Transcatheter radiofrequency pulmonary artery denervation in swine: the evaluation of lesion degree, hemodynamics and pulmonary hypertension inducibility.

BACKGROUND: Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. METHODS: In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)-PH modeling before and after PADN, group II (n = 4)-PADN only, or group III (n = 4)-PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination. RESULTS: In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (-0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction. CONCLUSIONS: Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.

An Ovine Model for Percutaneous Pulmonary Artery Laser Denervation: Perivascular Innervation and Ablation Lesion Characteristics.

BACKGROUND: Pulmonary artery denervation (PADN) is an evolving interventional procedure capable to reduce pulmonary artery (PA) pressure. We aimed to compare PA nerve distribution in different specimens and assess the feasibility of an ovine model for a denervation procedure and evaluate the acute changes induced by laser energy. METHODS: The experiment was divided into two phases: (1) the analysis of PA nerve distribution in sheep, pigs, and humans using histological and immunochemical methods; (2) fiberoptic PADN in sheep and postmortem laser lesion characteristics. RESULTS: PA nerve density and distribution in sheep differ from humans, although pigs and sheep share similar characteristics, nerve fibers are observed in the media layer, adventitia, and perivascular tissue in sheep. Necrosis of the intima and focal hemorrhages within the media, adventitia, and perivascular adipose tissue were evidenced post laser PADN. Among the identified lesions, 40% reached adventitia and could be classified as effective for PADN. The use of 20 W ablation energy was safer and 30 W-ablation led to collateral organ damage. CONCLUSIONS: An ovine model is suitable for PADN procedures; however, nerve distribution in the PA bifurcation and main branches differ from human PA innervation. Laser ablation can be safely used for PADN procedures.

Telocytes in the human sinoatrial node.

The sinoatrial node (SAN) is composed mostly of pacemaker, transitional and Purkinje-like cells. Pacemaker cells, especially in the centre of the SAN, are surrounded by dense fibrous tissue and do not have any contact with transitional cells. We hypothesize that the SAN contains telocytes that have contacts with pacemaker cells and contractile myocardium. Immunohistochemistry using antibodies against HCN4 and antibody combinations against CD34 and HCN4 was carried out on 12 specimens. Confocal laser scanning microscopy (CLSM) with two mixtures of primary antibodies, namely CD34/S100 and vimentin/S100, was performed in three cases. In two cases, CLSM was carried out with CD117 antibody. Specimens for electron microscopy and immunocytochemistry with HCN4 immunogold labelling were taken from another three patients. In our study, we found cells with the immunophenotype of telocytes in the SAN. There were twice as many of these cells in the centre of the SAN as in the periphery (20.3 ± 4.8 versus 10.8 ± 4.4 per high-power field). They had close contact with pacemaker cells and contractile cardiomyocytes and expressed HCN4. The ultrastructural characteristics of these cells are identical to those of telocytes observed earlier in other organs. Our study provides evidence that telocytes are present in the SAN.

Right ventricular endomyocardial biopsy in children and adolescents with drug-refractory arrhythmia.

Purpose This study aimed to assess the results of endomyocardial biopsy from the right ventricle to establish the possible cause for drug-refractory arrhythmias in children. Materials and methods We enrolled 19 consecutive young patients with drug-refractory arrhythmia, from 2010 to 2013, who underwent endomyocardial biopsy. Inclusion criteria were as follows: age <18 years with a structurally normal heart or mild changes in a structure of the heart initially diagnosed as arrhythmia-induced cardiomyopathy. Overall, 86 biopsies were performed in 19 patients. Histopathological analysis, immunohistochemistry, and polymerase chain reaction were used for the interpretation of the endomyocardial biopsy. RESULTS: The mean age of the patient population was 14.1±2.9 year (range from 7 to 17 years). All these patients had a history of drug-refractory arrhythmia for >5 months (mean 30 months). Patients underwent a complete history investigation, physical examination, laboratory studies, echocardiography, electrocardiography, treadmill test, and Holter monitoring before endomyocardial biopsy; two patients with arrhythmogenic right ventricular dysplasia had implantable cardioverter defibrillator implantation and further appropriate successful device shocks. Myocarditis was diagnosed based on histopathological and immunohistological analyses in nine (47.4%) patients. Polymerase chain reaction was positive for viral genome in four of them; five patients had active myocarditis. Radiofrequency ablation was performed in 17 patients; five out of six (83%) endomyocardial biopsy-proved myocarditis patients had successful radiofrequency ablation. No significant complication was reported during ablation and endomyocardial biopsy. CONCLUSIONS: Approximately half of the children with drug-refractory arrhythmia had unsuspected myocarditis according to the results of the endomyocardial biopsy.

Histological evidence of inflammatory reaction associated with fibrosis in the atrial and ventricular walls in a case-control study of patients with history of atrial fibrillation.

AIMS: Chronic inflammation in the atrial myocardium was shown to play an important role in the development of atrial fibrosis in patients with atrial fibrillation (AF). However, it is not clear to what extent atrial inflammatory reaction associated with AF extends on the ventricular myocardium. Our aim was to assess the extent of fibrosis and lymphomononuclear infiltration in human ventricular myocardium and explore its association with AF. METHODS AND RESULTS: Medical records from consecutive autopsies were checked for presence of AF. Heart specimens from 30 patients died from cardiovascular causes (64 ± 12 years, 17 men) were collected in three equal groups: no AF, paroxysmal AF, and permanent AF. Tissue samples were taken from the Bachmann's bundle, crista terminalis, posterior left atrium, left ventricle and right ventricle free walls and stained with Masson's trichrome for analysis of fibrosis extent. Immunohistochemistry was performed using antibodies against CD3- and CD45-antigens and quantified as number of antigen-positive cells per 1 mm2. Fibrosis extent, CD3+ and CD45+ cell counts were elevated in AF patients at all sites (P < 0.001 for all). Fibrosis extent demonstrated correlation with both CD3+ and CD45+ cell counts in the right (r = 0.781, P < 0.001 for CD45+ and r = 0.720, P < 0.001 for CD3+) and the left (r = 0.515, P = 0.004 for CD45+ and r = 0.573, P = 0.001 for CD3+) ventricles. Neither fibrosis nor inflammatory cell count showed association with either age or comorbidities. CONCLUSION: Histological signs of chronic inflammation affecting ventricular myocardium are strongly associated with AF and demonstrate significant correlation with fibrosis extent that cannot be explained by cardiovascular comorbidities otherwise.

Biatrial tachycardia following linear anterior wall ablation for the perimitral reentry: incidence and electrophysiological evaluations.

INTRODUCTION: A left atrial (LA) anterior ablation line (AnL), connecting the mitral annulus and right pulmonary veins or a roof line, has been suggested as an alternative to mitral isthmus (MI) ablation for perimitral flutter (PMF). Theoretically, the AnL can exclude the LA septal wall from the reentrant circle, and lead to involvement of the right atrium (RA) in a tachycardia (AT) mechanism. METHODS AND RESULTS: Among 807 patients undergoing atrial fibrillation ablation, PMF was diagnosed in 28 subjects, and AnL was performed in 13, and MI ablation in 15 cases. In 4 (31%) patients, AnL resulted in abrupt AT cycle length prolongation, which was associated with the development of a clockwise biatrial tachycardia (bi-AT). The bi-AT propagated along the lateral and posterior mitral annulus, entered the RA via the coronary sinus, and after activating the RA septum reentered the LA over the Bachmann's bundle. The bi-AT was terminated by ablation in Bachmann's bundle insertion areas in the RA or LA. No bi-AT was documented in the MI group. One patient in the AnL group died of stroke in 10 days following the procedure. Anatomic evaluation showed that at the level of the AnL the RA anteroseptal area was separated from the LA by the aortic root, and was free from ablation damage. CONCLUSION: A bi-AT can develop when an AnL is created for PMF termination. Biatrial entrainment mapping facilitates diagnosis. Termination of the bi-AT is feasible when ablated from either RA or LA.

P-wave characteristics and histological atrial abnormality.

BACKGROUND: Fibro-fatty transformation is believed to be the leading cause of deteriorated atrial conduction; however, any direct assessment in relation to P-wave characteristics is lacking. We sought to assess P-wave morphology (PWM) and duration (PWD) in relation to histology of the atrial myocardium. OBJECTIVE: Atrial specimens were collected from 11 patients who died from cardiovascular causes (7 men; median age 73 years). METHODS: Tissue samples were taken at the level of superior and inferior PVs, center of posterior left atrial wall, terminal crest (CT) and Bachmann's bundle (BB) for assessment of fibro-fatty tissue extent. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were used for manual assessment of P-wave. Partial interatrial block (pIAB) was defined as a prolonged (≥ 120 ms) and bimodal P-wave in any lead on 12-lead ECG. RESULTS: The median PWD was 160 (120-200) ms. Fibrosis extent in CT highly correlated to PWD (r=0.914, p<0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1%-41%), CT (18%, range 3%-47%) or superior PV (15%, range 6%-24%) correlated to PWD (r=0.627, p=0.039; r=0.795, p=0.003; and r=0.668, p=0.025, respectively). pIAB pattern was observed in 10 subjects; however, it was not associated with either fibrosis or fatty tissue content at any sampling location. CONCLUSIONS: Our findings further support causal association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes.

Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?

Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12-14 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.

CrossU-Net: Dual-modality cross-attention U-Net for segmentation of precancerous lesions in gastric cancer.

Gastric precancerous lesions (GPL) significantly elevate the risk of gastric cancer, and precise diagnosis and timely intervention are critical for patient survival. Due to the elusive pathological features of precancerous lesions, the early detection rate is less than 10%, which hinders lesion localization and diagnosis. In this paper, we provide a GPL pathological dataset and propose a novel method for improving the segmentation accuracy on a limited-scale dataset, namely RGB and Hyperspectral dual-modal pathological image Cross-attention U-Net (CrossU-Net). Specifically, we present a self-supervised pre-training model for hyperspectral images to serve downstream segmentation tasks. Secondly, we design a dual-stream U-Net-based network to extract features from different modal images. To promote information exchange between spatial information in RGB images and spectral information in hyperspectral images, we customize the cross-attention mechanism between the two networks. Furthermore, we use an intermediate agent in this mechanism to improve computational efficiency. Finally, we add a distillation loss to align predicted results for both branches, improving network generalization. Experimental results show that our CrossU-Net achieves accuracy and Dice of 96.53% and 91.62%, respectively, for GPL lesion segmentation, providing a promising spectral research approach for the localization and subsequent quantitative analysis of pathological features in early diagnosis.

Unsupervised domain adaptation for histopathology image segmentation with incomplete labels.

Stain variations pose a major challenge to deep learning segmentation algorithms in histopathology images. Current unsupervised domain adaptation methods show promise in improving model generalization across diverse staining appearances but demand abundant accurately labeled source domain data. This paper assumes a novel scenario, namely, unsupervised domain adaptation based segmentation task with incompletely labeled source data. This paper propose a Stain-Adaptive Segmentation Network with Incomplete Labels (SASN-IL). Specifically, the algorithm consists of two stages. The first stage is an incomplete label correction stage, involving reliable model selection and label correction to rectify false-negative regions in incomplete labels. The second stage is the unsupervised domain adaptation stage, achieving segmentation on the target domain. In this stage, we introduce an adaptive stain transformation module, which adjusts the degree of transformation based on segmentation performance. We evaluate our method on a gastric cancer dataset, demonstrating significant improvements, with a 10.01% increase in Dice coefficient compared to the baseline and competitive performance relative to existing methods.

New Scenarios in Heart Transplantation and Persistency of SARS-CoV-2 (Case Report).

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission in nonlung organ transplantation is still unclear. In this article we presented a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from a SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period, the heart disease worsened and the patient required cardiac transplantation. We examined the recipient's heart and made a diagnosis of left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed SARS-CoV-2 antigen expression in the donor's heart before transplantation, and after the transplantation, an endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and a single particle on the surface of the endothelium consistent with SARS-CoV-2 viral particles. Recent findings in the literature associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to postpartum recipient through a heart transplant and demonstrates the importance of endomyocardial biopsy before and after heart transplantation.

Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies.

The clinical manifestation study of post-acute sequelae of SARS-CoV-2 infection (PASC) has shown a lack of knowledge regarding its morphology and pathogenesis. The aim of this research was to investigate morphological manifestations of PASC in the myocardium. MATERIALS AND METHODS: The study included 38 patients requiring endomyocardial biopsy (EMB) during the post-acute phase of coronavirus infection and a control group including patients requiring EMB prior to the SARS-CoV-2 pandemic. The patients' clinical and laboratory data were analyzed. Histological examination and immunohistochemistry (IHC) of the myocardial tissue was conducted with antibodies to CD3, CD68, HLA-DR, MHC1, C1q, VP1 enteroviruses, spike protein SARS-CoV-2, Ang1, von Willebrand factor (VWF), and VEGF. The morphometric analysis included counting the mean number of inflammatory infiltrate cells per mm2 and evaluating the expression of SARS-CoV-2 spike protein, HLA-DR, MHC1, C1q, Ang1, VWF, and VEGF using a scoring system. If the expression of SARS-CoV-2 spike protein was >3 points, an additional IHC test with antibodies to ACE2, CD16 as well as RT-PCR testing of the myocardial tissue were performed. For two patients, immunofluorescence tests of the myocardial tissue were performed using antibody cocktails to SARS-CoV-2 spike protein/CD16, SARS-CoV-2 spike protein/CD68, CD80/CD163. The statistical data analysis was carried out using the Python programming language and libraries such as NumPy, SciPy, Pandas, and Matplotlib. RESULTS: The study demonstrated a significant increase in the number of CD68+ macrophages in the myocardium of PASC patients compared to patients who did not have a history of COVID-19 (p = 0.014 and p = 0.007 for patients with and without myocarditis, respectively), predominantly due to M2 macrophages. An increase in the number of CD68+ macrophages was more frequently observed in patients with shorter intervals between the most recent positive SARS-CoV-2 PCR test and the time of performing the EMB (r = -0.33 and r = -0.61 for patients with and without myocarditis, respectively). The expression scores of Ang1, VEGF, VWF, and C1q in PASC patients did not significantly differ from those in EMB samples taken before 2019. CONCLUSION: The myocardium of PASC patients demonstrated a significant increase in the number of CD68+ macrophages and a decrease in the expression of markers associated with angiopathy. No evidence of coronavirus-associated myocarditis was observed in any PASC patient.

Heart Transplantation as a Treatment Option for Recurrent Myxofibrosarcoma: A Clinical Case.

Myxofibrosarcoma is one of the most rare tumors of the heart. Surgical resection is the principal method of treatment; however, in some cases, radical removal of the tumor is not possible. Here, we present a case of heart transplant in a patient who experienced recurrent myxofibrosarcoma of the left atrium and examine the morphological features of this tumor. A 40-year-old female patient presented for treatment for heart failure of a high functional class. An examination revealed a tumor in the left atrial cavity, which was subsequently surgically removed. Morphological examination revealed an inflammatory myofibroblastic tumor. After 2 years, the patient's tumor recurred. The tumor was removed, and a morphological study again diagnosed myxofibrosarcoma of the heart. A year later, recurrence was again diagnosed. Instrumental examination determined that the tumor had incurred into the mitral valve and possibly spread to the myocardium. Tumor resection was not possible, and the need to perform a heart transplant was determined. The given case contributes to the practical conclusion that heart transplant contributes to an increase in the life expectancy for patients with inoperable cases of cardiac sarcoma.

High Risk of Heart Tumors after COVID-19.

An emergence of evidence suggests that severe COVID-19 is associated with an increased risk of developing breast and gastrointestinal cancers. The aim of this research was to assess the risk of heart tumors development in patients who have had COVID-19. METHODS: A comparative analysis of 173 heart tumors was conducted between 2016 and 2023. Immunohistochemical examination with antibodies against spike SARS-CoV-2 was performed on 21 heart tumors: 10 myxomas operated before 2020 (the control group), four cardiac myxomas, one proliferating myxoma, three papillary fibroelastomas, two myxofibrosarcomas, one chondrosarcoma resected in 2022-2023. Immunohistochemical analysis with antibodies against CD34 and CD68 was also conducted on the same 11 Post-COVID period heart tumors. Immunofluorescent examination with a cocktail of antibodies against spike SARS-CoV-2/CD34 and spike SARS-CoV-2/CD68 was performed in 2 cases out of 11 (proliferating myxoma and classic myxoma). RESULTS: A 1.5-fold increase in the number of heart tumors by 2023 was observed, with a statistically significant increase in the number of myxomas. There was no correlation with vaccination, and no significant differences were found between patients from 2016-2019 and 2021-2023 in terms of gender, age, and cardiac rhythm dis-orders. Morphological examination revealed the expression of spike SARS-CoV-2 in tumor cells, endothelial cells, and macrophages in 10 out of 11 heart tumors. CONCLUSION: The detection of SARS-CoV-2 persistence in endothelium and macrophages as well as in tumor cells of benign and malignant cardiac neoplasms, the increase in the number of these tumors, especially cardiac myxomas, after the pandemic by 2023 may indicate a trend toward an increased risk of cardiac neoplasms in COVID-19 patients, which re-quires further research on this issue and a search for new evidence.

Laser renal denervation: A comprehensive evaluation of microstructural renal artery lesions.

Renal artery denervation (RDN) has been proposed for resistant arterial hypertension. Beyond conventional radiofrequency (RF) ablation, there are emerging RDN technologies, including laser catheter ablation. We aimed at evaluamting the local effects of laser ablation on the renal artery and perivascular nerve injury in comparison with radiofrequency ablation. Thirteen pigs (mean weight 36.7 ± 4.7 kg, age 3 months) were divided into three groups: (1) laser ablation in normotensive pigs (LA; n = 3), (2) bipolar RF ablation in normotensive pigs (RF; n = 7), and (3) a sham group (SHAM; n = 3). Transcatheter laser and RF ablations were performed under general anesthesia. After euthanasia, pathology and immunohistochemical studies were performed. Artery wall and perivascular nerve lesions were found in the LA and RF groups. A lower rate of intimal microdissections was evaluated after laser ablation when compared with RF ablation (0 vs. 1.5 [1;2.75] per artery; p < .05). There was a numerical prevalence of nerves with tyrosine hydroxylase expression loss after laser RDN when compared with RF ablation (16.7 [4; 18] vs. 9.1 [0;18] per specimen). Laser ablation is noninferior to RF ablation regarding perivascular nerve injury and is associated with less intimal layer damage.

Comparative Study of the Myocardium of Patients from Four COVID-19 Waves.

BACKGROUND: Few studies have compared COVID-19 patients from different waves. This study aims to conduct a clinical and morphological analysis of patients who died from COVID-19 during four waves. METHODS: The study involved 276 patients who died from COVID-19 during four waves, including 77 patients in the first wave, 119 patients in the second wave, and 78 patients in the third wave. We performed a histological examination of myocardium samples from autopsies and additionally analyzed the samples by PCR. We conducted immunohistochemistry of the myocardium for 21 samples using antibodies against CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, enteroviral VP1, and SARS-CoV-2 spike protein. We also did immunofluorescent staining of three myocardial specimens using VP1/SARS-CoV-2 antibody cocktails. Further, we ran RT-ddPCR analysis for 14 RNA samples extracted from paraffin-embedded myocardium. Electron microscopic studies of the myocardium were also performed for two samples from the fourth wave. RESULTS: Among the 276 cases, active myocarditis was diagnosed in 5% (15/276). Of these cases, 86% of samples expressed VP1, and individual cells contained SARS-CoV-2 spike protein in 22%. Immunofluorescence confirmed the co-localization of VP1 and SARS-CoV-2 spike proteins. ddPCR did not confidently detect SARS-CoV-2 RNA in the myocardium in any myocarditis cases. However, the myocardium sample from wave IV detected a sub-threshold signal of SARS-CoV-2 by qPCR, but myocarditis in this patient was not confirmed. Electron microscopy showed several single particles similar to SARS-CoV-2 virions on the surface of the endothelium of myocardial vessels. A comparison of the cardiovascular complication incidence between three waves revealed that the incidence of hemorrhage (48 vs. 24 vs. 17%), myocardial necrosis (18 vs. 11 vs. 4%), blood clots in the intramural arteries (12 vs. 7 vs. 0%), and myocarditis (19 vs. 1 vs. 6%) decreased over time, and CD8-T-killers appeared. Immunohistochemistry confirmed the presence of endotheliitis in all 21 studied cases. CONCLUSIONS: This study compared myocardial damage in patients who died during three COVID-19 waves and showed a decrease in the incidence of endotheliitis complications (thrombosis, hemorrhage, necrosis) and myocarditis over time. However, the connection between myocarditis and SARS-CoV-2 infection remains unproven.

Dual-tracer PET/CT imaging to determine tumor heterogeneity in a patient with metastatic ACTH-secreting neuroendocrine neoplasm: A case report and literature review.

Introduction: We present a case of a patient with disseminated ACTH-secreting neuroendocrine neoplasm with biologic heterogeneity between a primary tumor and metastases. The diagnosis was obtained and multidisciplinary management was conducted with a positron emission tomography/computed tomography (PET/CT) scan with Gallium-68 [68Ga]-labeled dodecanetetraacetic acid-tyrosine-3-octreotate ([68Ga]-DOTA-TATE) and Fluor-18 [18F]-fluorodeoxyglucose ([18F]-FDG). Case report: A PET/CT scan revealed a difference between [68Ga]-DOTA-TATE and [18F]-FDG uptake in primary tumor and several metastases. PET/CT showed high [18F]-FDG uptake and lack of [68Ga]-DOTA-TATE in the primary tumor, whereas both [68Ga]-DOTA-TATE and [18F]-FDG hyperaccumulation were identified in the majority of metastases. Despite positive [68Ga]-DOTA-TATE PET/CT, which is associated with high affinity with the somatostatin receptor 2 subtype, immunohistochemical examination revealed overexpression of the somatostatin receptor 5 subtype only. Perhaps, this explained the ineffectiveness of the treatment with "cold" somatostatin analogs. Conclusion: This case had an aggressive clinical course, despite cytoreductive surgical treatment and somatostatin analog therapy. PET/CT imaging with two tracers is a molecular tool that demonstrates a biologic heterogeneity between a primary tumor and metastases and yields additional information that may influence the choice of the patient management strategy.

Case Report: Primary Leptomeningeal Medulloblastoma in a Child: Clinical Case Report and Literature Review.

Medulloblastoma is one of the most common pediatric central nervous system malignancies worldwide, and it is characterized by frequent leptomeningeal metastasizing. We report a rare case of primary leptomeningeal medulloblastoma of an 11-year-old Caucasian girl with a long-term disease history, non-specific clinical course, and challenges in the diagnosis verification. To date, 4 cases of pediatric primary leptomeningeal medulloblastoma are reported, and all of them are associated with unfavorable outcomes. The approaches of neuroimaging and diagnosis verification are analyzed in the article to provide opportunities for effective diagnosis of this disease in clinical practice. The reported clinical case of the primary leptomeningeal medulloblastoma is characterized by MR images with non-specific changes in the brain and spinal cord and by 18FDG-PET/CT images with diffuse heterogeneous hyperfixation of the radiopharmaceutical along the whole spinal cord. The immunohistochemistry and next-generation sequencing analyses of tumor samples were performed for comprehensive characterization of the reported clinical case.

The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome.

OBJECTIVES: Congenital hyperinsulinism (CHI) is a group of rare genetic disorders characterized by insulin overproduction. CHI causes life-threatening hypoglycemia in neonates and infants. Bloom syndrome is a rare autosomal recessive disorder caused by mutations in the BLM gene resulting in genetic instability and an elevated rate of spontaneous sister chromatid exchanges. It leads to insulin resistance, early-onset diabetes, dyslipidemia, growth delay, immune deficiency and cancer predisposition. Recent studies demonstrate that the BLM gene is highly expressed in pancreatic islet cells and its mutations can alter the expression of other genes which are associated with apoptosis control and cell proliferation. CASE PRESENTATION: A 5-month-old female patient from consanguineous parents presented with drug-resistant CHI and dysmorphic features. Genetic testing revealed a homozygous mutation in the KCNJ11 gene and an additional homozygous mutation in the BLM gene. While 18F-DOPA PET scan images were consistent with a focal CHI form and intraoperative frozen-section histopathology was consistent with diffuse CHI form, postoperative histopathological examination revealed features of an atypical form. CONCLUSIONS: In our case, the patient carries two distinct diseases with opposite metabolic phenotypes.