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Your search keyword '"Kyriakides, Theodoros"' showing total 5 results
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5 results on '"Kyriakides, Theodoros"'

1. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Author

Dispenzieri, Angela, Coelho, Teresa, Conceição, Isabel, Waddington-Cruz, Márcia, Wixner, Jonas, Kristen, Arnt V., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Gonzalez-Moreno, Juan, Maurer, Mathew S., Grogan, Martha, Chapman, Doug, Amass, Leslie, Pavia, Pablo Garcia, Tarnev, Ivaylo, Costello, Jose Gonzalez, Briseno, Maria Alejandra Gonzalez Duarte, Schmidt, Hartmut, Drachman, Brian, Barroso, Fabio Adrian, Yamashita, Taro, Lairez, Olivier, Sekijima, Yoshiki, Vita, Giuseppe, Jeon, Eun-Seok, Hanna, Mazen, Slosky, David, Luigetti, Marco, LoRusso, Samantha, Beamud, Francisco Munoz, Adams, David, Moelgaard, Henning, Press, Rayomand, Cirami, Calogero Lino, Nienhuis, Hans, Plana, Josep Maria Campistol, Inamo, Jocelyn, Jacoby, Daniel, Emdin, Michele, Quan, Dianna, Hummel, Scott, Witteles, Ronald, Dori, Amir, Shah, Sanjiv, Lenihan, Daniel, Azevedo, Olga, Murali, Srinivas, Zivkovic, Sasa, Low, Soon Chai, Nativi-Nicolau, Jose, Fine, Nowell, Tallaj, Jose, Tschoepe, Carsten, Torrón, Roberto Fernandéz, Polydefkis, Michael, Merlini, Giampaolo, Badelita, Sorina, Gottlieb, Stephen, Tauras, James, Correia, Edileide Barros, Ventura, Hector, Gess, Burkhard, Darstein, Felix, Oh, Jeeyoung, Marburger, Tessa, Van Cleemput, Johan, Salutto, Valeria Lujan, Parman, Yesim, Chao, Chi-Chao, Sarswat, Nitasha, Mueller, Christopher, Steidley, David, Ralph, Jeffrey, Warner, Alberta, Cotts, William, Hoffman, James, Rugiero, Marcelo, Misawa, Sonoko, Blanco, Jose Luis Munoz, Davila, Lucia Galan, Sadeh, Menachem, Luo, Jin, Kyriakides, Theodoros, Wang, Annabel, and Kaufmann, Horacio

Subjects
Male, Amyloid Neuropathies, Familial, Registry, Neurologi, Cardiomyopathy, General Medicine, Amyloidosis, Genetic Profile, Amyloid Neuropathies, Transthyretin, Phenotype, Familial, Neurology, Surveys and Questionnaires, Polyneuropathy, Humans, Prealbumin, Pharmacology (medical), Female, Genetics (clinical)
Abstract

Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.

Published
2022
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2. Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

Author

Waddington-Cruz, Márcia, Wixner, Jonas, Amass, Leslie, Kiszko, Jan, Chapman, Doug, Ando, Yukio, the THAOS investigators, Barroso, Fabio Adrian, Rugiero, Marcelo, Van Cleemput, Johan, Tarnev, Ivaylo, Kyriakides, Theodoros, Kristen, Arnt, Schmidt, Hartmut, Darstein, Felix, Gess, Burkhard, Plana, Josep Maria Campistol, Moreno, Juan Gonzalez, Costello, Jose Gonzalez, and Pavia, Pablo Garcia

Subjects
CARDIAC amyloidosis, AMYLOIDOSIS, TRANSTHYRETIN, TREATMENT effectiveness, STANDARD deviations, PATIENT surveys
Abstract

Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early- or late-onset disease. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late- (age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019). Results: Of 1389 patients with ATTRv Val30Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Late-onset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in late-onset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% early-onset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p < 0.001). Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to more timely diagnosis and improve patient outcomes. Trial Registration: ClinicalTrials.gov NCT00628745. [ABSTRACT FROM AUTHOR]

Published
2021
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3. Complement C1Q polymorphisms modulate onset in familial amyloidotic polyneuropathy TTR Val30Met

Author

Dardiotis, Efthymios, Koutsou, Pantelitsa, Zamba-Papanicolaou, Eleni, Vonta, Filia, Hadjivassiliou, Marilena, Hadjigeorgiou, Georgios M., Cariolou, Marios A., Christodoulou, Kyproula, Kyriakides, Theodoros, and Vonta, Filia [0000-0002-7897-6797]

Subjects
Male, Apolipoprotein E, complement component C1q, Apolipoprotein E2, Transthyretin, Gene Frequency, single nucleotide polymorphism, Genotype, Prealbumin, genetic polymorphism, chaperone, Age of Onset, Genetics, Greece, biology, adult, Amyloidosis, article, Exons, Middle Aged, Penetrance, aged, Serum Amyloid P-Component, female, familial amyloid polyneuropathy, priority journal, heterozygote detection, Neurology, nucleic acid base substitution, Female, TTR Val30Met, Polyneuropathy, Adult, onset age, Amyloid, gene sequence, prealbumin, Polymorphism, Single Nucleotide, male, medicine, Humans, controlled study, human, Allele, Aged, Amyloid Neuropathies, Familial, Complement C1q, Familial amyloidotic neuropathy, medicine.disease, major clinical study, Modifier genes, Cyprus, biology.protein, Neurology (clinical), Age of onset, Molecular Chaperones
Abstract

Background: Familial amyloidotic polyneuropathy (FAP) TTR Val30Met is a lethal autosomal dominant sensorimotor and autonomic neuropathy due to a substitution of methionine for valine at position 30 of the transthyretin (TTR) gene. Amyloid, composed of mutated TTR, is deposited in the peripheral nervous system, myocardium and kidneys. Considerable variability in the age of onset and penetrance of the disease occurs in different countries. Penetrance in Sweden, Cyprus and Portugal is 2%, 28% and 80% respectively. Environmental and genetic factors are believed to contribute to this variability. So far, no single modifier gene has been unequivocally associated with age of onset or penetrance. Methods: Candidate modifier genes were chosen from among those coding for chaperone proteins co-localized with TTR deposits in peripheral nerves. Seventy one TTRVal30Met carriers, 51 affected and 20 asymptomatic, belonging to 22 unrelated Greek-Cypriot families, and 59 normal controls were recruited for this study. Sequencing of the coding regions of TTR, serum amyloid P (APCS) and complement C1Q (A, B and C) genes was performed and APOE genotypes were determined. We searched for correlations between various polymorphisms of chaperone proteins and age of disease onset. Results: Four new and 4 previously described single nucleotide substitutions were identified. One polymorphic site in C1QA (rs172378) and one in C1QC (rs9434) as well as the ε2 allele correlated with age of onset (p < 0.05). Conclusions: Our study has identified polymorphisms which may influence the FAP-TTR Val30Met phenotype. Identifying modifier genes and their protein products may contribute to therapeutic advances. © 2009 Elsevier B.V. All rights reserved. 284 1-2 158 162 Cited By :16

Published
2009
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4. Transthyretin deposition in the eye in the era of effective therapy for hereditary ATTRV30M amyloidosis.

Author

Buxbaum, Joel N., Brannagan III, Thomas, Buades-Reinés, Juan, Cisneros, Eugenia, Conceicao, Isabel, Kyriakides, Theodoros, Merlini, Giampaolo, Obici, Laura, Plante-Bordeneuve, Violaine, Rousseau, Antoine, Sekijima, Yoshiki, Imai, Akira, Waddington Cruz, Márcia, and Yamada, Masahito

Subjects
TRANSTHYRETIN, LIVER transplantation, DISEASE duration, EYE, CONJUNCTIVA
Abstract

Background: Ocular abnormalities have been known to occur in hereditary amyloidotic polyneuropathy since the 1950s. While vitreous opacities and scalloped pupils were described early it has become evident that every component of the eye from the conjunctiva to the retinal vasculature can be involved. Reports from the major centres in Japan, Portugal and Sweden, which primarily treat patients with ATTRV30M, have indicated that with the increased longevity seen in patients treated with liver transplantation the frequency of the more severe eye findings, notably vitreous opacities and subsequent glaucoma, are being detected more frequently. Methods: In an attempt to confirm that the experience was similar in a broader range of locales we performed a survey of ten treatment centres in eight countries to determine the frequency of severe ocular abnormalities (vitreous opacities and glaucoma) in 804 patients with V30M disease and whether there was any relationship to treatment with liver transplantation or the transthyretin stabilizer tafamidis. Results: The data indicate that the frequency of these abnormalities increases with increasing duration of disease. In patients broadly matched for duration of disease the frequency was higher in subjects who had undergone liver transplantation than in those who were untreated. Conclusions: Retrospective surveys are subject to a number of potential biases. In this case, the major potential confounders were defining the time of disease onset and physician bias in choice of therapy, particularly regarding the choice of patients and the time in their course when they should undergo liver transplantation, and when and whether they should receive tafamidis. Nonetheless it appears that the incidence of severe ocular abnormalities in V30M subjects from centres around the world is similar to those found in centres in the areas endemic for this variant protein. The incidence increased with duration of disease regardless of therapy with the highest frequencies seen in patients more than ten years after diagnosis who had undergone liver transplantation. [ABSTRACT FROM AUTHOR]

Published
2019
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5. Epidemiological, clinical and genetic study of familial amyloidotic polyneuropathy in Cyprus

Author

Dardiotis, Efthymios, Koutsou, Pantelitsa, Papanicolaou, Eleni Zamba, Vonta, Filia, Kladi, Angelica, Vassilopoulos, Dimitrios C., Hadjigeorgiou, Georgios M., Christodoulou, Kyproula, Kyriakides, Theodoros, and Vonta, Filia [0000-0002-7897-6797]

Subjects
Proband, Male, Epidemiology, Genetic Carrier Screening, Transthyretin, sensorimotor neuropathy, middle aged, Prevalence, Prealbumin, genetics, gene mutation, Age of Onset, Genetics, biology, Incidence (epidemiology), adult, Incidence, article, Middle Aged, Penetrance, aged, female, familial amyloid polyneuropathy, priority journal, heterozygote detection, Female, Polyneuropathy, onset age, Adult, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adolescent, prevalence, prealbumin, male, Internal medicine, Internal Medicine, medicine, Humans, human, Aged, neuropathic pain, Amyloid Neuropathies, Familial, business.industry, Familial amyloidotic neuropathy, nucleotide sequence, medicine.disease, major clinical study, heterozygote, clinical feature, adolescent, Anticipation (genetics), Cyprus, biology.protein, incidence, Age of onset, business, autonomic neuropathy
Abstract

Objectives. To define the incidence and prevalence of familial amyloidotic polyneuropathy (FAP) TTRVal30Met on the island of Cyprus. To study the clinical phenotype and genetic features of FAP TTRVal30Met in the Cypriot population. Methods. The clinical and neurogenetic databases were used to identify probands with FAP TTRVal30Met and detailed family trees were constructed. Potential carriers of the mutation were identified from the family trees and assessed clinically and genetically. Transthyretin was completely sequenced in patients and potential carriers. Results. Thirty-six patients carrying the TTRVal30Met mutation (one homozygote) from 22 families were identified. On 1 December 2003 the prevalence of FAP was 3.72/100,000 while the incidence is estimated to be 0.69/100,000 per year. The phenotype observed was characteristic for a length dependent sensorimotor and autonomic neuropathy with neuropathic pain. Mean age of onset was 46 years. Penetrance is estimated to be 28% and positive anticipation in the age of onset is found. Conclusion. FAP is relatively prevalent in Cyprus which may be considered as another endemic focus of the disease in Europe. The mean age of onset and penetrance is different from the Portuguese and Swedish populations. Understanding the biological factors that determine these differences could potentially lead to therapeutic advances. 16 1 32 37 Cited By :12

Published
2009

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