RESUMEN
The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.
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Fármacos Gastrointestinales , Péptidos , Sistema de Registros , Síndrome del Intestino Corto , Humanos , Síndrome del Intestino Corto/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Péptidos/uso terapéutico , Adulto , Anciano , Fármacos Gastrointestinales/uso terapéutico , Insuficiencia Intestinal/tratamiento farmacológico , Resultado del Tratamiento , Enfermedad de Crohn/tratamiento farmacológicoRESUMEN
Positive thinking is a form of positive cognition and a coping strategy. The Positive Thinking Scale (PTS) is used to measure positive thinking, but the reliability and validity of the PTS-Chinese have yet to be tested. This study aims to examine the psychometric properties of the PTS-Chinese. A total of 154 patients post-hip fracture surgery completed the questionnaire in a hospital in Taiwan between April 2020 and December 2020. The scales in the questionnaire included the PTS, Automatic Thoughts Questionnaire-Positive, Automatic Thoughts Questionnaire-Negative, Barthel Index, and items related to happiness, demographics, and disease treatment. The results of the confirmatory factor analysis and average variance extracted show that the PTS-Chinese version exhibits construct validity. Scores on the PTS-Chinese version are positively related to scores on the Automatic Thoughts Questionnaire-Positive and happiness items and negatively related to scores on the Automatic Thoughts Questionnaire-Negative. This finding indicates that the PTS-Chinese demonstrates concurrent, predictive, and discriminant validity. The scale also presents acceptable reliability and test-retest reliability. Overall, the PTS-Chinese can be used to evaluate and track the positive thinking of patients. Further studies are needed to assess the psychometric properties of the PTS-Chinese in different cultures and ethnic groups.
RESUMEN
Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section and (d) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; CDSR (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.
Asunto(s)
Bibliometría , Factor de Impacto de la Revista , Brasil , Prevalencia , Revisiones Sistemáticas como AsuntoRESUMEN
Positive thinking is a form of positive cognition and a coping strategy. The Positive Thinking Scale (PTS) is used to measure positive thinking, but the reliability and validity of the PTS-Chinese have yet to be tested. This study aims to examine the psychometric properties of the PTS-Chinese. A total of 154 patients post-hip fracture surgery completed the questionnaire in a hospital in Taiwan between April 2020 and December 2020. The scales in the questionnaire included the PTS, Automatic Thoughts Questionnaire-Positive, Automatic Thoughts Questionnaire-Negative, Barthel Index, and items related to happiness, demographics, and disease treatment. The results of the confirmatory factor analysis and average variance extracted show that the PTS-Chinese version exhibits construct validity. Scores on the PTS-Chinese version are positively related to scores on the Automatic Thoughts Questionnaire-Positive and happiness items and negatively related to scores on the Automatic Thoughts Questionnaire-Negative. This finding indicates that the PTS-Chinese demonstrates concurrent, predictive, and discriminant validity. The scale also presents acceptable reliability and test-retest reliability. Overall, the PTS-Chinese can be used to evaluate and track the positive thinking of patients. Further studies are needed to assess the psychometric properties of the PTS-Chinese in different cultures and ethnic groups. (AU)
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Humanos , Masculino , Femenino , Anciano , Pacientes/psicología , Comparación Transcultural , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Optimismo , Psicometría , China , Análisis Factorial , Fracturas de Cadera/cirugíaRESUMEN
INTRODUCTION AND OBJECTIVES: HBV covalently closed circular (ccc) DNA is the key player in viral persistence and an important predictive biomarker for hepatitis relapse. Precise quantification of intracellular cccDNA is challenging because cccDNA is present in very low levels in hepatocytes, where it also co-exists with a large excess amount of relaxed circular (rc) DNA. We aimed to develop a highly sensitive cccDNA detection method for cccDNA quantification by digital PCR (dPCR). PATIENTS OR MATERIALS AND METHODS: A standard plasmid containing the whole HBV genome in the closed circular conformation was employed to characterize the performance of dPCR. rcDNA in the growth medium of HBV-producing HepAD38 cells was used as a matrix for cccDNA detection. Intrahepatic cccDNA measurement by dPCR and qPCR was performed to determine the correlation of the analysis results for the two methods. RESULTS: The limit of detection (LOD) of the cccDNA dPCR was 1.05copy/µl, and the linear range of detection was 1.02×104copies/µl, achieving a dynamic detection range of 104-fold. cccDNA measurement using excess rcDNA as the matrix did not reveal false-positive detection, indicating that dPCR was highly specific. In the HepAD38 cells, the cccDNA levels measured by dPCR were highly correlated with those measured by qPCR but had a higher sensitivity. The CDK inhibitor AZD-5438 was found to block intracellular cccDNA synthesis. CONCLUSIONS: Dpcr greatly improved the sensitivity and specificity of cccDNA detection. Host CDK activities are likely required for cccDNA synthesis. dPCR can potentially be applied for drug screening for effective cccDNA inhibitors.
Asunto(s)
Quinasas Ciclina-Dependientes/metabolismo , ADN Circular/análisis , ADN Viral/análisis , Virus de la Hepatitis B/genética , Hepatocitos/metabolismo , Reacción en Cadena de la Polimerasa/métodos , Línea Celular , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , ADN Circular/biosíntesis , ADN Viral/biosíntesis , Virus de la Hepatitis B/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Humanos , Imidazoles/farmacología , Pirimidinas/farmacologíaRESUMEN
Abstract Introduction: Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. Objective: To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. Methods: This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. Results: A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p = 0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age > 65 years) with an odds ratio (OR) of 2.76 (p = 0.03), and decreased in the hot season (mean temperature > 26 °C) (OR = 0.49, p = 0.04). No specific microorganism was associated with prolonged hospital stay. Conclusion: The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors.
Resumo Introdução: O Abscesso Peritonsilar é a infecção cervical profunda mais comum. O microrganismo infeccioso pode ser diferente de acordo com os fatores clínicos. Objetivo: Identificar o principal agente causador do abscesso peritonsilar e investigar a relação entre o patógeno causador, os fatores clínicos do hospedeiro e a duração da hospitalização. Método: Este estudo retrospectivo incluiu 415 pacientes hospitalizados diagnosticados com abscesso peritonsilar que foram internados em um centro médico terciário de junho de 1990 a junho de 2013. Coletamos dados através da análise dos arquivos médicos dos pacientes e analisamos variáveis como características demográficas, doença sistêmica subjacente, tabagismo, alcoolismo, hábito de mascar noz de betel, bacteriologia e duração da hospitalização. Resultados: Um total de 168 pacientes apresentaram resultados positivos para isolamento de patógenos. Streptococcus viridans (28,57%) e Klebsiella pneumoniae (23,21%) foram os microrganismos mais comuns identificados pela cultura da secreção. A taxa de isolamento de anaeróbios aumentou para 49,35% nos últimos 6 anos (p = 0,048). Os anaeróbios comuns foram Prevotella e Fusobacterium spp. A identificação de K. pneumoniae aumentou em pacientes idosos (idade > 65 anos) com razão de chances (Odds Ratio - OR) de 2,76 (p = 0,03) e diminuiu na estação do calor (temperatura média > 26 °C) (OR = 0,49, p = 0,04). Nenhum microrganismo específico foi associado à hospitalização prolongada. Conclusão: O patógeno mais comumente identificado através da cultura de secreção foi S. viridans, seguido por K. pneumoniae. A identificação de anaeróbios mostrou ter aumentado nos últimos anos. Os antibióticos selecionados inicialmente devem ser efetivos contra aeróbios e anaeróbios. A identificação bacteriana pode estar associada a fatores clínicos e fatores ambientais do hospedeiro.
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Humanos , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Absceso Peritonsilar/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Fusobacterium necrophorum/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Klebsiella , Absceso Peritonsilar/diagnóstico , Absceso Peritonsilar/terapia , Estudios Retrospectivos , Factores de Riesgo , Infecciones por Bacterias Grampositivas/terapia , Prevotella , Estreptococos Viridans/aislamiento & purificación , Infecciones por Fusobacterium/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Antibacterianos/uso terapéuticoRESUMEN
INTRODUCTION AND AIM: Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients. MATERIAL AND METHODS: The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence. RESULTS: NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2 level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. CONCLUSIONS: NEK2 plays a significant role in cell cycle progression in the inter- and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Quinasas Relacionadas con NIMA/metabolismo , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antígenos CD/metabolismo , Biomarcadores de Tumor/genética , Cadherinas/metabolismo , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Ciclina D1/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Quinasas Relacionadas con NIMA/genética , Invasividad Neoplásica , Estadificación de Neoplasias , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Riesgo , Transducción de Señal , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. OBJECTIVE: To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. METHODS: This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. RESULTS: A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p=0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age>65 years) with an odds ratio (OR) of 2.76 (p=0.03), and decreased in the hot season (mean temperature>26°C) (OR=0.49, p=0.04). No specific microorganism was associated with prolonged hospital stay. CONCLUSION: The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors.
Asunto(s)
Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Absceso Peritonsilar/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Infecciones por Fusobacterium/microbiología , Fusobacterium necrophorum/aislamiento & purificación , Infecciones por Bacterias Grampositivas/terapia , Humanos , Infecciones por Klebsiella , Klebsiella pneumoniae/aislamiento & purificación , Persona de Mediana Edad , Absceso Peritonsilar/diagnóstico , Absceso Peritonsilar/terapia , Prevotella , Estudios Retrospectivos , Factores de Riesgo , Estreptococos Viridans/aislamiento & purificación , Adulto JovenRESUMEN
INTRODUCTION: Experimental and clinical evidence points to a critical role of progesterone and the nuclear progesterone receptor (PR) in controlling mammary gland tumorigenesis. However, the molecular mechanisms of progesterone action in breast cancer still remain elusive. On the other hand, micro RNAs (miRNAs) are short ribonucleic acids which have also been found to play a pivotal role in cancer pathogenesis. The role of miRNA in progestin-induced breast cancer is poorly explored. In this study we explored progestin modulation of miRNA expression in mammary tumorigenesis. METHODS: We performed a genome-wide study to explore progestin-mediated regulation of miRNA expression in breast cancer. miR-16 expression was studied by RT-qPCR in cancer cell lines with silenced PR, signal transducer and activator of transcription 3 (Stat3) or c-Myc, treated or not with progestins. Breast cancer cells were transfected with the precursor of miR-16 and proliferation assays, Western blots or in vivo experiments were performed. Target genes of miR-16 were searched through a bioinformatical approach, and the study was focused on cyclin E. Reporter gene assays were performed to confirm that cyclin E 3'UTR is a direct target of miR-16. RESULTS: We found that nine miRNAs were upregulated and seven were downregulated by progestin in mammary tumor cells. miR-16, whose function as a tumor suppressor in leukemia has already been shown, was identified as one of the downregulated miRNAs in murine and human breast cancer cells. Progestin induced a decrease in miR-16 levels via the classical PR and through a hierarchical interplay between Stat3 and the oncogenic transcription factor c-Myc. A search for miR-16 targets showed that the CCNE1 gene, encoding the cell cycle regulator cyclin E, contains conserved putative miR-16 target sites in its mRNA 3' UTR region. We found that, similar to the molecular mechanism underlying progestin-modulated miR-16 expression, Stat3 and c-Myc participated in the induction of cyclin E expression by progestin. Moreover, overexpression of miR-16 abrogated the ability of progestin to induce cyclin E upregulation, revealing that cyclin E is a novel target of miR-16 in breast cancer. Overexpression of miR-16 also inhibited progestin-induced breast tumor growth in vitro and in vivo, demonstrating for the first time, a role for miR-16 as a tumor suppressor in mammary tumorigenesis. We also found that the ErbB ligand heregulin (HRG) downregulated the expression of miR-16, which then participates in the proliferative activity of HRG in breast tumor cells. CONCLUSIONS: In this study, we reveal the first progestin-regulated miRNA expression profile and identify a novel role for miR-16 as a tumor suppressor in progestin- and growth factor-induced growth in breast cancer.