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1.
J Pediatr Hematol Oncol ; 44(6): e945-e947, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796591

RESUMO

Vanishing bile duct syndrome (VBDS) is a condition resulting from progressive destruction and loss of intrahepatic bile ducts leading to cholestasis, biliary cirrhosis, and liver failure. It occurs secondary to various pathologic conditions like autoimmune diseases, graft versus host disease, drug reactions, and as a paraneoplastic syndrome in malignancies. We here described a 9-year-old girl who presented with cervical lymphadenopathy and jaundice. This child was diagnosed as a case of Hodgkin lymphoma. All other causes of cholestasis were ruled out by appropriate investigations (particularly autoimmune, metabolic, infections, and drug-induced possibilities). On liver biopsy, her diagnosis was established as VBDS. In view of hepatic dysfunction, alternative chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was given, and she was started on hepatoprotective measures with ursodeoxycholic acid. Hepatic function gradually improved after the initiation of chemotherapy. VBDS is considered a dismal paraneoplastic syndrome with a high-case fatality. This case report highlights the importance of early recognition and initiation of appropriate full-dose chemotherapy as the only way to achieve complete resolution of VBDS.


Assuntos
Colestase , Doença de Hodgkin , Icterícia , Síndromes Paraneoplásicas , Ductos Biliares Intra-Hepáticos/patologia , Criança , Colestase/etiologia , Feminino , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Icterícia/complicações , Icterícia/patologia
2.
Neurol India ; 70(3): 953-959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864624

RESUMO

Background: Introduction: Gliomas were previously classified histologically, although now the latest WHO classification incorporates several molecular markers to classify these. Detection of TERT promoter mutations is assuming increased importance due to its relevance to prognostication. Objective: : The aim of this study was to determine the frequency of TERT promoter mutations, association of TERT promoter mutations with other molecular alterations and to assess the role of TERT promoter mutations in overall survival and progression-free survival in relation to histological and molecular glioma subtypes. Materials and Methods: This study analyzed a cohort of 107 adult patients with diffuse gliomas, WHO grades II and III and glioblastoma, by immunohistochemistry for IDH and ATRX mutations, FISH for 1p/19q co-deletions and PCR sequencing for TERT promoter mutation. Further, five glioma molecular sub-groups were derived using three molecular alteration and included the sub-groups with: i) IDH mutations only, ii) IDH and TERT mutations only, iii) IDH and 1p/19q co-deletion only, iv) Triple negative, and v) Triple positive. Results: IDH mutations and 1p/19q co-deletions were individually and significantly associated with an improved progression free (P = 0.001 and P = 0.002, respectively) and overall survival (P = 0.000 and P = 0.005, respectively) in the present cohort of gliomas. TERT promoter mutations occurred frequently in anaplastic oligodendrogliomas (94%), oligodendrogliomas (87.5%) and glioblastomas (54%). Sub-division into molecular sub-groups showed that the triple-positive tumors carried the best prognosis, followed by IDH only, triple negative and finally the TERT mutation only tumors (P < 0.000). Conclusion: : This indicates that sub-classification using these molecular markers separates tumors into prognostically relevant categories.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Regiões Promotoras Genéticas , Telomerase , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Mutação/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Telomerase/genética
4.
Lancet Infect Dis ; 16(8): 905-14, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27156189

RESUMO

BACKGROUND: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. METHODS: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. FINDINGS: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk ratio 0·94, 95% CI 0·81-1·08; p=0·366). Azithromycin reduced faecal biomarkers of environmental enteropathy (calprotectin, myeloperoxidase, α1-antitrypsin) and the prevalence of bacterial but not viral or eukaryotic pathogens. Viral pathogens were associated with lower seroconversion. Three serious adverse events were reported (two in the azithromycin group and one in the placebo group), but none was considered related to the study interventions. INTERPRETATION: Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria. Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Vacina Antipólio Oral/administração & dosagem , Anticorpos Antivirais/sangue , Método Duplo-Cego , Humanos , Esquemas de Imunização , Imunogenicidade da Vacina , Índia , Lactente , Poliomielite/prevenção & controle , Poliovirus/imunologia , Vacina Antipólio Oral/imunologia , Vacinação/métodos
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