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Bronowicka-Szydełko A, Rabczyński M, Dumas I, Fiodorenko-Dumas Ż, Wojtczak B, Kotyra Ł, Kustrzeba-Wójcicka I, Lewandowski Ł, Ponikowska B, Kuzan A, Kluz J, Gamian A, Madziarska K. State of Knowledge About Thyroid Cancers in the Era of COVID-19-A Narrative Review. Biomedicines 2024; 12:2829. [PMID: 39767735 PMCID: PMC11672969 DOI: 10.3390/biomedicines12122829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 11/27/2024] [Accepted: 12/06/2024] [Indexed: 01/03/2025] Open
Abstract
Thyroid cancer (TC), due to its heterogeneous nature, remains a clinical challenge. Many factors can initiate the carcinogenesis process of various types of TC, which complicates diagnosis and treatment. The presented review gathers current information on specific types of TC, taking into account the effects of the COVID-19 pandemic. It is likely that COVID-19 has influenced and continues to influence the function of the thyroid gland. A high percentage of patients with COVID-19 showing simultaneous pathological changes in the thyroid suggests that SARS-CoV-2 may disrupt the function of this gland and initiate pro-oxidative mechanisms, inflammatory states, and autoimmune diseases, thereby promoting the formation of neoplastic changes. Furthermore, changes in the expression of the ACE2, TMPRSS2, CLEC4M and DPP4 genes, observed in TC, also occur in COVID-19. Therefore, it is probable that the interaction of SARS-CoV-2 with thyroid cell receptors may initiate carcinogenesis in this gland. Additionally, some drugs used in TC therapy (e.g., levothyroxine) may increase the affinity of SARS-CoV-2 for cells, which could contribute to a more severe course of COVID-19 and the emergence of long-term symptoms (post-COVID-19). Moreover, the consequences of sanitary restrictions (limited access to medical services, reduction in endocrinological and oncological procedures) that took place in many countries during the COVID-19 pandemic may lead in the future to an increased number of missed diagnoses and the emergence of aggressive cancers.
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Affiliation(s)
- Agnieszka Bronowicka-Szydełko
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.B.-S.); (Ł.K.); (I.K.-W.); (Ł.L.)
| | - Maciej Rabczyński
- Clinical Department of Diabetology, Hypertension and Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.R.); (J.K.); (K.M.)
| | - Ilias Dumas
- Department of Clinical Physiotherapy and Rehabilitation, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Żanna Fiodorenko-Dumas
- Department of Clinical Physiotherapy and Rehabilitation, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Beata Wojtczak
- University Center for General and Oncological Surgery, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Łukasz Kotyra
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.B.-S.); (Ł.K.); (I.K.-W.); (Ł.L.)
| | - Irena Kustrzeba-Wójcicka
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.B.-S.); (Ł.K.); (I.K.-W.); (Ł.L.)
| | - Łukasz Lewandowski
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (A.B.-S.); (Ł.K.); (I.K.-W.); (Ł.L.)
| | - Beata Ponikowska
- Department of Physiology and Pathophysiology, Division of Physiology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Aleksandra Kuzan
- Department of Preclinical Sciences, Pharmacology and Medical Diagnostics, Wroclaw University of Science and Technology, 51-377 Wroclaw, Poland;
| | - Joanna Kluz
- Clinical Department of Diabetology, Hypertension and Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.R.); (J.K.); (K.M.)
| | - Andrzej Gamian
- Hirszfeld Institute of Immunology and Experimantal Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;
| | - Katarzyna Madziarska
- Clinical Department of Diabetology, Hypertension and Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.R.); (J.K.); (K.M.)
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Uccella S, Dottermusch M, Erickson L, Warmbier J, Montone K, Saeger W. Inflammatory and Infectious Disorders in Endocrine Pathology. Endocr Pathol 2023; 34:406-436. [PMID: 37209390 PMCID: PMC10199304 DOI: 10.1007/s12022-023-09771-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/03/2023] [Indexed: 05/22/2023]
Abstract
A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.
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Affiliation(s)
- Silvia Uccella
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanule, Milan, Italy
- Pathology Service IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Matthias Dottermusch
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lori Erickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN USA
| | - Julia Warmbier
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kathleen Montone
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA USA
| | - Wolfgang Saeger
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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The Influence of SARS-CoV-2 Infection on the Thyroid Gland. Biomedicines 2023; 11:biomedicines11020614. [PMID: 36831150 PMCID: PMC9953074 DOI: 10.3390/biomedicines11020614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
It is important to acknowledge the impact that COVID-19 has on the thyroid gland and how the thyroid gland status before and during infection affects SARS-CoV-2 severity. To this day those dependencies are not fully understood. It is known that the virus uses angiotensin-converting enzyme-2 as the receptor for cellular entry and it can lead to multiple organ failures due to a cytokine storm. Levels of proinflammatory molecules (such as cytokines and chemokines) which are commonly elevated during infection were significantly higher in observed SARS-CoV-2-positive patients. In terms of hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases, there is no proof that those dysfunctions have a direct impact on the more severe courses of COVID-19. Regarding hyper- and hypothyroidism there was no consequential dependency between the frequency of SARS-CoV-2 infection morbidity and more severe post-infectious complications. When it comes to autoimmune thyroid diseases, more evaluation has to be performed due to the unclear relation with the level of antibodies commonly checked in those illnesses and its binding with the mentioned before virus. Nonetheless, based on analyzed works we found that COVID-19 can trigger the immune system and cause its hyperactivity, sometimes leading to the new onset of autoimmune disorders. We also noticed more acute SARS-CoV-2 courses in patients with mainly reduced free triiodothyronine serum levels, which in the future, might be used as a mortality indicating factor regarding SARS-CoV-2-positive patients. Considering subacute thyroiditis (SAT), no statistically important data proving its direct correlation with COVID-19 infection has been found. Nevertheless, taking into account the fact that SAT is triggered by respiratory tract viral infections, it might be that SARS-CoV-2 can cause it too. There are many heterogenous figures in the symptoms, annual morbidity distribution, and frequency of new cases, so this topic requires further evaluation.
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Ong WY, Satish RL, Herr DR. ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19. Neuromolecular Med 2022; 24:363-373. [PMID: 35451691 PMCID: PMC9023728 DOI: 10.1007/s12017-022-08706-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/01/2022] [Indexed: 12/29/2022]
Abstract
The SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood-brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are intimately connected to the hypothalamus, and the hypothalamus itself, these might be easy entry points for SARS-CoV-2 into the brain via the circulation. High ACE2 protein expression is found in the subfornical organ, area postrema, and the paraventricular nucleus of the hypothalamus (PVH). The subfornical organ and PVH are parts of a circuit to regulate osmolarity in the blood, through the secretion of anti-diuretic hormone into the posterior pituitary. The PVH is also the stress response centre in the brain. It controls not only pre-ganglionic sympathetic neurons, but is also a source of corticotropin-releasing hormone, that induces the secretion of adrenocorticotropic hormone from the anterior pituitary. It is proposed that the function of ACE2 in the circumventricular organs and the PVH could be diminished by binding with SARS-CoV-2, thus leading to a reduction in the ACE2/Ang (1-7)/Mas receptor (MasR) signalling axis, that modulates ACE/Ang II/AT1R signalling. This could result in increased presympathetic activity/neuroendocrine secretion from the PVH, and effects on the hypothalamic-pituitary-adrenal axis activity. Besides the bloodstream, the hypothalamus might also be affected by SARS-CoV-2 via transneuronal spread along the olfactory/limbic pathways. Exploring potential therapeutic pathways to prevent or attenuate neurological symptoms of COVID-19, including drugs which modulate ACE signalling, remains an important area of unmet medical need.
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Affiliation(s)
- Wei-Yi Ong
- Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
- Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore, 119260, Singapore.
| | - R L Satish
- Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore
| | - Deron R Herr
- Department of Pharmacology, National University of Singapore, Singapore, 119260, Singapore
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Elvan-Tüz A, Ayrancı İ, Ekemen-Keleş Y, Karakoyun İ, Çatlı G, Kara-Aksay A, Karadağ-Öncel E, Dündar BN, Yılmaz D. Are Thyroid Functions Affected in Multisystem Inflammatory Syndrome in Children? J Clin Res Pediatr Endocrinol 2022; 14:402-408. [PMID: 35770945 PMCID: PMC9724052 DOI: 10.4274/jcrpe.galenos.2022.2022-4-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Multisystem inflammatory syndrome in children (MIS-C), associated with Coronavirus disease-2019, is defined as the presence of documented fever, inflammation, and at least two signs of multisystem involvement and lack of an alternative microbial diagnosis in children who have recent or current Severe acute respiratory syndrome-Coronavirus-2 infection or exposure. In this study, we evaluated thyroid function tests in pediatric cases with MIS-C in order to understand how the hypothalamus-pituitary-thyroid axis was affected and to examine the relationship between disease severity and thyroid function. METHODS This case-control study was conducted between January 2021 and September 2021. The patient group consisted of 36 MIS-C cases, the control group included 72 healthy children. Demographic features, clinical findings, inflammatory markers, thyroid function tests, and thyroid antibody levels in cases of MIS-C were recorded. Thyroid function tests were recorded in the healthy control group. RESULTS When MIS-C and healthy control groups were compared, free triiodothyronine (fT3) level was lower in MIS-C cases, while free thyroxine (fT4) level was found to be lower in the healthy group (p<0.001, p=0.001, respectively). Although the fT4 level was significantly lower in controls, no significant difference was found compared with the age-appropriate reference intervals (p=0.318). When MIS-C cases were stratified by intensive care requirement, fT3 levels were also lower in those admitted to intensive care and also in those who received steroid treatment (p=0.043, p<0.001, respectively). CONCLUSION Since the endocrine system critically coordinates and regulates important metabolic and biochemical pathways, investigation of endocrine function in MIS-C may be beneficial. These results show an association between low fT3 levels and both diagnosis of MIS-C and requirement for intensive care. Further studies are needed to predict the prognosis and develop a long-term follow-up management plan.
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Affiliation(s)
- Ayşegül Elvan-Tüz
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey,* Address for Correspondence: University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey Phone: +90 537 028 97 93 E-mail:
| | - İlkay Ayrancı
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Endocrinology, İzmir, Turkey
| | - Yıldız Ekemen-Keleş
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey
| | - İnanç Karakoyun
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Medical Biochemistry, İzmir, Turkey
| | - Gönül Çatlı
- İstinye University Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
| | - Ahu Kara-Aksay
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey
| | - Eda Karadağ-Öncel
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey
| | - Bumin Nuri Dündar
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Endocrinology, İzmir, Turkey
| | - Dilek Yılmaz
- University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital, Clinic of Pediatric Infectious Diseases, İzmir, Turkey,İzmir Katip Çelebi University Faculty of Medicine, Department of Pediatric Infectious Diseases, İzmir, Turkey
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Ilias I, Milionis C, Koukkou E. COVID-19 and thyroid disease: An infodemiological pilot study. World J Methodol 2022; 12:99-106. [PMID: 35721248 PMCID: PMC9157630 DOI: 10.5662/wjm.v12.i3.99] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/11/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Google Trends searches for symptoms and/or diseases may reflect actual disease epidemiology. Recently, Google Trends searches for coronavirus disease 2019 (COVID-19)-associated terms have been linked to the epidemiology of COVID-19. Some studies have linked COVID-19 with thyroid disease.
AIM To assess COVID-19 cases per se vs COVID-19-associated Google Trends searches and thyroid-associated Google Trends searches.
METHODS We collected data on worldwide weekly Google Trends searches regarding “COVID-19”, “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)”, “coronavirus”, “smell”, “taste”, “cough”, “thyroid”, “thyroiditis”, and “subacute thyroiditis” for 92 wk and worldwide weekly COVID-19 cases' statistics in the same time period. The study period was split in half (approximately corresponding to the preponderance of different SARS-COV-2 virus variants) and in each time period we performed cross-correlation analysis and mediation analysis.
RESULTS Significant positive cross-correlation function values were noted in both time periods. More in detail, COVID-19 cases per se were found to be associated with no lag with Google Trends searches for COVID-19 symptoms in the first time period and in the second time period to lead searches for symptoms, COVID-19 terms, and thyroid terms. COVID-19 cases per se were associated with thyroid-related searches in both time periods. In the second time period, the effect of “COVID-19” searches on “thyroid’ searches was significantly mediated by COVID-19 cases (P = 0.048).
CONCLUSION Searches for a non-specific symptom or COVID-19 search terms mostly lead Google Trends thyroid-related searches, in the second time period. This time frame/sequence particularly in the second time period (noted by the preponderance of the SARS-COV-2 delta variant) lends some credence to associations of COVID-19 cases per se with (apparent) thyroid disease (via searches for them).
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Affiliation(s)
- Ioannis Ilias
- Department of Endocrinology, Diabetes & Metabolism, Elena Venizelou Hospital, Athens GR-11521, Greece
| | - Charalampos Milionis
- Department of Endocrinology, Diabetes & Metabolism, Elena Venizelou Hospital, Athens GR-11521, Greece
| | - Eftychia Koukkou
- Department of Endocrinology, Diabetes & Metabolism, Elena Venizelou Hospital, Athens GR-11521, Greece
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Boaventura P, Macedo S, Ribeiro F, Jaconiano S, Soares P. Post-COVID-19 Condition: Where Are We Now? Life (Basel) 2022; 12:life12040517. [PMID: 35455008 PMCID: PMC9029703 DOI: 10.3390/life12040517] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 02/06/2023] Open
Abstract
COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.
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Affiliation(s)
- Paula Boaventura
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; (S.M.); (F.R.); (P.S.)
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal
- Correspondence:
| | - Sofia Macedo
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; (S.M.); (F.R.); (P.S.)
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
| | - Filipa Ribeiro
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; (S.M.); (F.R.); (P.S.)
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
| | - Sónia Jaconiano
- School of Architecture, Art and Design (EAAD), University of Minho, 4800-058 Guimarães, Portugal;
| | - Paula Soares
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal; (S.M.); (F.R.); (P.S.)
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal
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