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Journal of the American Heart... Sep 2021Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and revised in 2010 by a Task Force. Although the Task Force criteria... (Review)
Review
Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and revised in 2010 by a Task Force. Although the Task Force criteria demonstrated a good accuracy for diagnosis of the original right ventricular phenotype (arrhythmogenic right ventricular cardiomyopathy), they lacked sensitivity for identification of the expanding phenotypic spectrum of ACM, which includes left-sided variants and did not incorporate late-gadolinium enhancement findings by cardiac magnetic resonance. The 2020 International criteria ("Padua criteria") have been developed by International experts with the aim to improve the diagnosis of ACM by providing new criteria for the diagnosis of left ventricular phenotypic features. The key upgrade was the incorporation of tissue characterization findings by cardiac magnetic resonance for noninvasive detection of late-gadolinium enhancement/myocardial fibrosis that are determinants for characterization of arrhythmogenic biventricular and left ventricular cardiomyopathy. The 2020 International criteria are heavily dependent on cardiac magnetic resonance, which has become mandatory to characterize the ACM phenotype and to exclude other diagnoses. New criteria regarding left ventricular depolarization and repolarization ECG abnormalities and ventricular arrhythmias of left ventricular origin were also provided. This article reviews the evolving approach to diagnosis of ACM, going back to the 1994 and 2010 International Task Force criteria and then grapple with the modern 2020 International criteria.
Topics: Arrhythmogenic Right Ventricular Dysplasia; Cardiomyopathies; Contrast Media; Gadolinium; Humans
PubMed: 34533054
DOI: 10.1161/JAHA.121.021987 -
Nature Communications Jan 2021Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune...
Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.
Topics: Animals; Cell Line, Tumor; Combined Modality Therapy; Coordination Complexes; Disease Models, Animal; Female; Gadolinium; Hemin; Humans; Immunogenic Cell Death; Mice; Nanoparticles; Neoplasms; Oxidative Stress; Polymers; Radioimmunotherapy
PubMed: 33420008
DOI: 10.1038/s41467-020-20243-8 -
The Medical Journal of Malaysia Mar 2021Sarcoidosis is a chronic, multisystem disorder. A 38 years old lady presented at Hospital Raja Perempuan Zainab II, Kota Bharu ,Malaysia with cough and breathless for 2...
Sarcoidosis is a chronic, multisystem disorder. A 38 years old lady presented at Hospital Raja Perempuan Zainab II, Kota Bharu ,Malaysia with cough and breathless for 2 months and constitutional symptoms of weight loss and loss of appetite. She was initially treated as smear negative pulmonary tuberculosis for 5 months. However, her clinical condition deteriorated with worsening New York Heart Association (NYHA) class 1 to class 3. Subsequently, workout of computed tomography( CT) thorax showed multiple perilymphatic distribution of nodules and multiple mediastinal lymphadenopathy coupled with pleura biopsy showed non caseating granuloma and cardiac magnetic resonance imaging (MRI) with positive late gadolinium enhancement revised the diagnosis of pulmonary sarcoidosis with cardiac involvement. Patient's functional status and cough improved with immunosuppresant was given in tapering dose fashion.
Topics: Adult; Contrast Media; Female; Gadolinium; Humans; Sarcoidosis; Sarcoidosis, Pulmonary; Tomography, X-Ray Computed
PubMed: 33742636
DOI: No ID Found -
European Journal of Medicinal Chemistry Aug 2022Metallofullerenols (MFs) are functionalized endohedral fullerenes connecting at least three levels of organization of matter: atomic, molecular, and supramolecular,... (Review)
Review
Metallofullerenols (MFs) are functionalized endohedral fullerenes connecting at least three levels of organization of matter: atomic, molecular, and supramolecular, resulting in their unique activity at the nanoscale. Biomedical applications of MFs started from gadolinium-containing contrasting agents, but today their potential medical applications go far beyond diagnostics and magnetic resonance imaging. In many cases, preclinical studies have shown a great therapeutic value of MFs, and here we provide an overview of interactions of MFs with high-energy radiation and with reactive oxygen species generated during radiation as a ground for potential applications in modern therapy of cancer patients. We also present the current knowledge on interactions of MFs with proteins and with other components of cells and tissues. Due to their antioxidant properties, as well as their ability to regulate the expression of genes involved in apoptosis, angiogenesis, and stimulation of the immune response, MFs can contribute to inhibition of tumor growth and protection of normal cells. MFs with enclosed gadolinium act as inhibitors of tumor growth in targeted therapy along with imaging techniques, but we hope that the data gathered in this review will help to accelerate further progress in the implementation of MFs, also the ones containing rare earth metals other than gadolinium, in a broad range of bioapplications covering not only diagnostics and bioimaging but also radiation therapy and cancer treatment by not-cytotoxic agents.
Topics: Contrast Media; Fullerenes; Gadolinium; Humans; Magnetic Resonance Imaging; Neoplasms
PubMed: 35665690
DOI: 10.1016/j.ejmech.2022.114481 -
Archives of Toxicology Feb 2022Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical... (Review)
Review
Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.
Topics: Animals; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Nephrogenic Fibrosing Dermopathy; Renal Insufficiency
PubMed: 34997254
DOI: 10.1007/s00204-021-03189-8 -
Herz May 2020Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and one of the most common causes of heart failure. It is characterized by left or biventricular... (Review)
Review
Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and one of the most common causes of heart failure. It is characterized by left or biventricular dilation and a reduced systolic function. The causes are manifold and range from myocarditis to alcohol and other toxins, to rheumatological, endocrinological, and metabolic diseases. Peripartum cardiomyopathy is a special form that occurs at the end of or shortly after pregnancy. Genetic mutations can be detected in approximately 30-50% of DCM patients. Owing to the growing possibilities of genetic diagnostics, increasingly more triggering variants and hereditary mechanisms emerge. This is particularly important with regard to risk stratification for patients with variants with an increased risk of arrhythmias. Patient prognosis is determined by the occurrence of heart failure and arrhythmias. In addition to the treatment of the underlying disease or the elimination of triggering harmful toxins, therapy consists in guideline-directed heart failure treatment including drug and device therapy.
Topics: Adult; Cardiomyopathies; Cardiomyopathy, Dilated; Child; Contrast Media; Female; Gadolinium; Humans; Myocarditis; Pregnancy
PubMed: 32107565
DOI: 10.1007/s00059-020-04903-5 -
Journal of Magnetic Resonance Imaging :... Mar 2022Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often... (Review)
Review
Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often requires multiple complex assessments of the cardiac and pulmonary systems. MRI is able to comprehensively assess cardiac structure and function, as well as lung parenchymal, pulmonary vascular, and functional lung changes. Therefore, MRI has the potential to provide an integrated functional and structural assessment of the cardiopulmonary system in a single exam. Cardiac MRI is used in the assessment of PH in most large PH centers, whereas lung MRI is an emerging technique in patients with PH. This article reviews the current literature on cardiopulmonary MRI in PH, including cine MRI, black-blood imaging, late gadolinium enhancement, T mapping, myocardial strain analysis, contrast-enhanced perfusion imaging and contrast-enhanced MR angiography, and hyperpolarized gas functional lung imaging. This article also highlights recent developments in this field and areas of interest for future research including cardiac MRI-based diagnostic models, machine learning in cardiac MRI, oxygen-enhanced H imaging, contrast-free H perfusion and ventilation imaging, contrast-free angiography and UTE imaging. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.
Topics: Contrast Media; Gadolinium; Humans; Hypertension, Pulmonary; Lung; Magnetic Resonance Imaging
PubMed: 34350655
DOI: 10.1002/jmri.27849 -
Molecules (Basel, Switzerland) Oct 2023MRI contrast agents are required in the clinic to detect some pathologies, such as cancers. Nevertheless, at the moment, only small extracellular and non-specific... (Review)
Review
MRI contrast agents are required in the clinic to detect some pathologies, such as cancers. Nevertheless, at the moment, only small extracellular and non-specific gadolinium complexes are available for clinicians. Moreover, safety issues have recently emerged concerning the use of gadolinium complexes; hence, alternatives are urgently needed. Manganese-based MRI contrast agents could be one of these alternatives and increasing numbers of studies are available in the literature. This review aims at synthesizing all the research, from small Mn complexes to nanoparticular agents, including theranostic agents, to highlight all the efforts already made by the scientific community to obtain highly efficient agents but also evidence of the weaknesses of the developed systems.
Topics: Humans; Contrast Media; Gadolinium; Magnetic Resonance Imaging; Manganese; Neoplasms
PubMed: 37959694
DOI: 10.3390/molecules28217275 -
The Cochrane Database of Systematic... May 2022Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration... (Review)
Review
BACKGROUND
Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.
OBJECTIVES
To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.
SELECTION CRITERIA
All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.
AUTHORS' CONCLUSIONS
For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.
Topics: Adult; Antibodies, Monoclonal, Humanized; Gadolinium; Humans; Interferon beta-1a; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 35583174
DOI: 10.1002/14651858.CD013247.pub2 -
Molecules (Basel, Switzerland) Dec 2021The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the... (Review)
Review
The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.
Topics: Animals; Chemical Phenomena; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Kinetics; Magnetic Resonance Imaging; Molecular Structure; Thermodynamics
PubMed: 35011290
DOI: 10.3390/molecules27010058