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Background: Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF) and amplifies regional kidney hypoxia, but their relationship to tissue inflammation and injury markers is poorly understood. We tested the hypothesis that renal injury, reflected by renal vein levels of neutrophil gelatinase associated lipocalin (NGAL) and inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) would be magnified with severe occlusive vascular disease in humans with ARAS. Methods: Inpatient studies performed in patients with ARAS (n=40, 71.3±11% occlusion by CT angiography) or essential hypertension (EH) (n=30), during fixed Na+ intake and ACE/ARB Rx. Single-kidney cortical and medullary perfusion and RBF were measured using multidetector CT, and glomerular filtration rate (GFR) by iothalamate clearance. Tissue deoxyhemoglobin levels (R2*) and fractional kidney hypoxia (% of axial area with R2*>30/s) were measured by BOLD-MRI at 3T. Results: Single kidney RBF, cortical and medullary perfusion were reduced in the post-stenotic kidney, as was GFR. Renal vein NGAL, MCP-1 and fractional hypoxia were higher in patients with ARAS than EH. NGAL and MCP-1 levels correlated directly with cortical R2* and fractional hypoxia (r = 0.52, P <0 .0001 and r = 0.4, P = 0.0006) and with the degree of artey stenosis (r = 0.37, P = 0.04 and r = 0.35, P = 0.05). GFR correlated inversely with NGAL (r= - 0.5, P <0.0001). Conclusions: Our results demonstrate that elevated renal venous markers of kidney inflammation (MCP-1) and injury (NGAL) in ARAS are correlated with the severity of tissue hypoxia as measured by BOLD MR, suggesting a possible link between kidney inflammation and hypoxia.

Background: Renal hypoxia is a complex function of post-glomerular medullary blood flow, active solute transport and is considered a major risk element for acute kidney injury. Previous studies indicate that sodium balance, diuretic administration and some drugs affect tissue oxygenation. Water loading in younger subjects lowers medullary deoxyhemoglobin. We sought to evaluate the effects of water loading on the day of BOLD imaging in older subjects undergoing protocol evaluation of atherosclerotic renovascular disease (ARVD). METHODS: Inpatient studies were performed in patients with hemodynamically severe ARVD (n=15, Doppler US velocity >270 cm/sec), during 150 mEq Na+ intake and ACE/ARB Rx. Two groups were studied: Group A (n=10) received oral water loading (20 ml/kg), whereas Group B (n=5) had none. Tissue R2* (index of deoxyhemoglobin levels) and fractional kidney hypoxia (medullary estimate) (% of renal coronal area with R2*>20/s) were measured in stenotic kidneys by BOLD-MRI at 3T, before and after IV injection of Furosemide (20gm). RESULTS: Cortical R2* and fractional tissue hypoxia were similar for the 2 groups (P =0.6 and 0.7). Both groups reduced cortical R2* and fractional hypoxia after furosemide injection to the same degree. Table CONCLUSION: These data demonstrate that water loading on the day of BOLD evaluation in older subjects with ARVD does not materially alter cortical or medullary estimates of oxygenation. Our results extend previous studies indicating that water loading in older individuals fails to alter medullary oxygenation unlike alterations in sodium intake, diuretic administration or blockade of the renin-angiotensin system.

Background: Left ventricular assist device (LVAD) implantation is a new therapy for advanced heart failure (HF). The number of HF patients eligible for LVAD and the cardiology providers’ comfort level with referral for LVAD remains unclear. Objective: To assess provider perception of LVAD candidacy and LVAD referral patterns in consecutive HF patients. Methods: Providers completed a survey for each HF patient seen between March 1, 2013 and April 26, 2013. The survey listed standard LVAD candidacy criteria and asked 1) if a patient was an LVAD candidate (yes, no, unsure); 2) reasons patients were not LVAD candidates (check list, table); and 3) whether the patient had been referred for LVAD evaluation (yes, no, unsure). Results: Patients (n=522) were seen in a tertiary HF outpatient clinic (n=357; 68%), a tertiary HF inpatient service (n=36; 7%), a tertiary general cardiology service (n=45; 9%) or a community based outpatient cardiac clinic (n=84; 16%) Median age of patients was 73 years and 65% were male. Provider assessment of LVAD candidacy was “no” in 443 (85%), “yes” in 35 (7%) and “unsure” in 43 (8%) with ineligibility for LVAD attributed to multiple concerns (Table). Ninety percent of patients considered “too old” for LVAD were over 78 years of age. Provider designation of LVAD candidacy as yes or unsure varied across practice setting: tertiary HF outpatient clinic, 12%; tertiary HF inpatient service, 42%; tertiary general cardiology service, 22%; and community based outpatient cardiac clinic, 13%. In patients with a provider designation of LVAD candidacy as yes or unsure (n=78), only 21 (27%) patients had been referred for LVAD evaluation. Conclusion: When provided with LVAD candidacy criteria, providers indicated 15% of HF patients were (7%) or were possibly (8%) LVAD candidates but indicated that few patients had undergone a formal LVAD evaluation. These data suggest that measures to improve evaluation of HF patients for LVAD are needed.

Introduction: Right ventricle (RV) dysfunction linked with acute Pulmonary embolism (PE) is associated with significant mortality. Several studies have documented use of RV free wall strain (RVS) for assessing mortality, but RV free wall systolic (RVSRs) and early diastolic strain rate (RVSRe) have not been explored. Hypothesis: The study aims to assess the RV function in longitudinal domain of contractility using 2 D speckle tracking echocardiography and evaluate if it was able to predict all-cause mortality at 30 days. Methods: This is a single center prospective study done between November 2012 to June 2020. 293 adult patients with acute PE having echocardiogram performed within 24 hours were enrolled and baseline comorbidities were recorded. 2 D Speckle tracking echocardiography was performed offline. Multiple logistic regression analyses and ROC were performed to evaluate if RV Strain (RVS) and strain rate (systolic-SRs, early diastolic-SRe) were able to predict all-cause mortality at 30 days. Results: Mean age was 65 ± 15 years, 60.7 % males and 41% had coronary artery disease, 29% had cancer and 11% had COPD. Mean free wall (FW) RVS was -19.7±7.7%, FW RV SRs was -0.9±0.4 s -1 , FW RV SRe was 0.8±0.3 s -1 . (Figure A) All-cause mortality was present in 11 patients (3.8%) at 30 days, 17 (5.8%) at 3 months and 29 (9.9%) at 6 months. In the Univariate analysis, FW RVS and FW RVSRs were significantly associated with 30 days all-cause, but after adjusting for age, cancer, and COPD, only FW RVSRs remains significant (p=0.02) with an AUC to predict 30-day all-cause mortality of 0.73 (95% CI 0.54-0.88) a cut-off value of -0.7 had a sensitivity of 73% and specificity of 64% (Figure B) Conclusions: The study demonstrated that RV Free wall SRs measured by 2 D STE is a good prognostic indicator for 30 days all-cause mortality in patients with acute PE. This novel modality could be used for risk stratification in the setting of acute PE.

Introduction: Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF). Hypothesis: Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility. Methods & Results: 166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40; p value <0.0001), SRs was similar (-0.97 s -1 ±0.10 vs. -0.98 s -1 ±0.02, p value 0.2528) and SRe was lower (0.85 s -1 ±0.0 vs. 1.05 s -1 ±0.02; p value <0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p<0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1). Conclusions: In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs & SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.

Introduction: Anthracyclines are a first-line chemotherapeutic agent used in the treatment of lymphoma. Myocardial injury can occur with cumulative doses of 250 to 350 mg/m 2 . Echocardiography is the imaging modality for identifying cardiac dysfunction; however, identifying diastolic changes in patients who received anthracyclines is not well represented in the literature. Variables used to identify diastolic dysfunction include lateral e’, medial e’, mitral E velocity, mitral A velocity, E/A, E/e’, and left atrial volume index (LAVI). This study aims to identify if diastolic abnormalities develop in a prospective cohort of patients with HL or NHL who received anthracycline-based chemotherapy. Methods: Lymphoma patients treated with anthracyclines from 2013 to 2020 were prospectively enrolled. Echocardiography was obtained at 3-time points: before the start of chemotherapy (T1), at 3-6 months (T2), and 9-12 months (T3). Diastolic variables were measured and analyzed based on the total cumulative dose of Doxorubicin per body surface area. Those that received greater than 250 mg/m 2 and greater than 300 mg/m 2 of Doxorubicin were compared to those that did not. Statistical analysis was done using one-way ANOVA, adjusting for age and gender. Results: 151 total patients (90 males, mean age 61 + 16 years); 21 (14%) HL, 130 (85%) NHL. 114 and 66 patients received a total cumulative dose of Doxorubicin greater than 250 mg/m 2 and 300 mg/m 2 , respectively. There was no significant association with 250 mg/m2. Lateral e’ at T3 vs. T1, was lower in those that received greater than 300 mg/ m 2 compared to those received less (0.09 vs 0.10, p < 0.02) (Table 1). Conclusions: Lateral e’ decreased at 1-year follow-up in those that received higher doses of Doxorubicin. These changes in the lateral e’ could reflect early relaxation abnormalities related to anthracycline-based chemotherapy and suggest that changes in lateral e’ should be considered by itself since E/e’ was normal.

Background The treatment of depression in children and adolescents is a substantial public health challenge. This study examined artificial intelligence tools for the prediction of early outcomes in depressed children and adolescents treated with fluoxetine, duloxetine, or placebo. Methods The study samples included training datasets ( N = 271) from patients with major depressive disorder (MDD) treated with fluoxetine and testing datasets from patients with MDD treated with duloxetine ( N = 255) or placebo ( N = 265). Treatment trajectories were generated using probabilistic graphical models (PGMs). Unsupervised machine learning identified specific depressive symptom profiles and related thresholds of improvement during acute treatment. Results Variation in six depressive symptoms (difficulty having fun, social withdrawal, excessive fatigue, irritability, low self‐esteem, and depressed feelings) assessed with the Children’s Depression Rating Scale‐Revised at 4–6 weeks predicted treatment outcomes with fluoxetine at 10–12 weeks with an average accuracy of 73% in the training dataset. The same six symptoms predicted 10–12 week outcomes at 4–6 weeks in (a) duloxetine testing datasets with an average accuracy of 76% and (b) placebo‐treated patients with accuracies of 67%. In placebo‐treated patients, the accuracies of predicting response and remission were similar to antidepressants. Accuracies for predicting nonresponse to placebo treatment were significantly lower than antidepressants. Conclusions PGMs provided clinically meaningful predictions in samples of depressed children and adolescents treated with fluoxetine or duloxetine. Future work should augment PGMs with biological data for refined predictions to guide the selection of pharmacological and psychotherapeutic treatment in children and adolescents with depression.

Routine antimicrobial susceptibility testing (AST) of Helicobacter pylori by agar dilution is difficult to perform and not practical in most clinical microbiology laboratories. The Etest gradient diffusion method can be a reliable alternative for H. pylori AST with the advantage of being a less laborious quantitative method. This work reveals that an optimized Etest method can provide acceptable performance for H. pylori AST and describes the challenges associated with this methodology.

AbstractAimsThe non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE).Methods and resultsWe prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure − PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61–0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69–0.91; P≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82–0.99; P &lt; 0.001) and 3 months (AUC 0.84; 95% CI 0.65–0.99; P = 0.003).ConclusionNon-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.