RESUMO

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with ß-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.

Assuntos

Citocinas , Citomegalovirus , Rejeição de Enxerto , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Transplante de Rim , Transplante de Fígado , Humanos , Transplante de Rim/efeitos adversos , Citocinas/sangue , Citocinas/metabolismo , Criança , Herpesvirus Humano 6/imunologia , Masculino , Feminino , Pré-Escolar , Transplante de Fígado/efeitos adversos , Citomegalovirus/imunologia , Rejeição de Enxerto/virologia , Rejeição de Enxerto/imunologia , Herpesvirus Humano 4/imunologia , Adolescente , Lactente , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/imunologia , Transplantados , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/imunologia , Herpesviridae

RESUMO

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by the development of polyps in the gastrointestinal tract, mucocutaneous pigmentation, and the risk of developing malignant neoplasms. This study aimed to analyze the epidemiological, clinical, and histopathological data of patients with PJS treated in a tertiary pediatric hospital. METHODS: We conducted a retrospective observational study to describe the epidemiological, clinical, endoscopic, and histological characterization of patients with PJS treated in a tertiary pediatric hospital in Mexico. RESULTS: We included 13 cases with a male-female ratio of 1.16:1. Abdominal pain was the main reason for consultation, followed by rectorrhagia. Patients showed mucocutaneous pigmentation and polyps in the gastrointestinal tract, frequently of the hamartomatous type, although inflammatory polyps, follicular hyperplasia, and adenomatous polyps were also found. Among the complications, there was a high prevalence of emergency surgery secondary to abdominal obstructive processes, the main reason for first-time consultation in these patients. CONCLUSIONS: The main clinical manifestations were mucocutaneous pigmentation, abdominal pain, and rectorrhagia. PJS should be included in the differential diagnosis in the presence of intestinal obstruction. The diagnosis of PJS should not be excluded if hamartomatous polyps are not evident on the first endoscopy. Nutritional assessment should be included due to the risk of presenting some degree of malnutrition.

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INTRODUCCIÓN: El síndrome de Peutz-Jeghers es una enfermedad hereditaria autosómica dominante poco frecuente, caracterizada por el desarrollo de pólipos en el tubo digestivo, pigmentación mucocutánea y riesgo de desarrollar neoplasias malignas. El objetivo de este estudio fue analizar los datos epidemiológicos, clínicos e histopatológicos de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel. MÉTODOS: Se llevó a cabo un estudio observacional retrospectivo, para describir las características epidemiológicas, clínicas, endoscópicas e histopatológicas de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel de atención en México. RESULTADOS: Se recopilaron 13 casos con una relación masculino-femenino de 1.16:1. El dolor abdominal fue el principal motivo de consulta, seguido por rectorragia. Los pacientes presentaban pigmentación mucocutánea y pólipos en el tubo digestivo, la mayoría del tipo hamartomatoso, aunque también se hallaron pólipos inflamatorios, hiperplasia folicular y adenomatosos. Dentro de las complicaciones se encontró una alta prevalencia de cirugías de emergencia secundarias a procesos obstructivos abdominales, motivo principal de consulta de primera vez en estos pacientes. CONCLUSIONES: Las principales manifestaciones clínicas fueron pigmentación mucocutánea, dolor abdominal y rectorragia. Ante un cuadro de obstrucción intestinal se debe considerar el SPJ en el diagnóstico diferencial. No se debe excluir el diagnóstico de SPJ si no se evidencian pólipos hamartomatosos en la primera endoscopia. Se debe incluir la valoración nutricional por el riesgo de presentar algún grado de desnutrición.

Assuntos

Síndrome de Peutz-Jeghers , Humanos , Feminino , Masculino , Criança , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/epidemiologia , Atenção Terciária à Saúde , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , México/epidemiologia

RESUMO

Abstract Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by the development of polyps in the gastrointestinal tract, mucocutaneous pigmentation, and the risk of developing malignant neoplasms. This study aimed to analyze the epidemiological, clinical, and histopathological data of patients with PJS treated in a tertiary pediatric hospital. Methods: We conducted a retrospective observational study to describe the epidemiological, clinical, endoscopic, and histological characterization of patients with PJS treated in a tertiary pediatric hospital in Mexico. Results: We included 13 cases with a male-female ratio of 1.16:1. Abdominal pain was the main reason for consultation, followed by rectorrhagia. Patients showed mucocutaneous pigmentation and polyps in the gastrointestinal tract, frequently of the hamartomatous type, although inflammatory polyps, follicular hyperplasia, and adenomatous polyps were also found. Among the complications, there was a high prevalence of emergency surgery secondary to abdominal obstructive processes, the main reason for first-time consultation in these patients. Conclusions: The main clinical manifestations were mucocutaneous pigmentation, abdominal pain, and rectorrhagia. PJS should be included in the differential diagnosis in the presence of intestinal obstruction. The diagnosis of PJS should not be excluded if hamartomatous polyps are not evident on the first endoscopy. Nutritional assessment should be included due to the risk of presenting some degree of malnutrition.

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Resumen Introducción: El síndrome de Peutz-Jeghers es una enfermedad hereditaria autosómica dominante poco frecuente, caracterizada por el desarrollo de pólipos en el tubo digestivo, pigmentación mucocutánea y riesgo de desarrollar neoplasias malignas. El objetivo de este estudio fue analizar los datos epidemiológicos, clínicos e histopatológicos de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel. Métodos: Se llevó a cabo un estudio observacional retrospectivo, para describir las características epidemiológicas, clínicas, endoscópicas e histopatológicas de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel de atención en México. Resultados: Se recopilaron 13 casos con una relación masculino-femenino de 1.16:1. El dolor abdominal fue el principal motivo de consulta, seguido por rectorragia. Los pacientes presentaban pigmentación mucocutánea y pólipos en el tubo digestivo, la mayoría del tipo hamartomatoso, aunque también se hallaron pólipos inflamatorios, hiperplasia folicular y adenomatosos. Dentro de las complicaciones se encontró una alta prevalencia de cirugías de emergencia secundarias a procesos obstructivos abdominales, motivo principal de consulta de primera vez en estos pacientes. Conclusiones: Las principales manifestaciones clínicas fueron pigmentación mucocutánea, dolor abdominal y rectorragia. Ante un cuadro de obstrucción intestinal se debe considerar el SPJ en el diagnóstico diferencial. No se debe excluir el diagnóstico de SPJ si no se evidencian pólipos hamartomatosos en la primera endoscopia. Se debe incluir la valoración nutricional por el riesgo de presentar algún grado de desnutrición.

RESUMO

Pompe disease (PD) is an autosomal recessive disorder by a deficiency of acid α-glucosidase (GAA) with intralysosomal glycogen accumulation in multiple tissues. We present the case of a 5-month-old male with hypertrophic cardiomyopathy, hypotony, feeding difficulties, and oxygen requirement since birth. At 3 months of age, he develops heart failure, respiratory impairment, and neurological deterioration. The echocardiogram revealed concentric hypertrophic cardiomyopathy with left-diastolic dysfunction. We found increased creatine-phosphokinase, lactate dehydrogenase, and urinary glucose tetrasaccharide levels, 50% of PAS-positive vacuolated lymphocytes in the peripheral blood smear, and low GAA activity. Sequencing of coding exons and flanking intronic sequences revealed a novel homozygous 4 bp deletion in exon 15 of the GAA gene (c.2066_2069delAGCC/p.Glu689Glyfs*6). IOPD was diagnosed. At 5 months old, we started enzyme replacement therapy with an alpha-alglucosidase of 20 mg/kg weekly and immunomodulation with intravenous immunoglobulin. He developed two cardiorespiratory arrests with subsequent neurologic deterioration, convulsive crisis, and respiratory failure and died at 9 months old. We found the usual PD hallmarks in the heart, striated muscle, and liver but also we found neuronal lesions characterized by cytoplasm vacuolization with PAS-positive granules in the central nervous system and myenteric plexus. We describe a novel GAA gene pathogenic variant with a particular phenotype characterized by classic IOPD and neurologic histopathological findings. Enhancing the knowledge of lysosomal diseases is critical to improving the diagnosis and treatment of these patients.

Assuntos

Cardiomiopatia Hipertrófica , Doença de Depósito de Glicogênio Tipo II , Cardiomiopatia Hipertrófica/genética , Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/patologia , Humanos , Masculino , Músculo Esquelético/patologia , alfa-Glucosidases/genética

RESUMO

Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities.