Miklós Pólos

Peripheral blood fibrocytes contribute to the formation of the avian spleen

Chick–quail chimeric studies were made to determine the origin of the cells of splenic ellipsoid. The ellipsoid is formed by supporting and phagocytic cells, which are embedded in a well‐organized extracellular matrix. Splenic and bursal anlage of 6‐ to 6.5‐day‐old quail embryos were transplanted into the coelomic cavity of 3‐day‐old chick embryos and further incubated for 17 days. CD45+ chicken hemopoietic cells colonized both organs. They formed the cells of the ellipsoid and the periellipsoidal white pulp of the transplanted quail spleen. Chicken‐specific collagen III was produced only in the donor quail spleen, but not in the bursa of Fabricius. The CD45+/collagen I+/collagen III+ cells are probably identical with the mammalian peripheral blood fibrocytes and contribute to the formation of supporting cells, whereas the CD45+/74.2+ ellipsoid‐associated macrophages are of monocytic origin. We provide, for the first time, experimental evidence that peripheral blood fibrocytes exist in the avian species; they are present in the circulation of the chicken embryo and contribute to the organogenesis of the spleen. Developmental Dynamics 232:55–66, 2005.

The role of transforming growth factor-beta in Marfan syndrome

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fibrillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact on the tissue homeostasis of microfibrils, and elastic fibers. We also investigate current data on the extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Together these factors, by the destruction of the connective tissue fibers, may play an important role in the development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for the treatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease.

Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome: Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome

Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta.

Personalized surgical repair of left ventricular aneurysm with computer-assisted ventricular engineering †

OBJECTIVES Although circular ventricular resection techniques are the gold standard of left ventricular (LV) restoration, these techniques can lead to suboptimal results. Postoperative systolic resection can be inadequate, because it must be planned on a heart stopped in diastole. Low cardiac output due to insufficient LV volume results in a potentially unstable condition, and cannot be corrected. Our aim was to find a preoperative method to minimize risk and maximize outcome with ventricular restoration. METHODS We created a novel method combining surgery with gadolinium-enhanced magnetic resonance to construct a preoperative 3D systolic heart model. The model was utilized to determine resection points that could be intraoperatively used. According to our calculations with the predetermined resection line, the calculated percentage reduction in LV volume was above 30%, and LV volumes were predicted above normal values; thus, performing the operation using these resection points is likely to be safe and effective. We had a mixed, real-life patient group: mitral insufficiency or pulmonary hypertension were not exclusion criteria. RESULTS Forty-one procedures (12 concomitant mitral valve plasty) were done on consecutive patients in a single-centre experience. The incidence rate of major adverse clinical events was 32% postoperatively (n = 13). Control MRI showed a significant improvement in ejection fraction (18.3 ± 4.3 vs 31.3 ± 3.3; P = 0.04). All patients improved their New York Heart Association (NYHA) class postoperatively (40 patients NYHA III/IV versus 40 NYHA I/II). During long-term follow-up, 1 patient died due to end-stage heart failure. CONCLUSIONS Using this model, we were able to find the optimal resection line providing an excellent postoperative result, thus minimizing the risk of low cardiac output syndrome.

Számítástechnikai döntéstámogató rendszer kiépítése a szívsebészetben: a 3D tervezéstől a posztoperatív eredményekig

INTRODUCTION Although surgical specialties utilize static models for preoperative planning, the evolution of dynamic planning methods and computer simulations created the opportunity for the introduction of dynamic parameters in cardiac surgery. Our aim was to apply 3D models in cardiac surgical practice, predicting fluid dynamic results, ventricular shape, volume and function before the operation. METHODS Using a script developed by us, the raw DICOM files were imported, the dilated left ventricle was modeled and fluid dynamic parameters were simulated, such as flow kinematic and profile analysis, turbulence calculation and myocardial response to shear stress. Then step-by-step simulation of the surgical ventricle restoration procedure was accomplished and the calculated variables were imbedded in silico model. The length of resection lines was modified based on the previous computer simulation and applied during the operation, if feasible. RESULTS The sphericity and conicity indexes were improved significantly in postoperative period (0.42 vs. 0.67 and 0.36 vs. 0.72, p < 0.05). The occurred shear stress at endocardium decreased 83% due to the normalization of flow kinematic pattern of the ventricle in postoperative period (132.21 ± 29.5 dyne/cm2 vs. 22.92 ± 10.3 p < 0.05 dyne/‌cm2). The postoperative turbulent flow pattern significantly decreased, according to our computational method (2712 vs. 1823, p < 0.0001). CONCLUSION With our method, the standardization of the surgical ventricle reconstruction was achievable and the surgical steps were predictable. Therefore, a new decision making support system was established in cardiac surgery for high risk patients. A personalized surgical technique was offered to our patients, improving their life expectancy and quality of life.INTRODUCTION Although surgical specialties utilize static models for preoperative planning, the evolution of dynamic planning methods and computer simulations created the opportunity for the introduction of dynamic parameters in cardiac surgery. Our aim was to apply 3D models in cardiac surgical practice, predicting fluid dynamic results, ventricular shape, volume and function before the operation. METHODS Using a script developed by us, the raw DICOM files were imported, the dilated left ventricle was modeled and fluid dynamic parameters were simulated, such as flow kinematic and profile analysis, turbulence calculation and myocardial response to shear stress. Then step-by-step simulation of the surgical ventricle restoration procedure was accomplished and the calculated variables were imbedded in silico model. The length of resection lines was modified based on the previous computer simulation and applied during the operation, if feasible. RESULTS The sphericity and conicity indexes were improved significantly in postoperative period (0.42 vs. 0.67 and 0.36 vs. 0.72, p < 0.05). The occurred shear stress at endocardium decreased 83% due to the normalization of flow kinematic pattern of the ventricle in postoperative period (132.21 ± 29.5 dyne/cm2 vs. 22.92 ± 10.3 p < 0.05 dyne/‌cm2). The postoperative turbulent flow pattern significantly decreased, according to our computational method (2712 vs. 1823, p < 0.0001). CONCLUSION With our method, the standardization of the surgical ventricle reconstruction was achievable and the surgical steps were predictable. Therefore, a new decision making support system was established in cardiac surgery for high risk patients. A personalized surgical technique was offered to our patients, improving their life expectancy and quality of life.

Hungarian Marfan family with large FBN1 deletion calls attention to copy number variation detection in the current NGS era

Copy number variations (CNVs) comprise about 10% of reported disease-causing mutations in Mendelian disorders. Nevertheless, pathogenic CNVs may have been under-detected due to the lack or insufficient use of appropriate detection methods. In this report, on the example of the diagnostic odyssey of a patient with Marfan syndrome (MFS) harboring a hitherto unreported 32-kb FBN1 deletion, we highlight the need for and the feasibility of testing for CNVs (>1 kb) in Mendelian disorders in the current next-generation sequencing (NGS) era.

Acute thrombosis of the ascending aorta causing right ventricular failure: first manifestation of antiphospholipid syndrome

Antiphospholipid syndrome is an autoimmune disorder with frequent clinical manifestation of arterial, venous or small vessel thromboembolic events and/or foetal morbidity. Hereby, we present a case report of a patient with a large arterial thrombus originating from the ostium of the right coronary artery accompanied by multiple systemic embolization and right ventricular failure. As a bridge-to-recovery strategy, an extracorporeal right ventricular assist device was successfully applied, representing an effective first choice option in selected patients with isolated acute right heart failure.

Routine aortic valve replacement followed by a myriad of complications: role of 3D printing in a difficult cardiac surgical case

Aortic valve replacement (AVR) is a routine cardiac surgical intervention that is rarely associated with severe complications. In this report, we present a complex and unique case following AVR in a middle-aged woman. We show the growing necessity for a strong cooperation between interventional cardiologists and cardiac surgeons, together with the emerging role of cardiac tomography based three-dimensional printing technique in planning and executing precision surgery within the chest.

Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

BackgroundA solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour.Case presentationA 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The echocardiographic examination revealed pericardial effusion and an inhomogeneous mobile mass located in the pericardial sac around the left ventricle. Cardiac magnetic resonance (MRI) examination showed an intrapericardial, semilunar-shaped mass attached to the pulmonary trunk with an intermediate signal intensity on proton density-weighted images and high signal intensity on T2-weighted spectral fat saturation inversion recovery images. First-pass perfusion and early and late gadolinium-enhanced images showed a vascularized mass with septated, patchy, inhomogeneous late enhancement. Coronary computed tomography angiography revealed no invasion of the coronaries. Based on the retrospectively analysed screening chest X-rays, the mass had started to form at least 7 years earlier. Complete resection of the tumour with partial resection of the pulmonary trunk was performed. Histological evaluation of the septated, cystic mass revealed tumour cells forming an irregular patternless pattern; immunohistochemically, the cells tested positive for vimentin, CD34, CD99 and STAT6 but negative for keratin (AE1-AE3), CD31 and S100. Thus, the diagnosis of an intrapericardial solitary fibrous tumour was established. There has been no recurrence for 3 years based on the regular MRI follow-up.ConclusionIntrapericardial SFTs, showing slow growth dynamics, can present with massive extent even in completely asymptomatic patients. MRI is exceedingly useful for characterizing intrapericardial masses, allowing precise surgical planning, and is reliable for long-term follow up.

Szívtranszplantáció és műszívkezelés költséghatékonysági elemzési modellje

Absztrakt A szivtranszplantacio kiemelt projekt lett a Semmelweis Egyetemen belul. Ennek megfelelően a szivatultetes es a mechanikus keringestamogatas finanszirozasa is rendkivuli jelentőseget kapott. A szerzők a transzplantacios es műszives betegek koltsegeinek osszehasonlitasarol vegzett koltseghatekonysagi szamitasi modell felepiteseről szamolnak be. A modell megalkotasanal direkt allokacios koltsegszamitast, dontesifa-modellt, inkrementalis koltseghatekonysagi ratat es koltseghatekonysagi terkepmodszert hasznaltak. Modszerukkel ossze tudjak hasonlitani a műszivbeultetesen atesett es a szivtranszplantacios betegcsoportok kezdeti, perioperativ es utokezelesi koltsegeit. Modelljuk alkalmas lehet hosszu tavu utankovetes es kellő elemszamu beteg bevonasaval koltseghatekonysagi elemzesek elkeszitesere, gazdasagi dontestamogato kovetkeztetesek meghozatalara.