Recommendations from the Association for European Paediatric and Congenital Cardiology for training in pulmonary hypertension

AbstractPulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.

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Therapeutic Approaches Targeting PAX3-FOXO1 and Its Regulatory and Transcriptional Pathways in Rhabdomyosarcoma

Molecules ◽

10.3390/molecules23112798 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2798 ◽

Cited By ~ 12

Author(s):

Thanh Hung Nguyen ◽

Frederic G. Barr

Keyword(s):

Skeletal Muscle ◽

Transcription Factor ◽

Young Adults ◽

Soft Tissue ◽

Chromosomal Translocation ◽

Murine Models ◽

Therapeutic Approaches ◽

Recent Developments ◽

Children And Young Adults ◽

Oncogenic Transcription Factor

Rhabdomyosarcoma (RMS) is a family of soft tissue cancers that are related to the skeletal muscle lineage and predominantly occur in children and young adults. A specific chromosomal translocation t(2;13)(q35;q14) that gives rise to the chimeric oncogenic transcription factor PAX3-FOXO1 has been identified as a hallmark of the aggressive alveolar subtype of RMS. PAX3-FOXO1 cooperates with additional molecular changes to promote oncogenic transformation and tumorigenesis in various human and murine models. Its expression is generally restricted to RMS tumor cells, thus providing a very specific target for therapeutic approaches for these RMS tumors. In this article, we review the recent understanding of PAX3-FOXO1 as a transcription factor in the pathogenesis of this cancer and discuss recent developments to target this oncoprotein for treatment of RMS.

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Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.558375 ◽

2020 ◽

Vol 8 ◽

Author(s):

Henry Ruiz-Garcia ◽

Keila Alvarado-Estrada ◽

Sunil Krishnan ◽

Alfredo Quinones-Hinojosa ◽

Daniel M. Trifiletti

Keyword(s):

Stem Cells ◽

Malignant Gliomas ◽

High Morbidity ◽

Therapeutic Approaches ◽

New Paradigm ◽

Current Standard ◽

Natural Properties ◽

Recent Developments ◽

Tumor Homing ◽

Antitumor Properties

Gliomas are a dismal disease associated with poor survival and high morbidity. Current standard treatments have reached a therapeutic plateau even after combining maximal safe resection, radiation, and chemotherapy. In this setting, stem cells (SCs) have risen as a promising therapeutic armamentarium, given their intrinsic tumor homing as well as their natural or bioengineered antitumor properties. The interplay between stem cells and other therapeutic approaches such as nanoparticles holds the potential to synergize the advantages from the combined therapeutic strategies. Nanoparticles represent a broad spectrum of synthetic and natural biomaterials that have been proven effective in expanding diagnostic and therapeutic efforts, either used alone or in combination with immune, genetic, or cellular therapies. Stem cells have been bioengineered using these biomaterials to enhance their natural properties as well as to act as their vehicle when anticancer nanoparticles need to be delivered into the tumor microenvironment in a very precise manner. Here, we describe the recent developments of this new paradigm in the treatment of malignant gliomas.

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Hallazgos oftalmológicos en enfermedad de Fabry: relación de su severidad en una familia mexicana

Latin american journal of clinical sciences and medical technology ◽

10.34141/ljcs4143209 ◽

2019 ◽

Vol 1 (1) ◽

pp. 43-49

Author(s):

Araceli Borja Borja ◽

Gabriela Salas Pérez ◽

Pablo Radillo Díaz

Keyword(s):

Premature Mortality ◽

Retinal Vessel ◽

Multiple Organ ◽

High Morbidity ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Non Invasive ◽

High Incidence ◽

Cornea Verticillata ◽

Gla Gene

Introduction. Fabry disease (FD) is a lysosomal storage disorder associated with multiple organ dysfunction which eventually leads to high morbidity and premature mortality. Ophthalmologic findings in FD are very common and have been described extensively. We describe the ophthalmologic findings of a family diagnosed with FD at Hospital de Especialidades de Puebla and establish their relationship with other phenotypic findings. Cases Presentation. A renal, cardiac, audiological, neurological, and ophthalmologic evaluation was carried out. The disease was confirmed by GLA gene sequencing. The ophthalmologic assessment was focused on the changes described in the literature, as well as the search for other anomalies possibly related to the disease. All the patients had the c.260delA (P.Glu87Glyfs*34) mutation in the GLA gene. The main ophthalmologic finding in our patients was cornea verticillata (in 100 % of the female patients). Other ophthalmologic manifestations were dry eye, retinal vessel tortuosity, ametropia, chromatic vision disorders, ocular annexes, eyelids, and conjuntiva disorders. Conclusions. Most of the assessed patients showed ophthalmologic changes, consistent with the results described in the literature. A remarkable finding in the sample was the high incidence of changes in women, in whom one would not expect the disease to be as severe because they are heterozygous. Ophthalmologic abnormalities in FD require deeper evaluation to establish their possible use as markers of disease progression and/or enzyme replacement therapy initiation due to the benefit of the non-invasive nature of ophthalmologic evaluations.

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Relationship between Invasive and Non-Invasive Hemodynamic Measures in Experimental Pulmonary Hypertension

Current Respiratory Medicine Reviews ◽

10.2174/1573398x16666200516180118 ◽

2020 ◽

Vol 16 (1) ◽

pp. 47-53

Author(s):

Vicente Benavides-Córdoba ◽

Mauricio Palacios Gómez

Keyword(s):

Heart Rate ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Right Ventricle ◽

Correlation Coefficient ◽

Pearson Correlation ◽

Systolic Pressure ◽

Control Group ◽

Pearson Correlation Coefficient ◽

Non Invasive

Introduction: Animal models have been used to understand the pathophysiology of pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal model. In this model, invasive and non-invasive hemodynamic variables that resemble human measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic measures in the monocrotaline-induced pulmonary hypertension model. Materials and Methods: Twenty 6-week old male Wistar rats weighing between 250-300g from the bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the relationships between invasive and non-invasive variables are sustained in different conditions (healthy, hypertrophy and treated). The animals were organized into three groups, a control group who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured. The functional relation between any two variables was evaluated by the Pearson correlation coefficient. Results: It was found that all correlations were statistically significant (p <0.01). The strongest correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other three variables studied, although with relatively low correlation. Conclusion: The correlations obtained in this study indicate that the parameters evaluated in the research related to experimental pulmonary hypertension correlate adequately and that the measurements that are currently made are adequate and consistent with each other, that is, they have good predictive capacity.

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FRI0152 PULMONARY HYPERTENSION IN NEWLY DIAGNOSED SPANISH PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM THE RELES COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4906 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 660.2-660

Author(s):

J. Álvarez Troncoso ◽

Á. Robles Marhuenda ◽

F. Mitjavila Villero ◽

F. J. García Hernández ◽

A. Marín Ballvé ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Pulmonary Hypertension ◽

Lupus Erythematosus ◽

Multivariable Analysis ◽

Systolic Pressure ◽

High Morbidity ◽

Inception Cohort ◽

Systemic Lupus ◽

Factors Associated ◽

Pulmonary Arterial

Background:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan involvement. Pulmonary hypertension (PH) is an uncommon manifestation with high morbidity and mortality whose characteristics, prevalence and evolution in SLE are not completely defined.Objectives:Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to to identify the factors associated with pulmonary hypertension (PH) in systemic lupus erythematosus (SLE).Methods:Prospective observational study on a multicenter Spanish inception cohort. Patients with SLE, diagnosed by the American College of Rheumatology (ACR) criteria, since January 2009, who had at least one transthoracic echocardiogram (TTE) performed were selected. Demographic data, diagnostic criteria, follow-ups, treatments and SLEDAI were analyzed.Results:Of 289 patients diagnosed with SLE with TTE performed, 15 (5.2%) patients were identified to have PH. Mean age was 56,9±7,7 years, of which 93,3% (14) were women and 80% (12) Caucasian. The ACR score at diagnosis was 4.66. Mean SLEDAI was 15. Only 5 patients had dyspnea at the time of diagnosis. Mean pulmonary arterial systolic pressure was 49.2±5.6 mmHg. Among the PH, 4 patients had pericarditis (26.6%), 3 (20%) valvulopathies (1 antiphospholipid syndrome), 1 patient pulmonary embolism and 1 shrinking lung. Multivariable analysis indicated that pericarditis (odds ratio (OR)=2.53), and valvulopathies (OR 8.96) were independently associated with the development of PH in SLE. Having PH was associated with older age at diagnosis (p<0.001), more dyspnea (p<0.001), higher ESR (p=0.007), more serositis (p<0.001), higher SLEDAI (p=0.011), higher SLICC (p <0.001), higher number of admissions (p=0.006) and higher mortality (p=0.003).Conclusion:PH in SLE is a serious comorbidity with high mortality. In the RELES cohort it was associated with increased disease activity, pericarditis and valvulopathies. Performing TTE in patients with SLE may favor early diagnosis and treatment.References:[1]Kim JS, Kim D, Joo YB, et al. Factors associated with development and mortality of pulmonary hypertension in systemic lupus erythematosus patients.Lupus. 2018;27(11):1769–1777.[2]Bazan IS, Mensah KA, Rudkovskaia AA, et al. Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.Respir Med. 2018;134:42–46.Disclosure of Interests:Jorge Álvarez Troncoso: None declared, Ángel Robles Marhuenda: None declared, Francesca Mitjavila Villero: None declared, Francisco José García Hernández: None declared, Adela Marín Ballvé: None declared, Antoni Castro Consultant of: Actelion pharmaceuticals, GSK, MSD., Gonzalo Salvador Cervelló: None declared, Eva Fonseca: None declared, Isabel Perales Fraile: None declared, Guillermo Ruiz-Irastorza: None declared

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Risk assessment in precapillary pulmonary hypertension: a comparative analysis

Respiratory Research ◽

10.1186/s12931-021-01624-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thomas Sonnweber ◽

Eva-Maria Schneider ◽

Manfred Nairz ◽

Igor Theurl ◽

Günter Weiss ◽

...

Keyword(s):

Risk Assessment ◽

Pulmonary Hypertension ◽

High Risk ◽

Risk Stratification ◽

Risk Prediction ◽

Mortality Risk ◽

Assessment Tool ◽

Risk Models ◽

Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

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Machine Learning and Radiomics Applications in Esophageal Cancers Using Non-Invasive Imaging Methods—A Critical Review of Literature

Cancers ◽

10.3390/cancers13102469 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2469

Author(s):

Chen-Yi Xie ◽

Chun-Lap Pang ◽

Benjamin Chan ◽

Emily Yuen-Yuen Wong ◽

Qi Dou ◽

...

Keyword(s):

Machine Learning ◽

Quantitative Imaging ◽

Risk Groups ◽

Review Of Literature ◽

Primary Tumors ◽

Non Invasive ◽

Significant Difference ◽

Recent Developments ◽

Health Significance ◽

Imaging Markers

Esophageal cancer (EC) is of public health significance as one of the leading causes of cancer death worldwide. Accurate staging, treatment planning and prognostication in EC patients are of vital importance. Recent advances in machine learning (ML) techniques demonstrate their potential to provide novel quantitative imaging markers in medical imaging. Radiomics approaches that could quantify medical images into high-dimensional data have been shown to improve the imaging-based classification system in characterizing the heterogeneity of primary tumors and lymph nodes in EC patients. In this review, we aim to provide a comprehensive summary of the evidence of the most recent developments in ML application in imaging pertinent to EC patient care. According to the published results, ML models evaluating treatment response and lymph node metastasis achieve reliable predictions, ranging from acceptable to outstanding in their validation groups. Patients stratified by ML models in different risk groups have a significant or borderline significant difference in survival outcomes. Prospective large multi-center studies are suggested to improve the generalizability of ML techniques with standardized imaging protocols and harmonization between different centers.

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Osteosarcoma: a review of current and future therapeutic approaches

BioMedical Engineering OnLine ◽

10.1186/s12938-021-00860-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xin Zhao ◽

Qirui Wu ◽

Xiuqing Gong ◽

Jinfeng Liu ◽

Yujie Ma

Keyword(s):

Bimodal Distribution ◽

Therapeutic Approaches ◽

Rapid Disease Progression ◽

New Ideas ◽

Degree Of Malignancy ◽

Primary Bone ◽

Children And Young Adults ◽

High Degree ◽

Single Lesion ◽

Tubular Bones

AbstractOsteosarcoma (OS) is the most common primary bone malignancy that affects children and young adults. OS is characterized by a high degree of malignancy, strong invasiveness, rapid disease progression, and extremely high mortality rate; it is considered as a serious threat to the human health globally. The incidence of OS is common in the metaphysis of long tubular bones, but rare in the spine, pelvis, and sacrum areas; moreover, majority of the OS patients present with only a single lesion. OS has a bimodal distribution pattern, that is, its incidence peaks in the second decade of life and in late adulthood. We examine historical and current literature to present a succinct review of OS. In this review, we have discussed the types, clinical diagnosis, and modern and future treatment methods of OS. The purpose of this article is to inspire new ideas to develop more effective therapeutic options.

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Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

Pharmaceutics ◽

10.3390/pharmaceutics13010045 ◽

2020 ◽

Vol 13 (1) ◽

pp. 45

Author(s):

Iman M. Alfagih ◽

Basmah Aldosari ◽

Bushra AlQuadeib ◽

Alanood Almurshedi ◽

Mariyam M. Alfagih

Keyword(s):

Messenger Rna ◽

Immune Cell ◽

Natural Infection ◽

Immunological Response ◽

Infection Process ◽

Dual Function ◽

Therapeutic Vaccines ◽

Non Invasive ◽

Recent Developments

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

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