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.

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.

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.

Long-term outcomes of third-line therapy with tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: A real-life experience.

Introduction: Tyrosine kinase inhibitor (TKI) therapy has greatly improved the prognosis of patients with chronic myeloid leukemia (CML), improving the survival expectancy of patients with chronic phase (CP) CML to that of the general population. However, despite these advances, nearly 50% of patients with CP CML experience failure to respond to frontline therapy, and most fail to respond to the subsequent second-line TKI. Treatment guidelines for patients failing second-line therapy are lacking. This study aimed to determine the efficacy of TKIs as third-line therapy in a "real-world" clinical practice setting and identify factors favorably influencing the long-term outcomes of therapy. Methods: We have retrospectively analyzed the medical records of 100 patients with CP CML. Results: The median age of the patients was 51 (range, 21-88) years, and 36% of the patients were men. The median duration of the third-line TKI therapy was 22 (range, 1- 147) months. Overall, the rate of achieving complete cytogenetic response (CCyR) was 35%. Among the four patient groups with different levels of responses at baseline, the best results were achieved in the groups with any CyR at the baseline of third-line therapy. Thus, СCyR was reached in all 15 and 8/ 16 (50%) patients with partial cytogenetic response (PCyR) or minimal or minor CyR (mmCyR), respectively, whereas CCyR was detected only in 12/69 (17%) patients without any CyR at baseline (p < 0.001). Univariate regression analysis revealed that the factors negatively associated with CCyR achievement in thirdline TKI therapy were the absence of any CyR on first- or second-line TKI therapy (p < 0.001), absence of CHR prior to third-line TKI (p = 0.003), and absence of any CyR prior to third-line TKI (p < 0.001). During the median observation time from treatment initiation to the last visit [56 (4-180) months], 27% of cases progressed into accelerated phase or blast phase CML, and 32% of patients died. Discussion: Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with CCyR on third-line than in the group without CCyR on third-line therapy. At the last visit, third-line TKI therapy was ongoing in 18% of patients, with a median time of treatment exposure of 58 (range, 6-140) months; 83% of these patients had stable and durable CCyR, suggesting that patients without CHR at baseline and without CCyR at least by 12 months on third-line TKI should be candidates for allogeneic stem cell transplantation, third-generation TKIs, or experimental therapies.