Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

Hughes-Stovin syndrome is a rare disease characterized by thrombophlebitis and multiple pulmonary and/or bronchial aneurysms. The etiology and pathogenesis of HSS are incompletely known. The current consensus is that vasculitis underlies the pathogenic process, and pulmonary thrombosis follows arterial wall inflammation. As such, Hughes-Stovin syndrome may belong to the vascular cluster with lung involvement of Behçet syndrome, although oral aphtae, arthritis, and uveitis are rarely found. Behçet syndrome is a multifactorial polygenic disease with genetic, epigenetic, environmental, and mostly immunological contributors. The different Behçet syndrome phenotypes are presumably based upon different genetic determinants involving more than one pathogenic pathway. Hughes-Stovin syndrome may have common pathways with fibromuscular dysplasias and other diseases evolving with vascular aneurysms. We describe a Hughes-Stovin syndrome case fulfilling the Behçet syndrome criteria. A MYLK variant of unknown significance was detected, along with other heterozygous mutations in genes that may impact angiogenesis pathways. We discuss the possible involvement of these genetic findings, as well as other potential common determinants of Behçet/Hughes-Stovin syndrome and aneurysms in vascular Behçet syndrome. Recent advances in diagnostic techniques, including genetic testing, could help diagnose a specific Behçet syndrome subtype and other associated conditions to personalize the disease management.

There are more anatomical variants in heaven and earth, Horatio, than are dreamt of in our philosophy: the precaval left renal artery.

AIM: To describe the CT findings in eight patients with left-sided inferior vena cava (IVC) in whom the left renal artery presented a precaval course (pLRA). MATERIALS AND METHODS: We searched the teaching files of six radiology departments for patients with pLRAs. Eight patients were found, and the available imaging studies and clinical histories were reviewed. Associated vascular and renal anomalies were noted. RESULTS: No patient had been examined for problems related to the vascular anomaly found. Four had a double IVC and two a solitary left IVC; in all, the left-sided IVCs had hemiazygos continuation. One patient had situs viscerum inversus. In one case, there was a left kidney in left iliac fossa. CONCLUSION: Although rare and probably overlooked, a pLRAs can be encountered in patients with situs viscerum inversus or presenting a left-sided IVC with hemiazygos continuation. These vessels can cause technical problems during surgery at the left renal hilum and should be specifically searched for in patients with vascular anomalies.

Ivemark syndrome-a rare entity with specific anatomical features.

Ivemark syndrome (IS) is a rare embryological disorder which results from failure of development of the left-right asymmetry of organs. It is often associated with cardiac and other organ abnormalities, which are the usual causes of death in early neonatal life. We report a 3 months old girl with IS with dextrocardia, transposition of the great vessels, atrio-ventricular connection, total anomalous pulmonary venous drainage, a right atrial and right pulmonary isomerism, a midline liver, a midline gallbladder, asplenia, intestinal malrotation and vena cava anomalies. To our knowledge, complete right heterotaxia syndrome has been rarely described in literature. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development are considered as defects of the primary developmental field. Therefore, additional malformations in IS can be synchronic defects in the primary developmental field rather than causally independent malformations.

Reply to Kawasaki et al. Comment on "Manole et al. Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review. Diagnostics 2022, 12, 158".

Thank you for your comment; it adds value to the article and highlights the importance of molecular testing [...].

A Late-Detected Paraganglioma in a Young Patient with Resistant Hypertension and Severe Aortic Regurgitation-A Case Report and Review of the Literature.

BACKGROUND: Paraganglioma is a rare neuroendocrine tumor derived from chromaffin cells. The overproduction of catecholamines accounts for the presenting symptoms and cardiovascular complications. The clinical presentation frequently overlaps with the associated cardiac diseases, delaying the diagnosis. Multimodality imaging and a multidisciplinary team are essential for the correct diagnosis and adequate clinical management. CASE SUMMARY: A 37-year-old woman with a personal medical history of long-standing arterial hypertension and radiofrequency ablation for atrioventricular nodal reentry tachycardia presented with progressive exertional dyspnea and elevated blood pressure values, despite a comprehensive pharmacological treatment with six antihypertensive drugs. The echocardiography showed a bicuspid aortic valve and severe aortic regurgitation. The computed tomography angiography revealed a retroperitoneal space-occupying solid lesion, with imaging characteristics suggestive of a paraganglioma. The multidisciplinary team concluded that tumor resection should be completed first, followed by an aortic valve replacement if necessary. The postoperative histopathology examination confirmed the diagnosis of paraganglioma. After the successful resection of the tumor, the patient was asymptomatic, and the intervention for aortic valve replacement was delayed. DISCUSSION: This was a rare case of a late-detected paraganglioma in a young patient with resistant hypertension overlapping the clinical presentation and management of severe aortic regurgitation. A multimodality imaging approach including transthoracic and transesophageal echocardiography, computed tomography, and magnetic resonance imaging had an emerging role in establishing the diagnosis and in guiding patient management and follow-up. The resection of paraganglioma was essential for the optimal timing of surgical correction for severe aortic regurgitation. We further reviewed various cardiovascular complications induced by pheochromocytomas and paragangliomas.

Prognostic Value of Myocardial Function Imaging Markers in Elderly Patients Undergoing Transcatheter Aortic Valve Replacement.

Background: Transcatheter aortic valve replacement (TAVR) became the leading therapeutic strategy for aortic valve replacement in older patients with severe symptomatic aortic stenosis. Echocardiographic parameters that mark the left ventricle and right ventricle reverse remodeling after the TAVR are not well established. The aim of the current study is to describe the dynamics of both left ventricle (LV) and right ventricle (RV) strain derived from speckle tracking echocardiography in elderly patients at 3-months after the TAVR procedure. Methods: We enrolled 52 consecutive patients (77 ± 4.9 years old, median STS score of 3.1) who underwent transfemoral TAVR at our tertiary care center. All patients were evaluated at baseline and 3 months following TAVR. Results: The LV global longitudinal strain (GLS) 3-month following TAVR was significantly improved compared with baseline values (-16 ±4.2% vs -16 ±4.2%; p < 0.001) but no significant changes in the RV GLS 3 and 6 segments model following TAVR were registered. The LV ejection fraction was significantly improved 3-months after the TAVR procedure. LV-GLS at baseline demonstrated a strong positive correlation with LV-GLS at 3 months (r = 0.69) and a moderate correlation with RV strain parameters (r = 0.38 and r = 0.56), but also a negative correlation with LVEF at follow-up (r=-0.61). Interestingly, in contrast to LVEF, none of the strain parameters correlated with age. NT-proBNP values were correlated with both LV-GLS (r = 0.37) and LVEF (r=-0.5) at baseline. However, at follow-up, baseline NT-proBNP values remained correlated only to LV-GLS at 3-months (r = 0.24), but the correlation was weak.

The Role of Multimodality Imaging in the Diagnosis and Follow-Up of Malignant Primary Cardiac Tumors: Myxofibrosarcoma-A Case Report and Literature Review.

Cardiac tumors are a very rare but heterogenous group of diseases that may reveal themselves through a variety of nonspecific cardiac symptoms that may pose a challenge to the diagnostic process. Myxofibrosarcoma is a particularly rare type of cardiac tumor that carries a poor prognosis, thus making accurate and timely diagnosis essential. A 61-year-old woman presented with fatigue and shortness of breath during mild exercise, symptoms that have progressively worsened during the previous year. Multimodality imaging consisting of transthoracic and transesophageal echocardiography (TTE and TEE), cardiac magnetic resonance (CMR), cardiac computer tomography (CCT), and fluorodeoxyglucose positron emission computer tomography (18F-FDG PET-CT) was used for the diagnosis and postoperative follow-up of a myxofibrosarcoma.

Diagnostic Challenges in Rare Causes of Arrhythmogenic Cardiomyopathy-The Role of Cardiac MRI.

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare genetic condition of the myocardium, with a significantly high risk of sudden death. Recent genetic research and improved understanding of the pathophysiology tend to change the ARVD definition towards a larger spectrum of myocardial involvement, which includes, in various proportions, both the right (RV) and left ventricle (LV), currently referred to as ACM (arrhythmogenic cardiomyopathy). Its pathological substrate is defined by the replacement of the ventricular myocardium with fibrous adipose tissue that further leads to inadequate electrical impulses and translates into varies degrees of malignant ventricular arrythmias and dyskinetic myocardium movements. Particularly, the cardio-cutaneous syndromes of Carvajal/Naxos represent rare causes of ACM that might be suspected from early childhood. The diagnostic is sometimes challenging, even with well-established rTFC or Padua criteria, especially for pediatric patients or ACM with LV involvement. Cardiac MRI gain more and more importance in ACM diagnostic especially in non-classical forms. Furthermore, MRI is useful in highlighting myocardial fibrosis, fatty replacement or wall movement with high accuracy, thus guiding not only the depiction, but also the patient's stratification and management.

Rare Case of Intravascular Myopericytoma-Imaging Characteristics and Review of the Literature.

Myopericytoma is a rare vessel wall tumor, a subtype of hemangiopericytoma that usually develops subcutaneously. Intravascular myopericytoma is a rarer subtype, with only few cases reported in the literature and even fewer with imaging modalities included. We report the case of a 36-year-old man who was referred to our institution with a painless, palpable mass in the right arm and was evaluated with MRI, grey-scale and Doppler-mode ultrasound. Tumor histopathology and imaging characteristics are presented together with the role that each imaging modality played in the management of the patient.

Associating Automated Breast Ultrasound (ABUS) and Digital Breast Tomosynthesis (DBT) with Full-Field Digital Mammography (FFDM) in Clinical Practice in Cases of Women with Dense Breast Tissue.

The purpose of the present study was to evaluate the value of full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in the diagnosis of breast cancer compared to FFDM associated with digital breast tomosynthesis (DBT). Methods: This retrospective study included 50 female patients with a denser framework of connective tissue fibers, characteristic of young women who underwent FFDM, DBT, handheld ultrasound (HHUS), and ABUS between January 2017 and October 2018. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy of FFDM+ABUS were 81.82% (95% CI [48.22-97.72]), 89.74% (95% CI [75.78-97.13]), 69.23% (95% CI [46.05-85.57]), 94.59% (95% CI [83.26-98.40]), and 88% (95% CI [75.69-95.47]), while for FFDM+DBT, the values were as follows: 91.67% (95% CI [61.52-99.79]), 71.79% (95% CI [55.13-85.00]), 50% (95% CI [37.08-62.92]), 96.55% (95% CI [80.93-99.46]), 76.47% (95% CI [62.51-87.21]). We found an almost perfect agreement between the two readers regarding FFDM associated with ABUS, and substantial agreement regarding FFDM+DBT, with a kappa coefficient of 0.896 and 0.8, respectively; p < 0.001. Conclusions: ABUS and DBT are suitable as additional diagnostic imaging techniques to FFDM in women at an intermediate risk of developing breast cancer through the presence of dense breast tissue. In this study, DBT reduced the number of false negative results, while the use of ABUS resulted in an increase in specificity.

Imaging Challenges in the Diagnosis of Anatomical Variations of the Supra-Aortic Vessels: A Case Report and Review of Literature.

A 73-year-old woman was referred to our Cardiology Department due to recurrent headaches and dizziness. She had a history of hypertension of 10 years. In the territorial hospital, left internal carotid artery significant stenosis was suspected. Neurological examination and laboratory tests were normal. A neck vascular ultrasound was performed, showing a low bifurcation of the left common carotid artery (CCA) and a hypoplastic left internal carotid artery (ICA) with a sinuous path at the cervical level. Therefore, a computed tomographic (CT) angiography examination of the head and neck vessels was performed. The images confirmed the presence of a hypoplastic left ICA, anatomic variation in the left CCA, and also showed that the left vertebral artery (VA) was stemming directly from the aortic arch, exhibiting a kinking trajectory.

Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review.

We report a case of a 52-year-old woman who was referred to our institution with a superior vena cava syndrome and was investigated through echocardiography, CT and MRI revealing a well-defined, encapsulated pericardial mass. The pathology, correlated with the immunohistochemical analysis, concluded it was an extremely rare primary pericardial synovial sarcoma. The patient underwent surgery and chemotherapy with a 16-month disease-free survival and passed away after a contralateral aggressive relapse. Moreover, we discuss the role of each imaging modality together with their pericardial synovial sarcoma reported features.

One Molecule for Mental Nourishment and More: Glucose Transporter Type 1-Biology and Deficiency Syndrome.

Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the SLC2A1 gene, impairing passive glucose transport across the blood-brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic SLC2A1 variants. There are also ongoing positive studies on erythrocytes' Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and SLC2A1 transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches.

Magnetic Resonance Assessment of Ejection Fraction Versus Echocardiography for Cardioverter-Defibrillator Implantation Eligibility.

BACKGROUND: The aim of this study was to investigate the potential impact of performing two-dimensional echocardiography (2DE) compared to cardiovascular magnetic resonance (CMR) for left ventricular ejection fraction (LVEF) on implantable cardioverter defibrillator (ICD) eligibility. METHODS: A prospective cohort of 166 consecutive patients with nonischemic cardiomyopathy (NICM) was designed to compare transthoracic 2DE and CMR imaging. RESULTS: Echocardiography measurements have important differences and large limits of agreement compared to CMR, especially when assessing ventricle volumes, and smaller but relevant differences when assessing LVEF. The agreement between CMR and 2DE regarding the identification of subjects with EF <= 35, respectively <= 30, and thus eligible for an ICD measured by Cohen's Kappa was 0.78 (95% CI: 0.68-0.88), p < 0.001, respectively 0.65 (95% CI: 0.52-0.78), p < 0.001. The disagreement represented 7.9%/11.3% of the subjects who had EF < 35%/< 30% as observed by CMR, who would have been classified as eligible for an ICD, resulting in an additional need to use an ICD. Moreover, 2.6%/3.3% would have been deemed eligible by echocardiography for an ICD. CONCLUSIONS: These measurement problems result in incorrect assignments of eligibility that may have serious implications on the quality of life and the prevention of death events for patients assessed for eligibility of an ICD.

Myocardial Fibrosis as a Predictor of Ventricular Arrhythmias in Patients With Non-ischemic Cardiomyopathy.

BACKGROUND/AIM: The aim of the study was to assess the relationship between myocardial fibrosis characteristics (percentage, localization, heterogeneity), evaluated by a non-invasive method such as cardiac magnetic resonance (CMR), with the extrasystolic ventricular arrhythmia in patients with non-ischemic cardiomyopathy. PATIENTS AND METHODS: The study prospectively included 173 consecutive patients who underwent electrocardiogram Holter monitoring, transthoracic echocardiography and CMR with late gadolinium enhancement (LGE). RESULTS: In univariate analysis, both the presence (OR=1.05, 95% CI=1.01-1.09; p=0.015), the percentage of fibrosis >15% (p=0.018), the septum size, the fibrosis in either lateral or septal walls (p=0.004), as well as fibrosis in the midwall (p=0.019) were statistically significant higher in the group with extrasystolic arrhythmia. After adjustment, the percentage of fibrosis >15%, had higher odds of extra systolic arrhythmia [OR=3.78 (95% CI=1.52-10.62, p=0.007)]. CONCLUSION: The presence, percentage, and localisation of left ventricle myocardial fibrosis characterized by LGE-CMR was associated with ventricular arrhythmias.

Asymptomatic COVID-19 cancer patients incidentally discovered during F18-FDG PET/CT monitoring.

BACKGROUND: The aim of the study was to present the PET/CT imaging features in a small series of asymptomatic patients with known cancer pathologies, infected with the SARS-CoV-2 virus, which were incidentally discovered during their monitoring scan of F18-FDG PET/CT. METHODS: We included in our study a number of five cases (3 female and 2 male) out of 478 patients examined by F18-FDG PET/CT between March - April 2020, with confirmed diagnostic of cancer. Four patients had lung damages suggestive for the mentioned viral infection and 1 patient had multiple lung metastases from thyroid cancer. All patients were asymptomatic for acute respiratory disease at the time of examination, being subsequently confirmed for the viral infection by specific PCR analysis. RESULTS: The asymptomatic positive SARS-CoV-2 cancer patients discovered incidentally in PET/CT F18-FDG represent 0.83% and their imaging characteristics were suggestive for high FDG activity in the lung despite the lack of respiratory symptoms. CONCLUSION: The SARS CoV-2 viral infection in asymptomatic cancer patients is a very rare possibility, but represents a challenging scenario both for the differential diagnosis in cancer and also for the epidemiologic context.

Rare Causes of Arterial Hypertension and Thoracic Aortic Aneurysms-A Case-Based Review.

Thoracic aortic aneurysms may result in dissection with fatal consequences if undetected. A young male patient with no relevant familial history, after having been investigated for hypertension, was diagnosed with an ascending aortic aneurysm involving the aortic root and the proximal tubular segment, associated with a septal atrial defect. The patient underwent a Bentall surgery protocol without complications. Clinical examination revealed dorso-lumbar scoliosis and no other signs of underlying connective tissue disease. Microscopic examination revealed strikingly severe medial degeneration of the aorta, with areas of deep disorganization of the medial musculo-elastic structural units and mucoid material deposition. Genetic testing found a variant of unknown significance the PRKG1 gene encoding the protein kinase cGMP-dependent 1, which is important in blood pressure regulation. There may be genetic links between high blood pressure and thoracic aortic aneurysm determinants. Hypertension was found in FBN1 gene mutations encoding fibrillin and in PRKG1 mutations. Possible mechanisms involving the renin-angiotensin system, the role of oxidative stress, osteopontin, epigenetic modifications and other genes are reviewed. Close follow-up and strict hypertension control are required to reduce the risk of dissection. Hypertension, scoliosis and other extra-aortic signs suggesting a connective tissue disease are possible clues for diagnosis.

Transthyretin cardiac amyloidosis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) may be an under recognized cause of heart failure (HF). TTR amyloidosis can be inherited, caused by variants in the TTR gene (ATTRv) or by deposition of wild-type TTR protein (ATTRwt), leading to high mortality if untreated. We report the case of a patient with hereditary TTR amyloidosis and mixed phenotype (both cardiac and neurological involvement). We highlight the importance of multimodal imaging in the evaluation of these patients, as early diagnosis and treatment might lead to better outcome.

Correlation between Volumes Determined by Echocardiography and Cardiac MRI in Controls and Atrial Fibrillation Patients.

AIMS: We aimed to compare cardiac volumes measured with echocardiography (echo) and cardiac magnetic resonance imaging (MRI) in a mixed cohort of healthy controls (controls) and patients with atrial fibrillation (AF). MATERIALS AND METHODS: In total, 123 subjects were included in our study; 99 full datasets were analyzed. All the participants underwent clinical evaluation, EKG, echo, and cardiac MRI acquisition. Participants with full clinical data were grouped into 63 AF patients and 36 controls for calculation of left atrial volume (LA Vol) and 51 AF patients and 30 controls for calculation of left ventricular end-diastolic volume (LV EDV), end-systolic volume (ESV), and LV ejection fraction (LV EF). RESULTS: No significant differences in LA Vol were observed (p > 0.05) when measured by either echo or MRI. However, echo provided significantly lower values for left ventricular volume (p < 0.0001). The echo LA Vol of all the subjects correlated well with that measured by MRI (Spearmen correlation coefficient r = 0.83, p < 0.0001). When comparing the two methods, significant positive correlations of EDV (all subjects: r = 0.55; Controls: r = 0.71; and AF patients: r = 0.51) and ESV (all subjects: r = 0.62; Controls: r = 0.47; and AF patients: r = 0.66) were found, with a negative bias for values determined using echo. For a subgroup of participants with ventricular volumes smaller than 49.50 mL, this bias was missing, thus in this case echocardiography could be used as an alternative for MRI. CONCLUSION: Good correlation and reduced bias were observed for LA Vol and EF determined by echo as compared to cardiac MRI in a mixed cohort of patients with AF and healthy volunteers. For the determination of volume values below 49.50 mL, an excellent correlation was observed between values obtained using echo and MRI, with comparatively reduced bias for the volumes determined by echo. Therefore, in certain cases, echocardiography could be used as a less expensive, less time-consuming, and contraindication free alternative to MRI for cardiac volume determination.

Contrast-enhanced ultrasonography in patients with glycogen storage disease type Ia and adenomas.

OBJECTIVE: The purpose of this series was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in the characterization of focal liver lesions (FLLs) in patients with glycogen storage diseases (GSDs). METHODS: Contrast-enhanced ultrasonographic data obtained for characterization of 8 FLLs (size, 0.9-10.2 cm) in 2 patients with GSD type Ia (GSD-Ia) and lesion growth or recurrent abdominal pain were reviewed and compared with computed tomographic (CT) and magnetic resonance imaging (MRI) data. After total and left hepatectomy, pathologic examination confirmed benign adenomas in 6 of the evaluated lesions. Follow-up confirmed benignity in the 2 remaining lesions. RESULTS: In all FLLs, CEUS showed marked hypervascularity in the early arterial phase. Centripetal filling was shown in only 1 lesion, and diffuse enhancement without any clear direction was shown in all other lesions. During the portal and late phases, 6 of the 8 lesions showed sustained enhancement, including 2 lesions that appeared heterogeneous during all phases of CT and MRI. In an aspect of 1 of these 6 large adenomas, late wash-out could be explained by sinusoid compression. The other 2 adenomas showed moderate wash-out but remained homogeneous. CONCLUSIONS: Focal liver lesions found in patients with GSD-Ia have similar patterns on CEUS compared with incidental adenomas. Global or partial hypoenhancement observed in the late phase did not indicate a transition to hepatocellular carcinoma but may have been related to ischemia.