Faculty Bibliography

OBJECTIVE:=0.08). CONCLUSIONS:F-NaF PET/CT may improve risk-stratification.

BACKGROUND:Macrophages and fibroblasts are 2 major cell types involved in healing after myocardial infarction (MI), contributing to myocardial remodeling and fibrosis. Post-MI fibrosis progression is characterized by a decrease in cardiac macrophage content. OBJECTIVES/OBJECTIVE:This study explores the potential of macrophages to express fibroblast genes and the direct role of these cells in post-MI cardiac fibrosis. METHODS:) transgenic mice. The expression of Yellow Fluorescent Protein (YFP) in these animals is restricted to myeloid lineage allowing the identification of macrophage-derived fibroblasts. The expression in YFP-positive cells of fibroblast markers was determined in myocardial tissue sections of hearts from these mice after MI. RESULTS:cells in the heart after MI. CONCLUSIONS:The data provide both in vitro and in vivo evidence for the ability of macrophages to transition and adopt a fibroblast-like phenotype. Therapeutic manipulation of this macrophage-fibroblast transition may hold promise for favorably modulating the fibrotic response after MI and after other cardiovascular pathological processes.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP⁺ exosomes. Moreover, uptake of CEMIP⁺ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

OBJECTIVES/OBJECTIVE:Both the open and endovascular techniques are commonly used for harvesting the radial artery (ORAH and ERAH, respectively), and yet, very little is known about the effects of these 2 techniques on endothelial integrity and function of the radial artery (RA). The aim of this study was to assess the endothelial integrity and function of RA harvested using the 2 approaches. METHODS:Two independent surgical teams working in the same institution routinely use the RA for coronary artery bypass grafting exclusively employing either ORAH or ERAH. Thirty-nine consecutive patients were enrolled in this comparative study. Endothelial function after ORAH or ERAH was assessed by using the wire myograph system. The integrity of the RA endothelium was evaluated by immunohistochemical staining for erythroblast transformation specific-related gene. RESULTS:The vasodilation in response to acetylcholine was significantly higher in RA harvested with ORAH (P ≤ 0.001 versus ERAH). Endothelial integrity was not different between the 2 groups. CONCLUSIONS:ORAH is associated with a significantly higher endothelium-dependent vasodilation. Further investigation on the potential implications of these findings in terms of graft spasm and patency as well as clinical outcomes are needed.

Introduction: Desmoplastic mesothelioma (DMM), a rare histological subtype of malignant pleural mesothelioma (MPM), is lethal and has very poor prognosis. Metastasis is commonly reported in DMM compared to other histological subtypes. Here we report a case of DMM with good survival (>1 year) despite lymph node metastasis. Case Report: A 62-year-old female with a history of smoking and possible asbestos exposure presented with cough and wheeze in 2012. Computed tomography (CT) revealed left-sided pleural plaques and multiple groundglass pulmonary nodules. In 2017, repeat CT showed increased diffuse left nodular pleural thickening. Positron emission tomography revealed hypermetabolic, nodular pleural thickening in the hemithorax, compatible with neoplasia. Needle biopsy in January 2018 showed pleural tissue with haphazard, nodular growth of spindled mesothelial cells, suspicious for desmoplastic mesothelioma. Definitive diagnosis was not possible due to lack of fat invasion and absence of supportive evidence by immunohistochemical stains. The patient underwent pleurectomy in February 2018. On histopathology, the majority of the tumor showed a desmoplastic pattern, composed of malignant spindled cells arranged haphazardly in a dense hyalinized stroma with chronic inflammatory infiltrate. AE1/AE3, calretinin, and D2-40 immunohistochemical stains highlighted the infiltrating neoplastic cells, which were negative for WT-1. BAP-1 was retained. The pattern of immunoreactivity supported the diagnosis of DMM. The tumor also involved visceral pleura, pulmonary parenchyma, and pericardium. It invaded into fat and displayed lymphovascular invasion. A metastatic focus of DMM was present in a lymph node. The tumor was staged as pT3N1. On recent examination, the patient only had complaints of mild breathlessness and stable hydro-pneumothorax, without any other comorbidities.
Conclusion(s): Our finding is unusual, since among the mesothelioma subtypes, DMM has the shortest survival, usually not more than 6 months. We report an extremely rare case of DMM with survival of >1 year despite invasion of lung parenchyma and lymph node metastasis

Calcification in a coronary artery is accepted as definite evidence of coronary atherosclerosis. The extent and density of calcification, as combined in the Agatston score, is associated with the risk of a patient experiencing a major acute coronary event (MACE). The higher the Agatston score, the greater the higher likelihood of MACE. Atherosclerosis occurs because damaged endothelial cells allow low density lipoprotein cholesterol (LDLc) to leak into subintimal tissue. Proteoglycans in subendothelial collagen have a high affinity for LDLc, retaining the lipoprotein cholesterol complex. As the endothelial damage is repaired, the subintimal LDLc is trapped in subintimal glycosaminoglycans. Trapped LDLc induces an inflammatory response in the overlying endothelium, resulting in expression of chemotactic peptides. Chemotactic peptides attract circulating monocytes, which follow the concentration gradient to enter the tissue and then become tissue macrophages to phagocytize and digest the LDLc. In the process of digesting LDLc, enzymes produced by these macrophages oxidize the LDLc complex. However, oxidized LDL is toxic to macrophages; when present in sufficient quantity, it may cause macrophage death, thereby further contributing to inflammation in the atheroma. In the necrotic inflammatory lesion, the regulatory mechanisms that normally control tissue concentrations of calcium and phosphorous are lost, allowing the solubility product of calcium phosphate to be exceeded, resulting in the formation of microscopic dystrophic calcium-phosphate crystals. With ongoing inflammation, additional calcium-phosphate crystals are formed, which may aggregate. When these aggregated calcium phosphate crystals exceed ~ 0.2mm, the lesions become visible on clinical CT as coronary calcifications. Serial gated CT scans of the heart have demonstrated that once formed, CT visible calcifications do not decrease significantly in size, but they may increase. Although dystrophic vascular calcification is a 'tombstone,' it does not identify the lesions likely to cause MACE. Atheroma that are actively undergoing calcification are the most likely to cause major acute events, and molecular PET/CT imaging with ionic 18F fluoride identifies such lesions. Recent data suggest that 18F-fluoride imaging may be a sensitive and specific marker of lesions likely to cause MACE. A multicenter trial is needed to define whether this marker identifies patients at high risk of MACE.

OBJECTIVES/OBJECTIVE:The aim of this study was to comprehensively evaluate the pathology of the lower extremity arteries across their entire length in subjects dying with abundant risk factors and to evaluate the clinical and imaging implications of the pathological characteristics. BACKGROUND:Lower extremity peripheral arterial disease is a major cause of cardiovascular morbidity, but a systematic characterization of the pathology has never been undertaken. METHODS:Twelve legs were obtained from 8 cadavers with histories of coronary risk factors (median age 82 years, 6 men); 8 of 12 legs were evaluated using computed tomography before the major peripheral arteries were dissected along their entire length. Dissected arteries were cut serially at 3 to 4 mm, and a total of 2,987 sections were examined. RESULTS:Luminal irregularities and stenosis were more commonly seen in computed tomography images of above-the-knee (AK) arteries. Atherosclerotic lesions were histologically confirmed and were more common in AK (95.7%) than below-the-knee (BK) (56.8%) arteries. Occluded vessels were observed at 18 sites, including 8 AK and 10 BK arteries. Pathologically, acute thrombus was observed in all 8 AK sites, of which 3 were associated with plaque rupture and 5 were related to calcified nodules. The 10 occluded BK arteries revealed chronic total occlusions, of which half were embolic in origin and half were associated with atherosclerotic lesions. Intimal (75.3%) and medial (86.2%) calcifications were commonly encountered. Proportionate to the neointimal atherosclerosis, intimal calcification was more severe in AK arteries; the severity of medial calcification was no different between AK and BK arteries. Calcification was significantly greater in arteries excised from subjects with compared with those without diabetes. CONCLUSIONS:Atherosclerosis occurs more commonly in AK arteries and luminal occlusion from acute thrombosis secondary to rupture or calcified nodules. BK occlusion was chronic in nature, and at least half of lesions were embolic in origin. Medial calcification was similarly common in AK and BK arteries but more prevalent in subjects with diabetes.

Purpose: In October 2018, a new US adult heart allocation scheme was enacted in which the etiology of cardiomyopathy can play a significant role in the prioritization of patients listed for transplantation. Given this, we embarked on a review of the diagnoses of patients who underwent therapy for advanced heart failure at our center.
Method(s): We retrospectively reviewed the etiology of cardiomyopathy of patients receiving either durable ventricular assist device (VAD) or orthotopic heart transplantation (OHT) at NYU Langone Medical Center in New York, NY between January 2011 and October 2018. We evaluated for discrepancies between the primary HF diagnosis at time of operation with the ultimate diagnosis, combining both clinical follow-up data and cardiac pathology.
Result(s): During the study period, a total of 110 patients were treated with advanced therapies, of which the majority (74.5%) were male. 40.9% were African American, 35.4% Caucasian, 4.5% Asian, and 23.6% Hispanic. 86.3% underwent VAD and 22.0% underwent OHT. The average age of those undergoing OHT and VAD were 58 and 61 respectively. The most common reported etiology of HF was dilated cardiomyopathy (57.3%), followed by ischemic (36.3%), familial DCM (1.8%), amyloidosis (1.8%), restrictive cardiomyopathy (1.8%), and sarcoidosis (0.9%). On final review of the diagnoses in these patients, 14 (12.7%) had a final diagnosis that was inconsistent with the prior reported one. 5 were clerical errors, but 9 were significant deviations from the prior diagnosis. The most common diagnoses that were misidentified prior to VAD or OHT were cardiac sarcoidosis (2), cardiac amyloidosis (2), and hypertrophic cardiomyopathy (2). Among those 9 patients, 7 patients received VAD with 5 eventually requiring OHT (median days to OHT = 248); 2 patients directly received OHT. All of those are alive except one patient who was lost to follow-up (transferred care to another center). Patients in whom the diagnosis was misidentified prior to VAD or OHT had smaller LV dimensions on transthoracic echocardiography on average than other LVAD or OHT patients with non-ischemic cardiomyopathy.
Conclusion(s): In this single-center review, we found that the majority of HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, although notably 8.1% had a missed diagnosis at time of intervention (VAD or OHT). Appropriately identifying the subtype of cardiomyopathy remains challenging especially in advanced HF patients but can significantly impact waiting list time in the current organ allocation scheme. A normal or minimally increased LV dimension on echocardiogram in a patient with advanced non-ischemic cardiomyopathy may warrant further workup for another diagnosis.
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Background/UNASSIGNED:There is a paucity of data regarding the role of wedge resection (WR) in the management of bronchial carcinoid (BC) tumors. In this study, we queried the Surveillance, Epidemiology, and End Results (SEER) database to compare the oncologic outcomes of patients with BC tumors treated with WR or anatomic resection. Methods/UNASSIGNED:) test or Mann Whitney U test. Overall and cancer specific survival (OS, CSS) were estimated using Kaplan-Meier method and differences were compared using log-rank test. Cox-regression multivariable analysis (MVA) was performed to explore factors associated with worse CSS. Propensity-score matching analysis was done to compare survival differences between WR and Lob/Seg. Results/UNASSIGNED:Lob/Seg) was not associated with CSS (HR =1.16, 95% CI: 0.85-1.60). Conclusions/UNASSIGNED:A WR may offer equivalent CSS in well-selected patients with early-stage TC. An anatomic resection appears warranted in AC.