Metástases Cutâneas de Carcinoma de Células de Hürthle da Tiróide

Overall, skin metastases from internal malignancies are a rare event, ranging from 0.9% to 4.4% in large autopsy studies and reaching 9% in large series of patients. Skin metastases from thyroid carcinoma are even rarer and, among them, follicular carcinomas have seldom been reported in this context, far less so than papillary and medullary carcinomas. A 57-year-old Caucasian male presented with an angioma-like papule on the parietal area of the scalp with a 4-month history. The patient had endured 2 years previously total thyroidectomy, radiotherapy and several chemotherapeutical regimens for a metastatic Hürthle cell carcinoma of the thyroid gland. Excisional biopsy of the nodules established the diagnosis of metastatic (lung and liver) follicular cell carcinoma on plain histological and immunohistochemical grounds. Lymph nodes, lungs and bones are the most common sites of distant metastases of thyroid carcinomas. Although accounting for about 12% of all thyroid carcinomas, skin metastases from follicular carcinomas have however only rarely been reported. These tumours are usually well-differentiated carcinomas, bearing a fair long-term prognosis and characterized pathologically by the presence of follicular structures and colloid material in the midst of diverse amounts of anaplasia and architectural disorganization. In our case, it is noteworthy the angioma-like morphology of the metastatic nodule, classically associated with renal cell carcinoma scalp metastases, as well as its aggressive nature which led eventually to a fatal outcome. This case is ichnographically depicted and a review of the relevant literature is done.Metástases cutâneas de neoplasias internas constituem um evento raro, ocorrendo em 0,9% a 4,4% em grandes estudos necrópsicos e atingindo 9% em grandes séries de doentes neoplásicos. Metástases cutâneas de carcinomas da tiróide são ainda mais raros e, entre eles, os de carcinomas foliculares foram mais raramente reportados, mais escassamente do que os de carcinomas papilares ou medulares. Um Eurocaucasiano de 57 A de idade recorreu à consulta por pápula angiomatoide na área parietal do couro cabeludo, com cerca de 4 meses de evolução. O doente tinha sido submetido, 2 anos antes, a tiroidectomia total, complementada com radioterapia e diversos esquemas quimioterapêuticos por um carcinoma metastático de células de Hürthle da tiróide. A biópsia excisional da pápula permitiu estabelecer, com recurso a estudos imuno-histoquímicos, o diagnóstico de metástase cutânea de carcinoma folicular da tiróide. Os gânglios linfáticos, pulmões e os ossos constituem as mais prevalentes localizações à distância das metástases do carcinoma folicular da tiróide. Embora estas neoplasias representem até 12% das neoplasias malignas da tiróide, metástases cutâneas destes tumores têm sido muito raramente reportadas. Estes tumores são habitualmente carcinomas bem diferenciados, com prognóstico favorável a longo termo e caracterizados histologicamente por estruturas foliculares com material colóide e variáveis anaplasia e distorção arquitectural. No caso apresentado merecem destaque a morfologia angiomatoide da lesão metastática, classicamente associada a metástases de tumores de células renais e a alguns casos já relatados de tumores de células de Hürthle, bem como o comportamento agressivo e a evolução fatal verificados. O caso é ilustrado iconograficamente e uma breve revisão da literatura é efectuada

Vitiligo Instabilizado em Contexto de Hipermelanose Difusa: Uma Apresentação Inusitada de uma Síndrome de Schmidt

Vitiligo is an acquired prevalent pigmentary disorder characterized by its chronicity, refractoriness and significant psychosocial burden. Concerning its pathogenesis, several genetic, environmental, oxidative stress mechanisms and immune disturbances combine in an intricate, complex way. Diverse immunemediated comorbidities do occur in a variable yet significant manner, so as to fully justify the careful approach and follow-up of these patients. polyglandular autoimmune syndrome type II – Schmidt`s syndrome – is defined by the association of Addison`s disease with immunemediated thyroid disease and/or type 1 diabetes mellitus. The case of a 64year old Caucasian female patient with a long lasting history of several immunemediated disorders (namely Hashimoto thyroiditis and hypothyroidism, atrophic gastritis, lichen planus and stable acrofacial vitiligo) is reported. who For the last 3 months her vitiligo had suffered significant extension and morphologic changes – confettilike lesions, trichromic vitiligo and Koebner`s phenomenon – along with discrete and subtle generalized hypermelanosis. Laboratory work up disclosed a state of hypocortisolism –further confirmed by functional, immunological and image studies: autoimmune Addison`s disease in the context of Schmidt`s syndrome. An effective endocrine insufficiency correction prompted for a quick patient`s recovery as far as hydroelectrolytic and metabolic metabolism, with a concomitant reversion of the hypermelanosis and a stabilization of the vitiligo. In this case it is noteworthy the rapid expansion of a previous stable vitiligo along with the acquisition of peculiar new morphologic features, in the context of a subtle diffuse hypermelanosis in a patient with a past history of several immunemediated disorders. We underline the need to acknowledge the possible association of vitiligo with immunemediated comorbidities, particularly whenever atypical semiological or evolutive features are present.O vitiligo, uma leucodermia adquirida particularmente prevalente, caracteriza-se pelo impacto psicossocial, cronicidade e resistência aos tratamentos. Na sua génese intervêm de forma intrincada mecanismos genéticos, ambientais, stress oxidativo e autoimunidade. As comorbilidades imunologicamente mediadas ocorrem com frequência variável mas significativa e devem justificar uma atenção redobrada por parte dos Dermatologistas. A síndrome de Schmidt – síndrome poliglandular autoimune do tipo II é definida pela ocorrência de doença de Addison e patologia autoimune da tiroideia e/ou diabetes mellitus tipo 1. Relatamos caso de uma doente com 64 anos de idade, com antecedentes de doenças imunologicamente mediadas, incluindo história de tiroidite autoimune e de vitiligo acrofacial estável o qual, nos últimos 3 meses, sofrera uma modificação impressiva nas suas extensão e morfologia, no contexto de uma melanodermia difusa recém-instalada. A avaliação laboratorial efectuada documentou hipocortisolismo, ulteriormente confirmado por provas funcionais, bem como marcadores imunológicos e imagiologia compatíveis: doença de Addison autoimune enquadrável numa síndrome de Schmidt. A correcção da insuficiência endócrina permitiu equilibrar a doente nos planos hidroelectrolítico e metabólico, tendo sido observados uma reversão da hipermelanose e estabilização do vitiligo. Salientamse a progressão importante de um vitiligo até então estável; as novas particularidades morfológicas da dermatose – lesões em confetti, vitiligo tricrómico e fenómeno de Koebner – e a hipermelanose difusa numa doente com história de múltiplas manifestações de autoimunidade. Conclui-se pela necessidade de reconhecer e, logo, suspeitar de comorbilidades imunologicamente mediadas do vitiligo, em particular quando na presença de atipias semiológicas ou evolutivas e no contexto de história clínica sugestiva

Diabetes insipidus and hypopituitarism in HIV: an unexpected cause

Central diabetes insipidus (DI) is a rare clinical entity characterized by low circulating levels of antidiuretic hormone (ADH) presenting with polyuria and volume depletion. Pituitary surgery is the most common cause of central DI in adults. Pituitary and hypothalamic disease, particularly invasive neoplasms, rarely cause DI, being idiopathic cases responsible for the majority of non-surgical cases. HIV patients, especially those with poor virulogical control, are prone to the development of CNS neoplasms, particularly lymphomas. These neoplasms usually become manifest with mass effects and seizures. Central DI and hypopituitarism are uncommon initial manifestations of primary CNS lymphomas. The authors describe the case of 29-year-old female, HIV-positive patient whose CNS lymphoma presented with DI

A Retrospective Cohort Study

Purpose Graves' disease (GD) is an autoimmune disorder caused by the presence of antibodies to the thyroid stimulating hormone (TSH) receptor (TRAbs), usually presenting with clinical signs of hyperthyroidism. Previous evidence suggests that higher serum levels of thyroid peroxidase antibodies (TPOAbs) may lead to more sustained remission of hyperthyroidism after treatment with antithyroid drugs (AT). However, doubts about the influence of TPOAbs in Graves' disease outcomes still remain. Methods A retrospective, unicenter cohort study was performed. All patients with GD (TRAbs > 1.58U/L), biochemical primary hyperthyroidism (TSH < 0.4 µUI/mL), and TPOAbs measurement at diagnosis, treated with AT between January 2008 and January 2021, were included for analysis. Results One hundred and forty-two patients (113 women) with a mean age of 52 ± 15 years old were included. They were followed up for 65.4 ± 43.8 months. TPOAbs positivity was present in 71.10% (n=101) of those patients. Patients were treated with AT for a median of 18 (IQR (12; 24)) months. Remission occurred in 47.2% of patients. Patients with remission presented with lower TRAbs and free thyroxine (FT4) levels at the diagnosis. (p-value <0.001, p-value 0.003, respectively). No association was found in the median TPOAbs serum levels of patients who remitted and those who maintained biochemical hyperthyroidism after the first course of AT. Relapse of hyperthyroidism occurred in 54 patients (57.4%). No difference was found in TPOAbs serum levels regarding the patient's relapse. Moreover, a time-based analysis revealed no differences in the relapse rate after 18 months of AT therapy between patients with and without TPOAbs positivity at the diagnosis (p-value 0.176). It was found a weak positive correlation (r=0.295; p-value <0.05) between TRAbs and TPOAbs titters at the moment of Graves' diagnosis. Conclusion In this study, a correlation between TRAbs measurements and TPOAbs titter was described, although no significant association was found between the presence of TPOAbs and the outcomes of patients with GD treated with AT. These results do not support the use of TPOAbs as a useful biomarker to predict remission or relapse of hyperthyroidism in GD patients.publishersversionpublishe

PARAGANGLIOMA E ANGIOEDEMA

Paragangliomas or extra-adrenal pheochromocytomas are rare tumors that arise from chromaffin tissues and tend to occur either sporadically or in the context of complex genetic disorders. They are clinically heterogeneous in nature - symptoms deriving either from the secretory profile of the tumor or from the mass effect of the neoplasm. Dermatologic symptoms are quite seldom described in the literature and have been classified in acute or chronic. The case of a 40 YO Caucasian female that had been enduring for the last 2 years recurring self-limited episodes of angioedema, diarrhoea, chest pain, hypertension or hypotension, dyspnoea and anxiety is reported. Biochemical studies and further imagiologic work up and, later on, pathologic exam allowed to identify a paraganglioma that drained to the left renal artery. Upon surgery, during tumor manipulation, the patient developed an additional systemic crisis that required active life support. Recovery was regular, with a quick and sustained normalization of lab results as well as on the clinical side, with no further episode for the last 17 years.Paragangliomas ou Feocromocitomas extra-suprarrenais são tumores raros derivados do tecido cromafim que tendem a ocorrer esporadicamente ou no contexto de doenças genéticas complexas. São tumores com apresentação clínica variada, dependente do seu perfil secretório ou do efeito de massa determinado pela neoplasia. Sintomas dermatológicos são raros, tendo sido classificados como agudos/paroxísticos ou crónicos. É apresentado caso de uma Eurocaucasiana de 40 anos de idade que referia, nos últimos 2 anos, episódios auto-limitados de angioedema, diarreia, toracalgia, hiper ou hipotensão arterial, dispneia e ansiedade. Estudos laboratoriais e, posteriormente, avaliação imagiológica e exame patológico permitiram identificar um paraganglioma drenante para a veia renal esquerda, o qual foi extirpado com sucesso. Durante a cirurgia, a manipulação do tumor desencadeou uma nova crise grave, a qual exigiu, com carácter de emergência, a instituição de medidas de suporte avançado de vida. A recuperação decorreu sem incidentes, tendo-se verificado uma rápida regularização dos valores laboratoriais a par de uma remissão clínica completa, sem novos episódios verificados durante 17 anos

Thyrotoxicosis leading to adrenal crises reveals primary bilateral adrenal lymphoma

Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 μU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma

Chromosome Mapping of Repetitive Sequences in Rachycentron canadum (Perciformes: Rachycentridae): Implications for Karyotypic Evolution and Perspectives for Biotechnological Uses

The cobia, Rachycentron canadum, a species of marine fish, has been increasingly used in aquaculture worldwide. It is the only member of the family Rachycentridae (Perciformes) showing wide geographic distribution and phylogenetic patterns still not fully understood. In this study, the species was cytogenetically analyzed by different methodologies, including Ag-NOR and chromomycin A3 (CMA3)/DAPI staining, C-banding, early replication banding (RGB), and in situ fluorescent hybridization with probes for 18S and 5S ribosomal genes and for telomeric sequences (TTAGGG)n. The results obtained allow a detailed chromosomal characterization of the Atlantic population. The chromosome diversification found in the karyotype of the cobia is apparently related to pericentric inversions, the main mechanism associated to the karyotypic evolution of Perciformes. The differential heterochromatin replication patterns found were in part associated to functional genes. Despite maintaining conservative chromosomal characteristics in relation to the basal pattern established for Perciformes, some chromosome pairs in the analyzed population exhibit markers that may be important for cytotaxonomic, population, and biodiversity studies as well as for monitoring the species in question

PHEOCHROMOCYTOMA AND NEUROFIBROMATOSIS 1

Introdução: Feocromocitomas são tumores originários de células cromafins do sistema simpato-adrenal. As suas manifestações clínicas são múltiplas e diversificadas, função do perfil secretório variável de múltiplos compostos, incluindo catecolaminas, neuropéptidos e outros compostos vasoactivos. A Neurofibromatose 1 (D de von Recklinghausen), a mais prevalente das variantes das neurofibromatoses, é genodermatose transmitida segundo padrão mendeliano autossómico dominante. O diagnóstico de NF1 assenta em critérios diagnósticos, entre os quais as alterações cutâneas, oculares e esqueléticas são as mais relevantes, embora múltiplas neoplasias envolvendo diversos orgãos e sistemas não possam ser esquecidas ou sub-valorizadas já que é bem conhecido que o produto genético do gene alterado da NF1 – a neurofibromina – é uma proteina de supressão tumoral. Feocromocitomas ocorrem em menos de 1% dos doentes com NF1; por outro lado, apenas 5% dos casos reportados de feocromocitoma estão associados com a NF I. No entanto, entre doentes hipertensos com NF1, a prevalência de feocromocitoma pode atingir os 50%.Caso clínico: É relatado caso de eurocaucasiana de 27 A de idade, com diagnóstico de NF1 com história de 4 meses de cólicas abdominais, hiperhidrose generalizada, dispneia e hipertensão arterial paroxística. As catecolaminas e metanefrinas urinárias estavam aumentadas e a exploração topográfica levada a cabo (RMN e I-MIBG) permitiram detectar uma massa na glândula suprarrenal direita, a qual, após adrenalectomia confirmou o diagnóstico de feocromocitoma. Conclusão: O caso apresentado enfatiza a necessidade de uma abordagem multissistémica, multidisciplinar a doentes com NF1, tendo em conta as manifestações sistémicas associadas, na base de um prognóstico por vezes fechado da doença.Introduction: Pheochromocytomas are tumours arising from chromaffin cells in the sympathetic nervous system. Clinical manifestations are protean, function of the variable secretory profile of several compounds including catecolamines, neuropeptides and other vasoactive molecules. Neurofibromatosis I (von Recklinghausen`s disease), a prevalent autosomal dominant disorder, is the most prevalent type among the neurofibromatoses. Among the diagnostic criteria proposed by the NIH Consensus Conference on Neurofibromatosis (1987), cutaneous, ocular and skeletal alterations are most relevant, although neoplastic disease involving a number of distinct organs cannot be overlooked as the altered NF I - gene product -neurofibromin - is a tumour supressor protein. Pheochromocytoma is a tumour that occurs in less than 1% of NF I patients; only 5% of pheochromocytoma reported cases are related to NF I. Nevertheless, among hypertensive NF I patients, the prevalence of pheochromocytoma may account for about 50%.Case report: The case of a 27 YO Caucasian NF I female patient, with a 4 month history of episodes of colicky abdominal pain, hyperhidrosis, dyspnoea and paroxystic hypertension is reported. Urinary catecholamines and metanephrines were raised and the topographic work up (RMN and I-MIBG) disclosed a right adrenal mass that, upon adrenalectomy, confirmed the diagnosis of Pheochromocytoma.Conclusion:  This case report intends to re-emphasize the relevance of a multisystem, multidisciplinary approach to NF I patients, bearing in mind the systemic, often ominous nature of the associated com plications

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality