Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias

This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues.

Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.

Multifaceted relationship between diabetes and kidney diseases:Beyond diabete

Diabetes mellitus is one of the most common causes of chronic kidney disease.Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure.The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments,such as the vascular system and glomeruli.Glomerular alterations include thickening of the glomerular basement membrane,loss of podocytes,and segmental mesangiolysis,which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules.Beyond lesions directly related to diabetes,awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing.These nondiabetic lesions include focal segmental glomerulosclerosis,IgA nephropathy,and other primary or secondary renal disorders.Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches.However,the relationship between diabetes and the kidney is bidirectional;thus,new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases.Here,we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course,differential diagnosis,and therapeutic opportunities offered by novel drugs.

Is Takotsubo cardiomyopathy still looking for its own nosological identity?

Despite several efforts to provide a proper nosological framework for Takotsubo cardiomyopathy(TCM),this remains an unresolved matter in clinical practice.Several clinical,pathophysiologic and histologic findings support the conceivable hypothesis that TCM could be defined as a unique pathologic entity,rather than a distinct subset of myocardial infarction with non-obstructive coronary arteries.Further investigations are needed in order to define TCM with the most appropriate disease taxonomy.

Oral mucositis induced by risperidone:rare side effect of a frequently prescribed medication

Risperidone is a safe second-generation antipsychotic which is rarely associated with the emergence of a few adverse effects,such as oral lesions and stomatitis.We report the case of a 77-year-old woman affected by a neurocognitive disorder with psychotic features and treated with risperidone 2 mg/day.After 1 week,she showed a burning mouth syndrome with oral lesions and risperidone was discontinued.Antipsychotic-induced oral ulcerations may be caused by the reduction of saliva protection with minor adverse effects related to oral movement disorders or impairment of the bacterial flora of saliva.

Impact of leg bending in the patient-specific computational fluid dynamics of popliteal stenting

Endovascular treatment of the femoro-popliteal artery has recently become a valuable therapeutic option for popliteal arterial aneurysms.However,its efficacy remains controversial due to the relatively high rate of complications,such as stent occlusion as result of intra-stent thrombosis.The elucidation of the interplay among vessel geometrical features,local hemodynamics,and leg bending seems crucial to understand onset and progression of popliteal intra-stent thrombosis.To this aim,patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm by stent-grafts and experiencing intra-stent thrombosis.Both Newtonian and non-Newtonian blood rheological models were considered.Results were presented in terms of tortuosity,luminal area exposed to low(<0.4 Pa)and high(>1.5 Pa)time-averaged wall shear stress(TAWSS),area exposed to high(>0.3)oscillatory shear index(OSI),and flow helicity.Study outcomes demonstrated that leg bending induced significant hemodynamic differences(>50%increase)in both patients for all the considered variables,except for OSI in one of the two considered patients.In both leg configurations,stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity,low velocity,low helicity,low TAWSS,and high OSI;while the distal part has higher tortuosity,velocity,helicity,TAWSS,and lower OSI.Sensitivity study on applied boundary conditions showed that the different inlet velocity profiles for a given inlet waveform affect slightly the numerical solution;conversely,the shape and magnitude of the prescribed inlet waveform is determinant.Focusing on the comparison between the Newtonian and non-Newtonian blood models,the area with low TAWSS is greater in the Newtonian model for both patients,while no significant difference occurs between the surfaces with high TAWSS.

Correction to: Impact of leg bending in the patient-specific computational fluid dynamics of popliteal stenting

In the original publication of the article a fund note has not been displayed appropriately in the acknowledgment section.The missing fund note is updated in this correction.