Retraction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Mimicking as Pulmonary Tuberculosis in an Inmate.

[This retracts the article DOI: 10.7759/cureus.8464.].

An Extremely Rare Case of Anomalous Left Main Coronary Artery Originating From Single Right Coronary Ostium Managed Using Heart Team Approach.

Anomalies of coronary artery origin are rare, difficult to diagnose using conventional testing methods and extremely challenging to eventually manage once diagnosed. The risk of adverse outcomes increases as such patients age and develop atherosclerosis in such vessels. A comprehensive and multidisciplinary approach may be required to best manage such difficult cases.  We present a case of a 65-year-old female with symptoms of chest pain concerning for unstable angina. She also complained of occasional diaphoresis and dizziness. Physical examination revealed a regular heart rhythm with no vascular bruits. An electrocardiogram (EKG) only showed normal sinus rhythm and left axis deviation. Non-invasive testing included an echocardiogram, which showed multiple wall motion abnormalities. A diagnostic cardiac catheterization via right radial artery approach was performed to delineate her coronary anatomy and rule out ischemic etiology. This led to diagnosis of anomalous coronary anatomy with an anomalous left main coronary artery from single right coronary ostium. Furthermore, it showed significant obstructive multi-vessel coronary artery disease involving distal left main artery, proximal left anterior descending artery, left circumflex and right coronary arteries. The patient had a right dominant system with absent left coronary cusp. Percutaneous vs surgical revascularization options were considered. Given high Syntax score and acceptable Society of Thoracic Surgeons (STS) risk, Heart Team approach was pursued and the patient was referred for multi-vessel surgical revascularization.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Mimicking as Pulmonary Tuberculosis in an Inmate.

Coronavirus disease 2019 (COVID-19) is an emerging global infectious disease with emerging medical knowledge. Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is very variable amongst patients, and the literature about unusual presentations is growing rapidly. This lack of knowledge leads to diagnostic, therapeutic, and management challenges in such patients. Here, we describe a case of SARS-CoV-2 infection in a low prevalence area which was initially diagnosed and managed as pulmonary tuberculosis (TB) in a high-risk inmate population. These ambiguous presentations can lead to mismanagement of such patients resulting in potentially fatal outcomes and public health crises in confined facilities. This also highlights the significance of a high index of clinical suspicion for SARS-CoV-2 especially in high risk and vulnerable populations.

CardioMEMSTM System in the Daily Management of Heart Failure: Review of Current Data and Technique of Implantation.

INTRODUCTION: Heart failure (HF) leads to significant morbidity and mortality and imposes a large economic burden. Although there have been several advances in HF monitoring and management, HF-rehospitalization remains a significant problem. Remote monitoring of HF to detect early signs of decompensation has emerged in past years as an option to prevent or reduce the incidence of HF rehospitalization. The CardioMEMSTM HF system is a wireless pulmonary artery (PA) pressure monitoring system that detects changes in PA pressure and transmits data to the healthcare provider. Since changes in PA pressure happen early in the course of HF decompensation, the CardioMEMSTM system allows the provider to institute timely intensification of HF therapies to alter the course. In trial and registry data, the use of the CardioMEMSTM HF system has been associated with reduction in HF hospitalization, improvement in quality of life, symptoms, and physical activity. AREAS COVERED: This review will focus on the available data supporting its utilization in patients with HF. EXPERT OPINION: CardioMEMSTM is relatively safe and cost-effective, reduces heart failure hospitalization rates, and fits into intermediate to high-value medical care.

Diagnostic Challenge in a Symptomatic Patient of Arteria Lusoria with Retro-esophageal Right Subclavian Artery and Absent Brachiocephalic Trunk.

A combination of absent brachiocepahlic trunk and anomalous left circumflex artery with a retro-esophageal right subclavian artery is an extremely rare finding. This can clinically manifest as episodic dysphagia and chest pain. Routine coronary angiography via femoral access could be misleading and right radial access in such cases can be particularly challenging and has never been reported in literature before. We present a case of a 42-year-old female with symptoms of chest, back, and left neck pain. She also complained of occasional dysphagia, dizziness, and palpitations. Physical examination revealed a regular heart rhythm with no vascular bruits. An electrocardiogram (EKG) only showed normal sinus rhythm and incomplete right bundle branch block. Noninvasive testing included an echocardiogram and previously done exercise stress test, and myocardial perfusion scans were noted to be normal. A diagnostic cardiac catheterization via right radial approach was performed to delineate her coronary anatomy and rule out ischemic etiology. This led to diagnosis of anomalous coronary anatomy (retro-esophageal right subclavian artery arising from descending aorta in association with an anomalous right circumflex artery with absent innominate artery) through a technically difficult and risky procedure. Significant vessel tortuosity and abnormal catheter angulations were encountered and were overcome by using specific catheters. Meticulous use of 6 French MP, WR, JL, and JR4 catheters along with an exchange length wire was required to negotiate the anatomical variations and complete the coronary angiogram via right radial artery. From a procedural stand-point, coronary angiography via right radial access in presence of such rare anatomical variations can be particularly challenging. Routine femoral catheterization may fail to depict this important anatomical variation. Coronary angiogram via right radial access in the presence of a combination of anatomical variations of great vessels and anomalous coronary arteries is particularly challenging from a procedural stand point due to vessel tortuosity and shape of catheters. Choice of anatomically appropriate diagnostic catheters and specific maneuvers are imperative in these coronary angiographic procedures.

The Use of Fractional Flow Reserve for Physiological Assessment of Indeterminate Lesions in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a prevalent disorder in the United States, associated with significant morbidity and mortality. Fractional Flow Reserve (FFR) is a physiological test used to assess the hemodynamic significance of intermediate lesions on conventional angiography. It is well studied in coronary artery disease and is as an important tool to guide decisions regarding revascularization in a significant percentage of patients with intermediate lesions. As compared to coronary FFR, the use of FFR in peripheral artery disease (PFFR) is much less prevalent. Overall data regarding the use of the PFFR is sparse. There are limited studies that have shown the correlation of PFFR with non-invasive testing including ankle-brachial index (ABI) and Doppler Imaging. Unlike coronary FFR, the optimal pharmaceutical agents and doses to induce maximal hyperemia in the peripheral vascular bed are also not well established. Moreover, there are no established standardized procedural protocols for measuring PFFR. Various studies have employed varying techniques, hyperemic agents and doses. The aim of this literature review is to summarize the current evidence on PFFR, the correlation with noninvasive studies used in PAD and to increase awareness of the potential role of the PFFR in peripheral interventions.

Autoreactivity to glucose regulated protein 78 links emphysema and osteoporosis in smokers.

RATIONALE: Emphysema and osteoporosis are epidemiologically associated diseases of cigarette smokers. The causal mechanism(s) linking these illnesses is unknown. We hypothesized autoimmune responses may be involved in both disorders. OBJECTIVES: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers. METHODS: Replicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers. Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG. Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays. MEASUREMENTS AND MAIN RESULTS: Circulating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects. Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7-5.7, p = 0.003). Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7-13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006). Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03). Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively). CONCLUSIONS: Humoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis. These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders.

Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses.

RATIONALE: Diverse autoantibodies are present in most patients with idiopathic pulmonary fibrosis (IPF). We hypothesized that specific autoantibodies may associate with IPF manifestations. OBJECTIVES: To identify clinically relevant, antigen-specific immune responses in patients with IPF. METHODS: Autoantibodies were detected by immunoblots and ELISA. Intrapulmonary immune processes were evaluated by immunohistochemistry. Anti-heat shock protein 70 (HSP70) IgG was isolated from plasma by immunoaffinity. Flow cytometry was used for leukocyte functional studies. MEASUREMENTS AND MAIN RESULTS: HSP70 was identified as a potential IPF autoantigen in discovery assays. Anti-HSP70 IgG autoantibodies were detected by immunoblots in 3% of 60 control subjects versus 25% of a cross-sectional IPF cohort (n = 122) (P = 0.0004), one-half the patients with IPF who died (P = 0.008), and 70% of those with acute exacerbations (P = 0.0005). Anti-HSP70 autoantibodies in patients with IPF were significantly associated with HLA allele biases, greater subsequent FVC reductions (P = 0.0004), and lesser 1-year survival (40 ± 10% vs. 80 ± 5%; hazard ratio = 4.2; 95% confidence interval, 2.0-8.6; P < 0.0001). HSP70 protein, antigen-antibody complexes, and complement were prevalent in IPF lungs. HSP70 protein was an autoantigen for IPF CD4 T cells, inducing lymphocyte proliferation (P = 0.004) and IL-4 production (P = 0.01). IPF anti-HSP70 autoantibodies activated monocytes (P = 0.009) and increased monocyte IL-8 production (P = 0.049). ELISA confirmed the association between anti-HSP70 autoreactivity and IPF outcome. Anti-HSP70 autoantibodies were also found in patients with other interstitial lung diseases but were not associated with their clinical progression. CONCLUSIONS: Patients with IPF with anti-HSP70 autoantibodies have more near-term lung function deterioration and mortality. These findings suggest antigen-specific immunoassays could provide useful clinical information in individual patients with IPF and may have implications for understanding IPF progression.

Early treatment with fumagillin, an inhibitor of methionine aminopeptidase-2, prevents Pulmonary Hypertension in monocrotaline-injured rats.

Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients.

Cytokine-like factor 1 gene expression is enriched in idiopathic pulmonary fibrosis and drives the accumulation of CD4+ T cells in murine lungs: evidence for an antifibrotic role in bleomycin injury.

Idiopathic pulmonary fibrosis (IPF) is a progressive and typically fatal lung disease. To gain insight into the pathogenesis of IPF, we reanalyzed our previously published gene expression data profiling IPF lungs. Cytokine receptor-like factor 1 (CRLF1) was among the most highly up-regulated genes in IPF lungs, compared with normal controls. The protein product (CLF-1) and its partner, cardiotrophin-like cytokine (CLC), function as members of the interleukin 6 (IL-6) family of cytokines. Because of earlier work implicating IL-6 family members in IPF pathogenesis, we tested whether CLF-1 expression contributes to inflammation in experimental pulmonary fibrosis. In IPF, we detected CLF-1 expression in both type II alveolar epithelial cells and macrophages. We found that the receptor for CLF-1/CLC signaling, ciliary neurotrophic factor receptor (CNTFR), was expressed only in type II alveolar epithelial cells. Administration of CLF-1/CLC to both uninjured and bleomycin-injured mice led to the pulmonary accumulation of CD4(+) T cells. We also found that CLF-1/CLC administration increased inflammation but decreased pulmonary fibrosis. CLF-1/CLC leads to significantly enriched expression of T-cell-derived chemokines and cytokines, including the antifibrotic cytokine interferon-γ. We propose that, in IPF, CLF-1 is a selective stimulus of type II alveolar epithelial cells and may potentially drive an antifibrotic response by augmenting both T-helper-1-driven and T-regulatory-cell-driven inflammatory responses in the lung.