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BACKGROUND: Herpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment. CASE PRESENTATION: A 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity. CONCLUSIONS: Clinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.
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Encefalite por Herpes Simples , Encefalite , Herpes Simples , Herpesvirus Humano 1 , Miocardite , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Herpesvirus Humano 1/genética , Miocardite/tratamento farmacológico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Aciclovir/uso terapêutico , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Encefalite por Herpes Simples/tratamento farmacológicoRESUMO
Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently the two leading causes of death among infectious diseases. As we progress towards a "new normal", more information is required regarding post-COVID-19 syndromes. We present a case of latent tuberculosis reactivation 3 months after a successful inpatient treatment of COVID-19. A 74-year-old female from the Philippines presented with a new left mid-lung infiltrate with worsening shortness of breath and lethargy for one week prior to admission. The clinical course of the patient deteriorated despite broad-spectrum antibiotics, diuretics, and high-dose steroid therapy requiring intubation and mechanical ventilation. Her sputum culture yielded the microbiological diagnosis of TB. Anti-tubercular medications were started and the patient had a favorable clinical outcome. Our case demonstrates that immunosuppression secondary to COVID-19 and its treatments may promote the development of an active TB infection from a latent infection. It is important to be aware of this potential increase in risk during and after a COVID-19 treatment. This is especially important in high-risk populations to ensure an early diagnosis and prompt management as well as to reduce transmission.
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Septic shock is the most common type of shock in the intensive care unit with an associated mortality close to 50%. Infective endocarditis (IE) is a rare cause of septic shock but carries significant morbidity and mortality. Group B Streptococcus IE (GBS-IE) is an invasive infection with an incidence of approximately 1.7%. It affects immunocompromised patients such as intravenous drug users, alcoholics, those with HIV and elderly among others. IE with severe acute valvular heart disease challenges physicians when assessing fluid status during the early resuscitation in patients with septic shock. We present a case of GBS-IE complicated by severe acute aortic regurgitation with rapidly progressive acute respiratory failure in the setting of septic shock management.
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Insuficiência da Valva Aórtica/diagnóstico , Endocardite Bacteriana/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae , Alcoolismo , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico por imagem , Diabetes Mellitus Tipo 2 , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico por imagem , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Choque Séptico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico por imagemRESUMO
INTRODUCTION: Zika virus, an arbovirus of the Flaviviridae family, is a mosquito-borne virus known to cause microcephaly through vertical transmission. Infection presents with mild, self-limiting symptoms. Currently, a Zika virus outbreak has spread across most of South and Central America. Travel-related and sexually transmitted cases have been reported across the United States. However, the vector-borne transmission has been limited to Florida and Texas. We present seven cases of Zika virus infection that presented at a single institution in South Florida. METHODS: Patients were included that had real-time polymerase-chain reaction (RT-PCR) for Zika virus RNA in urine or serum or enzyme-linked immunosorbent assay (ELISA) for Immunoglobulin M (IgM) antibody against Zika virus in serum. RESULTS: All seven patients reported recent travel or employment in areas of active Zika virus transmission and at least two of the four most commonly reported symptoms (fever, arthralgia, rash, and conjunctivitis) with a rash present in all patients. All patients had positive RT-PCR for Zika virus RNA in urine. RT-PCR for Zika virus RNA in serum was negative in four of five patients that were tested, indicating that these patients likely presented one to two weeks after symptom onset. CONCLUSION: The future of Zika virus outbreaks in other cities in the United States is still uncertain. However, it is clear that prevention and control policies are urgently needed. We have presented seven confirmed cases of Zika virus infection in South Florida. In addition to conducting research concerning both the diagnostic and therapeutic aspects of the virus, there is a need for public awareness of its presentation, methods of transmission, and subsequent clinical outcomes.
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Kruppel-like factor 6 splice variant 1 (KLF6-SV1) is an oncogenic splice variant of the KLF6 tumor suppressor gene that is specifically overexpressed in a number of human cancers. Previously, we have demonstrated that increased expression of KLF6-SV1 is associated with decreased survival in lung adenocarcinoma patient samples and that targeted reduction of KLF6-SV1 using siRNA induced apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Here, we demonstrate that chemoresistant lung cancer cells express increased levels of KLF6-SV1. Furthermore, targeted reduction of KLF6-SV1 using RNA interference restores chemotherapy sensitivity to lung cancer cells both in culture and in vivo through induction of apoptosis. Conversely, overexpression of KLF6-SV1 resulted in a marked reduction in chemotherapy sensitivity in a tumor xenograft model. Combined, these findings highlight a functional role for the KLF6-SV1 splice variant in the regulation of chemotherapy response in lung cancer and could provide novel insight into lung cancer therapy.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Fator 6 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , Transdução GenéticaRESUMO
Gastric cancer is the second most common cancer and a leading cause of cancer-related death worldwide. The Kruppel-like factor 6 (KLF6) tumour suppressor gene had been previously shown to be inactivated in a number of human cancers through loss of heterozygosity (LOH), somatic mutation, decreased expression and increased alternative splicing into a dominant negative oncogenic splice variant, KLF6-SV1. In the present study, 37 gastric cancer samples were analysed for the presence of loss of heterozygosity (LOH) of the KLF6 locus and somatic mutation. In total, 18 of 34 (53%) of the gastric cancer samples analysed demonstrated KLF6 locus specific loss. Four missense mutations, such as T179I, R198G, R71Q and S180L, were detected. Interestingly, two of these mutations R71Q and S180L have been identified independently by several groups in various malignancies including prostate, colorectal and gastric cancers. In addition, decreased wild-type KLF6 (wtKLF6) expression was associated with loss of the KLF6 locus and was present in 48% of primary gastric tumour samples analysed. Functional studies confirmed that wtKLF6 suppressed proliferation of gastric cancer cells via transcriptional regulation of the cyclin-dependent kinase inhibitor p21 and the oncogene c-myc. Functional characterisation of the common tumour-derived mutants demonstrated that the mutant proteins fail to suppress proliferation and function as dominant negative regulators of wtKLF6 function. Furthermore, stable overexpression of the R71Q and S180L tumour-derived mutants in the gastric cancer cell line, Hs746T, resulted in an increased tumourigenicity in vivo. Combined, these findings suggest an important role for the KLF6 tumour suppressor gene in gastric cancer development and progression and identify several highly cancer-relevant signalling pathways regulated by the KLF6 tumour suppressor gene.