Induced erotomania by online romance fraud - a novel form of de Clérambault's syndrome.

BACKGROUND: Although the impact of internet usage on mental health is extensively documented, there is a notable scarcity of reports in the literature concerning internet-induced erotomania. Erotomania is a rare and likely underdiagnosed delusional disorder. It is characterized by an irrational belief held by the affected persons that someone of higher socioeconomic status harbor romantic feelings toward them. Here, we describe the psychopathology of erotomanic delusion induced by online romantic fraud in a female patient. Employing this case as a focal point, we illuminate novel aspects of erotomania that warrant attention and examination. CASE PRESENTATION: We present a compelling case involving a 70-year-old married Caucasian woman diagnosed with medically controlled persistent depressive disorder for several years. The intricacies of her condition became evident as she became deeply engrossed in online profiles featuring the image of a renowned musician, inadvertently falling victim to an online romantic fraud. Subsequently, this distressing experience triggered the emergence of erotomanic delusions and a suicide attempt. The patient's history reveals an array of medical conditions and stressful life events, contributing to her vulnerability. The diagnosis of erotomanic delusional disorder, dysthymia, and mild cognitive impairment with cerebral vascular background was established. Treatment involved her previous antidepressant with low-dose risperidone, alongside supportive individual and group therapy. Her delusion showed remission four weeks later, prompting her discharge for outpatient follow-up. Although she retained some false beliefs, the intensity of the symptoms had notably diminished and her functionality improved. CONCLUSION: This case underscores the complex interplay between mental health, online activities, and the consequences of delusions, including suicidal thoughts, shedding light on the need for a comprehensive approach in addressing such challenging psychiatric scenarios.

[Predictive factors for treatment failure of post-sternotomy wound infections]. / A poststernotomiás sebfertozések kezelési sikertelenségének prediktív faktorai.

INTRODUCTION AND AIM: Post-sternotomy wound infection is still a major concern and it affects morbidity, mortality, and hospital costs. Reconstruction failure may further increase these risks with significant financial implications. METHOD: Here, we attempted to verify some factors that may significantly influence the success of the surgical treatment. We performed a single-center retrospective analysis of data from 3177 consecutive patients who underwent midline sternotomy. The diagnostic signs of post-sternotomy wound infections were observed in 60 patients (1.9%). These data were thoroughly analyzed. RESULTS: Beside late diagnosis, the positive microbiological culture of the wounds, radical surgical intervention and peripheral vascular disease were found to significantly contribute to the development of surgical reconstruction failure. Radical surgical reconstruction was associated with a higher success rate (81.8 vs. 11.1%), p<0.001. CONCLUSION: Identification of the predictive factors that may lead to treatment failure can assist in developing treatment algorithms and improving the success rates of surgical reconstructions. Orv Hetil. 2018; 159(14): 566-570.

Incisional negative pressure wound therapy in reconstructive surgery of poststernotomy mediastinitis.

The efficacy of negative pressure wound therapy in the treatment of poststernotomy mediastinitis has been revealed in many reports. The present retrospective observational study examined the efficacy of incisional negative pressure wound therapy in the reconstructive surgery of poststernotomy mediastinitis. We retrospectively examined 1034 consecutive patients, who underwent median sternotomy in the period between October 2013 and September 2015. Mediastinitis developed in 21 patients (2%), who subsequently underwent surgical reconstruction. We applied incisional negative pressure wound therapy (iNPWT) after primary closure of the wound over redon drains in ten patients (iNPWT + redon group). In 11 patients, only redons were used (redons only group). We observed the time between the introduction and removal of redon drains, hospital stay until final wound closure and the rate of failure of treatment. Failure of treatment is defined as the need for further surgical reconstruction. In the iNPWT + redon group, the duration of redon drainage therapy was 6·9 ± 5·2 days versus 13·36 ± 11·58 in the redons only group. Hospital stay was 11·4 ± 8·6 versus 101·64 ± 89·2, and failure of treatment was 10% versus 45·5%, respectively. The primary results of this study appear to support the beneficial effect of iNPWT after radical wound reconstruction.

Myocardial viability and survival in ischemic left ventricular dysfunction.

BACKGROUND: The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain. METHODS: In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of prespecified thresholds. RESULTS: Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P=0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P=0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P=0.53). CONCLUSIONS: The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone. (Funded by the National Heart, Lung, and Blood Institute; STICH ClinicalTrials.gov number, NCT00023595.).

Severe mitral regurgitation and heart failure due to caseous calcification of the mitral annulus.

Caseous calcification is a rare form of mitral annular calcification. Echocardiography reveals an echodense mass in the inferior mitral annulus with smooth borders and an echolucent inner core. We present a case where caseous calcification of the mitral annulus caused severe mitral regurgitation, atrial fibrillation and heart failure. Transthoracic echocardiography, transesophageal echocardiography, cardiac magnetic resonance and computed tomography were performed and ensured the diagnosis. The mass was surgically removed and a prosthetic valve was implanted. We conclude that caseous calcification of the mitral annulus should be considered not only in the differential diagnosis of cardiac masses but also in the background of mitral regurgitation, atrial fibrillation and heart failure. This case also represents the usefulness of multimodal imaging in identifying cardiac masses.

[Endoscopic harvesting of saphenous vein during coronary artery bypass operations]. / A vena saphena magna endoszkópos kivétele coronaria-bypassmutétek során.

UNLABELLED: The great saphenous vein is the most commonly applied conduit in coronary bypass surgery during the treatment of ischaemic heart disease. Regarding the increasing age of patients, multiple comorbid factors and poor patient's general state, the minimally invasive approach is of basic significance during these operations. OBJECTIVES: The aim of study was to evaluate the possibilities of endoscopic saphenous vein harvesting and the quality of saphenous veins harvested endoscopically. METHODS: The authors applied the endoscopic approach for saphena harvesting in 24 patients undergoing coronary bypass surgery or combined bypass surgery with valve reconstruction. Ten of the harvested veins were sent for histologic examination to evaluate the structure of the endothelial layer. RESULTS: No wound complications were noted with the endoscopic approach. The harvested veins were used as conduits during surgery except for 2 cases, where the calibre of the vein was too small to apply. The histologic examination revealed normal structure of the endothelial layer in all of the 10 cases. CONCLUSION: The endoscopic approach can be used in the harvesting of saphenous vein during coronary bypass surgery. For the time being, the apply of this approach is restricted by the longer operation time, which hopefully would be reduced in the future.

[Late postinfarction rupture of the interventricular septum]. / Késoi posztinfarktusos kamrai septumdefektus.

UNLABELLED: Postinfarction ventricular septal rupture complicates 1 to 2% of cases of acute myocardial infarction and accounts for 5% of early mortality. This severe complication usually occurs within two weeks after acute myocardial infarction, and the elderly are more susceptible. We present a case of late rupture of the septum. CASE REPORT: In a 75-year-old man, a ventricular septal defect developed more than two months after an extensive inferoseptal myocardial infarction due to occlusion of the right coronary artery. After more than two months of no symptoms he was referred to hospital due to symptoms of right ventricle failure. The diagnosis was made by echocardiography, pulmonary artery catheterization and ventriculography. Coronarography was also performed. Intraaortic balloon pump was introduced and the patient was transferred to the operating room. The defect was repaired using a circular polytetrafluoroethylene patch supported by buttressed interrupted sutures from both sides. Due to significant mitral valve regurgitation mechanical bileaflet mitral valve was implanted with preservation of the entire mitral apparatus and the left descending artery was revascularized using a saphenous graft. CONCLUSION: This case is reported to emphasize that later postinfarction rupture of the ventricular septum may occur with symptoms of right ventricle failure dominating the clinical course.

Xiphoid-sparing midline sternotomy reduces wound infection risk after coronary bypass surgery.

BACKGROUND: Because of its advantages, full midline sternotomy has remained the main approach for cardiac surgery. However, the development of post-sternotomy wound infections is its primary disadvantage. We evaluated the impact of xiphoid process (XIP)-sparing midline sternotomy regarding reducing the risk of deep sternal wound infections (DSWIs). METHODS: Data from 446 patients who underwent coronary artery bypass grafting by one surgeon, from January 2007 through May 2017, were retrospectively analyzed. Patients were divided into preliminary (from 2007-2011; n=202) and contemporary (January 2012-May 2017; n=244) groups. Traditional midline sternotomy was performed in the preliminary group, while xiphoid-sparing midline sternotomy was performed in the contemporary group. To adjust for differences in baseline and operative characteristics, the inverse probability of treatment weighting (IPTW) was applied. The generalized linear model was used to compare xiphoid-sparing and conventional sternotomy regarding the development of sternal wound infections. RESULTS: The sternal infection rates were 0.8% and 4.5% in the xiphoid-sparing and standard sternotomy groups, respectively (P=0.014). After adjustment for the IPTW, the xiphoid-sparing group showed a decreased risk for DSWIs (odds ratio 0.171, 95% confidence interval, 0.036-0.806, P=0.026) compared to the traditional sternotomy group. CONCLUSIONS: XIP-sparing midline sternotomy may be an alternative approach in coronary artery bypass surgery and seemed to reduce the risk of post-sternotomy wound infections in this study.

Is sternal rewiring mandatory in surgical treatment of deep sternal wound infections?

BACKGROUND: Deep sternal wound infections (DSWIs) are a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. We compared treatment outcomes after conventional sternal rewiring and reconstruction with no sternal rewiring in patients with a sternal wound infection. METHODS: We retrospectively enrolled patients who developed a DSWI after an open-heart procedure with median sternotomy at the Department of Cardiac Surgery, at the St. Rafael Hospital, Zalaegerszeg, Hungary, between 2012 and 2016. All patients received negative pressure wound and antibiotic therapy before surgical reconstruction. Patients were divided into groups determined by the reconstruction technique and compared. Subjects were followed up for 12 months, and the primary end-points were readmission and 90-day mortality. RESULTS: Among 3,177 median sternotomy cases, 60 patients developed a DSWI, 4 of whom died of sepsis before surgical treatment. Fifty-six patients underwent surgical reconstruction with conventional sternal rewiring (23 cases, 41%) or another interventions with no sternal refixation (33 cases, 59%). Eighty-one percent of sternal wound infections followed coronary bypass surgery (alone or combinated with another procedures), and 60% were diagnosed after hospital discharge. Staphylococcus aureus was cultured in 30% of all wounds and, 56.5% of cases reconstructed by sternal rewiring vs. 26.5% with no sternal rewiring, (P=0.022). Hospital readmission occurred in 63.6% of the sternal rewiring group vs. 14.7% of the no sternal rewiring group. The rate of death before wound healing or the 90th postoperative day was 21.7% in the sternal rewiring group vs. 0% in the no sternal rewiring group. The median hospital stay was longer in the sternal rewiring group than in the other group (51 vs. 30 days, P=0.006). CONCLUSIONS: Sternal rewiring may be associated with a higher rate of treatment failure than other forms of treatment for sternal wound infections.

Impact of Test Conditions on ADP-Induced Platelet Function Results With the Multiplate Assay: Is Further Standardization Required?

BACKGROUND: Platelet function testing was suggested to help tailor P2Y12-inhibitor therapy; however, the lack of proper standardization is still a limitation. METHODS: In a prospective study, we enrolled clopidogrel-treated and P2Y12-inhibitor naive patients to investigate the influence of (1) time from blood collection, (2) stability of the stored Adenosine diphosphate (ADP) reagent, and (3) the use of enoxaparin on results of the Multiplate assay. Measurements were performed from samples kept for 0, 30, 60, 120, and 240 minutes at room temperature before processing. To determine the impact of the reagent stability, freshly thawed ADP was compared with ADP kept for 3 to 5 or 8 to 13 days at 2°C to 8°C. Finally, samples containing enoxaparin at therapeutic or prophylactic doses were compared with enoxaparin-free blood. RESULTS: A total of 180 measurements were performed. ADP-stimulated platelet reactivity values decreased significantly over time (67 ± 40 U to 68 ± 37 U to 58 ± 37 U to 45 ± 33 U to 35 ± 33 U; P < .0001). Consequently, a dramatic reduction was observed in the proportion of patients with high platelet reactivity ( P < .0001). A significant drop in platelet reactivity was observed with ADP stored for 8 to 13 days as compared to freshly thawed ADP ( P = .011). Enoxaparin triggered a slight, concentration-dependent increase in platelet reactivity ( P < .05). CONCLUSION: Test conditions may have profound impacts on the obtained results with the Multiplate assay. Our findings highlight the large influence of the time from sample collection until testing, suggesting that measurements should be performed within an hour of blood collection.

Is cold blood cardioplegia absolutely superior to cold crystalloid cardioplegia in aortic valve surgery?

BACKGROUND: Experimental evidence suggests that blood cardioplegia (BCP) may be superior to cold crystalloid cardioplegia (CCP) for myocardial protection. However, robust clinical data are lacking. We compared postoperative outcome of patients undergoing aortic valve replacement (AVR) using cold anterograde-retrograde intermittent BCP versus anterograde (CCP). METHODS: Adult consecutive isolated AVR performed between April 2006 and February 2011 at the Royal Infirmary Hospital of Edinburgh were retrospectively analyzed. The use of anterograde CCP was compared with that of intermittent anterograde-retrograde cold BCP. End points were intra-operative mortality, 30-day hospital re-admission, need for RBC or platelet transfusion, mechanical ventilation time and renal failure. RESULTS: Of total 774 cases analyzed, 592 cases of BCP and 182 cases of CCP were identified. Demographics did not differ between groups (mean age: 67±12 years in CCP and 69±12 years in BCP). Groups (BCP vs. CCP) were indistinguishable (P>0.05, not significant) based on: average aortic cross clamp time 77.01±14.47 vs. 75.78±18.78 minutes, cardiopulmonary bypass time 104.07±43.70 vs. 100.34±25.90 minutes, surgery time 190.53±61.80 vs. 204.04±51.09 minutes and postoperative total blood consumption 1.38±2.11 vs. 1.61±2.4 units. The percentage of patients who required platelets' transfusion was similar: 12.8% BCP and 18.7% CCP (Fisher's exact test, P=0.053). Prevalence of respiratory failure was lower in BCP than in CCP: 2.6% vs. 6.3% (P=0.028). Admission time (days) at ICU was 3.63± 21.90 in BCP and 3.07±8.04 in CCP (not significant). Intra-hospital mortality, 30-day hospital re-admission, renal failure, sepsis, wound healing and stroke did not differ between groups. CONCLUSIONS: BCP was strictly not superior to CCP in every aspect. In particular it was definitely not superior in terms of postoperative ventricular function. Our results question the absolute superiority of BCP over CCP in terms of hard outcomes. Likelihood of serious complications should be considered to improve risk profile of patients before choosing a cardioplegic solution.

Influence of dextran-70 on systemic inflammatory response and myocardial ischaemia-reperfusion following cardiac operations.

INTRODUCTION: Experimental studies have demonstrated that dextran-70 reduces the leukocyte-endothelium interaction, but clinical evidence is still lacking. Our objective was to justify the anti-inflammatory effect of dextran-70 following cardiac operations. METHODS: Forty patients undergoing coronary bypass surgery (n = 32) or aortic valve replacement (n = 8) were enrolled in this prospective, randomized, double-blind study. Two groups were formed. In group A (n = 20), dextran-70 infusion was administered at a dose of 7.5 ml/kg before the initiation of cardiopulmonary bypass and at a dose of 12.5 ml/kg after the cessation of cardiopulmonary bypass. Group B served as a control with identical amounts of gelatin infusion (n = 20). The plasma concentration of procalcitonin, C-reactive protein, IL 6, IL 6r, IL 8, IL 10, soluble endothelial leukocyte adhesion molecule-1, soluble intercellular adhesion molecule-1, cardiac troponin-I and various haemodynamic parameters were measured in the perioperative period. Multivariate methods were used for statistical analysis. RESULTS: In group A, lower peak (median) plasma levels of procalcitonin (0.2 versus 1.4, p < 0.001), IL 8 (5.6 versus 94.8, p < 0.001), IL 10 (47.2 versus 209.7, p = 0.001), endothelial leukocyte adhesion molecule-1 (88.5 versus 130.6, p = 0.033), intercellular adhesion molecule-1 (806.7 versus 1,375.7, P = 0.001) and troponin-I (0.22 versus 0.66, p = 0.018) were found. There was no significant difference in IL 6, IL-6r and C-reactive protein values between groups. Higher figures of the cardiac index (p = 0.010) along with reduced systemic vascular resistance (p = 0.005) were noted in group A. CONCLUSION: Our investigation demonstrated that the use of dextran-70 reduces the systemic inflammatory response and cardiac troponin-I release following cardiac operation. TRIAL REGISTRATION NUMBER: ISRCTN38289094.

[The etiology, differential diagnosis and therapy of pericardial effusion]. / A pericardialis folyadékok etiológiája, differenciáldiagnosztikája és terápiája.

Considerable etiologic factors may lead to the development of pathologic pericardial effusion. In many cases these factors remain unidentified, the fact which leads to difficulties in choosing the appropriate therapeutic strategy. The therapy of pericardial effusion associated with purulent pericarditis must be different than that effusion developed as a consequence of neoplasm or autoimmune disease. The cytological examination of the fluid and the hystological examination of the pericardial tissue play an important role in identifying the accurate etiologic diagnosis. In case of recurrent pericardial effusions, performing pericardioperitoneal, pericardiopleural shunt or pericardial window may be indicated. This palliative solution serves to prevent the development of pericardial tamponade and its haemodynamic consequences.

[Evaluation of the EuroSCORE model in the patient population of our department of cardiac surgery]. / A EuroSCORE-modell értékelése szívsebészeti osztályunk megoperált betegei között.

INTRODUCTION: The objective of current study is the evaluation of the accuracy and precision of EuroSCORE in the population of those patients undergone cardiac surgery in our department. MATERIAL AND METHODS: We have analyzed the data of 1839 consecutive patients who had their operations between 1/January 2003 and 31/December 2005. We have compared the mortality rates predicted preoperatively by additive and logistic EuroSCORE with the actual 30-day mortality figures. On statistical analysis the discriminative accuracy of the methods has been defined with the use of C-statistics. The calibration and precision of the methods have been checked by the Hosmer-Lemeshow statistics. RESULTS: The overall mortality rate in the above period was 3.3%. Additive and logistic EuroSCORE predicted 4.1 +/- 2.8 and 4.5 +/- 6.1%, consecutively. Based on the C-statistics the area below the Receiver Operating Characteristic curve has measured 0.699 (0.629-0.769) and 0.711 (0.642-0.779). The kappa 2 value for the Hosmer-Lemeshow statistics has proved 6.5 ( p = 0.475) and 12.5 ( p = 0.131). CONCLUSION: Logistic EuroSCORE has appropriate discriminative power and satisfactory precision, whilst the accuracy of additive EuroSCORE only comes near to the acceptable level, but at the same time it has an adequate calibration value. These results suggest that logistic EuroSCORE is more suitable for the preoperative risk assessment of these patients.

Total proximal anastomosis detachment after classical bentall procedure.

INTRODUCTION: Since its introduction in 1968, the Bentall procedure has been the primary surgical solution for aneurysms of the aortic root. However, many surgeons have reported serious procedural complications such as detachment of coronary ostia and pseudoaneurysm formation at anastomosis sites. Therefore, the Bentall procedure has undergone several modifications to eliminate those complications. Partial or total detachment of the proximal anastomosis is rarely reported. PRESENTATION OF CASE: We report a total detachment of the proximal anastomosis after a Bentall operation with emphasis on the possible practical mechanisms, which might have led to the development of this very rare complication. The diagnosis was confirmed at a routine follow up examination and urgent surgery was performed. We also report our operative solution and review other possible surgical solutions that might be considered in this setting. DISCUSSION: The Bentall procedure and its modifications continue to be considered the gold standard for treating aneurysms involving the aortic root. Various modifications can serve as optimal solutions for procedure-related complications. CONCLUSION: Surgeons performing the Bentall procedure must be familiar with all existing modifications because they are complementary to the original surgical procedure. In the absence of endocarditis left ventricle outflow tract elongation may be an acceptable surgical solution to deal with total detachment of the proximal anastomosis.

Using Na3PO4 to Enhance In vitro Animal Models of Aortic Valve Calcification.

BACKGROUND/OBJECTIVES: The pathogenesis of calcific aortic valvular disease (CAVD) involves an active inflammatory process of valvular interstitial cells (VICs) characterized by the activation of specific osteogenic signaling pathways and apoptosis. This process can be studied by analyzing certain molecular markers and gene expression pathways of spontaneous calcification. The purpose of our study is to investigate the role of sodium phosphate (Na3PO4) as a calcification promoter, with the aim of improving in vitro animal models for testing potential calcification inhibitors. MATERIALS AND METHODS: VICs were extracted from 6 healthy 6-month-old fresh porcine hearts by serial collagenase digestion. Quantitative polymerase chain reaction (qPCR) was used to quantify trans-differentiation of genes of interest during spontaneous calcification of VICs. Spontaneous calcification of VICs was increased by adding Na3PO4 (3 mM, pH 7.4). The degree of calcification was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. Additionally, the enzymatic activity of alkaline phosphatase (ALP) was measured by a kinetic assay. For statistical analysis we used SPSS and Microsoft Office Excel 2013. RESULTS: Porcine VICs calcify spontaneously with demonstrable calcium and collagen deposition. In this study we observed an increase of calcium and collagen deposition from day 0 to day 14 (calcium: 376%; P<0.001, collagen: 3553%; P<0.001). qPCR analysis of mRNA by day 14 showed the following results: α-actin, a marker of myoblast phenotype, was increased to 1.6-fold; P<0.001. Runx2, an osteoblast marker, rose to 1.3 fold; P<0.05, TGF-ß, a promoter of osteogenesis, increased to 3.2-fold; P<0.001, and RhoA, a regulator of nodular formation in myoblasts, increased to 4.5-fold; P<0.001, compared to their levels at day 0. RANKL mRNA and calponin did not change significantly. Treatment of porcine VICs with Na3PO4 (3 mM, pH 7.4) led to a marked increase in calcium deposition by day 14 (522%; P<0.001), and a significant increase in ALP activity by day 7 (228%; P<0.05). There were no significant changes in ALP activity between the groups by day 14. CONCLUSION: This study has demonstrated the upregulation of some specific molecules during spontaneous calcification of aortic VICs with an active increase of calcium, collagen and ALP activity. In this in vitro model it was possible to increase spontaneous VICs calcification with Na3PO4 (3 mM, pH 7.4) to a level in which inhibitors of calcification could be tested to identify a novel potential therapeutic strategy against calcific aortic stenosis.

Iatrogenic ventricular septal defect: A rare complication of surgical reconstruction of mitral paravalvular dehiscence.

INTRODUCTION: Iatrogenic ventricular septal defect is a rare complication after the surgical replacement of cardiac valves. Small defects may have no hemodynamic significance or remain unremarked at the end of the surgical procedure. Understanding of the valvular anatomy alone is not always enough to avoid such complications, especially in the hands of young surgeons. PRESENTATION OF CASE: We present a case of iatrogenic ventricular septal defect that developed early after the surgical closure of a hemodynamically significant mitral paravalvular leak. Although the patient's critical state did not allow surgical intervention and he died, we think the lessons drawn from this case could be helpful to avoid such horrible complications in the future. DISCUSSION: This case documents a rare disastrous complication after imperfect surgical closure of a mitral paravalvular leak. Despite the unfortunate end, in reporting this case we try to direct the light to the possible mechanisms that led to the development of this injury focusing on the embryological and anatomical background. CONCLUSION: Understanding the anatomical and embryological structure of the cardiac fibrotic skeleton should keep cardiac surgeons more vigilent in detecting iatrogenic ventricle septal defects before the development of a devastating hemodynamic state.

Denosumab could be a Potential Inhibitor of Valvular Interstitial Cells Calcification in vitro.

OBJECTIVE: Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-ß ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. We aimed to elucidate the effect of Denosumab in the process of spontaneous and induced calcification in an in vitro porcine valvular interstitial cells (VICs) model. MATERIALS AND METHODS: VICs were extracted from fresh porcine hearts by serial collagenase digestion. Spontaneous calcification of VICs was increased in vitro by adding Na3PO4 (3 mM, pH 7.4) and different concentrations (0.1, 1 and 10 ng/ml) of transforming growth factor beta (TGFß). The degree of calcification before and after treatment with Denosumab was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. For statistical analysis we used SPSS and Microsoft Office Excel 2013. RESULTS: Porcine aortic VICs in vitro were induced to calcify by the addition of either 3 mM Na3PO4, showing a 5.2 fold increase by 14 days (P<0.001), or 3 mM Na3PO4 + 10 ng/ml of TGFß, showing a 7 fold increase by Day 14 (P<0.001). Denosumab inhibited induced calcification by 3 mM Na3PO4 and 3 mM Na3PO4 with the addition of TGFß at either 0.1, 1 or 10 ng/ml to basal levels only at a concentration of 50 µg/ml (P<0.001). CONCLUSION: This study has proved that Denosumab could be a potential inhibitor of the calcification of VICs in vitro. A fuller understanding of the actions of Denosumab may identify a novel therapeutic strategy for clinical intervention against aortic valve calcification and aortic stenosis.

Cardiac Repair and Regeneration: The Value of Cell Therapies.

Ischaemic heart disease is the predominant contributor to cardiovascular morbidity and mortality; one million myocardial Infarctions occur per year in the USA, while more than five million patients suffer from chronic heart failure. Recently, heart failure has been singled out as an epidemic and is a staggering clinical and public health problem associated with significant mortality, morbidity and healthcare expenditures, particularly among those aged ≥65 years. Death rates have improved dramatically over the last four decades, but new approaches are nevertheless urgently needed for those patients who go on to develop ventricular dysfunction and chronic heart failure. Over the past decade, stem cell transplantation has emerged as a promising therapeutic strategy for acute or chronic ischaemic cardiomyopathy. Multiple candidate cell types have been used in preclinical animal models and in humans to repair or regenerate the injured heart, either directly or indirectly (through paracrine effects), including: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), neonatal cardiomyocytes, skeletal myoblasts (SKMs), endothelial progenitor cells, bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (MSCs) and, most recently, cardiac stem cells (CSCs). Although no consensus has emerged yet, the ideal cell type for the treatment of heart disease should: (a) improve heart function; (b) create healthy and functional cardiac muscle and vasculature, integrated into the host tissue; (c) be amenable to delivery by minimally invasive clinical methods; (d) be available 'off the shelf' as a standardised reagent; (e) be tolerated by the immune system; (f) be safe oncologically, i.e. not create tumours; and (g) circumvent societal ethical concerns. At present, it is not clear whether such a 'perfect' stem cell exists; what is apparent, however, is that some cell types are more promising than others. In this brief review, we provide ongoing data on agreement and controversy arising from clinical trials and touch upon the future directions of cell therapy for heart disease.