Lymphomatoid Granulomatosis and Tuberculosis, Coincidence or Cohabitation—A Case Report

Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis. Case presentation: An 80-year-old female patient presented to the emergency unit for steadily increasing dyspnea, with workup revealing bilateral pulmonary nodules and mediastinal lymph node enlargement on chest imaging. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined with azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade 2 LYG. Treatment with corticosteroids and weekly rituximab was initiated, leading to rapid improvement of respiratory symptoms. After the second dose of rituximab, sputum cultures that were initially collected were found to be positive for Mycobacterium tuberculosis. Rituximab was suspended, and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both tuberculosis and LYG, with at least a partial remission of the latter. Conclusions: Our case highlights the importance of a complete diagnostic workup when a diagnosis of LYG is made, to avoid missing a concomitant pulmonary disease, such as tuberculosis, even when definite pathologic and clinical features of the former are present

The conjunction of uncommon diagnoses: a case report of concomitant lymphomatoid granulomatosis and pulmonary tuberculosis

Abstract Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible with the disease. Lymphatic involvement is uncommon. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis in an elderly woman. Case presentation: An 80-year-old woman presented to the emergency unit for steadily increasing dyspnea, with a workup revealing bilateral nodules and mediastinal lymph node enlargement on chest imaging, associated with a mildly elevated C-reactive protein (CRP). She had no relevant prior medical history and no known immunodepression. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined to azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade I lymphomatoid granulomatosis. Treatment with corticosteroids and weekly rituximab was initiated, leading to a rapid improvement of respiratory symptoms. After the second dose of rituximab, initially collected sputum cultures were found positive for Mycobacterium tuberculosis. Rituximab was suspended and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both infectious and hematological diseases with at least a partial remission of the lymphomatoid granulomatosis. Conclusions: This case report highlights both diagnosis and therapeutic challenges in a rare but plausible situation. Lymph-node involvement in lymphomatoid granulomatosis should always be questioned in LYG as it is seldom seen in the disease. Finally, pathologic confirmation for LYG should not eliminate the need for a comprehensive workup to eliminate other differential diagnoses with management-changing potential.</jats:p

Inteligência artificial na saúde: uma perspectiva jurídica

No Projeto “Direito e IA na Saúde: uma perspectiva jurídica”, oferecido no primeiro semestre de 2024, os alunos e alunas refletiram sobre os avanços e desafios da inserção de tecnologias, especificamente de inteligência artificial, no setor da saúde com seus impactos jurídicos, econômicos, sociais e éticos. O curso partiu de leituras e debates para que os(as) estudantes desenvolvessem domínio da legislação nacional e internacional sobre IA e saúde, sendo instados a pensar crítica e analiticamente sobre a relação regulatória entre direito e tecnologia e a compreender o funcionamento de estruturas regulatórias e análise de risco (como matriz de risco) no setor. A partir do conhecimento dos conceitos e estruturas, eles(as) elaboraram soluções jurídicas práticas para enfrentar os riscos e desafios da regulação de novas tecnologias no setor da saúde, com aplicação das noções sobre responsabilidade, diferenciação da linguagem jurídica da linguagem computacional e de parâmetros internacionais de direitos humanos. O livro reúne uma coleção de artigos elaborados pelos alunos e alunas do Projeto de Prática Multidisciplinar que discute desde as diretrizes regulatórias até os desafios práticos, éticos, jurídicos e tecnológicos enfrentados pelo Poder Público, por startups e grandes empresas na área da saúde

Functional Consequences of RNA 5′-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation

Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5'-terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication. In this study, we assessed the consequences of the genomic deletions observed in vivo for coxsackievirus B3 biology. Using cell extracts from HeLa cells, as well as transfection of luciferase replicons in two types of cardiomyocytes, we demonstrated that coxsackievirus RNAs harboring 5' deletions ranging from 7 to 49 nucleotides in length can be translated nearly as efficiently as those of wild-type virus. However, these 5' deletions greatly reduced the synthesis of viral RNA in vitro, which was detected only for the 7- and 21-nucleotide deletions. Since 5' stem-loop I RNA forms a ribonucleoprotein complex with cellular and viral proteins involved in viral RNA replication, we investigated the binding of the host cell protein PCBP2, as well as viral protein 3CDpro, to deleted positive-strand RNAs corresponding to the 5' end. We found that binding of these proteins was conserved but that ribonucleoprotein complex formation required higher PCBP2 and 3CDpro concentrations, depending on the size of the deletion. Overall, this study confirmed the characteristics of persistent CVB3 infection observed in heart tissues and provided a possible explanation for the low level of RNA replication observed for the 5'-deleted viral genomes-a less stable ribonucleoprotein complex formed with proteins involved in viral RNA replication.IMPORTANCE Dilated cardiomyopathy is the most common indication for heart transplantation worldwide, and coxsackie B viruses are detected in about one-third of idiopathic dilated cardiomyopathies. Terminal deletions at the 5' end of the viral genome involving an RNA secondary structure required for RNA replication have been recently reported as a possible mechanism of virus persistence in the human heart. These mutations are likely to disrupt the correct folding of an RNA secondary structure required for viral RNA replication. In this report, we demonstrate that transfected RNAs harboring 5'-terminal sequence deletions are able to direct the synthesis of viral proteins, but not genomic RNAs, in human and murine cardiomyocytes. Moreover, we show that the binding of cellular and viral replication factors to viral RNA is conserved despite genomic deletions but that the impaired RNA synthesis associated with terminally deleted viruses could be due to destabilization of the ribonucleoprotein complexes formed