Research Spotlight

Roberts, W.C., Everett, B.P., Won, V.S. and Kondapalli, N. (2020). “Diagnostic Usefulness of Histological Examination of the Left Ventricular “Core” Excised to Insert a Left Ventricular Assist Device in Patients with Severe Heart Failure.” Am J Cardiol Oct 1;S0002-9149(20)31013-4. [Epub ahead of print.].

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The left ventricular assist device (LVAD) has proven to be beneficial for patients with severe heart failure poorly responsive to anti heart failure medicine. To examine both grossly and histologically the portion of left ventricular (LV) free wall excised (“the left ventricular core”) to insert a LVAD in 337 patients with severe heart failure from a variety of causes. We collected together all photographs of LV “cores” and the histologic sections prepared from them and reexamined both. Despite the fact that these LV cores usually weighed >100 times the quantity of myocardium available to examine compared to that available by biotome inserted via a transvenous catheter, the number in which histologic study allowed an unequivocal diagnosis was limited. Examination of the clinical records usually was required to establish the definitive diagnosis. Although the presence of a scarred myocardial wall usually suggested ischemic cardiomyopathy (IC), the scarring may not have involved the LV apex resulting in a non-scarred portion of myocardium simulating idiopathic dilated cardiomyopathy (IDC). Moreover, about 10% of the patients with IDC have myocardial scars thus simulating IC. Involvement of the LV core by amyloid, sarcoid, myocarditis, and acute infarction, of course, allowed a specific anatomic diagnosis. Despite the presence of ample tissue to secure a definitive diagnosis, the combination of clinical input and morphologic assessment was required to arrive at a definite diagnosis in most patients.

Kamity, R., Ferrara, L., Dumpa, V., Reynolds, J., Islam, S. and Hanna, N. (2020). “Simultaneous Videofluoroscopy and Endoscopy for Dysphagia Evaluation in Preterm Infants-A Pilot Study.” Front Pediatr 8: 537.

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Introduction: The assessment of dysphagia in preterm infants has been limited to clinical bedside evaluation followed by videofluoroscopic swallow study (VFSS) in selected patients. Recently, fiberoptic endoscopic evaluation of swallowing (FEES) is being described more in literature for preterm infants. However, it is unclear if one test has a better diagnostic utility than the other in this population. Furthermore, it is also unclear if performing FEES and VFSS simultaneously will increase the sensitivity and specificity of detecting dysphagia compared to either test performed independently. Objectives: The primary objective of this study is to evaluate the feasibility of performing VFSS and FEES simultaneously in preterm infants. Our secondary objective is to determine whether simultaneously performed VFSS-FEES improves the diagnostic ability in detecting dysphagia in preterm infants compared to either test done separately. Methods: In this pilot study, we describe the process involved in performing simultaneous VFSS-FEES in five preterm infants (postmenstrual age ≥36 weeks) with dysphagia. A total of 26 linked VFSS-FEES swallows were analyzed, where the same bolus during the same swallow was compared using simultaneous fluoroscopy and endoscopy. The sensitivity and specificity of detecting penetration and aspiration were evaluated in simultaneous VFSS-FEES compared with each test done independently. Results: Our results demonstrated that performing simultaneous VFSS-FEES is feasible in preterm infants with dysphagia. All patients tolerated the procedures well without any complications. Our pilot study in these five symptomatic preterm infants demonstrated a low incidence of aspiration but a high incidence of penetration. Simultaneous VFSS-FEES (26 linked swallows) improved the ability to detect penetration compared to each test done separately. Conclusion: To our knowledge, this study is the first to demonstrate the feasibility of performing VFSS and FEES simultaneously in symptomatic preterm infants with dysphagia resulting in potentially higher diagnostic yield than either procedure done separately.

Petrescu, A.D., Grant, S., Williams, E., Frampton, G., Reinhart, E.H., Nguyen, A., An, S., McMillin, M. and DeMorrow, S. (2020). “Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis.” Sci Rep 10(1): 16024.

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The orexigenic peptide ghrelin (Ghr) stimulates hunger signals in the hypothalamus via growth hormone secretagogue receptor (GHS-R1a). Gastric Ghr is synthetized as a preprohormone which is proteolytically cleaved, and acylated by a membrane-bound acyl transferase (MBOAT). Circulating Ghr is reduced in cholestatic injuries, however Ghr’s role in cholestasis is poorly understood. We investigated Ghr’s effects on biliary hyperplasia and hepatic fibrosis in Mdr2-knockout (Mdr2KO) mice, a recognized model of cholestasis. Serum, stomach and liver were collected from Mdr2KO and FVBN control mice treated with Ghr, des-octanoyl-ghrelin (DG) or vehicle. Mdr2KO mice had lower expression of Ghr and MBOAT in the stomach, and lower levels of circulating Ghr compared to WT-controls. Treatment of Mdr2KO mice with Ghr improved plasma transaminases, reduced biliary and fibrosis markers. In the liver, GHS-R1a mRNA was expressed predominantly in cholangiocytes. Ghr but not DG, decreased cell proliferation via AMPK activation in cholangiocytes in vitro. AMPK inhibitors prevented Ghr-induced FOXO1 nuclear translocation and negative regulation of cell proliferation. Ghr treatment reduced ductular reaction and hepatic fibrosis in Mdr2KO mice, regulating cholangiocyte proliferation via GHS-R1a, a G-protein coupled receptor which causes increased intracellular Ca(2+) and activation of AMPK and FOXO1, maintaining a low rate of cholangiocyte proliferation.

Tirado, M., Dobin, S.M., Fernandez, M.P. and Rao, A. (2020). “Pleomorphic mastocytoma associated with loss of chromosome 5, PDGFRA, and HRAS mutations: A case of cutaneous mastocytosis with severe atypia and indolent behavior.” J Cutan Pathol Sep 8. [Epub ahead of print.].

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A 21-year-old female presented with a 5-year history of an erythematous papule on her right breast. The biopsy showed a dense, dermal nodular infiltrate, extending focally into the subcutaneous tissue. The infiltrate was composed predominantly of pleomorphic cells with bi-lobed, multi-lobed, horseshoe, or ring-shaped nuclei. There was a smaller subset of monomorphous cells characterized by a round, reniform, or elongated single-lobed nucleus. Accompanying cells included few foamy histiocytes, lymphocytes, and numerous scattered eosinophils. No necrosis, vascular invasion, or ulceration was present. The pleomorphic and monomorphic granular cells were positive for Giemsa stain as well as for tryptase, CD117, CD68, CD2, and CD30 immunohistochemistry and negative for S100, CD1a, myeloperoxidase, lysozyme, and CD56. Clinical examination was negative for any additional similar lesions and serum tryptase was within normal limits. The bone marrow was not biopsied. In addition, fluorescent in situ hybridization revealed multiple clones with loss of number 5 chromosome and PDGFRA and HRAS mutations. The lesion did not recur or progress after a 6-year clinical follow-up. To our full knowledge, we report the first case of pleomorphic mastocytoma with loss of chromosome 5 and PDGFRA and HRAS mutations.

Potluri, S.P., Hamandi, M., Basra, S.S., Shinn, K.V., Tabachnick, D., Vasudevan, A., Filardo, G., DiMaio, J.M., Brinkman, W.T., Harrington, K., Squiers, J.J., Szerlip, M.I., Brown, D.L., Holper, E. and Mack, M.J. (2020). “Comparison of Frequency of Vascular Complications With Ultrasound-Guided Versus Fluroscopic Roadmap-Guided Femoral Arterial Access in Patients Who Underwent Transcatheter Aortic Valve Implantation.” Am J Cardiol 132: 93-99.

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To compare outcomes of ultrasound guidance (USG) versus fluoroscopy roadmap guidance (FG) angiography for femoral artery access in patients who underwent transfemoral (TF) transcatheter aortic valve implantation (TAVI) to determine whether routine USG use was associated with fewer vascular complications. Vascular complications are the most frequent procedural adverse events associated with TAVI. USG may provide a decreased rate of access site complications during vascular access compared with FG. Patients who underwent TF TAVI between July 2012 and July 2017 were reviewed and outcomes were compared. Vascular complications were categorized by Valve Academic Research Consortium-2 criteria and analyzed by a multivariable logistic regression adjusting for potential confounding risk factors including age, gender, body mass index, peripheral vascular disease, Society of Thoracic Surgeons score and sheath to femoral artery ratio. Of the 612 TAVI patients treated, 380 (63.1%) were performed using USG for access. Routine use of USG began in March 2015 and increased over time. Vascular complications occurred in 63 (10.3%) patients and decreased from 20% to 3.9% during the study period. There were fewer vascular complications with USG versus FG (7.9% vs 14.2%, p = 0.014). After adjusting for potential confounding risk factors that included newer valve systems, smaller sheath sizes and lower risk patients, there was still a 49% reduction in vascular complications with USG (odds ratio 0.51, 95% confidence interval 0.29 to 0.88, p = 0.02). In conclusion, USG for TF TAVI was associated with reduced vascular access site complications compared with FG access even after accounting for potential confounding risk factors and should be considered for routine use for TF TAVI.