Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

For the love of loeffler

Background: Loeffler (Eosinophilic) endocarditis is a rare disease in which eosinophils infiltrate and damage theendocardium, leading to intense inflammation, thrombus formation and ultimately endocardial fibrosis. Stroke may be a presenting symptom. Multimodality imaging facilitates accurate diagnosis and appropriate treatment. Case: A 70-year-old male with a past medical history significant forprostate cancer in remission presented to his primary care provider with a complaint of left-sided weakness and ipsilateral facial droop. Labs on presentation revealed a significant troponin elevation concerning for an acute coronary syndrome. A brain MRI was performed and revealed bilateral strokes with concern for cardioembolic origin. An echocardiogram was performed and revealed normal left ventricular function, however was notable for a fixed mass on the lateral wall of the ventricle, measuring 35 mm x 16 mm. Decision-Making: Contrast enhanced echocardiography was used to narrow the differential as likely thrombus. Explanation for a large lateral wall thrombus was limited considering no wall motion abnormality, pseudoaneurysm, or evidence of infection. On review of records the patient was noted to have peripheral eosinophilia (8000 cells/uL) with levels greater than 2000 cells/uL for one year prior, raising concern for Loefflerendocarditis. Endocardial biopsy is the gold-standard fordiagnosis, however risks of the procedure were considered too high. A cardiac MRI was performed revealing diffuse abnormal subendocardial delayed enhancement with corresponding T2 signal hyperintensity, as well as superimposed non-enhancing thrombus, consistent with eosinophilic infiltration and superimposed thrombus. A decision was made to treat with high-dose steroids and systemic anticoagulation. Follow-up echocardiogram 6 months later revealed near complete resolution of themass. Conclusions: This case highlight\u27s stroke as a presenting symptom in patients with Loeffler\u27s endocarditis. Multimodality imaging, lab-work and thepatient\u27s response to treatment cemented the diagnosis. Rapid diagnosis and treatment are vital as advanced stages have very high morbidity and mortality

Smoldering recurrent pericarditis presenting as a loculated pericardial effusion mimicking pericardial cyst

Background Pericardial effusion could manifest as a loculated cyst on cardiac imaging. Anakinra (Interleukin-1 receptor antagonist) is showing promising results for treating recurrent resistant pericarditis. Case A 24-year-old male with no medical history presented with pleuritic chest pain after flu-like symptoms. He notes 3-4 similar episodes in past few years. Workup revealed diffuse ST elevations on EKG and a new right middle lobe opacity on chest X-ray. Chest CTA showed a pericardial cyst corresponding to the opacity seen on radiograph. No pericardial cyst or effusion was identified on echocardiogram. Further testing resulted in a positive rhinovirus/enterovirus PCR with unremarkable autoimmune workup. Decision-making Outpatient Cardiac MR to follow on the pericardial cyst was completed 6 weeks after the initial presentation. Interestingly, an interval resolution of the pericardial cyst seen on the prior CT chest noted. Patient endorsed recurrent symptoms with doubling of colchicine dose and resuming non-steroidal agents. He continued to have pericarditis flares, and a short course of prednisone was added. Eventually, patient was started on Anakinra, in addition to colchicine and ibuprofen, with improvement in symptoms. Conclusion Loculated pericardial effusion could mimic a pericardial cyst. Clinical correlation is imperative. Interleukin-1 receptor antagonists could result in symptomatic relieve in patients suffering from recurrent persistent pericarditis

The use of coronary sinus reducer for refractory angina in the U.S.: A case series

Chronic refractory angina remains a common and debilitating condition for millions of people, with up to 30% of patients experiencing persistent angina despite successful revascularization. We share our experience with the implantation of a coronary sinus reducer in two complex CAD patients with refractory angina despite multiple revascularization strategies and maximally tolerated medical therapy

Optimal TR-band weaning strategy while minimizing vascular access site complications

Background: Transradial cardiac catheterization is increasing in the United States due to the advantages of less access site complications and patient preference. A compression device is most commonly used to achieve hemostasis following sheath removal, however the optimalweaning strategy to expedite TR-band removal whileminimizing access site complications has yet to be defined. The purpose of this study was to develop an optimal TR-Band weaning strategy while minimizing vascular accesssite complications of hematoma or radial artery occlusion. Methods: The trial was a randomized, prospective, single center study of 129 patients who underwent cardiac catheterization via the radial artery. Group A was an accelerated protocol in which weaning was initiated 20 minutes after sheath removal. Group B was an adjusted protocol, in which weaning was dependent on the amount of anti-platelet or anti-coagulation used. All patients underwent radial artery ultrasound to demonstrate arterial patency. Results: Baseline characteristics were similar in both groups, and PCI was performed in 36.7% of patients in Group A and 37.7% of patients in Group B. RAO occurred in 7.7% of patients overall, with no statistical difference between groups (Group A 5% versus Group B 10.1%, p-value = 0.337). Hematoma formation greater than 5 cm in diameter occurred in 4.6% of patients in the overall cohort, without statistical difference between groups (Group A 5.0% versus Group B 4.3%, p-value = 1). The TR-Band duration was signifcantly shorter in Group A compared to Group B (112.9 ± 50.7 versus 130.7 ± 51.1 in minutes, respectively, p-value = 0.013). Conclusion: We have demonstrated an accelerated weaning protocol without increased vascularsite complications of radial artery occlusion or hematoma formation, which could potentially reduce hospital stay in same-day procedures

Optimal TR-band weaning strategy while minimizing vascular access site complications

INTRODUCTION: The purpose of the study is to develop an optimal TR-Band weaning strategy while minimizing vascular access site complications of hematoma or radial artery occlusion (RAO). METHODS: The trial was a randomized, prospective, single center study of 129 patients who underwent cardiac catheterization via the radial artery. Group A was an accelerated protocol in which weaning was initiated 20 min after sheath removal. Group B was an adjusted protocol, in which weaning was dependent on the amount of anti-platelet or anti-coagulation used. All patients underwent radial artery ultrasound to demonstrate arterial patency. RESULTS: Baseline characteristics were similar in both groups, and PCI was performed in 36.7% of patients in Group A and 37.7% of patients in Group B. RAO occurred in 7.7% of patients overall, with no statistical difference between groups (Group A 5% versus Group B 10.1%, p-value = 0.337). Hematoma formation \u3e5 cm in diameter occurred in 4.6% of patients in the overall cohort, without statistical difference between groups (Group A 5% versus Group B 4.3%, p-value = 1). The TR-Band duration was significantly shorter in Group A compared to Group B (112.9 ± 50.7 versus 130.7 ± 51.1 in minutes, respectively, p-value = 0.013). CONCLUSION: We have demonstrated an accelerated weaning protocol is simple to utilize for nursing staff without increased vascular site complications of RAO or hematoma formation

Inverse Relationship of Maximal Exercise Capacity to Hospitalization Secondary to Coronavirus Disease 2019

OBJECTIVE: To investigate the relationship between maximal exercise capacity measured before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalization due to coronavirus disease 2019 (COVID-19). METHODS: We identified patients (≥18 years) who completed a clinically indicated exercise stress test between January 1, 2016, and February 29, 2020, and had a test for SARS-CoV-2 (ie, real-time reverse transcriptase polymerase chain reaction test) between February 29, 2020, and May 30, 2020. Maximal exercise capacity was quantified in metabolic equivalents of task (METs). Logistic regression was used to evaluate the likelihood that hospitalization secondary to COVID-19 is related to peak METs, with adjustment for 13 covariates previously identified as associated with higher risk for severe illness from COVID-19. RESULTS: We identified 246 patients (age, 59±12 years; 42% male; 75% black race) who had an exercise test and tested positive for SARS-CoV-2. Among these, 89 (36%) were hospitalized. Peak METs were significantly lower (P\u3c.001) among patients who were hospitalized (6.7±2.8) compared with those not hospitalized (8.0±2.4). Peak METs were inversely associated with the likelihood of hospitalization in unadjusted (odds ratio, 0.83; 95% CI, 0.74-0.92) and adjusted models (odds ratio, 0.87; 95% CI, 0.76-0.99). CONCLUSION: Maximal exercise capacity is independently and inversely associated with the likelihood of hospitalization due to COVID-19. These data further support the important relationship between cardiorespiratory fitness and health outcomes. Future studies are needed to determine whether improving maximal exercise capacity is associated with lower risk of complications due to viral infections, such as COVID-19

Health Care Resource Utilization: A Cluster Randomized Trial of a Rapid, High-Sensitivity Cardiac Troponin Protocol

Background and Objectives: Data on the impact of new rapid rule-out protocols using high sensitivity cardiac troponin I (hs-cTnI) in the US is lacking. We compared healthcare resource utilization between a traditional protocol and a new 0/1-hour, hs-cTnI protocol for exclusion of acute myocardial infarction (AMI). Methods: A pragmatic, stepped wedge, randomized trial of patients evaluated for possible AMI in 9 emergency departments (ED) from 7/2020-3/2021. The trial arms included a new 0/1-hour rapid protocol and standard care. Randomization occurred by ED site. We included all adult ED patients for whom the treating clinician ordered an ECG and cardiac troponin. We excluded patients with STEMI, any hs-cTnI \u3e18 ng/L in the ED, or a traumatic cause of symptoms. In the rapid protocol, MI was excluded, and ED discharge advised if hs-cTnI \u3c 4 ng/L at time 0, or =4 ng/L at time 0 with 1 hour \u3c 8 ng/L. In standard care, troponin was measured at 0 and 3 hours, clinicians were blinded to values ≤18 ng/L, and ≤18 ng/L was used to exclude AMI and guide ED discharge. Outcomes included ED discharge and observation rates, length of stay, and cardiac testing. The analysis included a mixed effect model adjusting for ED site, time, sex, age, and race. We report adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: There were 32,609 patients, of whom 13,505 were in the standard care and 19,104 in the rapid protocol arms. Unadjusted ED discharge rates were lower under the rapid protocol (58.0%) vs. standard care (59.8%). The proportion of patients receiving cardiac stress testing (4.0% vs. 3.4%) and coronary catheterization (1.3% vs. 1.0%) fell under the rapid protocol. In adjusted analysis, there was no statistically significant difference in rates of ED discharge (aOR 1.03, 95% CI 0.94-1.13) with the rapid protocol. There was a reduction in the odds of observation placement (aOR 0.90, 95% CI 0.82-0.99) as well as a reduced overall length of stay for patients discharged from the ED or observation unit (aOR 0.95, 95% CI 0.91–0.99) under the rapid protocol. The difference in odds of coronary catheterization was not statistically significant (aOR 0.83, 95% CI 0.36 – 1.86), but there were reduced odds of cardiac stress testing under the rapid protocol (aOR 0.71, 95% CI 0.53 – 0.95). Conclusion: Implementation of a rapid 0/1-hour protocol to evaluate for AMI in the ED was associated with modest reductions in healthcare resource utilization