Autopsy findings in cancer patients infected with SARS-CoV-2 show a milder presentation of COVID-19 compared to non-cancer patients.

COVID-19, caused by SARS-CoV-2, manifests with differing severity across distinct patient subgroups, with outcomes influenced by underlying comorbidities such as cancer, which may cause functional and compositional alterations of the immune system during tumor progression. We aimed to investigate the association of SARS-CoV-2 infection and its complications with cancer in a large autopsy series and the role of COVID-19 in the fatal sequence leading to death. A total of 2641 adult autopsies were investigated, 539 of these were positive for SARS-CoV-2. Among the total number of patients analyzed, 829 had active cancer. Overall, the cohort included 100 patients who simultaneously had cancer and SARS-CoV-2 infection. The course of COVID-19 was less severe in cancer patients, including a significantly lower incidence of viral and bacterial pneumonia, occurring more frequently as a contributory disease or coexisting morbidity, or as SARS-CoV-2 positivity without viral disease. SARS-CoV-2 positivity was more frequent among non-metastatic than metastatic cancer cases, and in specific tumor types including hematologic malignancies. COVID-19 was more frequently found to be directly involved in the fatal sequence in patients undergoing active anticancer therapy, but less frequently in perioperative status, suggesting that the underlying malignancy and consequent surgery are more important factors leading to death perioperatively than viral disease. The course of COVID-19 in cancer patients was milder and balanced during the pandemic. This may be due to relative immunosuppressed status, and the fact that even early/mild viral infections can easily upset their condition, leading to death from their underlying cancer or its complications.

Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins, superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions.

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well-known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti-desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts.

The Relationship between Tricuspid Annular Longitudinal and Sphincter-like Features of Its Function in Healthy Adults: Insights from the MAGYAR-Healthy Study.

INTRODUCTION: The tricuspid valve is an atrioventricular valve located on the right side of the heart, which consists of the fibrous tricuspid annulus (TA), three valvular leaflets and a supporting apparatus, the papillary muscles and the tendinous chords. The TA is an oval-shaped three-dimensional (3D) fibrous structure with a complex spatial movement during the cardiac cycle. Three-dimensional echocardiography (3DE) could help during "en-face" assessment of TA dimensions and related functional properties featuring its "sphincter-like" function. TA plane systolic excursion (TAPSE) is a displacement of the lateral edge of the TA toward the apex in systole measured in apical long-axis using M-mode echocardiography (MME). The aim of this study was to determine potential relationships between TA size and its "sphincter-like" and "longitudinal" functions in healthy adults with no functional tricuspid regurgitation. METHODS: The present study consisted of 119 healthy patients (age: 34.6 ± 11.5 years, 70 men) who underwent routine echocardiography with M-mode-derived TAPSE measurement and 3DE. Two subgroups of healthy subjects were compared with each other. A total of 29 subjects with TAPSE between 17 and 21 mm were compared with 90 cases with TAPSE ≥ 22 mm. RESULTS: Subjects with TAPSE of 17-21 mm had tendentiously dilated TA dimensions compared with subjects with TAPSE ≥ 22 mm. Significant differences could be detected in the end-systolic TA area (5.85 ± 1.90 cm2 vs. 3.70 ± 1.22 cm2, p < 0.05), leading to impaired TAFAC (24.8 ± 9.0% vs. 35.1 ± 9.1%, p < 0.05) in subjects with lower TAPSE (17-21 mm) compared with subjects with TAPSE ≥ 22 mm. TAPSE did not show correlations with any TA size or "sphincter-like" functional parameters as determined using 3DE. CONCLUSIONS: Three-dimensional echocardiography is capable of measuring TA dimensions and functional "sphincter-like" properties, which are associated with MME-derived TAPSE, suggesting a sensitive and harmonic TA function in healthy adults without functional tricuspid regurgitation.

Tricuspid annular and right atrial volume changes are associated in healthy adults-insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Introduction: The tricuspid valve and its annulus (TA) and the right atrium (RA) play a significant role in regulating blood flow in the right heart. However, their effect on each other is not fully understood even in normal circumstances. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is able to simultaneously assess TA and RA at the same time in a non-invasive way. The present study aimed to examine associations between tricuspid annular (TA) dimensions and right atrial (RA) volumes in healthy adults by 3DSTE. Methods: The present study comprised 144 healthy subjects (mean age: 34.4 ± 12.6 years, 72 males), who participated in this study on a voluntary basis for screening between 2011 and 2015. In all subjects, electrocardiography, two-dimensional Doppler echocardiography and 3DSTE have been performed. Results: With increasing end-systolic maximum RA volume, all end-systolic and end-diastolic TA dimensions showed simultaneous increase, but in various degrees resulting in (non-significant) reduction of TA functional properties. Similarly, with increasing diastolic pre-atrial contraction and minimum RA volumes, TA dimensions increased simultaneously (except end-diastolic TA diameter), but in various degrees resulting in reduced TA fractional shortening and fractional area change. With increasing RA dimensions, end-systolic and end-diastolic TA dimensions showed simultaneous increase, but in different, sometimes not significant degrees. While RA stroke volumes showed increasing pattern with TA dilation, RA emptying fractions have not changed substantially. Conclusions: 3DSTE is suitable for non-invasive assessment of TA dimensions and RA volumes at the same time using the same 3D echocardiographic dataset. Significant associations between TA size and RA volumes exist in healthy circumstances. Strong associations in case of dilation of TA in the presence of higher RA volumes could partly explain functional tricuspid regurgitation later developing in subjects in sinus rhythm.

Discovery of two new isoforms of the human DUT gene.

In human cells two dUTPase isoforms have been described: one nuclear (DUT-N) and one mitochondrial (DUT-M), with cognate localization signals. In contrast, here we identified two additional isoforms; DUT-3 without any localization signal and DUT-4 with the same nuclear localization signal as DUT-N. Based on an RT-qPCR method for simultaneous isoform-specific quantification we analysed the relative expression patterns in 20 human cell lines of highly different origins. We found that the DUT-N isoform is expressed by far at the highest level, followed by the DUT-M and the DUT-3 isoform. A strong correlation between expression levels of DUT-M and DUT-3 suggests that these two isoforms may share the same promoter. We analysed the effect of serum starvation on the expression of dUTPase isoforms compared to non-treated cells and found that the mRNA levels of DUT-N decreased in A-549 and MDA-MB-231 cells, but not in HeLa cells. Surprisingly, upon serum starvation DUT-M and DUT-3 showed a significant increase in the expression, while the expression level of the DUT-4 isoform did not show any changes. Taken together our results indicate that the cellular dUTPase supply may also be provided in the cytoplasm and starvation stress induced expression changes are cell line dependent.

Proteome alterations in human autopsy tissues in relation to time after death.

Protein expression is a primary area of interest for routine histological diagnostics and tissue-based research projects, but the limitations of its post-mortem applicability remain largely unclear. On the other hand, tissue specimens obtained during autopsies can provide unique insight into advanced disease states, especially in cancer research. Therefore, we aimed to identify the maximum post-mortem interval (PMI) which is still suitable for characterizing protein expression patterns, to explore organ-specific differences in protein degradation, and to investigate whether certain proteins follow specific degradation kinetics. Therefore, the proteome of human tissue samples obtained during routine autopsies of deceased patients with accurate PMI (6, 12, 18, 24, 48, 72, 96 h) and without specific diseases that significantly affect tissue preservation, from lungs, kidneys and livers, was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the kidney and liver, significant protein degradation became apparent at 48 h. For the lung, the proteome composition was rather static for up to 48 h and substantial protein degradation was detected only at 72 h suggesting that degradation kinetics appear to be organ specific. More detailed analyses suggested that proteins with similar post-mortem kinetics are not primarily shared in their biological functions. The overrepresentation of protein families with analogous structural motifs in the kidney indicates that structural features may be a common factor in determining similar postmortem stability. Our study demonstrates that a longer post-mortem period may have a significant impact on proteome composition, but sampling within 24 h may be appropriate, as degradation is within acceptable limits even in organs with faster autolysis.

[Multimodality imaging of adult patients with surgically corrected tetralogy of Fallot. Results from the CSONGRAD Registry] / A mutétileg korrigált Fallot-tetralógiával élo felnott betegek multimodális képalkotó vizsgálata. Eredmények a CSONGRAD Regiszterbol

INTRODUCTION: There is an increasing ratio of surviving patients with congenital heart disease including tetralogy of Fallot. OBJECTIVE: The aim of the present study was a comparative assessment of echocardiographic and cardiac magnetic resonance imaging-derived findings in patients with tetralogy of Fallot following early total reconstruction versus early palliation/late correction. METHODS: The study comprised 17 patients with tetralogy of Fallot (mean age: 28.6 ± 10.4 years; 10 males). Early total reconstruction was performed in 10 cases (mean age: 25.0 ± 8.0 years; 8 males), while early palliation/late construction was done in 7 subjects (mean age: 33.7 ± 11.8 years; 2 males). Complete two-dimensional Doppler echocardiography and cardiac resonance imaging were performed in all patients. RESULTS: During long-term follow-up, lower left ventricular end-systolic (40.50 ± 10.55 ml/m2 vs. 58.14 ± 19.07 ml/m2, p = 0.013) and end-diastolic volume indices (86.60 ± 12.62 ml/m2 vs. 116.70 ± 23.70 ml/m2, p = 0.002) and stroke volume index (46.00 ± 6.77 ml/m2 vs. 58.43 ± 7.11 ml/m2, p = 0.001) could be detected, which were associated with higher echocardiographic left ventricular ejection fraction (69.75 ± 6.80% vs. 61.67 ± 8.80%, p = 0.038) in patients with tetralogy of Fallot following early total reconstruction as compared to that of subjects late after early palliation/late correction. In regard with the right heart, larger right ventricular muscle mass (72.33 ± 21.03 g/m2 vs. 51.33 ± 22.33 g/m2, p = 0.044) could be seen in patients with tetralogy of Fallot following early total reconstruction. CONCLUSION: Beneficial left ventricular morphological and functional parameters, but more pronounced right ventricular hypertrophy could be detected in patients with tetralogy of Fallot following early total reconstruction as compared to that of subjects late after early palliation/late correction. Orv Hetil. 2023; 164(5): 186-194.

Normal reference values of tricuspid annular dimensions and functional properties in healthy adults using three-dimensional speckle-tracking echocardiography (insights from the MAGYAR-Healthy Study).

Background: Three-dimensional speckle-tracking echocardiography (3DSTE) is a relatively new non-invasive imaging modality with ability for simultaneous chamber quantifications and determination of valvular dimensions. The aim of the present retrospective cohort study was to determine normal reference values of 3DSTE-derived tricuspid annular (TA) dimensions and functional properties and to evaluate their age- and gender dependency. Methods: The present study comprised 156 healthy adult subjects, from which 28 cases were excluded due to inferior image quality, therefore the remaining group consisted of 128 cases with the mean age of 35.4±12.5 years (72 males). The subject population was further divided into the following categories: 18-29 years (n=57; mean age: 25.2±2.8 years, 51 males), 30-39 years (n=29; mean age: 34.1±2.5 years, 31 males), 40-49 years (n=17; mean age: 44.1±3.2 years, 11 males) and ≥50 years of age (n=25, mean age: 59.2±6.4 years, 14 males). Results: End-diastolic TA diameter (2.2±0.3 vs. 2.5±0.3 cm, P<0.05), area (7.1±1.3 vs. 8.1±1.7 cm2, P<0.05) and perimeter (10.3±0.9 vs. 11.0±1.2 cm, P<0.05) were lower in females than in males in the 18-29 year-old group and TA area (6.1±0.8 vs. 8.0±1.2 cm2, P<0.05) and TA perimeter (9.7±0.8 vs. 11.0±0.9 cm, P<0.05) were lower in females than in males in the 40-49 year-old group. End-systolic TA diameter were lower in females than in males in the 18-29 year-old group (1.8±0.2 vs. 1.9±0.3 cm, P<0.05) and TA area (4.7±0.3 vs. 6.3±1.2 cm2, P<0.05) and TA perimeter (8.6±0.4 vs. 9.5±0.9 cm, P<0.05) were lower in females than in males in the 40-49 year-old group. TA fractional area change was found to be reduced in the 40-49 year-old group as compared to the 30-39 year-old group (21.7%±8.7% vs. 29.2%±10.0%, P<0.05). Conclusions: 3DSTE is a novel method for non-invasive assessment of TA dimensions and functional properties. Results highlight the importance of age- and gender-specific reference values in case of TA diameter, area and perimeter and calculated functional features respecting the cardiac cycle.

Screening for Myocardial Injury after Mild SARS-CoV-2 Infection with Advanced Transthoracic Echocardiography Modalities.

Although the clinical manifestations of SARS-CoV-2 viral infection affect mainly the respiratory system, cardiac complications are common and are associated with increased morbidity and mortality. While echocardiographic alterations indicating myocardial involvement are widely reported in patients hospitalized for acute COVID-19 infection, much fewer data available in non-hospitalized, mildly symptomatic COVID-19 patients. In our work, we aimed to investigate subclinical cardiac alterations characterized by parameters provided by advanced echocardiographic techniques following mild SARS-CoV-2 viral infection. A total of 86 patients (30 males, age: 39.5 ± 13.0 yrs) were assessed 59 ± 33 days after mild SARS-CoV-2 viral infection (requiring no hospital or <5 days in-hospital treatment) by advanced echocardiographic examination including 2-dimensional (2D) speckle tracking echocardiography and non-invasive myocardial work analysis, and were compared to an age-and sex-matched control group. Altogether, variables from eleven echocardiographic categories representing morphological or functional echocardiographic parameters showed statistical difference between the post-COVID patient group and the control group. The magnitude of change was subtle or mild in the case of these parameters, ranging from 1−11.7% of relative change. Among the parameters, global longitudinal strain [−20.3 (−21.1−−19.0) vs. −19.1 (−20.4−−17.6) %; p = 0.0007], global myocardial work index [1975 (1789−2105) vs. 1829 (1656−2057) Hgmm%; p = 0.007] and right ventricular free wall strain values (−26.6 ± 3.80 vs. −23.8 ± 4.0%; p = 0.0003) showed the most significant differences between the two groups. Subclinical cardiac alterations are present following even mild SARS-CoV-2 viral infection. These more subtle alterations are difficult to detect by routine echocardiography. Extended protocols, involving speckle-tracking echocardiography, non-invasive measurement of cardiac hemodynamics, and possibly myocardial work are necessary for detection and adequate follow-up.

Tricuspid Annular Abnormalities in Isolated Left Ventricular Non-compaction-Insights From the Three-dimensional Speckle-Tracking Echocardiographic MAGYAR-Path Study.

Introduction: Prominent trabecular left ventricular (LV) meshwork and deep intertrabecular LV recesses are featuring LV non-compaction (LVNC). The aim of this study was to evaluate tricuspid annular (TA) morphological and functional abnormalities by three-dimensional speckle-tracking echocardiography (3DSTE) in patients with LVNC without right ventricular (RV) involvement. Materials and Methods: This study consisted of 21 patients with isolated LVNC, from which 6 cases were excluded due to inferior image quality. The remaining patient group consisted of 15 subjects with a mean age of 52.1 ± 11.4 years (9 males). LVNC was defined according to the Jenni's criteria. Their results were compared to 21 age- and gender-matched healthy controls (mean age: 52.4 ± 3.9 years, 14 males). Complete routine 2-dimensional Doppler echocardiographic examination was performed in all the patients with isolated LVNC and healthy controls. End-systolic and end-diastolic TA dimensions were assessed on selected planes derived from full-volume 3D echocardiographic datasets during 3DSTE. Results: Patients with isolated LVNC showed significantly dilated end-systolic and end-diastolic TA diameter and area, which were accompanied with preserved TA functional properties and associated with right atrial (RA) volumes. TA plane systolic excursion (TAPSE) showed mild correlations with TA fractional area change (TAFAC) and TA fractional shortening (TAFS). No correlations could be demonstrated between TAPSE and TA morphological features. Extent of LVNC did not correlate with any echocardiographic parameters. Conclusion: TA is dilated with preserved sphincter-like function in patients with isolated LVNC. Longitudinal (TAPSE) and sphincter-like (TAFAC and TAFS) TA movements correlate with each other. TA dilation is associated with an increased RA volumes respecting cardiac cycle.

The tricuspid annulus in amyloidosis with cardiac involvement: Detailed analysis from the three-dimensional speckle tracking echocardiographic MAGYAR-Path Study.

Introduction: Amyloidosis is a rare condition due to extracellular deposition of excessive amount of protein in parenchymal tissues including the heart. The present study aimed to test whether cardiac amyloidosis (CA) is associated with morphological and functional abnormalities of the tricuspid annulus (TA). For this aim, the results of patients having CA were compared to age- and gender-matched healthy controls by three-dimensional speckle-tracking echocardiography (3DSTE). Moreover, differences in TA parameters between light-chain CA (AL-CA) and transthyretin CA (TTR-CA) were studies as well. Materials and Methods: The study comprised 27 CA patients (mean age: 62.7 ±â€¯9.1 years, 21 males), their results were compared to those of 20 age- and gender-matched healthy volunteers (59.3 ±â€¯3.8 years, 13 males). Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all CA patients and controls. Results: Dilated end-diastolic and end-systolic TA diameter, area and perimeter could be detected in all CA patients and in the AL-CA and TTR-CA subgroups, as well. Although only a few TTR-CA patients were involved, morphologic TA parameters proved to be tendentiously higher as compared to those of AL-CA patients. Functional parameters of TA were found to be reduced in CA patients, which were more deteriorated in AL-CA patients. Conclusions: Dilated TA is associated with its functional deterioration in CA.

Real 3D Visualization of the Circumflex Artery Surrounding the Mitral Annulus.

BACKGROUND: The circumflex coronary artery is located close to the mitral annulus. Consequently, it is not immune to iatrogenic damage during mitral valve procedures. Our objective was to visualize the circumflex artery from a surgeon's point of view, emphasizing its proximity. Furthermore, comparing it to coronary angiograms might support preoperative planning. METHODS: Ten adult human hearts preserved in 4% formaldehyde solution were investigated (left coronary artery injected with contrast agent). After performing coronary angiographies from LAO (left anterior oblique) 40/cranial 20, RAO (right anterior oblique) 10/cranial 40, and true lateral projections, anatomical preparations were performed. Images were captured throughout the full course of the circumflex coronary artery from multiple angles. Finally, the mean distances were measured in every 5 mm between the investigated artery and the annulus of the mitral valve. RESULTS: Three-dimensional model of the circumflex coronary artery and its surroundings was successfully achieved from a left atrial surgical viewpoint. The main branches were identified on the coronary angiograms. The closest distance was measured under the region of the left auricle (2.02 ± 0.69 mm; 1-3.1 mm). Afterward, the circumflex artery was observed to make a loop away from the annular region. CONCLUSION: Our observations show correlation with previous anatomical studies and case reports addressing iatrogenic lesions on the circumflex coronary artery. Based on all these, we could determine a "danger zone" on the vessel. The simultaneous evaluation of the anatomical preparations and the angiograms might improve the acknowledgment of this vulnerable region serving to avoid any damage to the coronary artery.

Identification of new reference genes with stable expression patterns for gene expression studies using human cancer and normal cell lines.

Reverse transcription-quantitative real-time PCR (RT-qPCR) is a ubiquitously used method in biological research, however, finding appropriate reference genes for normalization is challenging. We aimed to identify genes characterized with low expression variability among human cancer and normal cell lines. For this purpose, we investigated the expression of 12 candidate reference genes in 13 widely used human cancer cell lines (HeLa, MCF-7, A-549, K-562, HL-60(TB), HT-29, MDA-MB-231, HCT 116, U-937, SH-SY5Y, U-251MG, MOLT-4 and RPMI-8226) and, in addition, 7 normal cell lines (HEK293, MRC-5, HUVEC/TERT2, HMEC, HFF-1, HUES 9, XCL-1). In our set of genes, we included SNW1 and CNOT4 as novel candidate reference genes based on the RNA HPA cell line gene data from The Human Protein Atlas. HNRNPL and PCBP1 were also included along with the "classical" reference genes ACTB, GAPDH, IPO8, PPIA, PUM1, RPL30, TBP and UBC. Results were evaluated using GeNorm, NormFiner, BestKeeper and the Comparative ΔCt methods. In conclusion, we propose IPO8, PUM1, HNRNPL, SNW1 and CNOT4 as stable reference genes for comparing gene expression between different cell lines. CNOT4 was also the most stable gene upon serum starvation.

Human Cadaveric Artificial Lung Tumor-Mimic Training Model.

Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice. Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions-apical, hilar and two peripheral-were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers. Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumor-mimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features. Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.

The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia.

Human reproduction is controlled by ~2000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here, we report the discovery and characterization of additional ~150,000-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Nearly all extrahypothalamic GnRH neurons expressed the cholinergic marker enzyme choline acetyltransferase. Similarly, hypothalamic GnRH neurons were also cholinergic both in embryonic and adult human brains. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen showed selective expression of GNRH1 and GNRHR1 autoreceptors in the cholinergic cell population and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. The role and changes of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson's and Alzheimer's diseases, need to be explored.

Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region.

Congenital heart defects (CHD) are the most common developmental abnormalities, affecting approximately 0.9% of livebirths. Genetic factors, including copy number variations (CNVs), play an important role in their development. The most common CNVs are found on chromosome 22q11.2. The genomic instability of this region, caused by the eight low copy repeats (LCR A-H), may result in several recurrent and/or rare microdeletions and duplications, including the most common, ∼3 Mb large LCR A-D deletion (classical 22q.11.2 deletion syndrome). We aimed to screen 22q11.2 CNVs in a large Hungarian pediatric and adult CHD cohort, regardless of the type of their CHDs. All the enrolled participants were cardiologically diagnosed with non-syndromic CHDs. A combination of multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis and droplet digital PCR methods were used to comprehensively assess the detected 22q11.2 CNVs in 212 CHD-patients. Additionally, capillary sequencing was performed to detect variants in the TBX1 gene, a cardinal gene located in 22q11.2. Pathogenic CNVs were detected in 5.2% (11/212), VUS in 0.9% and benign CNVs in 1.8% of the overall CHD cohort. In patients with tetralogy of Fallot the rate of pathogenic CNVs was 17% (5/30). Fifty-four percent of all CNVs were typical proximal deletions (LCR A-D). However, nested (LCR A-B) and central deletions (LCR C-D), proximal (LCR A-D) and distal duplications (LCR D-E, LCR D-H, LCR E-H, LCR F-H) and rare combinations of deletions and duplications were also identified. Segregation analysis detected familial occurrence in 18% (2/11) of the pathogenic variants. Based on in-depth clinical information, a detailed phenotype-genotype comparison was performed. No pathogenic variant was identified in the TBX1 gene. Our findings confirmed the previously described large phenotypic diversity in the 22q11.2 CNVs. MLPA proved to be a highly efficient genetic screening method for our CHD-cohort. Our results highlight the necessity for large-scale genetic screening of CHD-patients and the importance of early genetic diagnosis in their clinical management.

Left ventricular rotational abnormalities in adult patients with corrected tetralogy of Fallot following different surgical procedures (Results from the CSONGRAD Registry and MAGYAR-Path Study).

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). Abnormal aortic dimensions and elasticity parameters have been long described for corrected TOF (cTOF) together with left ventricular (LV) rotational abnormalities, but results are conflicting. The present study focuses on investigating LV rotational mechanics in cTOF, and possible correlation of these parameters with aortic elasticity. It was also aimed to be examined whether different surgical strategies have any effect on these results. METHODS: The study involved 26 adult cTOF patients, from which 14 had palliative surgery first and a late total correction (pcTOF), while early total correction was the treatment of choice in 12 patients (etrTOF). Their results were compared to those of 37 age- and gender-matched healthy adults. Routine transthoracic two-dimensional Doppler echocardiography extended with assessment of aortic elastic properties and three-dimensional speckle-tracking echocardiography (3DSTE) was performed in all cTOF patients and controls. RESULTS: Sixteen out of 26 cTOF patients showed normally directed LV rotational mechanics, while apical or basal LV rotations were in the same clockwise or counterclockwise directions in 7 and 3 cTOF cases, respectively (LV 'rigid body rotation', RBR). Significantly reduced LV apical rotation and twist could be demonstrated in all cTOF patients with preserved LV basal rotation regardless of previous procedure. pcTOF patients showed significantly reduced LV apical rotation as compared to that of etrTOF cases. Significant correlations could be demonstrated between LV apical rotation and aortic stiffness index (r=-0.55, P=0.03) and aortic distensibility (r=0.52, P=0.04). CONCLUSIONS: Significant LV rotational abnormalities could be demonstrated in cTOF with the high prevalence of LV-RBR. pcTOF patients showed significantly reduced LV apical rotation as compared to that of etrTOF cases. Unexpected abnormal physiologic response of LV rotational mechanics to increased aortic stiffness can be detected in cTOF patients without LV-RBR.

Left ventricular strains correlate with aortic elastic properties in adult patients with corrected tetralogy of Fallot (Results from the CSONGRAD Registry and MAGYAR-Path Study).

BACKGROUND: Aortopathy is a common phenomenon in tetralogy of Fallot (TOF). The current study was designed to detect left ventricular (LV) deformation abnormalities and its relation to aortic stiffness in corrected TOF (cTOF) using the novel three-dimensional (3D) speckle-tracking echocardiography (3DSTE). Detailed comparative analysis between patients with early palliation-late correction (pcTOF) and early total reconstruction (etrTOF) was also performed. METHODS: The present study consisted of 28 cTOF patients (35.0±15.7 years, 11 males) from which 15 and 13 proved to be pcTOF and etrTOF, respectively. Their clinical parameters were compared to those of 39 matched healthy adults (35.5±6.0 years, 16 males). RESULTS: cTOF patients showed significantly lower global LV longitudinal, circumferential and area strains as compared to controls. In etrTOF patients, global LV 3D strain was higher than in controls. In pcTOF patients, all LV strains proved to be significantly lower as compared to those of etrTOF patients and controls. In all cTOF patients, several moderate correlations could be detected between LV strain parameters and aortic elastic properties. CONCLUSIONS: Significant LV deformational abnormalities could be demonstrated in cTOF patients. etrTOF patients have beneficial LV strain parameters as compared to those of pcTOF patients. LV strains show correlations with aortic elastic properties.

Graft survival using cadaver and multiorgan donors between 2008 and 2017 in our department / Cadaverbol és multiorgan donorból származó szaruhártyák túlélése 2008 és 2017 között klinikánkon.

Összefoglaló. Bevezetés: Az elso szaruhártya-bank 1944-es alapítása óta jelentos változásokon ment át. A szaruhártya túlélését számos tényezo befolyásolja, így a tárolási mód, melynek a szövet lejárati ideje szerint rövid, közép és hosszú távú módszereit fejlesztették ki. Célkituzés: Retrospektív vizsgálatunk célja a 2008. január 1. és 2017. december 31. között perforáló és lamelláris keratoplasztika során felhasznált cadaverbol és multiorgan donorból származó szaruhártyák túlélésének vizsgálata volt a Semmelweis Egyetem Szemészeti Klinikáján. Módszer: Feljegyeztük a recipiens nemét, életkorát, a mutétet indikáló klinikai diagnózist, a mutét idopontját, a szövettani vizsgálat eredményét, valamint, hogy a beültetett szaruhártya cadaverbol vagy multiorgan donorból származott. Meghatároztuk, hogy a recipiens életkora korrelált-e a rekeratoplasztikáig eltelt idovel. Eredmények: 1451 szaruhártya-átültetés történt 1088 beteg (44,6% férfi) 1159 szemén (életkor 62,8 ± 18,5 év), melyek között 938 (64,6%) cadaver és 262 (18,0%) multiorgan donor került felhasználásra, 251 esetben (17,2%) nem állt rendelkezésre adat. A leggyakoribb primer diagnózis a szaruhártya-dekompenzáció volt (325 eset, 28%). A primer keratoplasztikák során felhasznált szaruhártyák 740 esetben (63,8%) cadaverbol, 212 esetben (18,2%) multiorgan donorból származtak, 207 esetben (17,8%) nem állt rendelkezésre adat. Elso rekeratoplasztika a primer keratoplasztikák közül 217 esetben (18,7%) történt. A leggyakoribb szövettani diagnózis az endothelsejt-degeneráció volt (130 esetben, 60,4%). 146 esetben (67,2%) korábban cadaver, 31 esetben (14,2%) multiorgan donor esetén került sor ismételt mutétre, 40 esetben (18,4%) nem állt rendelkezésre adat. Következtetés: Klinikánkon elsosorban cadaverbol származó donorok biztosítják a szaruhártya átültetésekhez szükséges szövetet. Cadaverbol vagy multiorgan donorból származó szaruhártyák esetén nem kerül gyakrabban sor rekeratoplasztikára. A szaruhártya-banki tevékenység további fejlesztésével növelheto a donorok túlélése hazánkban. Orv Hetil. 2021; 162(13): 488-496. INTRODUCTION: Corneal banking methods have been changing since the foundation of the first corneal bank in 1944. Corneal graft survival may be affected by several factors, among others the storage method, which may be short-, middle- and long-term storage. OBJECTIVE: To investigate corneal graft survival at the Department of Ophthalmology, Semmelweis University between 1 January 2008 and 31 December 2017, using cadaver and multiorgan donors for penetrating and lamellar keratoplasty, retrospectively. METHOD: Recipient sex, age, clinical diagnosis, date of surgery, histological examination results and origin of donors (cadaver or multiorgan donor) were recorded. Correlation between recipient age and time to repeat keratoplasty was also analyzed. RESULTS: There were 1451 keratoplasties in 1159 eyes (age 62.8 ± 18.5 years) of 1088 patients (44.6% male) using 938 (64.6%) cadaver and 262 (18.0%) multiorgan donors, data was not available in 251 (17.2%) cases. There was repeat keratoplasty in 217 patients (18.7% of first keratoplasties). The most common histological diagnosis was endothelial decompensation (130 cases, 60.4%) in these cases. In patients with a first repeat keratoplasty, in 146 cases (67.2%) the first donor originated from cadavers, in 31 cases (14.2%) from multiorgan donors and in 40 cases (18.4%) data were not available. CONCLUSION: Corneal donors mainly originate from cadavers at our Department. The necessity of repeat keratoplasties does not differ using cadaver or multiorgan donors. With further development of corneal banking, donor survival may be increased in Hungary. Orv Hetil. 2021; 162(13): 488-496.

Tricuspid annular abnormalities in repaired dextro-transposition of the great arteries following Senning and Mustard procedures (Insights from the CSONGRAD Registry and MAGYAR-Path Study).

BACKGROUND: In dextro-transposition of the great arteries (dTGA), the aorta and the pulmonary artery are transposed in position, when aorta arises from the right ventricle and pulmonary artery arises from the left ventricle. The present study was designed to assess three-dimensional speckle-tracking echocardiography-derived tricuspid annular (TA) abnormalities in adult patients with dTGA late after atrial switch operations. It was also examined whether differences in TA morphology and function exist between Senning- and Mustard-procedures. METHODS: The study consisted of 14 adult dTGA patients (mean age: 29.9±8.3 years, 6 males), who underwent Mustard-procedure (n=7) at the age of 1.57±0.53 years or Senning-procedure (n=7) at the age of 1.42±0.53 years. Their results were compared to 28 age- and gender-matched healthy subjects (30.3±4.9 years, 14 males). RESULTS: Dilated end-systolic and end-diastolic TA diameters, areas and perimeters could be detected in dTGA patients as compared to those of controls. TA functional properties calculated from TA diameter (TAFS) and area (TAFAC) data proved to be deteriorated in dTGA patients. No differences could be detected either in TA dimensions, or in TA functional properties between Senning- and Mustard-operated dTGA patients. TA plane systolic excursion (TAPSE) was reduced, which did not correlate with TAFAC and TAFS in dTGA patients. CONCLUSIONS: In dTGA, dilated end-systolic and end-diastolic TA is accompanied with deteriorated TA functional properties regardless of which atrial switch procedure was performed. Correlations between TAPSE representing longitudinal movement of the TA and TAFAC and TAFS representing sphincter-like movement of the TA disappeared, which could partially explain accompanying tricuspid functional regurgitations. KEYWORDS: Tricuspid annulus; function; three-dimensional echocardiography; speckle-tracking; transposition of the great arteries.