Advent of severe mitral regurgitation in surgical ventricular restoration and ventricular septal rupture repair.

BACKGROUND: Per-procedural severe mitral regurgitation is a rare complication in concomitant surgical ventricular restoration and postinfarction ventricular septal rupture repair. It is challenging to discover the underlying etiology and adopt an appropriate strategy, in particular, in a high-risk patient. CASE PRESENTATION: Semi-emergent surgical ventricular restoration combined with ventricular septal rupture closure and coronary artery bypassing was performed in a 67-year-old male patient. Severe mitral regurgitation was detected after the weaning of cardiopulmonary bypass. Two key questions arose in the management of this condition: did the regurgitation exist previously and was dissimulated by significant left-to-right shunt, or it occurred secondarily to the Dor procedure? Which was the better management strategy, chordal-sparing mitral valve replacement or mitral plasty? We believed that severe mitral regurgitation was under-estimated pre-operatively and we performed an downsizing annuloplasty to treat mitral regurgitation. The outcomes were promising and the patient did well in follow-up. CONCLUSIONS: Our case brought out an open discussion on the etiology and therapeutic strategies of this complicated condition.

Hydroxychloroquine is effective in oral lichen planus: A multicenter, randomized, controlled trial.

OBJECTIVES: This study was aimed to evaluate the safety and benefit of short-term application of hydroxychloroquine in the management of atrophic/erosive/ulcerative oral lichen planus (OLP). METHODS: This multicenter, randomized, controlled, evaluator-blinded, prospective clinical trial was performed from October 1, 2019, to September 1, 2022. A total of 99 patients were randomized to receive systemic use of hydroxychloroquine (n = 50), or topical use of 0.05% dexamethasone (n = 49) for 4 weeks. The response to both treatment modalities was evaluated according to reticulation, hyperemic, and ulceration (RHU) score and visual analog scale (VAS) score. RESULTS: After 4 weeks of medication, both groups showed substantial reduction in RHU and VAS score (p < 0.05). In hydroxychloroquine group, the average of RHU score was reduced from 10.60 to 7.68 (dropped 27.49%), and the average of VAS score was reduced from 3.74 to 2.47 (dropped 34.09%). There were no differences between the two groups in reduction of RHU score and VAS score (p > 0.05). Single factor analysis found hyperemic area (p = 0.019) and erosive/ulcerative area (p = 0.024) had impacts on drug efficacy of hydroxychloroquine, and logistic regression revealed that no factors (p > 0.05) influenced its efficacy. CONCLUSION: These findings indicate hydroxychloroquine is a safe and effective agent in treating atrophic/erosive/ulcerative OLP.

Fifteen-Year Outcomes After Valve-Sparing Aortic Root Remodelling or Exclusion of the Non-Coronary Sinus: When to Preserve the Sinuses of Valsalva?

BACKGROUND: Isolated exclusion of the non-coronary sinus (NCS) is an attractive strategy in valve-sparing aortic root surgery, which avoids the mobilisation and re-implantation of coronary ostia. However, the long-term durability of aortic valve repair and the fate of remnant sinuses of Valsalva remain unclear. METHOD: From January 2006 to December 2013, 29 patients underwent replacement of the ascending aorta extending to the NCS (group NCS) and 56 patients underwent a modified Yacoub procedure (group MY) in our centre by a single surgeon. Significant difference of preoperative parameters was observed between two groups in the presence of bicuspid aortic valve (41.4% vs 12.5%, p=0.002) and the diameter of the sinus of Valsalva (47.3±4.7 mm vs 51.5±4.9 mm, p=0.01). RESULTS: The group NCS, as compared to the group MY, was associated with significantly shorter cardiopulmonary bypass time (106.6±40.5 min vs 138.4±37.5 min, p=0.001) and aortic cross clamping time (69.0±21.8 min vs 105.4±27.8 min, p<0.01). The mean follow-up was 11.5±2.8 years. No surgical re-intervention was performed for aortopathies of the aortic root; the neo-sinus were not dilated in either groups (38.2±4.2 mm vs 34.0±4.0 mm, p<0.01). The 10-year freedom from aortic valve-related re-operation was estimated to be 96.6±3.4% and 94.5±3.1% (p=0.58), and the cumulative 10-year survival rates were 95.2±4.6% and 85.6±4.7% (p=0.61) in the group NCS and the group MY, respectively. CONCLUSIONS: Aortic valve-sparing isolated NCS replacement can be safely performed in selected patients; its early outcomes, overall survival and long-term freedom from aortic valve-related or aortopathy-related re-intervention were comparable to those obtained with the Yacoub procedure.

Fifteen-Year Outcomes Following Valve-Sparing Aortic Root Replacement in Elderly Patients.

BACKGROUND: Valve-sparing aortic root replacement (VSRR) techniques have several advantages such as preservation of physiological haemodynamics of the native aortic valve and avoidance of prosthetic valve-related complications. However, VSRR procedures are generally performed in young patients and the long-term results in elderly patients (≥65 years) are scarce. METHODS: Fifty-six (56) consecutive patients underwent VSRR surgery by a single surgeon at the current centre between January 2006 and December 2013; a modified "remodelling technique" was typically performed. The mean age was 58.86±12.5 years; Marfan syndrome and bicuspid aortic valve were both present in six patients (10.7%); 38 patients (67.8%) presented with greater than moderate aortic regurgitation; and 17 patients (30.4%) were in New York Heart Association (NYHA) class III before surgery. They were divided into two groups according to their ages receiving VSRR surgery: Group E (elderly patients aged ≥65 years, n=24) and Group Y (young patients aged <65 years, n=32). The primary outcomes were aortic valve-related reoperation, cardiovascular reoperation, all-cause mortality, and functional status. RESULTS: One (1) patient in Group E was converted to aortic valve replacement as a result of a failed aortic valve repair. No perioperative mortality was observed. The mean follow-up was 11.5±2.9 years. Aortic valve-related reoperation was noted in two patients of each group (one with endocarditis, one with severe aortic regurgitation). Cardiovascular reoperations were observed in three and six patients, and all-cause deaths in seven and two patients in Group E and Group Y, respectively. The 10-year freedom from aortic valve-related reoperation was estimated to be 91.7±5.6% and 92.7±5.0% (p=0.594), the 10-year freedom from cardiovascular reoperation was 86.4±7.3% and 81.1±7.7% (p=0.781), and the cumulative 10-year survival rates were 74.0±9.2% and 93.8±4.3% (p=0.018) in Group E and Group Y, respectively. During follow-up, 6.7% of patients were in NYHA class III and 6.4% of patients developed moderate-to-severe aortic regurgitation. Cox regression analysis failed to identify predictors for primary outcomes. CONCLUSION: Valve-sparing aortic root replacement can safely be performed in elderly patients with low early mortality and satisfactory long-term freedom from aortic valve-related and cardiovascular re-intervention.

The role of mechanical stimuli in the vascular differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are among the most promising and suitable stem cell types for vascular tissue engineering. Substantial effort has been made to differentiate MSCs towards vascular cell phenotypes, including endothelial cells and smooth muscle cells (SMCs). The microenvironment of vascular cells not only contains biochemical factors that influence differentiation, but also exerts hemodynamic forces, such as shear stress and cyclic strain. Recent evidence has shown that these forces can influence the differentiation of MSCs into endothelial cells or SMCs. In this Commentary, we present the main findings in the area with the aim of summarizing the mechanisms by which shear stress and cyclic strain induce MSC differentiation. We will also discuss the interactions between these mechanical cues and other components of the microenvironment, and highlight how these insights could be used to maintain differentiation.

Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin-angiotensin-aldosterone system (RAAS) dysregulation.

The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), has had a dramatic negative impact on public health and economies worldwide. Recent studies on COVID-19 complications and mortality rates suggest that there is a higher prevalence in cardiovascular diseases (CVD) patients. Past investigations on the associations between pre-existing CVDs and susceptibility to coronavirus infections including SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), have demonstrated similar results. However, the underlying mechanisms are poorly understood. This has impeded adequate risk stratification and treatment strategies for CVD patients with SARS-CoV-2 infections. Generally, dysregulation of the expression of angiotensin-converting enzyme (ACE) and the counter regulator, angiotensin-converting enzyme 2 (ACE2) is a hallmark of cardiovascular risk and CVD. ACE2 is the main host receptor for SARS-CoV-2. Although further studies are required, dysfunction of ACE2 after virus binding and dysregulation of the renin-angiotensin-aldosterone system (RAAS) signaling may worsen the outcomes of people affected by COVID-19 and with preexisting CVD. Here, we review the current knowledge and outline the gaps related to the relationship between CVD and COVID-19 with a focus on the RAAS. Improved understanding of the mechanisms regulating viral entry and the role of RAAS may direct future research with the potential to improve the prevention and management of COVID-19.

Transverse isotropic modelling of left-ventricle passive filling: Mechanical characterization for epicardial biomaterial manufacturing.

Biomaterials applied to the epicardium have been studied intensively in recent years for different therapeutic purposes. Their mechanical influence on the heart, however, has not been clearly identified. Most biomaterials for epicardial applications are manufactured as membranes or cardiac patches that have isotropic geometry, which is not well suited to myocardial wall motion. Myocardial wall motion during systole and diastole produces a complex force in different directions. Membrane or cardiac patches that cannot adapt to these specific directions will exert an inappropriate force on the heart, at the risk of overly restricting or dilating it. Accurately characterizing the mechanical properties of the myocardial wall is thus essential, through analysis of muscle orientation and elasticity. In this study, we investigated the Hertz contact theory for characterizing cardiac tissue, using nanoindentation measurements to distinguish different patterns in the local myocardium. We then evaluated the predictive accuracy of this model using Finite Element Analysis (FEA) to mimic the diastolic phase of the heart. Our results, extracted from instrumented nanoindentation experiments in a liquid environment using five pig hearts, revealed variations in elasticity according to the local orientation of the myocardial tissue. In addition, applying the Finite Element Method (FEM) in our model based on transverse isotropy and local tissue orientation proved able to accurately simulate the passive filling of a left ventricle (LV) in a representative 3D geometry. Our model enables improved understanding of the underlying mechanical properties of the LV wall and can serve as a guide for designing and manufacturing biomedical material better adapted to the local epicardial tissue.

Outbreak of SARS-CoV-2: challenge for diagnosis and medical management in patients with left ventricular assist device: a case series.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) exposes vulnerable patients to high risk of mortality. Patients with left ventricular assist device (LVAD) usually have symptoms such as cough, fever, and shortness of breath because of their cardiac condition and comorbidity, therefore these related symptoms challenge the correct diagnosis in time within the COVID-19 pandemic. CASE SUMMARY: We report two case studies of patients with LVAD in whom COVID-19 related symptoms were overlapped by their cardiac status and comorbidities. In the first case, the patient was admitted for suspicion of COVID-19 due to cough and shortness of breath for 1 month. The blood test evocated a high index of suspicion of COVID-19. The nasopharyngeal test for COVID-19 performed on admission and at Day 2 was inconclusive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the test obtained on Day 3 of admission was positive, whereas computed tomography confirmed the diagnosis of COVID-19. This patient developed acute respiratory distress syndrome (ARDS) and nasal epistaxis within 48 h during hospitalization. The ARDS was treated by non-invasive ventilation and probabilistic antibiotics for 3 days and resulted significant improvement. The nasal epistaxis due to international normalized ratio increase was treated by nasal packing and vitamin K antagonist was switched to parenteral heparin infusion. The patient was kept hospitalized for 1 month for further supportive treatment. In the second case, the patient was admitted for recurrent anaemia due to melaena, the patient was tested for COVID-19 because of new-onset symptoms of cough and rhinorrhoea. The first nasopharyngeal test was positive, and sudden increase of anticoagulation status was noted in the setting of gastrointestinal bleeding. The anticoagulation status was controlled by parenteral heparin infusion, and the melaena was disappeared at Day 3. The moderate dyspnoea of the patient was quickly improved with nasal oxygen delivery for 4 days. The patient was discharged at Day 5. DISCUSSION: COVID-19 specific symptoms are challenging to distinguish in patients with LVADs, although radiological evidence can be beneficial in the COVID-19 diagnosis. We also observed the need for precise anticoagulation control to avoid bleeding or thrombotic events in these patients.

Stem cell-based approaches in cardiac tissue engineering: controlling the microenvironment for autologous cells.

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms.

Isolated tricuspid valve surgery after congenital versus left heart-disease surgery: mid-term outcomes.

BACKGROUND: Left heart involvement might be a differential factor in the physiopathology and prognosis of severe tricuspid regurgitation (TR) following cardiac surgery. We aimed to compare the outcomes of isolated tricuspid valve surgery (ITVS) after congenital versus left heart-disease surgery. METHODS: We retrospectively studied and followed up 58 patients who underwent ITVS for TR following cardiac surgery in our center from January 2012 to December 2017. According to the different etiologies of TR, the participants were divided into one group of TR following surgery for congenital heart diseases (CHD) (pCHD group, n=24), and another group of TR following surgery for left heart disease (pVHD group, n=34). RESULTS: Compared to the pCHD group, the pVHD group presented with a more advanced age (P<0.001), higher model for end-stage liver disease (MELD) score calculation (P=0.04), and higher EuroSCORE II calculation (P=0.01). In the post-operative course, the pVHD group showed a longer mechanical ventilation time (P<0.001) and longer intensive care unit stay (P=0.001). However, there was no significant difference between the two groups in in-hospital mortality (8.8% vs. 0, P=0.26), or the incidence of major adverse cardiac and cerebrovascular events (MACCE) (20.6% vs. 12.5%, P=0.47) at follow-up. CONCLUSIONS: Severe TR following surgery for left heart disease is associated with higher surgical risks and a remarkable frailty as compared to that following surgery for CHDs; however, with the development of surgical techniques and peri-operative management, ITVS can be safely performed in both conditions with promising contemporary mid-term outcomes.

Chitosan ascorbate hydrogel improves water uptake capacity and cell adhesion of electrospun poly(epsilon-caprolactone) membranes.

The most important prerequisites for wound coverage matrices are biocompatibility, adequate porosity, degradability and exudate uptake capacity. A moderate hydrophilicity and exudate uptake capacity can often favour cell adhesion and wound healing potential, however, most of the synthetic polymers like polycaprolactone (PCL) are hydrophobic. Hydrogels based on natural polymers can improve the hydrophilicity and exudate uptake capacity of synthetic dressings and improve healing. In this work, we report the development of chitosan ascorbate-infiltrated electrospun PCL membranes. Our study demonstrated that chitosan ascorbate infiltration improves the hydrophilicity as well as water uptake capacity of the membranes and highly favoured the adhesion of human umbilical vein endothelial cells and human mesenchymal stem cells on the membranes.

Nanoceria Can Act as the Cues for Angiogenesis in Tissue-Engineering Scaffolds: Toward Next-Generation in Situ Tissue Engineering.

Next-generation tissue engineering exploits the body's own regenerative capacity by providing an optimal niche via a scaffold for the migration and subsequent proliferation of endogenous cells to the site of injury, enhancing regeneration and healing and bypassing laborious in vitro cell-culturing procedures. Such systems are also required to have a sufficient angiogenic capacity for the subsequent patency of implanted scaffolds. The exploitation of redox properties of nanodimensional ceria (nCeO2) in in situ tissue engineering to promote cell adhesion and angiogenesis is poorly investigated. As a novel strategy, electrospun polycaprolactone based tissue-engineering scaffolds loaded with nCeO2 were developed and evaluated for morphological and physicomechanical features. In addition, in vitro and in vivo studies were performed to show the ability of nCeO2-containing scaffolds to enhance cell adhesion and angiogenesis. These studies confirmed that nCeO2-containing scaffolds supported cell adhesion and angiogenesis better than bare scaffolds. Gene-expression studies had shown that angiogenesis-related factors such as HIF1α and VEGF were up-regulated. Overall results show that incorporation of nCeO2 plays a key role in scaffolds for the enhancement of angiogenesis, cell adhesion, and cell proliferation and can produce a successful outcome in in situ tissue engineering.

Hydrogen peroxide biosensor based on chitosan/2D layered double hydroxide composite for the determination of H2O2.

The composites (LDH-CMC) composed of carboxymethyl chitosan (CMC) and 2D ZnAl layered double hydroxide (LDH) were successfully prepared using the one-step urea method; these composites were characterized by XRD, FT-IR, UV-vis DRS, SEM, BJH/BET, TG-DTG and pHzpc analyses, cyclic voltammetry, and electrochemical impedance spectroscopy. The use of CMC could impact the textural and surface chemical properties of the LDH-CMC composites, where the composites still maintained the 2D layered structure. Incorporating a moderate amount of CMC could increase both the surface area and the permanent charge density of the composites, leading to improved electrochemical performances. The LDH-CMC composite was used as a support matrix for the immobilization of horseradish peroxidase (HRP) on the glass carbon (GC) electrode to construct a biosensor that provides a biocompatible microenvironment for HRP and a pathway for H2O2 diffusion via the high surface area. The HRP biosensor displayed a satisfactory sensitivity and fast response (<3 s) toward H2O2 over a wide linear range of 0.02-6.0 mmol·L-1 with a low detection limit of 12.4 µmol·L-1, good anti-interference ability and long-term storage stability. The proposed HRP biosensor was found to be a sensitive, rapid, and disposable sensor with low cost, easy preparation and high selectivity; thus, the proposed biosensor can be used for the real-time detection of trace H2O2 in the biological, clinical and environmental fields.

Human-derived extracellular matrix from Wharton's jelly: An untapped substrate to build up a standardized and homogeneous coating for vascular engineering.

One of the outstanding goals in tissue engineering is to develop a natural coating surface which is easy to manipulate, effective for cell adhesion and fully biocompatible. The ideal surface would be derived from human tissue, perfectly controllable, and pathogen-free, thereby satisfying all of the standards of the health authorities. This paper reports an innovative approach to coating surfaces using a natural extracellular matrix (ECM) extracted from the Wharton's jelly (WJ) of the umbilical cord (referred to as WJ-ECM). We have shown by atomic force microscopy (AFM), that the deposition of WJ-ECM on surfaces is homogenous with a controllable thickness, and that this easily-prepared coating is appropriate for both the adhesion and proliferation of human mesenchymal stem cells and mature endothelial cells. Furthermore, under physiological shear stress conditions, a larger number of cells remained adhered to WJ-ECM than to a conventional coating such as collagen - a result supported by the higher expression of both integrins α2 and ß1 in cells cultured on WJ-ECM. Our data clearly show that Wharton's jelly is a highly promising coating for the design of human biocompatible surfaces in tissue engineering as well as in regenerative medicine. STATEMENT OF SIGNIFICANCE: Discovery and design of biomaterial surface are a hot spot in the tissue engineering field. Natural matrix is preferred to mimic native cell microenvironment but its use is limited due to poor resource availability. Moreover, current studies often use single or several components of natural polymers, which is not the case in human body. This paper reports a natural extracellular matrix with full components derived from healthy human tissue: Wharton's jelly of umbilical cord. Reconstituting this matrix as a culture surface, our easily-prepared coating provides superior biocompatibility for stem and mature cells. Furthermore, we observed improved cell performance on this coating under both static and dynamic condition. This novel human derived ECM would be a promising choice for regenerative medicine.

Human umbilical cord derived matrix: A scaffold suitable for tissue engineering application.

BACKGROUND: Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. OBJECTIVE: We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. METHODS: An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. RESULTS: The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. CONCLUSION: We developed a new matrix derived from human source that can be further used in tissue engineering.