An examination of the emerging field of community paramedicine: a national cross-sectional survey of community paramedics.

BACKGROUND: Community Paramedicine is an evolving community-based model that expands paramedic roles from emergency and transport care to a focus on non-emergent and preventive health services tailored to local community needs. Though community paramedicine is a growing field and acceptance is gradually increasing, there is limited information on community paramedics (CPs) perceptions of their expanded roles. The study's aim is to assess CPs' perceptions about their training, roles, role clarity, role readiness, role satisfaction, professional identity, interprofessional collaboration, and the future of the community paramedicine care model. METHODS: Using the National Association of Emergency Medical Technicians-mobile integrated health (NAEMT-MIH) listserv, a cross-sectional survey was conducted in July/August 2020 using a 43-item web-based questionnaire. Thirty-nine questions evaluated CPs' training, roles, role clarity, role readiness, role satisfaction, professional identity, interprofessional collaboration, and program/work characteristics. Four open-ended questions examined perceptions of the future of community paramedicine care models and challenges/opportunities encountered during the COVID-19 pandemic. Data was analyzed using Spearman's correlation, Wilcoxon Mann-Whitney U, and Kruskal-Wallis tests. Open-ended questions were analyzed using qualitative content analyses. RESULTS: Responses from fifty-seven CPs were analyzed. Most (80%) completed didactic and/or clinical training. Nearly all respondents (96.5%) performed health assessments; only 38.6% administered vaccines. Overall, participants were neutral about their role readiness with a mean score of 3.3/5.0. The mean role clarity was 15.5 (range 4-29; higher scores = higher clarity), professional identity was 46.8 (range 30-55; higher scores = higher identity), role satisfaction was 4.4/5 with 5 = very satisfied, and interprofessional collaboration was 9.5/10 (10 = very important). Role clarity training (rho = 0.4, p = 0.0013) and higher interprofessional collaboration (rho = 0.4, p = 0.0015) were found to be significantly associated with the enhancement of professional identity. Respondents who completed training showed higher role satisfaction compared to those who did not (p = 0.0114). COVID-19 challenges included keeping up with emerging policies/procedures, CPs' well-being, and inadequate funding to meet service needs; opportunities identified included service delivery expansion and CPs meeting community needs in a flexible manner. Respondents reported that sustainable payment models, expanding services, and geographic reach were important to the future of community paramedicine. CONCLUSIONS: Interprofessional collaboration is important to fulfill CPs roles. Role clarity and readiness could be improved, which aligns with the emerging nature of community paramedicine. The future of the community paramedicine care model is dependent on funding and expanding reach of services.

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI. METHODS: The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial's design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA. CONCLUSIONS: This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD. TRIAL REGISTRATION NUMBER: NCT03354273.

The soft palate is an important site of adaptation for transmissible influenza viruses.

Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.

T2 Relaxation Times at Cardiac MRI in Healthy Adults: A Systematic Review and Meta-Analysis.

Background T2 mapping is an important cardiac MRI technique with applications in various conditions. However, a comprehensive evaluation of the T2 literature for normal values is lacking. Purpose To characterize the ranges of normal values and variability of myocardial T2 relaxation times using a systematic review and meta-analysis of the T2 literature. Materials and Methods PubMed and Cochrane Central were searched from June 2019 to January 2020 for myocardial T2 measurements in healthy adults. Studies quantifying T2 relaxation times conducted at 1.5 T or 3.0 T using gradient and spin-echo (GRASE) or T2-prepared balanced steady-state free precession sequences were included. Summary means were generated using a random-effects model. Subgroup analysis and meta-regression were performed to assess factors causing heterogeneity. Results Of the 2481 articles retrieved, 42 studies were included with 954 healthy adults (mean age, 42.4 years ± 10.5 [standard deviation]; 538 men). The pooled mean of T2 across studies was 52 msec at 1.5 T (95% confidence interval [CI]: 51 msec, 53 msec) and 46 msec at 3.0 T (95% CI: 44 msec, 48 msec) (P ≤ .001). I2 was 98% at 1.5 T and 3.0 T. Meta-regression at 1.5 T and 3.0 T identified vendor (ß at 1.5 T = -4 msec [with Philips as reference], P < .001; ß at 3.0 T = -5 msec, P = .02) and pulse sequence (ß at 1.5 T = -5 msec [with GRASE as reference], P < .001; ß at 3.0 T = -6 msec, P = .002) as significant covariates, but it did not identify any association with covariates of age (ß at 1.5 T = 0 msec per year, P = .70; ß at 3.0 T = 0 msec per year, P = .83) or sex (ß at 1.5 T = -1 msec, P = .88; ß at 3.0 T = 6 msec, P = .42). Conclusion The pooled mean of T2 relaxation times in healthy adults had marked heterogeneity across studies with field strength, vendor, and pulse sequence identified as covariates associated with T2. T2-prepared measurements were similar between vendors at each field strength. © RSNA, 2020 Online supplemental material is available for this article.

Typical angina in a patient with Takayasu arteritis.

Takayasu arteritis (TA) is a well-reported form of large-vessel vasculitis that primarily affects the aorta and its major branches. Cardiac manifestations of TA have been reported and can include typical angina secondary to coronary artery involvement; however, typical angina in the setting normal coronary arteries is uncommon. We describe a case of typical angina in a patient with TA with normal coronary arteries secondary to diastolic hypotension, in the absence of significant aortic regurgitation, likely from poor aortic distensibility and elevated left ventricular end-diastolic pressure.

Nuclear cardio-oncology: From its foundation to its future.

Cardio-oncology is a growing field focused on the prevention and treatment of cardiovascular disease in oncologic patients. While a major focus of chemotherapy-related cardiac dysfunction has been on left ventricular ejection fraction, oncologic treatment can lead to cardiovascular pathology in a variety of ways. The use of multimodality imaging is essential to the care of these patients, with nuclear cardiology playing an important role. We will review nuclear cardiology's history, its current role, and its promising future in cardio-oncology and the management of these patients.

Functional and Anatomical Imaging in Patients with Ischemic Symptoms and Known Coronary Artery Disease.

PURPOSE OF REVIEW: This review is aimed at summarizing recent advances in functional, anatomical, and hybrid imaging techniques used in the assessment of ischemic complaints in patients with known coronary artery disease (CAD). RECENT FINDINGS: Cardiovascular imaging has seen significant growth over the last decade in the fields of coronary computed tomography angiography (CCTA), FFR derived from CCTA, cardiac magnetic resonance, radionuclide myocardial perfusion imaging, and hybrid imaging for the purposes of evaluating symptoms concerning for ischemia. This growth stems from refinement of imaging techniques and hardware and software advances that have made current techniques more accurate with less acquisition time. However, every anatomic and functional imaging modality has important technical and patient-specific limitations. This review assesses these issues, guides a patient-centered imaging approach, and identifies important research questions to resolve. Recent advances in non-invasive cardiovascular imaging can provide important information in patients with known CAD beyond traditional imaging techniques; the use of these novel tools refines the clinical management of complex patients with ischemic symptoms and known CAD.

Dual miRNA targeting restricts host range and attenuates neurovirulence of flaviviruses.

Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3'NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4) replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics.

Post-myocardial Infarction Left Ventricular Aneurysm With Contained Rupture and Hemopericardium.

Left ventricular aneurysms (LVAs) represent a rare yet critical complication arising from late-presenting myocardial infarction (MI). Here, we present the case of an 88-year-old male with chest pressure, elevated troponin, B-type natriuretic peptide, and lactate. The electrocardiogram showed sinus tachycardia and an old right bundle branch block. The patient was started on heparin infusion, but progressively worsening hypotension necessitated transfer to the intensive care unit and the initiation of vasopressors. The echocardiogram identified a focal aneurysm in the mid-anterolateral wall, moderate pericardial effusion with a coagulum, and tamponade physiology. Computed tomography angiography of the chest confirmed a moderate pericardial effusion with density consistent with hemopericardium. LVAs pose a substantial threat of cardiovascular morbidity and mortality. While echocardiography serves as the initial assessment method, supplemental imaging modalities may need to be utilized. Various complications have been reported with LVA, including thromboembolization, ventricular arrhythmias, pericardial effusion with tamponade, and left ventricular rupture which accounts for 5%-24% of all in-hospital deaths related to MI. Although LVAs are the most common mechanical complications following an MI, instances of contained aneurysm rupture leading to hemopericardium are infrequent and scarcely reported. High clinical suspicion and prompt imaging with echocardiography are essential for diagnosis. Determining the optimal timing and selection between surgical and percutaneous interventions necessitates additional research for informed decision-making.

Right Coronary Artery-to-Right Atrial Fistula Accompanied by Multiple Right Coronary Artery Aneurysms: A Case Report.

A coronary artery aneurysm (CAA) denotes a localized dilation of the coronary artery, while a coronary artery fistula signifies an aberrant connection between a coronary artery and a cardiac chamber or adjacent vessel. Here, we present a case study of a 68-year-old female with a previously diagnosed right coronary artery-to-right atrial fistula concomitant with multiple right coronary artery aneurysms. Initially asymptomatic, the patient subsequently manifested atrial fibrillation. Management involved augmenting the patient's home regimen with metoprolol tartrate, followed by successful cardioversion and restoration of sinus rhythm. Given the stability of the fistula and the absence of symptomatic exacerbation, no further interventional measures were undertaken. The patient was discharged with an adjusted metoprolol regimen and scheduled follow-up with her cardiologist. Subsequent imaging assessments unveiled progressive fistula expansion alongside the development of concurrent CAA, inciting deliberations concerning optimal treatment modalities.

Replacement of conserved or variable sequences of the mosquito-borne dengue virus 3' UTR with homologous sequences from Modoc virus does not change infectivity for mosquitoes.

The genus Flavivirus includes both vector-borne and no known vector (NKV) species, but the molecular determinants of transmission mode are not known. Conserved sequence differences between the two groups occur in 5' and 3' UTRs. To investigate the impact of these differences on transmission, chimeric genomes were generated, in which UTRs, UTRs+capsid, or the upper 3' UTR stem-loop of mosquito-borne dengue virus (DENV) were replaced with homologous regions from NKV Modoc virus (MODV); the conserved pentanucleotide sequence (CPS) was also deleted from the DENV genome. Virus was not recovered following transfection of these genomes in three different cell types. However, DENV genomes in which the CPS or variable region (VR) of the 3' UTR were replaced with MODV sequences were recovered and infected Aedes aegypti mosquitoes with similar efficiencies to DENV. These results demonstrate that neither vector-borne CPS nor VR is required for vector-borne transmission.

A Case of Left Ventricular Masson's Tumor: Not Every Heart Tumor Is a Myxoma.

Masson's tumor is a benign tumor that usually arises secondary to vascular trauma or thrombi, leading to vascular proliferation. Masson's tumors are most commonly reported in the head, neck, and extremities. Cases in the heart are exceedingly rare, with most case reports describing the left atrium as the most common location. Even though the tumor is benign, excision is recommended due to the risk of embolization. This is a case of Masson's tumor located in the left ventricle. The patient is a 24-year-old female, who presented complaining of palpitations and lightheadedness. Transthoracic echocardiography showed a mobile echodensity in the left ventricle. Cardiac MRI showed characteristics similar to a myxoma. The patient underwent surgical resection and a biopsy showed Masson's tumor. This case report focuses on the histopathological features and imaging findings of Masson's tumor.

The Complex Management of Mechanical Prosthetic Valve Thrombosis.

Mechanical prosthetic valve thrombosis (PVT) is a serious condition that is associated with various life-threatening complications. The utilization of multimodality imaging techniques is critical in identifying this etiology. Its management is complex and often requires repeat surgical valve replacements. Our report describes the case of a 48-year-old female who presented with mechanical mitral valve thrombosis in the setting of subtherapeutic anticoagulation. Due to her complex surgical history, nonsurgical therapeutic options were initially pursued for management. Through shared decision-making and after exhaustion of other alternatives, she was maintained on optimized medical therapy and was scheduled for repeat elective surgery. After compliance with medical therapy and close monitoring, she improved significantly, and her underlying pathology completely resolved, eliminating the need for surgery. This report indicates that the management of mechanical prosthetic valve thrombosis should be individualized and emphasizes the importance of involving a multidisciplinary team of medical and surgical professionals to achieve the best clinical outcomes.

CD62L expression marks a functionally distinct subset of memory B cells.

The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients.

Background: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. Methods: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. Results: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination. Conclusion: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.

Replacement of the 3' untranslated variable region of mosquito-borne dengue virus with that of tick-borne Langat virus does not alter vector specificity.

The four major flavivirus clades are transmitted by mosquitoes, ticks, directly between vertebrates or directly between arthropods, respectively, but the molecular determinants of mode of transmission in flaviviruses are unknown. To assess the role of the UTRs in transmission, we generated chimeric genomes in which the 5' UTR, capsid and/or 3' UTR of mosquito-borne dengue virus serotype 4 (rDENV-4) were replaced, separately or in combination, with those of tick-borne Langat virus (rLGTV). None of the chimeric genomes yielded detectable virus following transfection. Replacement of the variable region (VR) in the rDENV-4 3' UTR with that of rLGTV generated virus rDENV-4-rLGTswapVR, which showed lower replication than its wild-type parents in mammalian but not mosquito cells in culture and was able to infect mosquitoes in vivo. Neither rDENV-4 nor rDENV-4-rLGTswapVR could infect larval Ixodes scapularis ticks immersed in virus, while rLGTV was highly infectious via this route.

The New Role of Cardiac Imaging Following the ISCHEMIA Trial.

PURPOSE OF REVIEW: This review is aimed at summarizing the recently published ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) and how its findings may impact cardiac imaging for stable ischemic heart disease (SIHD) moving forward. RECENT FINDINGS: The ISCHEMIA trial compared an initial invasive management strategy with goal of complete coronary revascularization versus an initial medical therapy strategy among stable patients with newly diagnosed moderate to severe myocardial ischemia on non-invasive testing. The trial results showed that an early invasive strategy did not reduce the incidence of major cardiovascular events over 3.2 years of follow-up as compared to optimal medical therapy in patients with SIHD. SUMMARY: The results of the landmark ISCHEMIA trial solidified the importance of guideline-directed medical therapy and have provided more evidence against the prevailing dogma that moderate to severe ischemia on traditional stress testing mandates coronary revascularization. This trial was not designed to compare different cardiac imaging and stress testing modalities for the assessment of coronary artery disease in patients undergoing their index evaluation for SIHD; however, its design, which included coronary computed tomographic angiography (CCTA) in most patients, and results have generated robust discussion regarding ways to improve non-invasive testing strategies in similar patient populations. We believe that increased utilization of CCTA to identify patients with and without high-risk SIHD, and advanced tests for ischemia, such as positron emission tomography and stress cardiac magnetic resonance imaging, when selected based on individual patient characteristics, may allow for improved decision-making and outcomes.

Long-term outcomes in patients with normal coronary arteries, nonobstructive, or obstructive coronary artery disease on invasive coronary angiography.

BACKGROUND: Normal or near normal coronary arteries (NNCA) or nonobstructive coronary artery disease (CAD) are commonly found on invasive coronary angiography (ICA). HYPOTHESIS: We aimed to determine long-term outcomes by severity of CAD in a contemporary cohort of patients undergoing ICA for evaluation for ischemic heart disease. METHODS: We assessed a consecutive cohort of 925 patients who underwent non-emergent ICA over 24 months. Cardiac death (CD), nonfatal myocardial infarction (NFMI), late revascularization, and medication use were assessed. RESULTS: Follow-up data was available in 850 patients. Of patients without heart failure, at a median of 6.0 years, there was a significant decrease in survival free from CD or NFMI, and from all cardiac events, for those with obstructive CAD compared with patients with NNCAs or nonobstructive CAD (p < .001 for both). No differences between NNCA and nonobstructive CAD patients in rates of CD or NFMI (2.0% vs. 2.1%/year, p = .58) or all cardiac events (2.4% vs. 2.9%/year, p = .84) were observed. CONCLUSION: Long-term follow-up in a contemporary cohort of consecutive patients undergoing non-emergent ICA for detection of CAD showed no difference in annual rates of CD or NFMI, or total cardiac events, in patients with NNCAs versus those with nonobstructive CAD, whereas patients with obstructive CAD had significantly more events. Event rates were low and similar by gender. Use of aspirin, lipid lowering therapy, and beta-blockers increased in all subgroups after ICA. We speculate this may explain the low incidence of subsequent cardiac events, and similar event rates in patients with NNCA and nonobstructive CAD, even in patients presenting with non-ST-elevation MI.

Lead aVR predicts early revascularization but not long-term events in patients referred for stress electrocardiography.

BACKGROUND: Exercise stress electrocardiography (ExECG) is recommended as a first-line tool to assess ischemia, but standard ST-analysis has limited diagnostic accuracy. ST elevation in lead aVR has been associated with left main and LAD disease in the population undergoing coronary angiography but has not been studied in the general population undergoing stress testing for the initial evaluation of CAD without coronary angiography. We sought to determine the predictive value of lead aVR elevation for ischemia, early revascularization, and subsequent cardiac events in consecutive patients undergoing ExECG. METHODS AND RESULTS: The study cohort included 641 subjects referred for ExECG who were dichotomized by presence or absence of aVR elevation ≥1mm and compared for prevalence and predictors of ischemia and a composite of cardiac death, nonfatal myocardial infarction, and late revascularization. The cohort had a median age of 57 and 57% were male. The prevalence of aVR elevation was 11.5%. The prevalence of significant ischemia on patients who received imaging was significantly higher with aVR elevation (14.3% vs 2.3%, p<0.001). Early revascularization occurred in 10.9% with vs 0.2% without aVR elevation, p<0.001. No subjects without aVR elevation or ST-depression underwent early revascularization. However, cardiac event rates were similar over a median 4.0 years of follow-up with and without aVR elevation (2.8% vs. 2.6%, p = 0.80). aVR elevation did not predict long-term cardiac events by Kaplan-Meier survival analysis (p = 0.94) or Cox proportional hazards modeling (p = 0.35). CONCLUSIONS: aVR elevation during ExECG predicts ischemia on imaging and early revascularization but not long-term outcomes and could serve as a useful adjunct to standard ST-analysis and potentially reduce the need for concurrent imaging.