RESUMO
BACKGROUND: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them. AIM: The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing. METHODS: This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients. RESULTS: During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed. CONCLUSION: The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Gammaproteobacteria , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Centros de Atenção Terciária , beta-Lactamases/genéticaRESUMO
PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status. Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase was performed. Clinical characteristics and prognostic relevance were assessed. RESULTS: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H) tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI-L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of overall and disease-free survival were similar between EMAST and non-EMAST tumors. CONCLUSION: EMAST is more closely related to MSI-H than MSI-L or MSS status. The clinical and molecular characteristics of EMAST were distinct in terms of tumor location, thymidylate synthase expression, MSI status and hMSH3 expression. Our preliminary findings support the utility of EMAST as a new potential classifier in CRC.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Repetições de Microssatélites/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Fenótipo , PrognósticoRESUMO
AIDS: Gene therapy is a descriptive term for a method of correcting a disease by genetic manipulation. Early reports of rapid progress in gene therapy for HIV have been exaggerated, and many in the research community have called for an increased emphasis on basic research. Several different approaches to gene therapy, gene transfer methods, antiviral gene therapies, CD8 HIV-specific cytotoxic T-cells, ribozymes, and transdominant negative mutants, are briefly discussed. Although this is a promising field of research for HIV treatments, effective tools are not expected for another three to five years.^ieng
Assuntos
Terapia Genética , Infecções por HIV/terapia , Técnicas de Transferência de Genes , Vetores Genéticos , HumanosRESUMO
AIDS: The Food and Drug Administration (FDA) approved the first protease inhibitor, saquinavir, for combination treatment with approved nucleoside analogs in adults with advanced HIV. However, it denied the use of saquinavir as a monotherapy. Protease inhibitors prevent infected cells from reproducing viral particles. All saquinavir studies have used a dose of 600mg 3 times per day. Another formulation of saquinavir and higher dosages of the present formulation are being tested to increase the bioavailability. In AZT-naive patients, a combination of saquinavir and AZT produces better improvements in CD4 counts and in viral load reduction compared to either of the drugs alone. In patients with extensive prior AZT therapy, saquinavir in combination with ddC provided greater and longer surrogate marker benefits compared to either drug alone. Saquinavir also improved the activity of ddC plus AZT. The most common side effects were diarrhea and nausea. Altogether, only four percent of patients receiving saquinavir had side effects. Toxicity was not increased when saquinavir was added to AZT and ddC. Cross resistance to other PIs has been found, so the use of saquinavir may limit the benefits of future PIs.^ieng
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Isoquinolinas/uso terapêutico , Quinolinas/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Quimioterapia Combinada , HIV/efeitos dos fármacos , HIV/fisiologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Saquinavir , Replicação Viral/efeitos dos fármacos , Zidovudina/administração & dosagem , Zidovudina/uso terapêuticoRESUMO
AIDS: The Fifth European Conference on Clinical Aspects and Treatment of HIV Infection, held in Denmark in 1995, included presentations on protease inhibitor drugs. Highlights from these presentations, as well as those on the issue of cross-resistance, are presented. In addition, some recent results from the European/Australian Delta study that compared AZT/ddI and AZT/ddC with AZT monotherapy are presented. The results indicate that adding ddI or ddC to AZT significantly improves survival and delays clinical progression in individuals with no prior antiretroviral therapy. Final comments address smaller studies, and results supporting Delta's findings are highlighted.^ieng
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV , Contagem de Linfócito CD4 , Ensaios Clínicos como Assunto , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , HIV-1/genética , HumanosRESUMO
AIDS: An overview of the Fourth International Workshop on HIV Drug Resistance held in 1995 is presented. Topics concern the dual resistance to AZT and 3TC, viral resistance to protease inhibitors, and recent laboratory findings on viral resistance patterns that have provided impetus for the design of clinical studies to evaluate rational combinations of protease inhibitors. VX-478, indinavir, and ritonavir study data are presented.^ieng
Assuntos
Antivirais/farmacologia , Resistência Microbiana a Medicamentos , Inibidores da Protease de HIV/farmacologia , HIV/efeitos dos fármacos , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Carbamatos , Furanos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Humanos , Indinavir , Isoquinolinas/farmacologia , Isoquinolinas/uso terapêutico , Lamivudina , Piridinas/farmacologia , Piridinas/uso terapêutico , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Ritonavir , Saquinavir , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Valina/farmacologia , Valina/uso terapêutico , Viremia , Zalcitabina/análogos & derivados , Zalcitabina/farmacologia , Zalcitabina/uso terapêutico , Zidovudina/farmacologia , Zidovudina/uso terapêuticoRESUMO
AIDS: The authors examine the development, theories, research, and use of antivirals in the response to HIV infection and AIDS progression and address the question of how effective this novel approach may be. The article includes discussions that detail the antisense and triple helix candidates for HIV and related conditions, the hurdles that exist in the development of antisense oligonucleotides, and the way triple helix and antisense oligonucleotides disrupt a genetic message.^ieng
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Oligodesoxirribonucleotídeos Antissenso , Oligonucleotídeos Antissenso/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/metabolismo , Antivirais/farmacologia , Sítios de Ligação , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , DNA Viral/metabolismo , HIV/genética , Humanos , Conformação de Ácido Nucleico , Oligonucleotídeos Antissenso/metabolismo , Oligonucleotídeos Antissenso/farmacologia , RNA Viral/metabolismo , Tionucleotídeos/farmacologia , Tionucleotídeos/uso terapêuticoRESUMO
AIDS: Scientists will undertake the first clinical study using gene therapy against HIV by giving cells the gene for a double ribozyme, which cleaves HIV's genetic RNA material at two distinct sites. The double ribozyme has exhibited more potent anti-HIV effects in cell cultures than the single ribozyme, the U5 hairpin, used in previous studies and may be less vulnerable to resistance. In phase I of the proposed study, white blood cells will be removed from six HIV-infected volunteers on AZT therapy with CD4 counts greater than 250. CD4 cells will be selected out, proliferated, and infected with a harmless virus shell containing the gene for the double ribozyme. Cells will be infused back into the body and tracked for number and longevity.^ieng