COPYRIGHT © 2022 Palermo, Aretz and Holmboe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Competency frameworks in health professions education

Healthcare is becoming increasingly complex across the globe; technology, delivery models, economic requirements, demographics and the epidemiology of disease are changing at a rapid pace. Despite the multiple efforts in defining common competencies and standards that all healthcare professionals should meet, it has become clear that educational and training programs have to adjust to the needs of societies they serve, and that the institutions that design and deliver those programs need to be accountable to society for the products they produce. Academic institutions that educate healthcare professionals will have to interact differently with the many stakeholders needed to create effective and efficient, and culturally appropriate healthcare systems. Present day medical education has its roots in the European university which traditionally valued academic freedom, autonomy and independent research over serving society and the job market; future efforts will require a fundamental shift in the outlook and measures of success for academic institutions. The recent outcomes and competency movement is a first step in that direction but more will need to be done. Rather than being one participant, possibly a reluctant one, academia should become the catalyst for change, the hub for stakeholder interactions, and the breeding ground for the new healthcare workforce.

Background— Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of &bgr;-amyloid impair cell function and lead to cell death. Methods and Results— We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca2+ homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a. Conclusions— On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca2+ handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function.

Background: Recent efforts to identify the essential skills and competencies required for medical practice have resulted in an expansion of the educational outcomes for which medical schools are accountable. Teachers in the preclinical years, formerly focused on the transmission of biomedical principles and factual information, are now charged with presenting discipline-specific concepts with an emphasis on clinical relevance while advancing active learning, critical thinking, communication skills, and other professional competencies. Problem-based learning has been widely introduced to support these educational goals but other, less resource-intensive, discussion methodologies have not been extensively explored.Aim: To examine the feasibility of case-method teaching (CMT) during the preclinical curricula to integrate basic science concepts in the management of clinical problems.Methods: CMT sessions were conducted with students during the first- and second-year of hybrid curricula at two US medical schools.Results: First- and second-year medical classes of 40-95 students prepared for and actively engaged in single session case discussions and were able to productively apply basic science principles in clinical problem-solving.Conclusion: CMT represents a feasible and resource-conservative pedagogical format to promote critical thinking and to integrate basic science principles during the preclinical curriculum.

Background: Fluoroscopy‐guided catheter placement is limited in its ability to determine electrode‐endocardial contact and involves radiation exposure. We hypothesized that (1) intracardiac echocardiography (ICE) would provide superior assessment of linear electrode contact compared to fluoroscopy and (2) slow temperature decay upon discontinuation of the radiofrequency current (time for temperature to fall 90% after a 10‐second test application of the radiofrequency current T90) would indicate optimal electrode‐myocardial contact.

Background-In classic Fabry patients, accelerated coronary atherosclerosis and left ventricular hypertrophy manifest in the fourth decade; however, signs of cardiovascular disease also are observed later in life in "cardiac variant" patients and symptomatic female heterozygotes. These disturbances are caused by globotriaosylceramide (GL-3) accumulation in the heart resulting from lysosomal alpha-galactosidase A deficiency.Methods and Results-We analyzed pretreatment and posttreatment endomyocardial biopsies from 58 Fabry patients enrolled in a 5-month, phase 3, double-blind, randomized, placebo-controlled trial, followed by a 54-month open-label extension study of recombinant human alpha-galactosidase A. Baseline evaluations revealed GL-3 deposits in interstitial capillary endothelial cells and large, laminated inclusions within cardiomyocytes. In this study, we evaluated microvascular GL-3 clearance; no clearance of GL-3 was observed in the cardiomyocytes during this trial. Five months of recombinant human alpha-galactosidase A treatment in the phase 3 trial resulted in complete microvascular clearance of GL-3 from 72% of treated patients compared with only 3% of placebo patients (P<0.001). The placebo group achieved similar results after 6 months of treatment in the open-label trial. In addition, the capillary endothelium remained free of GL-3 for up to 60 months in 6 of 8 patients who consented to an end-of-study biopsy.Conclusions-The findings suggest that long-term treatment with recombinant human alpha-galactosidase A may halt the progression of vascular pathology and prevent the clinical manifestations of atherosclerotic disease. This histopathological study should be a useful guide for clinicians and pathologists who diagnose and follow Fabry patients. (Circulation. 2009; 119: 2561-2567.)

Background— The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution (≈10 μm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Methods and Results— Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non-ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying ≥2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively ( P =0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 μm, respectively ( P =0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness ≤65 μm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group ( P =0.012). No procedure-related complications occurred. Conclusions— OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.

OBJECTIVES This study was designed to determine in a dog model of coronary thrombosis whether short-term eptifibatide (Ep) combined with low-dose plasminogen activator (rt-PA) inhibits platelet recruitment at sites of endothelial damage after normalization of platelet function.BACKGROUND Ep plus reduced-dose rt-PA has not previously been shown to render a recanalized coronary artery resistant to platelet recruitment after normalization of platelet function.METHODS Inhibition of platelet recruitment was studied by scanning electron microscopy (SEM) in a canine model of left anterior descending (LAD) thrombosis. In phase I treatment groups were: 1) Ep (n = 6); 2) Ep + rt-PA (n = 6); 3) rt-PA (n = 6); and 4) placebo (n = 4). Coronary blood flow was monitored and LAD segments excised for SEM after 90-min infusion of study drug. In phase 11, dogs were randomized to Ep alone (n = 5) or to Ep + rt-PA (n = 5). Coronary blood flow was monitored during and 120 min after cessation of drug when platelet function had returned to normal and LAD segments were excised.RESULTS All animals except placebo showed reflow. In phase 1, SEM showed an absence of platelet aggregates with Ep alone and with Ep + rt-PA, but not with rt-PA alone. In phase 11, SEM showed an intimal surface devoid of mural thrombus and platelet aggregates only in Ep + rt-PA treated arteries. Ep-alone treated arteries showed new platelet aggregates at sites of residual mural thrombus.CONCLUSIONS Short-term infusion Ep plus low-dose rt-PA acutely neutralizes the ability of damaged endothelial surfaces to recruit new platelets by inhibiting platelet aggregation and eliminating residual mural thrombus. (C) 2004 by the American College of Cardiology Foundation.

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3(-/-) mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3(-/-) than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3(-/-) than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3(-/-) than in WT mice at 28 days after TAC. Mortality was greater in NOS3(-/-) than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3(-/-) mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.

OBJECTIVES This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome.BACKGROUND The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo.METHODS Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectorls, unstable angina pectoris, and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation.RESULTS A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80).CONCLUSIONS Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy. (C) 2004 by the American College of Cardiology Foundation.

Medical Journal of AustraliaVolume 178, Issue 4 p. 147-148 Editorial How good is the newly graduated doctor and can we measure it? H Thomas Aretz MD, H Thomas Aretz MD Medical Director; and Associate Professor of Pathology, Harvard Medical School Harvard Medical International, Boston, MA, USA.Search for more papers by this author H Thomas Aretz MD, H Thomas Aretz MD Medical Director; and Associate Professor of Pathology, Harvard Medical School Harvard Medical International, Boston, MA, USA.Search for more papers by this author First published: 17 February 2003 https://doi.org/10.5694/j.1326-5377.2003.tb05126.xCitations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume178, Issue4February 2003Pages 147-148 RelatedInformation

OBJECTIVES:We report an in-depth postmortem morphologic analysis of atrial myocardium in human pulmonary veins (PVs) from patients with and without atrial fibrillation (AF). BACKGROUND:Electrophysiologic studies established the critical role of PVs in the initiation of AF. To date, a paucity of data exists about PV morphology as an arrhythmogenic substrate. METHODS:Longitudinal tissue-strips of PVs were excised and histologically analyzed from the distal part to just beyond the atriovenous junction in the left atrium from 20 patients, obtained at autopsy. Anatomical measurements, including diameters, lengths, and wall-thicknesses of PVs, obtained at autopsy, were made. RESULTS:Histological analysis revealed extension of atrial myocardium into 89% of all PVs. Prevalence of myocardial extension was significantly higher in veins of 6 patients with compared with 14 patients without AF. Other significant differences in the histology of PVs between the two groups were a higher frequency of discontinuity and hypertrophy and a higher degree of fibrosis of the atrial myocardium in the PVs of patients with AF. A marked variation existed in anatomical dimensions of PVs, although no differences were observed between patients with or without AF. CONCLUSIONS:Atrial myocardium was more often present in the PVs of patients with compared with patients without AF. In the first group, the atrial myocardium in the PVs was characterized by more severe discontinuity, hypertrophy, and fibrosis. A marked variation in anatomical dimensions of the PVs existed.

Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.

Background— Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of ≈10 μm. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. Methods and Results— OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density ( r =0.84, P <0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density ( r =−0.56, P <0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. Conclusions— The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.

Intravascular OCT was performed in patients following myocardial infarction. Atherosclerotic plaque type and structure were compared for disrupted and non-disrupted locations. Our results suggest that intravascular OCT provides an accurate method for identifying vulnerable plaques.

HomeCirculationVol. 105, No. 15Fibrillary/Immunotactoid Glomerulopathy With Cardiac Involvement Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBFibrillary/Immunotactoid Glomerulopathy With Cardiac Involvement Marc S. Sabatine, H. Thomas Aretz, Leslie S.T. Fang and G. William Dec Marc S. SabatineMarc S. Sabatine From the Division of Cardiology (M.S.S., G.W.D.), Department of Pathology (H.T.A.), and Renal Associates (L.S.T.F.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass. , H. Thomas AretzH. Thomas Aretz From the Division of Cardiology (M.S.S., G.W.D.), Department of Pathology (H.T.A.), and Renal Associates (L.S.T.F.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass. , Leslie S.T. FangLeslie S.T. Fang From the Division of Cardiology (M.S.S., G.W.D.), Department of Pathology (H.T.A.), and Renal Associates (L.S.T.F.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass. and G. William DecG. William Dec From the Division of Cardiology (M.S.S., G.W.D.), Department of Pathology (H.T.A.), and Renal Associates (L.S.T.F.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass. Originally published16 Apr 2002https://doi.org/10.1161/01.CIR.0000016155.44486.59Circulation. 2002;105:e120–e121A 44-year-old woman with end-stage renal disease due to fibrillary/immunotactoid glomerulopathy presented with progressive symptoms of heart failure. An echocardiogram showed a dilated left ventricle with diffuse hypokinesis. An endomyocardial biopsy revealed patchy fibrosis. Immunofluorescence demonstrated interstitial staining with immunoglobulin G and complement component C3. Electron microscopy (Figure 1) revealed deposition of fibrils with diameters ranging from 8.0 to 12.4 nm that were negative on Congo red staining and were similar to the fibrils noted on her kidney biopsy 5 years earlier (Figure 2). After aggressive fluid removal and control of her hypertension, the patient's symptoms resolved. Download figureDownload PowerPointFigure 1. Myocardial biopsy specimens. Electronmicrographs of the myocardial biopsy specimen demonstrate interstitial deposits (asterisks) (A), which on higher power (B) are fibrils of dimensions and morphological characteristics similar to those found on the patient's renal biopsy 5 years earlier. A, Magnification ×3000; 1.5-cm bar=4.9 μm. B, Magnification ×24 200; 1.5-cm bar=0.62μm.Download figureDownload PowerPointFigure 2. Renal biopsy specimens. Electronmicrographs of the renal biopsy specimen demonstrate intramembranous and mesangial deposits of randomly arranged fibrils with a measured diameter of 13 nm. Magnification ×24 200; 1.5-cm bar=0.62 μm.This case suggests that fibrillary/immunotactoid glomerulopathy may be a systemic disease process, such as the monoclonal gammopathies or cryoglobulinemia. Immune complexes with strong intermolecular attraction may be in concentrations too low to be measured in the serum but may become concentrated in different parts of the body. Clinicians should add cardiac involvement to the expanding list of extrarenal manifestations of fibrillary/immunotactoid glomerulopathy.Presented in part at the Laennec Society Young Clinician Competition, 73rd Scientific Sessions of the American Heart Association, New Orleans, La, November 12–15, 2000.The editor of Images in Cardiovascular Medicine is Hugh A. McAllister, Jr, MD, Chief, Department of Pathology, St Luke's Episcopal Hospital and Texas Heart Institute, and Clinical Professor of Pathology, University of Texas Medical School and Baylor College of Medicine.Circulation encourages readers to submit cardiovascular images to the Circulation Editorial Office, St Luke's Episcopal Hospital/Texas Heart Institute, 6720 Bertner Ave, MC1-267, Houston, TX 77030.Dr Sabatine is the recipient of the William A. Schreyer Clinical Fellowship in Cardiology.FootnotesCorrespondence to Marc Sabatine, MD, Bulfinch B001, Cardiology Division, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. E-mail [email protected] eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Brown J, Trivedi S, Kwok F, Rowczenio D, Thomas L and Varikatt W (2019) Novel apolipoprotein AII mutation associated renal amyloidosis and fibrillary/immunotactoid cardiomyopathy, Pathology, 10.1016/j.pathol.2019.07.011, 51:7, (759-762), Online publication date: 1-Dec-2019. Pliquett R, Mohr P, El Din Mukhtar B, Girndt M and Markau S (2012) Plasmapheresis leading to remission of refractory nephrotic syndrome due to fibrillary glomerulonephritis: a case report, Journal of Medical Case Reports, 10.1186/1752-1947-6-116, 6:1, Online publication date: 1-Dec-2012. Ordóñez N and Rosai J (2011) Urinary tract Rosai and Ackerman's Surgical Pathology, 10.1016/B978-0-323-06969-4.00024-6, (1101-1286), . Herrera G and Turbat-Herrera E (2010) Renal Diseases With Organized Deposits: An Algorithmic Approach to Classification and Clinicopathologic Diagnosis, Archives of Pathology & Laboratory Medicine, 10.5858/134.4.512, 134:4, (512-531), Online publication date: 1-Apr-2010. Satoskar A, Calomeni E, Nadasdy G, Tozbikan G, Hitchcock C, Hebert L and Nadasdy T (2009) Fibrillary Glomerulonephritis with Splenic Involvement: A Detailed Autopsy Study, Ultrastructural Pathology, 10.1080/01913120801937723, 32:3, (113-121), Online publication date: 1-Jan-2008. Joh K (2007) Pathology of glomerular deposition diseases, Pathology International, 10.1111/j.1440-1827.2007.02139.x, 57:9, (551-565), Online publication date: 1-Sep-2007. Garibaldi D, Gottsch J, de la Cruz Z, Haas M and Green W (2005) Immunotactoid keratopathy: a clinicopathologic case report and a review of reports of corneal involvement in systemic paraproteinemias, Survey of Ophthalmology, 10.1016/j.survophthal.2004.10.002, 50:1, (61-80), Online publication date: 1-Jan-2005. Sears C, Bryant S, Ashley E, Lygate C, Rakovic S, Wallis H, Neubauer S, Terrar D and Casadei B (2003) Cardiac Neuronal Nitric Oxide Synthase Isoform Regulates Myocardial Contraction and Calcium Handling, Circulation Research, 92:5, (e52-e59), Online publication date: 21-Mar-2003. Hvala A, Ferluga D, Vizjak A and Koselj-Kajtna M (2009) Fibrillary Noncongophilic Renal and Extrarenal Deposits: A Report on 10 Cases, Ultrastructural Pathology, 10.1080/01913120390231672, 27:5, (341-347), Online publication date: 1-Jan-2003. April 16, 2002Vol 105, Issue 15 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000016155.44486.59PMID: 11956134 Originally publishedApril 16, 2002 PDF download Advertisement