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1.
Int J Mol Sci ; 25(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39000594

ABSTRACT

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67 × 10-132, 2.23 × 10-107), the cytotoxic T-cell markers CD8a, LAGE3 and CD49a (p = 0.0006, p < 0.0001, and p = 0.0118) and proinflammatory caspase-1 (p = 0.0055) in CHD. Gene-set enrichment identified mitochondrial dysfunctional pathways, predominately changes within oxidative phosphorylation processes. The negative regulation of mitochondrial functions and metabolism was identified in the network analysis, with dysregulation of the mitochondrial complex formation. A histological analysis confirmed an increase in cellular bodies in the CHD RV tissue and positive staining for both CD45 and CD8, which was absent in the control. The deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). The network analysis identified positive regulation of the immune system and cytokine signalling clusters in the inflammation functional network, as there were lymphocyte activation and leukocyte differentiation. Utilising RV tissue from paediatric patients undergoing CHD cardiac surgery, this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T-cell presence prior to reparative surgery.


Subject(s)
Gene Expression Profiling , Heart Defects, Congenital , Inflammation , Mitochondria , Transcriptome , Humans , Heart Defects, Congenital/genetics , Heart Defects, Congenital/surgery , Heart Defects, Congenital/metabolism , Heart Defects, Congenital/pathology , Female , Male , Mitochondria/metabolism , Mitochondria/genetics , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Infant , Child , Child, Preschool , Gene Regulatory Networks
2.
Front Bioeng Biotechnol ; 12: 1360221, 2024.
Article in English | MEDLINE | ID: mdl-38464540

ABSTRACT

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy. Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry. Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded. Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

3.
G Ital Cardiol (Rome) ; 25(4): 252-261, 2024 Apr.
Article in Italian | MEDLINE | ID: mdl-38526361

ABSTRACT

About 280 000 heart valve replacements are performed worldwide every year. Since the first prosthetic valve implantation in 1952 there have been notable developments. There are a lot of types of prosthetic valves that can be summarized into two categories: biological prosthetic valves or mechanical prosthetic valves. Biological prostheses, made of bovine or porcine pericardium, homografts, or autografts, degenerate over time becoming dysfunctional. Mechanical prostheses have a potentially unlimited lifespan but require oral anticoagulation which can affect patients' quality of life. Generally, biological prostheses are particularly suitable for elderly patients while mechanical prostheses for young people, with some distinctions. For example, in case of age <60 years, in the presence of preoperative oral anticoagulant therapy, metabolic syndrome, hemodialysis or hyperparathyroidism, a mechanical valve is the preference. The choice of the prosthesis in patients aged between 55 and 70 years is particularly challenging because the advantages and disadvantages of the two categories of prosthesis overlap in middle-aged patients. The choice of the prosthesis should be made after discussion with the surgeon, according to the patient's preferences, and keeping in mind the pros and cons of biological and mechanical prostheses.


Subject(s)
Prostheses and Implants , Quality of Life , Aged , Middle Aged , Humans , Animals , Cattle , Swine , Adolescent , Prosthesis Implantation , Anticoagulants , Catheters
4.
Infect Dis Rep ; 14(1): 101-105, 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35200440

ABSTRACT

Infection of surgical wounds with acid-fast bacilli, including tubercle bacilli, is rare, and is poorly described in the literature. We present the case of a 74-year-old male who developed a sternal wound infection after cardiac surgery due to Mycobacterium tuberculosis complex, diagnosed post-mortem. SARS-CoV-2 infection contributed to worsened clinical conditions and surgical site infection. A high degree of suspicion to avoid unnecessary treatments and progression to severe disease with dismal prognosis is necessary in these types of infections.

5.
JACC Case Rep ; 3(5): 823-828, 2021 May.
Article in English | MEDLINE | ID: mdl-33723533

ABSTRACT

Heart failure symptoms, in particular dyspnea, may be difficult to frame in a patient with cancer. We report the case of an oncological patient whose dyspnea could have been attributable to various causes and whose management was challenging in the context of the coronavirus disease-2019 pandemic. (Level of Difficulty: Beginner.).

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