-free survival (PLog-rank < 0.0001). Furthermore, our restricted cubic spline analysis revealed that the relationship between e24hUNaETanaka and HR of osteoporosis was negative curvilinear in males and postmenopausal females and positive linear in premenopausal females. Our findings suggest that lower sodium intake was a significant predictor of incipient osteoporosis and there was wide variation in this relationship according to sex and female hormone status.

Clinical outcomes and echocardiographic characteristics between African American and Caucasian patients with acute pulmonary embolism.

BACKGROUND: Despite socioeconomic disparities, no association between clinical presentation and poor outcomes explains a higher mortality in African Americans with pulmonary embolism (PE). The objective is to identify the co-morbidities and echocardiographic characteristics associated with increased mortality in African American patients. METHODS: This is a cross-sectional study of Caucasian or African American patients with PE diagnosed between October 2015 and December 2017 at University of Maryland Medical Center. The outcomes were in-hospital death, length of stay, and bleeding. RESULTS: There were 303 African Americans and 343 Caucasians. Caucasians were older (p = 0.007), males (p = 0.01) with history of coronary artery revascularization (CABG (p = 0.001), coronary stents (p = 0.001)), trauma (p = 0.007), and/or recent surgeries (p = 0.0001). African Americans exhibited higher rates of diabetes (p = 0.01), chronic kidney disease (p = 0.0005), and smoking (p = 0.04). Severity of PE was similar between groups and there was no difference in clot burden size. African Americans had more right ventricular strain on Computer Tomography (p = 0.001) and echocardiogram (p = 0.004); also, underfilled left ventricles (p = 0.02) and higher right ventricular systolic pressures (p = 0.001). There was no difference in hospital mortality (7.1% vs. 7.9%, p = 0.71), length of stay (13.1 ± 16.7 vs 12.8 ± 14.9, p = 0.80) and bleeding (9.0% vs.8.3%. p = 0.72). Mortality was higher in African Americans who received advanced therapies (3.8% vs. 18.8%, p = 0.02). The risk of death increased with age (OR 1.04; 95%CI 1.020-1.073) and with advanced therapies (OR 2.43; 95%CI 1.029-5.769). CONCLUSIONS: Differences in co-morbidities, radiologic findings, and echocardiographic characteristics that may contribute to higher mortality in African American patients, specifically those receiving advanced therapies.

Motion correction using coil arrays (MOCCA) for free-breathing cardiac cine MRI.

In this study, we present a motion correction technique using coil arrays (MOCCA) and evaluate its application in free-breathing respiratory self-gated cine MRI. Motion correction technique using coil arrays takes advantages of the fact that motion-induced changes in k-space signal are modulated by individual coil sensitivity profiles. In the proposed implementation of motion correction technique using coil arrays self-gating for free-breathing cine MRI, the k-space center line is acquired at the beginning of each k-space segment for each cardiac cycle with 4 repetitions. For each k-space segment, the k-space center line acquired immediately before was used to select one of the 4 acquired repetitions to be included in the final self-gated cine image by calculating the cross correlation between the k-space center line with a reference line. The proposed method was tested on a cohort of healthy adult subjects for subjective image quality and objective blood-myocardium border sharpness. The method was also tested on a cohort of patients to compare the left and right ventricular volumes and ejection fraction measurements with that of standard breath-hold cine MRI. Our data indicate that the proposed motion correction technique using coil arrays method provides significantly improved image quality and sharpness compared with free-breathing cine without respiratory self-gating and provides similar volume measurements compared with breath-hold cine MRI.

A case of an anomalous superior vena cava with anomalous pulmonary veins-when two wrongs do not make a right.

Intravenous agitated saline injection is useful in identifying right-to-left shunting at the atrial or intrapulmonary level. Anomalous systemic venous drainage to the left atrium is a rare but easily correctable cause of right-to-left shunting which, if left undiagnosed, may have serious consequences, including meningitis and pyogenic brain abscesses. This case illustrates an unusual cause of right-to-left shunting and the utility of venous microbubble injection in its diagnosis.

Prevalence and clinical characteristics of antibiotics associated drug induced liver injury.

BACKGROUND: The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury (DILI) also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI. METHODS: This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set. RESULTS: Antibiotics associated with DILI (64.0%) are the most common reason agent among consulting to hepatology department. Rheumatoid arthritis related drugs (11.0%), health supplements (5.0%), herbal medicines (4.0%), anti-viral drugs, anti-inflammatory analgesics/acetaminophen and lipid-lowering agents (3.0%) were next common causative drug for DILI in inpatients setting (training set). The frequency of antibiotics associated with DILI was high in order of flomoxef, cetrazole, ceftriaxone, vancomycin, piperacillin/tazobactam and amoxicillin/clavulanate. In the same period, 32% of the patients who prescribed flomoxef showed elevated liver enzyme levels above the upper normal limit. The prevalence of flomoxef induced DILI (>3 folds of ALT) was 13% and liver enzyme levels were five times higher than upper normal limits in 5% of flomoxef groups. Hypertension or diabetes was the risk factor of flomoxef associated with DILI. CONCLUSIONS: The Prevalence of antibiotics associated with DILI was 2-14%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.