RESUMEN

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).

Asunto(s)

Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae , Gammaproteobacteria , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/epidemiología , Humanos , Centros de Atención Terciaria , beta-Lactamasas/genética

RESUMEN

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.

Asunto(s)

Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Repeticiones de Microsatélite/genética , Anciano , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Inestabilidad de Microsatélites , Fenotipo , Pronóstico

RESUMEN

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

Asunto(s)

Terapia Genética , Infecciones por VIH/terapia , Técnicas de Transferencia de Gen , Vectores Genéticos , Humanos

RESUMEN

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

Asunto(s)

Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Isoquinolinas/uso terapéutico , Quinolinas/uso terapéutico , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Quimioterapia Combinada , VIH/efectos de los fármacos , VIH/fisiología , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/farmacocinética , Humanos , Isoquinolinas/administración & dosificación , Isoquinolinas/efectos adversos , Isoquinolinas/farmacocinética , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/farmacocinética , Saquinavir , Replicación Viral/efectos de los fármacos , Zidovudina/administración & dosificación , Zidovudina/uso terapéutico

RESUMEN

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

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH , Recuento de Linfocito CD4 , Ensayos Clínicos como Asunto , Farmacorresistencia Microbiana , Quimioterapia Combinada , VIH-1/genética , Humanos

RESUMEN

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

Asunto(s)

Antivirales/farmacología , Farmacorresistencia Microbiana , Inhibidores de la Proteasa del VIH/farmacología , VIH/efectos de los fármacos , Antivirales/uso terapéutico , Recuento de Linfocito CD4 , Carbamatos , Furanos , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Indinavir , Isoquinolinas/farmacología , Isoquinolinas/uso terapéutico , Lamivudine , Piridinas/farmacología , Piridinas/uso terapéutico , Quinolinas/farmacología , Quinolinas/uso terapéutico , Ritonavir , Saquinavir , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico , Valina/farmacología , Valina/uso terapéutico , Viremia , Zalcitabina/análogos & derivados , Zalcitabina/farmacología , Zalcitabina/uso terapéutico , Zidovudina/farmacología , Zidovudina/uso terapéutico

RESUMEN

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

Asunto(s)

Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH/efectos de los fármacos , Oligodesoxirribonucleótidos Antisentido , Oligonucleótidos Antisentido/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antivirales/metabolismo , Antivirales/farmacología , Sitios de Unión , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Retinitis por Citomegalovirus/complicaciones , Retinitis por Citomegalovirus/tratamiento farmacológico , ADN Viral/metabolismo , VIH/genética , Humanos , Conformación de Ácido Nucleico , Oligonucleótidos Antisentido/metabolismo , Oligonucleótidos Antisentido/farmacología , ARN Viral/metabolismo , Tionucleótidos/farmacología , Tionucleótidos/uso terapéutico

RESUMEN

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

Asunto(s)

Terapia Genética , Infecciones por VIH/terapia , ARN Catalítico/genética , VIH/fisiología , Infecciones por VIH/genética , Humanos