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Prenatal opioid exposures lead to extensive cognitive and emotion-regulation problems in children, persisting at least through school-age. Methadone, an opioid typically used for the treatment of opioid use disorder, has been approved for use in pregnant women for several decades. Importantly, however, the impacts of prenatal methadone exposure (PME), particularly on offspring as they progress into adulthood, has not been extensively examined. In recent years, children and young animal models have shown cognitive deficits related to PME, including evidence of hippocampal dysfunction. The present work aims to examine the persistent nature of these deficits, as well as determine how they may differ by sex. Pregnant Sprague-Dawley rats either received subcutaneous methadone or water injections twice daily from gestational days 3-20 or were left undisturbed. Following postnatal day 70, male and female offspring were behaviourally tested for impairments in recognition memory using the Novel Object Recognition task and working spatial memory through Spontaneous Alternation. Additionally, using whole-cell patch-clamp electrophysiology, hippocampal dentate granule cell function was examined in adult offspring. Results indicate that methadone-exposed females showed decreased excitability and increased inhibition of dentate granule cells compared to naïve controls, while males did not. These findings were accompanied by impairments in female working spatial memory and altered behaviour in the Object Recognition task. Overall, this work supports the continued investigation of the long-term effects of PME on adult male and female learning and memory, as well as promotes further exploration of adult hippocampal function as a neural mechanism impacted by this exposure., (© 2022 Society for the Study of Addiction.)

Coronary computed tomographic angiography (CCTA) may provide both anatomic and CT fractional flow reserve data (CTFFR). The objective is to use Bayesian analysis to develop a model wherein the probability of significant coronary artery disease (CAD) by CTFFR can be determined given the prior probability (P) of the combined clinical and CCTA result. 172 patients referred for CCTA and subsequently underwent coronary angiography were automatically referred to CTFFR analysis. A clinical P risk score (CRS) was calculated per patient. CCTA exams were scored using CAD-RADS classification. CTFFR results were generated. CAD was defined as ≥ 3 RAD class for CCTA and ≤ .80 by CTFFR. P was calculated using CCTA and CTFFR accuracy from a prior clinical trial: post-test P for the CCTA result used the CRS as the prior risk, and CTFFR P used the post-test CRS + CCTA P as the prior risk (tri-variable). Patients were classified for each model into low (< 5%), intermediate, (5-70%) and high (> 70%) risk groups. There were 100 patients (58%), who had significant CAD at angiography. 58 patients had discordant CCTA/CTFFR results. The inclusion of the CRS and CRS + CCTA in the prior progressively reduced the intermediate risk cohort from 83 to 41% (p < 0.0001). Correct classifications (low-risk, negative angiogram plus high-risk, positive angiogram) increased by model: CRS = 12%, CRS + CCTA = 25%, CRS + CTFFR = 33%, CRS + CCTA + CTFFR = 44% (p < 0.001). Incorrect classifications were reduced to 15%. The tri-variable model performed better than either CCTA or CTFFR alone for all patients and for the sub-group with discordant imaging results. Discrepant CCTA and CTFFR results are present in one third of patients. The use of both the CRS and CCTA as the prior risk synergistically maximized the accuracy of the accuracy of the CTFFR technique., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine., (© 2021. The Author(s).)

Background: Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients., Hypothesis: The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function., Methods/results: This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96)., Conclusions: Reduced cardiac function is highly prevalent among hospitalized COVID-19 patients with biomarkers of myocardial injury and is independently associated with mortality., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Purpose: The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low-cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur., Methods: Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab, were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire., Results: Over a 6-month period, the left ventricular ejection fraction (%) decreased (64.15±5.30 to 60.41±5.77, P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased (124.73±20.25 to 132.21±19.33, P<0.04 and 45.16±11.88 to 52.57±11.65, P<0.00, respectively). The LV mass (g) did not change (73.06±11.51 to 69.21±15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594±0.098 to 0.530±0.124, P<0.04)., Conclusions: In low-cardiac-risk women with nonmetastatic breast cancer, the increased LV volume and a mildly decreased left ventricular ejection fraction during and after chemotherapy do not seem to be associated with laboratory or clinical evidence of increased risk for heart failure.

A 68year old female patient underwent coronary artery bypass surgery (CABG) 1year previously. At that time she had a giant coronary artery aneurysm (CAA) of the proximal right coronary artery and severe 3 vessel disease including a severe ostial right coronary artery stenosis, severe stenosis of the proximal and mid left anterior descending artery (LAD) and a totally occluded left circumflex artery. She underwent CABG including left internal mammary artery to LAD, aorto-saphenous venous graft (ASVG) to posterior descending artery and ASVG sequential to the first diagonal and obtuse marginal branch. Subsequent computed tomography and invasive angiography demonstrated increasing size of the aneurysm (from 42 by 37mm to 50 by 42mm) which was now fed retrograde via the graft to the posterior descending artery in addition to being fed antegrade by the native vessel through a high grade stenosis. Percutaneous covered stent insertion was planned. The aneurysm was traversed with a guide wire, but passage of Viabahn covered stents was difficult due to the 8 Fr guide catheter and the bulky and rigid structure of the Viabahn stent. Using a distal anchoring technique and dual guide catheters, successful passage of two Viabahn stents (two of 5 by 50mm) was accomplished. The technique utilized is described., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white matter hyperintensities (WMHs) on magnetic resonance imaging can occur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating 2 levels of ambulatory blood pressure (ABP) control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded end points, in patients ages ≥75 years with elevated 24-hour systolic blood pressure (BP) (145 mm Hg in the untreated state) who do not have unstable cardiovascular disease, heart failure, or stroke. The primary and key secondary outcomes in the trial are change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes in diffusion tensor imaging. Approximately 300 patients will be enrolled, and 200 randomized to 1 of 2 levels of ABP control (intensive to achieve a goal 24-hour systolic BP of ≤130 mm Hg or standard to achieve a goal 24-hour systolic BP of ≤145 mm Hg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ABP monitoring rather than clinic BP to reduce cerebrovascular disease., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background and Objectives: Direct observation (DO) is considered to be an effective way to evaluate patient care. This study assesses if weekly direct observation with formal feedback (DO-FF) increases (1) clinical skills and (2) comfort with patient care skills (CWPCS) during the first 12 weeks of internship., Methods: A single-blinded, stratified, randomized controlled trial (RCT) with allocation concealment incorporating interns at a community hospital family medicine residency program was performed. Interns (n=14) were stratified by the predicted number of calls in a 2:1 ratio of intervention: control group. The intervention group received DO-FF four times/month on inpatient history and physicals (H&Ps) by a family medicine senior resident or fellow. To assess skills, all interns were videotaped doing H&Ps at the beginning, middle, and end of the study. These were scored by two independent, blinded physicians using a validated tool. For self-assessment, all interns took a patient care comfort survey (PCCS) at baseline, 6 weeks, and 12 weeks. Analysis was done via intention to treat., Results: At 6 weeks, interns who received weekly DO-FF had greater CWPCS on 32 of 35 questions. Eight were significantly different: (1) discussing end of life issues, (2) chest X ray interpretation, management of (3) congestive heart failure, (4) chronic obstructive pulmonary disease, (5) diabetes mellitus, (6) diabetic ketoacidosis, (7) stroke, and (8) venous thromboembolism/pulmonary embolism. In all but three questions, differences resolved by 12 weeks. Video data were not significantly different between groups., Conclusions: In certain aspects of patient care, DO-FF improved intern CWPCS at 6 weeks. There was no difference in the video assessments of clinical skills between the treatment groups. These results need to be further explored. However, this study showed that a well-designed RCT is feasible for educational research questions.

Objective: To determine the utility of an antibiogram in predicting the susceptibility of Pseudomonas aeruginosa isolates to targeted antimicrobial agents based on the day of hospitalization the specimen was collected., Design: Single-center retrospective cohort study., Setting: A 750-bed tertiary care medical center., Patients and Methods: Isolates from consecutive patients with at least 1 clinical culture positive for P. aeruginosa from January 1, 2000, to June 30, 2007, were included. A study antibiogram was created by determining the overall percentages of P. aeruginosa isolates susceptible to amikacin, ceftazidime, ciprofloxacin, gentamicin, imipenem-cilastin, piperacillin-tazobactam, and tobramycin during the study period. Individual logistic regression models were created to determine the day of infection after which the study antibiogram no longer predicted susceptibility to each antibiotic., Results: A total of 3,393 isolates were included. The antibiogram became unreliable as a predictor of susceptibility to ceftazidime, imipenem-cilastin, piperacillin-tazobactam, and tobramycin after day 10 and ciprofloxacin after day 15 but longer for gentamicin (day 21) and amikacin (day 28). Time to unreliability of the antibiogram varied for antibiotics based on location of isolation. For example, the time to unreliability of the antibiogram for ceftazidime was 5 days (95% confidence interval [CI], <1-8) in the intensive care unit (ICU) and 12 days (95% CI, 7-21) in non-ICU hospital wards (P = .003)., Conclusions: The ability of the antibiogram to predict susceptibility of P. aeruginosa decreases as duration of hospitalization increases.

Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM in the non-Japanese population (1% to 2%). Diagnostic dilemma occurs when this type of HCM is newly discovered in a patient previously diagnosed with left ventricular hypertrophy (LVH) secondary to hypertension. We describe an atypical presentation of an apical HCM in the setting of chronic hypertension (HTN) and review the literature of this rare variant of HCM. Our patient presented with chest pain and was found to have apical HCM with inducible apical ischemia and an abnormal blood pressure response to exercise. Multimodality imaging approach is proposed to evaluate the LVH when both apical HCM and hypertension are present given the impact of an accurate diagnosis on prognosis and management.

Doxorubicin, an anthracycline antibiotic commonly used as a chemotherapeutic agent for breast cancer, is well known to cause cardiotoxicity. We report the case of an active, otherwise healthy 57-year-old breast cancer survivor who, 17 years after chemotherapy, presented with symptoms of overt heart failure. She had no cardiac risk factors, and neither laboratory nor imaging findings suggested myocarditis or dilated cardiomyopathy. Echocardiographic findings and differential diagnosis led us to attribute her condition to late doxorubicin-induced cardiomyopathy. By virtue of tapered medical therapy, her left ventricular ejection fraction improved from 0.20 to 0.55 in 8 months, and she was asymptomatic after 1 year. The reversibility of left ventricular dysfunction in our patient and the very late appearance of cardiotoxicity secondary to doxorubicin therapy raise questions about the pathogenesis and prevalence of late doxorubicin-induced cardiomyopathy and how to improve outcomes in patients who present with related symptoms of heart failure.

Combination therapy is recommended for patients with blood pressure (BP) significantly above goal by recent consensus guidelines around the globe. The use of angiotensin II receptor blockers (ARBs) alone or in combination with a thiazide diuretic is a preferred treatment strategy due to both efficacy and safety considerations. However, there are few data known about the benefits of ARB-diuretic combination therapy in patients with moderate-to-severe hypertension. We performed a subanalysis from two large clinical trials that compared the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg, both combined with hydrochlorothiazide (HCTZ) 25 mg in a subpopulation of 725 patients with moderate-to-severe hypertension (systolic BP SBP ≥ 160 mm Hg). Treatment with telmisartan-HCTZ induced significantly greater reductions in BP (-31.1/-18.3 mm Hg) than valsartan-HCTZ (-28.4/-16.3 mm Hg; SBP P = 0.0265, diastolic BP P = 0.0041). More patients receiving the telmisartan combination achieved a BP goal < 140/90 mm Hg than those receiving valsartan-HCTZ. There were similar safety and tolerability data for the two active treatment groups. These findings support the use of longer-acting ARBs combined with higher doses of thiazide diuretic to improve BP control in patients with moderate-to-severe hypertension.

Objective: Inflammation plays a key role in the development of vascular diseases. Monocytes and macrophages express α(v)β(3) integrin. We used an α(v) integrin-specific tracer, (99m)Tc-NC100692, to investigate integrin-targeted imaging for detection vessel wall inflammation., Methods and Results: The binding of a fluorescent homologue of NC100692 to α(v)β(3) on human monocytes and macrophages was shown by flow cytometry. Vessel wall inflammation and remodeling was induced in murine carotid arteries through adventitial exposure to CaCl(2). NC100692 micro single photon computed tomography/CT imaging was performed after 2 and 4 weeks and showed significantly higher uptake of the tracer in CaCl(2)-exposed left carotids compared with sham-operated contralateral arteries. Histological analysis at 4 weeks demonstrated significant remodeling of left carotid arteries and considerable macrophage infiltration, which was confirmed by real-time polymerase chain reaction. There was no significant difference in normalized α(v), β(3), or β(5) mRNA expression between right and left carotid arteries. Finally, NC100692 uptake strongly correlated with macrophage marker expression in carotid arteries., Conclusions: NC100692 imaging can detect vessel wall inflammation in vivo. If further validated, α(v)-targeted imaging may provide a noninvasive approach for identifying patients who are at high risk for vascular events and tracking the effect of antiinflammatory treatments.

Objective: To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification., Methods and Results: Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a (99m)Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery., Conclusions: MMP activation predicts the progression of vascular remodeling and can track the effect of dietary modification after vascular injury.