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Background: Mitral valve repair using expanded polytetrafluoroethylene sutures to replace mitral chordae tendineae is a well-established procedure. However, the incidence of neo-chordae failure causing recurrent mitral regurgitation is not well defined., Methods: We have reviewed the reported cases of complications after mitral valve repair related to the use of neo-chordae. This study was mainly carried out through PubMed, Medline, and Google Chrome websites., Results: We have identified a total of 26 patients presenting with rupture of polytetrafluoroethylene neo-chordae, mostly being described as isolated cases. Few other cases of recurrent mitral regurgitation with hemolysis were found, where reoperation was not caused by neo-chordal failure but most likely by technical errors. At pathological investigation the findings were substantially similar in all reported cases. The neo-chordae retained their length and pliability, became covered with host tissue and rupture was mainly related to suture size. Mild calcification was observed not interfering with chordal function; chordal infection did never occur., Conclusions: The use of artificial neo-chordae provides excellent late results with durable mitral valve repair stability. Chordal rupture may occur late postoperatively leading to reoperation because of recurrent mitral regurgitation. Despite its rarity, this potential complication should not be overlooked during follow-up of patients after mitral valve repair using artificial neo-chordae., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid infiltration into the atrial wall, and the cardiotoxic damage of atrial cardiomyocytes by amyloid precursors. Atrial amyloidosis is an early manifestation of CA, and is associated with an increased risk of atrial fibrillation and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and ventricular involvement. This condition is named isolated atrial amyloidosis and is due to a local overproduction of atrial natriuretic peptide. In this review we summarize the evidence on the mechanisms and clinical relevance of atrial amyloidosis., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: We sought to evaluate the diagnostic accuracy of post-mortem cardiac magnetic resonance (PMCMR) of explanted hearts to detect the cardiac causes of sudden death., Methods: PMCMR was performed in formalin-fixed explanted hearts of 115 cases of sudden death. Histological sampling of myocardium was performed using two different approaches: (1) guideline-based sampling; (2) guideline-based plus PMCMR-driven sampling., Results: Forensic diagnosis of cardiac cause of death was ascertained in 72 (63%) patients. When the guideline-driven histological sampling was used, the PMCMR interpretation matched with final forensic diagnosis in 93 out of 115 cases (81%) with sensitivity of 88% (79-95%), specificity of 65% (47-80%), PPV of 84% (78-90%), NPV of 73% (58-84%), accuracy of 81% (72-88%), and AUC of 0.77 (0.68-0.84). When a PMCMR-driven approach was added to the guideline-based one, the matching increased to 102 (89%) cases with a PMCMR sensitivity of 89% (80-94%), a specificity of 86% (67-96%), PPV of 95% (89-98%), NPV of 73% (59-83%), accuracy of 89% (81-93%), and AUC of 0.88 (0.80-0.93)., Conclusions: PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement or demonstrating signs of myocardial ischemia.

In histology, the correct handling and orientation of small/thin biopsies is often crucial for diagnosis. Automation is progressively growing and modifying the routine work in the histopathology laboratories, providing new chances for quality improvement and workload optimization. We have tested the use of Paraform orientation gels together with an automated embedding system for processing small/thin biopsies, first skin, but also other tissue/organ biopsies. The study aimed to assess the benefits and challenges of routinely using orientation gels in a high throughput pathology laboratory. Gel introduction required a short training of the pathologists, including trainees, at grossing; it did not cause significant delay at grossing, interference with embedding, or microtome steps, whereas re-do inclusions and re-cut slides were significantly reduced. In conclusion, orientation gel and automatic embedding constituted an efficient system for small/thin biopsies that had to be correctly placed and orientated, allowing the re-modeling of technicians' workflow and very safe handling of small/thin biopsies that were not manipulated further after grossing., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50-76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events.

Purpose: Primary oral mucosal melanoma (OMM) is a rare neoplasm accounting for the 0.2% to 0.8% of all melanomas. The aim of the present manuscript is (1) to describe 2 cases of primary OMM treated at our department, and (2) to perform a systematic literature review on primary OMM occurrence and treatment., Methods: Two cases of primary OMM were described. A systematic review is presented in order to assess the treatment options, recurrence, metastasis development, and survival rate of primary OMM., Results: Two patients were referred for the development of a lesion of the hard palate and the maxillary gingival mucosa, respectively. An incisional biopsy was performed in both patients, followed by extensive surgical resection after a thorough consideration of patient history and systemic involvement. The literature search retrieved 447 primary OMM cases. In the 30% of cases, distant metastases were already present at the time of diagnosis. The management of primary OMM most frequently involved surgical treatment and adjuvant radiotherapy., Conclusions: Primary OMM still represents a challenge for the clinician, as the diagnosis is often performed when metastases have already developed. The prognosis is generally poor, thus highlighting the need for further investigations to improve early diagnosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. We assessed mechanisms of sex-related PON-induced cardiotoxicity and identified rescue strategies in a murine model. PON+scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells (%TdT+6.12 ± 0.17), higher percentage of SA-β-gal-positive senescent cardiac area (%SA-β-gal 1.41 ± 0.59) and a lower reactivity degree (RD) for the survival marker Bmi1 [Abs (OD) 5000 ± 703] compared to female (%TdT+3.75 ± 0.35; %SA-β-gal 0.77 ± 0.02; Bmi1 [Abs (OD) 8567 ± 2173]. Proteomics analysis of cardiac tissue showed downstream activation of cell death in PON+siRNA scrambled compared to vehicle or PON+siRNA-Notch1-treated male mice. Upstream analysis showed beta-oestradiol activation, and downstream analysis showed activation of cell survival and inhibition of cell death in PON+scrambled siRNA compared to vehicle or PON+siRNA-Notch1-treated female mice. PON+scrambled siRNA-treated mice also had a downregulation of cardiac actin-more marked in males-and vessel density-more marked in females. Female hearts showed greater cardiac fibrosis than their male counterparts at baseline, with no significant change after PON treatment. PON+siRNA-scrambled mice had less fibrosis than vehicle or PON+siRNA-Notch1-treated mice. The left ventricular systolic dysfunction showed by PON+scrambled siRNA-treated mice (male %EF 28 ± 9; female %EF 36 ± 7) was reversed in both PON+siRNA-Notch1-treated male (%EF 53 ± 9) and female mice (%EF 52 ± 8). We report sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can help to identify biomarkers and potential mechanisms underlying sex-related differences in PON-induced cardiotoxicity., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objectives: We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the time interval between the onset of ischemia and SCD is ≤ 90 min., Methods: PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia., Results: At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (p = 0.0008), and lower T2 (p = 0.007) and T2* (p = 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others., Conclusion: PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques., Key Points: • Post-mortem MRI may help to understand cause of sudden cardiac death. • Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia. • Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia., (© 2021. European Society of Radiology.)

Rationale: Despite advances in treatment of acute myocardial infarction (AMI), many patients suffer significant myocardial damage with cardiac dysfunction. Sympathetic renal denervation (RD) may reduce adrenergic activation following AMI., Objective: To investigate the potential role of RD limiting myocardial damage and remodeling when performed immediately after AMI., Methods and Results: Sixteen farm pigs underwent 90 min left anterior descending artery balloon occlusion. Eight pigs underwent RD immediately after reperfusion. LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance 5 and 30 days after AMI. 123 I-MIBG scintigraphy was performed 31 days after AMI to image myocardial sympathetic innervation. Heart norepinephrine was quantified (from necrotic, border and remote zone). RD and control did not differ in myocardium at risk extent (59 ± 9 vs 55 ± 11% of LV mass) at 5 days. At 30 days CMR, RD pigs had smaller necrotic areas than control as assessed by gadolinium delay enhancement (18 ± 7 vs 30 ± 12% of LV mass, p = 0.021) resulting in improved myocardial salvage index (60 ± 11 vs 44 ± 27%, p < 0.001). RD pigs had higher cardiac output (3.7 ± 0.8 vs 2.66 ± 0.7 L/min, p < 0.001) and lower LV end diastolic volume (98 ± 16 vs 113 ± 31 ml, p = 0.041). 123 I-MIBG defect extension was smaller in RD than control (60 ± 28 vs 78 ± 17%, p < 0.05) with significant reduction in the difference between innervation and perfusion defects (25 ± 12 vs 36 ± 30%, p = 0.013). NE content from necrotic area (238; IQR 464 vs 2546; IQR 1727 ng/g in RD and control, respectively, p < 0.001) and from border zone (295; IQR 264 vs 837; IQR 207 in RD and control, respectively, p = 0.031) was significantly lower in RD than control., Conclusions: RD results in increased myocardial salvage and better cardiac function, when performed immediately after AMI. Reduction of sympathetic activation with preservation of cardiac sympathetic functionality warranted by RD may sustain these effects.

Objective: Myxomas are rare benign mesenchymal soft tissue tumors that seldom affect the head and neck area. The present report describes a rare case of intramuscular myxoma of the oral cavity and briefly reviews the literature regarding the occurrence of these lesions in the maxillofacial area., Study Design: A 59-year-old patient was referred for the development of a slow-growing tumefaction in the right buccal mucosa in the previous 12 months. Magnetic resonance imaging was performed to characterize the lesion's dimensions and its relationship with the surrounding structures, and it revealed intramuscular localization in correspondence with the medial pterygoid muscle. Incisional biopsy was carried out to aid in the final diagnosis., Results: Histology revealed the presence of an intramuscular myxoma, characterized by discontinuous margins and locally infiltrating muscular fibers. A second surgery was performed to totally remove the lesion. Follow-up at 6 months did not show any signs of recurrence. A literature search was performed to retrieve data on the incidence of oral intramuscular myxomas., Conclusions: To the best of our knowledge, this is the first case of intramuscular myxoma of the medial pterygoid muscle reported in the literature. Although rarely encountered, intramuscular myxomas should be considered when performing differential diagnoses of soft tissue masses at the level of the masticatory muscles., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue-measured iron concentration by using a segmental approach and we assessed the iron distribution., Methods: Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network. A multislice multiecho R2* approach was adopted. After CMR, used as guidance, the heart was cut in three short-axis slices and each slice was cut into different equiangular segments according to AHA segmentation and differentiated into endocardial and epicardial layers. Tissue iron concentration was measured by atomic absorption spectrometer technique., Results: Fifty-five samples were used since only for two hearts all the 16 samples were analyzed. Mean iron concentration was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. The coefficient of variability of iron for myocardial segments ranged from 8.08 to 24.54% (mean 13.49 ± 6.93%). Iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 vs 4.84 ± 4.87 mg/g dw; p = 0.042). Four different circumferential regions (anterior, septal, inferior, and lateral) were defined. A circumferential heterogeneity was noted, with more iron in the anterior region, followed by the inferior region. The direct nonlinear fitting of R2* and [Fe] data led to the calibration curve: [Fe] = 0.0022 ∙ (R2*-ROI) 1.462 (R-square = 0.956)., Conclusions: Our data further validate R2* CMR using a segmental approach as a sensitive and early technique for quantifying iron distribution in the current clinical practice., Key Points: • Calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration was provided. • A circumferential heterogeneity in cardiac iron distribution was detected: more iron was observed in the anterior region, followed by the inferior region. This finding corroborates the use of a segmental T2* CMR approach in the clinical practice to detect a heterogeneous iron distribution. • The comparison between the cardiac T2* values obtained with the region-based and the pixel-wise approaches showed a significant correlation and no significant difference but, in presence of significant iron load, the region-based approach resulted in significantly higher T2* values.

Antenatal cardiac intervention affords new prospects for hypoplastic left heart syndrome. Its success, however, may come not only from absence of impediments to blood flow but also from a sufficiently developed cardiac wall. Here, we examined the feasibility to perfuse selectively the fetal coronary circulation for treatment with growth promoting agents. Pregnant sheep (94-114 days gestation, term 145 days) were used. An aortic stop-flow procedure was developed for intracoronary access in the nonexposed fetus and human mesenchymal stem cells and their exosomes served as test agents. We found that aortic stop-flow ensures preferential distribution of fluorescent microspheres to the heart. However, intracoronary administration of stem cells or exosomes was detrimental, with fetal demise occurring around surgery or at variable intervals afterwards. Coincidentally, stop-flow caused by itself a marked rise of intraluminal pressure within the occluded aorta along with histological signs of coronary obstruction. We conclude that it is feasible to perfuse selectively the coronary circulation of the preterm fetus, but treatments are not compatible with survival of the animals. The cause for failure is found in the absence of hemodynamic compensation to stop-flow via a left-to-right shunt. This unexpected event is attributed to a largely membranous foramen ovale, characteristic of sheep, that collapses under pressure.

The objectives of this study are to evaluate the incidence of aortitis on a surgical population, establish any relationship with systemic diseases, verify early and late surgical results and provide clinical and radiological follow-up to determine factors potentially predicting progression of the disease and influencing late outcome. From 2009 to 2017, 237 patients underwent elective operations on the ascending aorta. Segments of the excised tissues were routinely sent for histologic evaluation, providing adequate data in 178 (75%) for a clinical and pathologic correlation. Patients with aortitis (Group 1) (n = 26) were compared with 152 with atherosclerotic or degenerative disease (Group 2). Incidence of aortitis was 15%, being clinically isolated in 73%. In 24 patients (92%), a giant cell aortitis was found. Actuarial survival at 3 years is 88% in Group 1 and 98% in Group 2 and 74% and 98% at 5 years, respectively (P = 0.016). A control angio-computed tomography revealed an increased descending aorta diameter in 2 out of 14 late survivors. A positron emission tomography showed presence of arteritis in other vascular segments in 3 patients. Clinically isolated aortitis is extremely frequent in patients with inflammatory aortic disease. The diagnosis is often difficult and may be supported by routine pathologic evaluation of surgical explants and by multimodality imaging. The latter should be employed to allow adequate patient follow-up and to disclose potential recurrences in untreated aortic segments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Herein we report an unusual case of sudden death occurring in a 65 year old woman during a minor oral surgery. The subject, who had a medically treated anxiety, had a history of two reversible left ventricle dysfunction episodes consistent with recurrent Takotsubo Syndrome that had occurred seven and six years before, respectively. She also suffered from moderate, well treated post-menopausal systemic hypertension. Post-mortem examination showed apical biventricular ballooning of the heart with no cardiac rupture, coronary artery lesion or other cardiac/extra-cardiac disease. Toxicological tests and forensic investigations excluded unnatural causes of death, including pharmacological or iatrogenic causes related to medical malpractice. Only non-specific contraction bands and mild hypertrophy were observed by histology in the left ventricle myocytes. Takotsubo syndrome is usually an acute and reversible heart failure syndrome with acute left ventricle apex ballooning, no coronary artery disease or other macroscopic or microscopic cardiac changes; physical or emotional stress are well known triggering factors. Nevertheless, recurrent forms, major cardiac adverse events and even sudden death may occur in a minority of cases, meaning that a diagnosis of Takotsubo syndrome must be considered in cases of sudden death and in forensic investigations.

Cardiac sarcoma is the commonest histology among primary cardiac tumors but it is a rare clinical entity and it is characterized by late stage presentation, poor prognosis from the time of detection and a variety of clinical presentations depending on the size and extent of the mass. We report the case of a high-grade right atrial angiosarcoma presenting with pulmonary embolism and cardiac tamponade. The patient underwent surgical resection and reconstruction of the atrial wall with bovine pericardial patch. This case report underscores the great heterogeneity of the clinical presentation, often non-specific, and the fatal prognosis of angiosarcoma, mostly related to the lack of evidence supporting a standardized therapeutic approach.

The capacity of inducing angiogenesis is a recognized hallmark of cancer cells. The cancer microenvironment, characterized by hypoxia and inflammatory signals, promotes proliferation, migration and activation of quiescent endothelial cells (EC) from surrounding vascular network. Current anti-angiogenic drugs present side effects, temporary efficacy, and issues of primary resistance, thereby calling for the identification of new therapeutic targets. MICALs are a unique family of redox enzymes that destabilize F-actin in cytoskeletal dynamics. MICAL2 mediates Semaphorin3A-NRP2 response to VEGFR1 in rat ECs. MICAL2 also enters the p130Cas interactome in response to VEGF in HUVEC. Previously, we showed that MICAL2 is overexpressed in metastatic cancer. A small-molecule inhibitor of MICAL2 exists (CCG-1423). Here we report that 1) MICAL2 is expressed in neo-angiogenic ECs in human solid tumors (kidney and breast carcinoma, glioblastoma and cardiac myxoma, n = 67, were analyzed with immunohistochemistry) and in animal models of ischemia/inflammation neo-angiogenesis, but not in normal capillary bed; 2) MICAL2 protein pharmacological inhibition (CCG-1423) or gene KD reduce EC viability and functional performance; 3) MICAL2 KD disables ECs response to VEGF in vitro. Whole-genome gene expression profiling reveals MICAL2 involvement in angiogenesis and vascular development pathways. Based on these results, we propose that MICAL2 expression in ECs participates to inflammation-induced neo-angiogenesis and that MICAL2 inhibition should be tested in cancer- and noncancer-associated neo-angiogenesis, where chronic inflammation represents a relevant pathophysiological mechanism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Attenuated Listeria monocytogenes (Lm at -LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lm at -LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensitivity to BRAF inhibitors or degree of stemness. We also show that, when administered in the therapeutic setting to Braf/Pten genetically engineered mice, Lm at -LLO causes a strong decrease in the size and volume of primary melanoma tumors, as well as a reduction of the metastatic burden. At the molecular level, we confirm that the anti-melanoma activity exerted in vivo by Lm at -LLO depends also on its ability to potentiate the immune response of the organism against the infected tumor. Our data pave the way to the preclinical testing of listeria-based immunotherapeutic strategies against metastatic melanoma, using a genetically engineered mouse rather than xenograft models.

Background: Myxomas are the most frequent cardiac tumours. Their diagnosis requires prompt removal. In our centre, for valve surgery we use a minimally invasive approach. Here, we report our experience of cardiac myxoma removal through right lateral mini-thoracotomy (RLMT) with particular focus on its feasibility, efficacy and patient safety., Methods: Between February 2006 and January 2017, 30 consecutive patients (aged 66±12.6years, range 35-83 years) underwent atrial myxoma resection through video-assisted RLMT. Percutaneous venous drainage was performed in all patients and direct cannulation of the ascending aorta was performed in 28 out of 30 (93.3%). The diagnosis of atrial myxoma was confirmed by histology., Results: Complete surgical resection was achieved in all patients. The mean cardiopulmonary bypass (CPB) time was 76.5±40.8minutes and average aortic cross-clamping time was 41.5±29.8minutes. No patient suffered postoperative complications. Five patients (16.7%) received a blood transfusion. Mechanical ventilation ranged from 3 to 51hours (median 6hours), intensive care unit (ICU) stay ranged from 1 to 5days (median 1day). Total hospital length of stay (HLOS) was 5.6±2 days. Home discharge rate was 56.7%. No in-hospital mortality was reported. During follow-up (55.6±32.3 months; range 4-132 months), one tumour recurrence was observed. There were three late non-cardiac deaths. Overall survival was 100%, 85.7% and 85.7% at 1, 5 and 10 years, respectively., Conclusions: The use of video-assisted RLMT is an effective and reproducible strategy in all patients requiring expedited surgery for left atrial myxoma, independently of coexisting morbidity such as systemic embolisation or previous surgery. This technique leads to complete tumour resection, prompt recovery, early home discharge and high freedom from both symptoms and tumour recurrence., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy. Gene expression analyses of α-smooth muscle actin, endothelial CD31 antigen, alpha-cardiac actin, matrix metalloprotease-2 (MMP2) and tissue inhibitor of matrix metalloprotease-1 (TIMP1) was performed on cDNA obtained from either microdissected neoplastic cells or whole tumor sections. We found very little or absent CD31 and α-Smooth Muscle Actin expression in the microdissected cells as compared to the whole tumors, whereas TIMP1 and MMP2 genes were highly expressed in both ones, greater levels being found in patients with embolic phenomena. α-Cardiac Actin was not detected. Confocal microscopy disclosed two different signals corresponding to calretinin-positive myxoma cells and to endothelial CD31-positive cells, respectively. In conclusion, the neoplastic (lepidic) cells showed a distinct gene expression pattern and no consistent overlapping with endothelial and smooth muscle cells or cardiac myocytes; the expression of TIMP1 and MMP2 might be related to clinical presentation; larger series studies using also systematic transcriptome analysis might be useful to confirm the present results.

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The aim of our study is to compare two different surgical procedures, lymphatic vessels and arterioles sparing microsurgical inguinal varicocelectomy (LASMIV) without delivery of the testis and LASMIV with delivery of the testis and ligature of collateral and gubernacular veins., Materials and Methods: Seventy adolescents suffering from varicocele and reduction of the ipsilateral testicular volume greater than 20% were prospectively assigned to two homogenous groups according to age and Tanner stage. The patients, operated from 2008 to 2013, were randomized to undergo either LASMIV without delivery of the testis or LASMIV with delivery and ligature of collateral and gubernacular veins. All patients were evaluated clinically and sonographically 6 months and 12 months after surgery, to measure testicular volume and to rule out any complications or recurrences., Results: The catch up growth of testicular volume is significantly higher at 6 (p value = 0.008) and 12 months (p value = 0.004) in patients treated with LASMIV with delivery. The rate of varicocele recurrence in patients who underwent the delivered maneuver is 0%, whereas is 2.8% without delivery; however this findings is not statistically significant (p value > 0.01). None of the patients of both groups presented secondary hydrocele., Conclusions: LASMIV with delivery of the testis and ligature of all collateral and gubernaculuar veins results in significantly higher left testicular catch up growth.

The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy.

Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Although specifically designed aortic clamps are mainstay of minimally invasive cardiac surgery, so far, no comparative reports about their mechanical properties and interaction with the aortic wall have been reported. In this study, the generated force in the clamps' jaws and the biological response of the aorta after clamping are evaluated., Methods: The jaw force of five commercially available clamps [Geister, Cygnet, Cardiovision (CV) 195.10, CV 195.40, and CV 195.83] was assessed by clamping a 2.2-mm compression load cell with a dedicated computer universal serial bus interface at the proximal, the middle, and the distal site from the fulcrum. Biological response of the aortic wall was assessed in five minipigs (weight, 38-40 kg) that underwent thoracic aorta clamping and leakage point test. Immunohistochemistry and morphometric analysis were carried out for each aortic segment tested., Results: Force generation pattern is peculiar of each clamp, being higher in the proximal and the middle portion and lower in the distal part. One clamp (Cygnet) exhibited homogeneous maximal force generation at all three sites. All clamps exhibited peculiar crushing artifacts. A variable degree of endothelial layer disruption occurred in all clamping tests; three clamps (CV 195.10, Cygnet, and Geister) had the lower amount of intact endothelium. The clamping force was not associated with the degree of endothelial disruption (P value was not significant)., Conclusions: The choice of a clamp that is not only minimally invasive in design but also least traumatic will help avoid complications of aortic manipulation.

The Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology have produced this position paper concerning the current role of endomyocardial biopsy (EMB) for the diagnosis of cardiac diseases and its contribution to patient management, focusing on pathological issues, with these aims: • Determining appropriate EMB use in the context of current diagnostic strategies for cardiac diseases and providing recommendations for its rational utilization • Providing standard criteria and guidance for appropriate tissue triage and pathological analysis • Promoting a team approach to EMB use, integrating the competences of pathologists, clinicians, and imagers., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The use of expanded polytetrafluoroethylene (ePTFE) sutures has become an established method to correct mitral regurgitation due to elongated or ruptured mitral chordae. Mitral valve repair using artificial chordae has demonstrated excellent long-term results, particularly as ePTFE retains its flexibility with time and is highly resistant to mechanical stress. On conducting a literature review, four cases were found of recurrent mitral regurgitation due to the late (6-14 years postoperatively) rupture of ePTFE chordae. Herein, the case is described of artificial chordal rupture that required reoperation at 11 years after the initial mitral valve repair. In all previously reported cases, chordal rupture was related to the calcification of ePTFE, whereas in the present case only minimal calcification was observed at histology, and chordal rupture was most likely due to ePTFE fatigue-induced lesion. Although rare, rupture of the artificial chordae may cause recurrent mitral regurgitation; hence, the continuous monitoring of these patients, especially when the follow up extends beyond 10 years, appears mandatory.

This article shows a case of double-chambered left ventricle in asymptomatic 60-year-old man. This rare congenital entity is usually diagnosed in the neonatal or paediatric age, and it is characterized by the subdivision of the left ventricle in two chambers by an abnormal septum or muscle band. Differential diagnosis includes two other congenital left ventricular (LV) outpouching entities, such as diverticulum and aneurysm. As shown in our case, double-chambered left ventricle exhibits mixed features. A comprehensive cardiovascular magnetic imaging study is useful in the distinction of these closely related congenital diseases and, therefore, important for the correct final diagnosis.

The methods currently utilized to track stem cells by cardiac MRI are affected by important limitations, and new solutions are needed. We tested human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Swine cardiac stem/progenitor cells were transduced with a lentiviral vector to overexpress hFTH and cultured to obtain cardiospheres (Cs). Myocardial infarction was induced in rats, and, after 45 min, the animals were subjected to intramyocardial injection of ∼200 hFTH-Cs or nontransduced Cs or saline solution in the border zone. By employing clinical standard 1.5-Tesla MRI scanner and a multiecho T2* gradient echo sequence, we localized iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 wk after infarction, and its size did not change significantly after 4 wk (6.33 ± 3.05 vs. 4.41 ± 4.38 mm(2)). Cs transduction did not affect their cardioreparative potential, as indicated by the significantly better preserved left ventricular global and regional function and the 36% reduction in infarct size in both groups that received Cs compared with control infarcts. Prussian blue staining confirmed the presence of differentiated, iron-accumulating cells containing mitochondria of porcine origin. Cs-derived cells displayed CD31, α-smooth muscle, and α-sarcomeric actin antigens, indicating that the differentiation into endothelial, smooth muscle and cardiac muscle lineage was not affected by ferritin overexpression. In conclusion, hFTH can be used as a MRI reporter gene to track dividing/differentiating stem cells in the beating heart, while simultaneously monitoring cardiac morpho-functional changes.

Saldino-Mainzer syndrome is part of a group disorders, the conorenal syndromes, that are characterized by cone-shaped epiphyses with chronic renal disease in childhood and are variously associated with retinitis pigmentosa, cerebral ataxia, and/or abnormalities of the proximal epiphyses and femur metaphyses. Saldino-Mainzer syndrome usually has sporadic presentation. The present report shows the unusual findings of a 23-year-old woman, affected by the Saldino-Mainzer syndrome and has undergone kidney transplantation, highlights the possible association with maxillofacial and cephalometric abnormalities.

The Italian Scientific Associations of Cardiologists and Cardiovascular Pathologists have produced this consensus document on the diagnostic role of endomyocardial biopsy (EMB) in terms of techniques, analysis and reporting. The document is intended for clinical cardiologists, hemodynamic experts, electrophysiologists, surgical pathologists, and cardiac surgeons. It has three main aims: a) to collocate EMB in the context of currently available tools for diagnosis of heart diseases; b) to provide recommendations for rational implementation; c) to outline key characteristics (standards) for Italian cardiology and surgical pathology centers that perform and analyze EMB. A general lack of prospective, controlled studies addressing EMB prohibited the use of traditional evidence-based recommendations that rely on classes of available evidence. Thus, it was agreed that three key points should be taken into account: a) the specific pathology to be diagnosed (or excluded); b) the existence of any alternative, non-invasive diagnostic techniques; c) the overall consequences of reaching a definite diagnosis on patients' clinical management. Accordingly, we propose recommendations for EMB based on the following levels of diagnostic value: level 1: no alternative method exists to reach a definite diagnosis that can have obvious consequences for clinical management; level 2a: no alternative method exists to reach a definite diagnosis; however, the implications for clinical management are uncertain; level 2b: no alternative method exists to reach a definite diagnosis; however, the diagnosis would not influence clinical management; level 3: an alternative method exists to reach a definite diagnosis. The second part of the document proposes current protocols for the preparation, analysis and reporting of EMB in the context of each main pathologic entity. Particular attention is given to tissue characterization and implementation of molecular tests.

In this review we report the literature about ovarian function of young women with McCune-Albright Syndrome and describe our personal experience in the follow-up of a small cohort.Collectively, the existing data demonstrate that ovarian hyperfunction with ovarian cysts and hyperestrogenism persists in those women who had precocious puberty. The recording of menstrual cycles and the analysis of gonadotropin and estrogen secretion indicate that, when hypothalamic-pituitary pubertal activation begins, alternating episodes of gonadotropin control and ovarian autonomy can be seen. The persistence of estrogen hypersecretion causes menstrual disturbances and hypofertility. The long term consequences of this condition are hypothesized to be an increased risk of ductal breast cancer, which seems to be higher when growth hormone hypersecretion is also present. Therefore, young MAS women should receive counseling regarding fertility and ongoing surveillance for the development of estrogen related diseases.