Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
Int J Cancer ; 154(4): 679-691, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37861205

RESUMEN

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.


Asunto(s)
Metilación de ADN , Neoplasias Ováricas , Humanos , Femenino , Estudios de Casos y Controles , Estudios Prospectivos , Detección Precoz del Cáncer/métodos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Biomarcadores de Tumor/genética , Antígeno Ca-125 , Factores de Transcripción de Tipo Kruppel/genética
2.
Int J Cancer ; 155(5): 800-806, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38739012

RESUMEN

Endometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need. Here, we demonstrate that the stability of the WID-qEC test remains consistent regardless of: (i) the cervicovaginal collection device and sample media used (Cervex brush and PreservCyt or FLOQSwab and eNAT), (ii) the collector of the specimen (gynaecologist- or patient-based), and (iii) the precise sampling site (cervical, cervicovaginal and vaginal). Furthermore, we demonstrate sample stability in eNAT medium for 7 days at room temperature, greatly facilitating the implementation of the test into diagnostic laboratory workflows. When applying FLOQSwabs (Copan) in combination with the eNAT (Copan) sample collection media, the sensitivity and specificity of the WID-qEC test to detect uterine (i.e., endometrial and cervical) cancers in gynaecologist-taken samples was 92.9% (95% confidence interval [CI] = 75.0%-98.8%) and 98.6% (95% CI = 91.7%-99.9%), respectively, whilst the sensitivity and specificity in patient collected self-samples was 75.0% (95% CI = 47.4%-91.7%) and 100.0% (95% CI = 93.9%-100.0%), respectively. Taken together these data confirm the robustness and clinical potential of the WID-qEC test.


Asunto(s)
Metilación de ADN , Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/genética , Neoplasias Endometriales/diagnóstico , Manejo de Especímenes/métodos , Persona de Mediana Edad , Sensibilidad y Especificidad , Neoplasias Uterinas/genética , Neoplasias Uterinas/diagnóstico , Anciano , Detección Precoz del Cáncer/métodos , Adulto , Biomarcadores de Tumor/genética
3.
J Emerg Nurs ; 50(2): 187-191, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37999694

RESUMEN

INTRODUCTION: Nurses' preparedness to provide hemorrhage control aid outside of the patient care setting has not been thoroughly evaluated. We evaluated nurses' preparedness to provide hemorrhage control in the prehospital setting after a proof-of-concept training event. METHODS: We performed a secondary analysis of evaluations from a voluntary hemorrhage control training offered to a group of experienced nurses. Education was provided by a nurse certified in Stop the Bleed training and using the Basic Bleeding Control 2.0 materials. The training lasted approximately 1 hour and included a didactic portion followed by hands-on practice with task trainer legs. Participants were surveyed after training to assess their preparedness to provide hemorrhage control aid using a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree); comments and feedback were also requested. Mean (SD) was used to analyze Likert scale data. Content analysis was performed to identify common themes in qualitative data. RESULTS: Forty-five experienced nurses participated in the voluntary training. Nursing experience included obstetrics, pediatrics, critical care, acute care, community health, and psychiatric/mental health. Only 39% of participants reported having previously completed a similar course. After training completion, participants reported an increase in their preparedness to provide hemorrhage control aid (mean 3.47 [SD = 1.40] vs mean 4.8 SD [.04], P < .01). Major themes identified included wanting to feel prepared to help others, refreshing skills, and knowing how to respond in an emergency. DISCUSSION: Regardless of background and experience, nurses may benefit from more advanced hemorrhage control education to prepare them to provide aid in prehospital emergency settings.


Asunto(s)
Hemorragia , Enfermeras y Enfermeros , Embarazo , Femenino , Humanos , Niño , Hemorragia/prevención & control , Salud Pública , Escolaridad , Cuidados Críticos , Encuestas y Cuestionarios
4.
J Emerg Nurs ; 50(1): 44-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37930287

RESUMEN

INTRODUCTION: Accurate triage assessment by emergency nurses is essential for prioritizing patient care and providing appropriate treatment. Undertriage and overtriage remain an ongoing issue in care of patients who present to the emergency department. The purpose of this literature review was to examine factors associated with triage accuracy in the emergency department. METHODS: We conducted an evidence-based literature review using the Cumulative Index to Nursing and Allied Health Literature, PubMed, and Embase. The search focused on peer-reviewed articles in English, available in full text, published between January 2011 and December 2021. RESULTS: A total of 14 articles met inclusion criteria and revealed the following 3 themes for triage accuracy: triage nurse characteristics, patient characteristics, and work environment. Triage nurses' accuracy rates ranged from 59.3% to 82%, with experience in triage associated with higher accuracy. Patient characteristics influenced triage accuracy, with nontrauma patients being undertriaged and trauma patients often overtriaged. The work environment played a role, as accuracy rates varied based on shift time and patient volume. Competing systems between prehospital and ED triage posed challenges and affected accuracy during fluctuations in patient volumes. DISCUSSION: This review underscores the complex nature of ED triage accuracy. It highlights the importance of nurse experience, training programs, patient characteristics, and the work environment in enhancing triage decision making. Enhanced understanding of these factors can inform strategies to optimize triage accuracy and improve patient outcomes.


Asunto(s)
Servicio de Urgencia en Hospital , Triaje , Humanos
5.
Lancet Oncol ; 24(12): 1375-1386, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37944542

RESUMEN

BACKGROUND: To detect uterine cancer, simpler and more specific index tests are needed to triage women with abnormal uterine bleeding to a reference histology test. We aimed to compare the performance of conventional index imaging tests with the novel WID-qEC DNA methylation test in terms of detecting the presence or absence of uterine cancers in women with abnormal uterine bleeding. METHODS: EPI-SURE was a prospective, observational study that invited all women aged 45 years and older with abnormal uterine bleeding attending a tertiary gynaecological diagnostic referral centre at University College London Hospital (London, UK) to participate. Women meeting these inclusion criteria who consented to participate were included. Pregnant women and those with previous hysterectomy were excluded. A cervicovaginal sample for the WID-qEC test was obtained before standard assessment using index imaging tests (ie, ultrasound) and, where applicable, reference histology (ie, biopsy, hysteroscopy, or both) was performed. Technicians performing the WID-qEC test were masked to the final clinical outcome. The result of the WID-qEC test is defined as the sum of the percentage of fully methylated reference (ΣPMR) of the ZSCAN12 and GYPC regions. Patients were followed until diagnostic resolution or until June 12, 2023. The primary outcome was to assess the real-world performance of the WID-qEC test in comparison with ultrasound with regard to the area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. EPI-SURE is registered with ISRCTN (16815568). FINDINGS: From June 1, 2022, to Nov 24, 2022, 474 women were deemed eligible to participate. 74 did not accept the invitation to participate, and one woman withdrew after providing consent. 399 women were included in the primary analysis cohort. Based on 603 index imaging tests, 186 (47%) women were recommended for a reference histology test (ie, biopsy, hysteroscopy, or both). 12 women were diagnosed with cancer, 375 were not diagnosed with cancer, and 12 had inconclusive clinical outcomes and were considered study dropouts. 198 reference histology test procedures detected nine cases of cancer and missed two; one further cancer was directly diagnosed at hysterectomy without a previous reference test. The AUC for detection of uterine cancer based on endometrial thickness in mm was 87·2% (95% CI 71·1-100·0) versus 94·3% (84·7-100·0) based on WID-qEC (p=0·48). Endometrial thickness assessment on ultrasound scan was possible in 379 (95%) of the 399 women and a prespecified cut-off of 4·5 mm or more showed a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 79·1% (74·5-82·9), a positive predictive value of 11·8% (6·5-20·3), and a negative predictive value of 99·6% (98·0-99·9). The WID-qEC test was possible in 390 (98%) of the 399 patients with a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 92·1% (88·9-94·4), a positive predictive value of 25·6% (14·6-41·1), and a negative predictive value of 99·7% (98·3-99·9), when the prespecified threshold of 0·03 ΣPMR or more was applied. When a higher threshold (≥0·3 ΣPMR) was applied the specificity increased to 97·3% (95% CI 95·1-98·5) without a change in sensitivity. INTERPRETATION: The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and specifically reduce the false positive rate. FUNDING: The Eve Appeal, Land Tirol, and the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme.


Asunto(s)
Neoplasias Uterinas , Femenino , Humanos , Embarazo , Estudios Prospectivos , Sensibilidad y Especificidad , Reino Unido , Hemorragia Uterina/diagnóstico por imagen , Hemorragia Uterina/etiología , Hemorragia Uterina/patología , Neoplasias Uterinas/diagnóstico por imagen
6.
Int J Cancer ; 152(6): 1269-1274, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36056582

RESUMEN

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.


Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Estudios de Factibilidad , Endometrio/patología , Citodiagnóstico , Sensibilidad y Especificidad , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/patología , Displasia del Cuello del Útero/diagnóstico , Frotis Vaginal , Infecciones por Papillomavirus/diagnóstico
7.
Int J Cancer ; 152(9): 1977-1988, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36533702

RESUMEN

The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID-EC (Women's cancer risk IDentification-Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid-based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB). We validated the WID-EC test in an independent external validation set of 64 endometrial cancer cases and 225 controls. We further validated the test in 150 healthy women (prospective set) who provided a cervical sample as part of the routine Swedish cervical screening programme, 54 of whom developed endometrial cancer within 3 years of sample collection. The WID-EC test identified women with endometrial cancer with a receiver operator characteristic area under the curve (AUC) of 0.92 (95% CI: 0.88-0.97) in the external set and of 0.82 (95% CI: 0.74-0.89) in the prospective validation set. Using an optimal cutoff, cancer cases were detected with a sensitivity of 86% and a specificity of 90% in the external validation set, and a sensitivity and specificity of 52% and 98% respectively in the prospective validation set. The WID-EC test can identify women with or at risk of endometrial cancer.


Asunto(s)
Neoplasias Endometriales , Neoplasias del Cuello Uterino , Femenino , Humanos , Detección Precoz del Cáncer , Estudios de Casos y Controles , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Sensibilidad y Especificidad
8.
J Cutan Pathol ; 50(1): 62-65, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36054580

RESUMEN

Actinic keratoses (AKs) are pre-malignant skin lesions that can give rise to squamous cell carcinomas. Involvement of adnexal structures by AKs has been postulated to confer resistance to therapy and facilitate malignant progression. In our study, we identified several factors associated with increased risk of adnexal involvement of AKs. We found an increased risk of follicular involvement in AKs on the head and neck, a slightly increased risk of eccrine involvement with increasing age, and an increased risk of eccrine involvement in organ transplant patients. Additionally, our data showed a higher overall rate of follicular involvement of AKs than previously reported.


Asunto(s)
Carcinoma de Células Escamosas , Queratosis Actínica , Trasplante de Órganos , Neoplasias Cutáneas , Humanos , Queratosis Actínica/patología , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/patología , Piel/patología , Trasplante de Órganos/efectos adversos
9.
J Natl Compr Canc Netw ; 20(3): 285-308, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35276674

RESUMEN

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.


Asunto(s)
Linfadenopatía Inmunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/patología , Linfadenopatía Inmunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia
10.
J Trauma Nurs ; 29(3): 119-124, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35536339

RESUMEN

BACKGROUND: Uncontrolled hemorrhage is the primary preventable cause of death following trauma. Stop the Bleed training exists to promote identification and basic treatment of life-threatening bleeding in the prehospital or community setting. Limited qualitative research is available on participant evaluation of hemorrhage control training for laypersons. OBJECTIVE: To evaluate the experience and satisfaction with Stop the Bleed training among lay community members in an urban public school setting. METHODS: Three group interviews were conducted with public high school personnel (faculty and staff) who received Stop the Bleed training. Personnel were asked to evaluate the training and provide suggestions for improvement. Responses were digitally recorded and transcribed verbatim. Content analysis for common themes was performed using NVivo. RESULTS: A total of eight participants were interviewed. Participants expressed satisfaction with hands-on training and dissatisfaction with crowded and rushed training conditions. Major themes included: (1) skill acquisition, retention, and decay, (2) training format and setting, and (3) use of simulation. CONCLUSIONS: Current Stop the Bleed training is considered satisfactory among public school educators. Suggestions for improvement include annual retraining programs and simulation-enhanced training opportunities.


Asunto(s)
Hemorragia , Entrenamiento Simulado , Hemorragia/prevención & control , Humanos , Investigación Cualitativa , Instituciones Académicas
11.
Nurs Educ Perspect ; 42(4): 257-258, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32404770

RESUMEN

ABSTRACT: Effective teaching methods are critical to the acquisition of physical assessment skills. This article describes the combined use of deliberate practice, standardized patient simulation, and peer evaluation in improving physical assessment skills among first-semester nursing students. Students prepared for a physical assessment check-off by using deliberate practice throughout the semester; they then received peer feedback after a standardized patient simulation. Students felt the integrated experience improved their physical assessment performance. Incorporating this innovative educational trio can provide opportunities for physical assessment skill enhancement.


Asunto(s)
Bachillerato en Enfermería , Estudiantes de Enfermería , Competencia Clínica , Humanos , Simulación de Paciente , Examen Físico
12.
J Natl Compr Canc Netw ; 18(11): 1460-1467, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33152703

RESUMEN

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.


Asunto(s)
Linfoma de Células T , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/epidemiología , Linfoma de Células T/terapia , Guías de Práctica Clínica como Asunto , Pronóstico
13.
Proc Natl Acad Sci U S A ; 114(10): E1951-E1957, 2017 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-28223500

RESUMEN

Contact-dependent growth inhibition (CDI) is a mechanism by which bacteria exchange toxins via direct cell-to-cell contact. CDI systems are distributed widely among Gram-negative pathogens and are thought to mediate interstrain competition. Here, we describe tsf mutations that alter the coiled-coil domain of elongation factor Ts (EF-Ts) and confer resistance to the CdiA-CTEC869 tRNase toxin from enterohemorrhagic Escherichia coli EC869. Although EF-Ts is required for toxicity in vivo, our results indicate that it is dispensable for tRNase activity in vitro. We find that CdiA-CTEC869 binds to elongation factor Tu (EF-Tu) with high affinity and this interaction is critical for nuclease activity. Moreover, in vitro tRNase activity is GTP-dependent, suggesting that CdiA-CTEC869 only cleaves tRNA in the context of translationally active GTP·EF-Tu·tRNA ternary complexes. We propose that EF-Ts promotes the formation of GTP·EF-Tu·tRNA ternary complexes, thereby accelerating substrate turnover for rapid depletion of target-cell tRNA.


Asunto(s)
Endorribonucleasas/química , Escherichia coli Enterohemorrágica/genética , Proteínas de Escherichia coli/química , Regulación Bacteriana de la Expresión Génica , Proteínas de la Membrana/química , Factor Tu de Elongación Peptídica/química , Factores de Elongación de Péptidos/química , ARN de Transferencia/química , Antibiosis/genética , Secuencia de Bases , Sitios de Unión , Inhibición de Contacto/genética , Cristalografía por Rayos X , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Escherichia coli Enterohemorrágica/metabolismo , Escherichia coli Enterohemorrágica/patogenicidad , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Modelos Moleculares , Conformación de Ácido Nucleico , Factor Tu de Elongación Peptídica/genética , Factor Tu de Elongación Peptídica/metabolismo , Factores de Elongación de Péptidos/genética , Factores de Elongación de Péptidos/metabolismo , Unión Proteica , Biosíntesis de Proteínas , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , ARN de Transferencia/metabolismo , Especificidad por Sustrato
14.
Lancet Oncol ; 20(8): 1171-1182, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31300207

RESUMEN

BACKGROUND: Various factors-including age, family history, inflammation, reproductive factors, and tubal ligation-modulate the risk of ovarian cancer. In this study, our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome. METHODS: We did a case-control study in two sets of women aged 18-87 years in the Czech Republic, Germany, Italy, Norway, and the UK. The ovarian cancer set comprised women with epithelial ovarian cancer and controls (both healthy controls and those diagnosed with benign gynaecological conditions). The BRCA set comprised women with a BRCA1 mutation but without ovarian cancer and controls who were wild type for BRCA1 and BRCA2 (both healthy controls and those with benign gynaecological conditions). Cervicovaginal samples were gathered from all participants with the ThinPrep system and then underwent 16S rRNA gene sequencing. For each sample, we calculated the proportion of lactobacilli species (ie, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, and Lactobacillus jensenii), which are essential for the generation of a protective low vaginal pH, in the cervicovaginal microbiota. We grouped samples into those in which lactobacilli accounted for at least 50% of the species present (community type L) and those in which lactobacilli accounted for less than 50% of the species present (community type O). We assessed the adjusted association between BRCA1 status and ovarian cancer status and cervicovaginal microbiota community type, using a logistic regression model with a bias reduction method. FINDINGS: Participants were recruited between Jan 2, 2016, and July 21, 2018. The ovarian cancer set (n=360) comprised 176 women with epithelial ovarian cancer, 115 healthy controls and 69 controls with benign gynaecological conditions. The BRCA set (n=220) included 109 women with BRCA1 mutations, 97 healthy controls wild type for BRCA1 and BRCA2 and 14 controls with a benign gynaecological condition wild type for BRCA1 and BRCA2. On the basis of two-dimensional density plots, receiver-operating characteristic curve analysis, and age thresholds used previously, we divided the cohort into those younger than 50 years and those aged 50 years or older. In the ovarian cancer set, women aged 50 years or older had a higher prevalence of community type O microbiota (81 [61%] of 133 ovarian cancer cases and 84 [59%] of 142 healthy controls) than those younger than 50 years (23 [53%] of 43 cases and 12 [29%] of 42 controls). In the ovarian cancer set, women younger than 50 years with ovarian cancer had a significantly higher prevalence of community type O microbiota than did age-matched controls under a logistic regression model with bias correction (odds ratio [OR] 2·80 [95% CI 1·17-6·94]; p=0·020). In the BRCA set, women with BRCA1 mutations younger than 50 years were also more likely to have community type O microbiota than age-matched controls (OR 2·79 [95% CI 1·25-6·68]; p=0·012), after adjustment for pregnancy (ever). This risk was increased further if more than one first-degree family member was affected by any cancer (OR 5·26 [95% CI 1·83-15·30]; p=0·0022). In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status (eg, OR for community type O for cases aged <40 years in the ovarian cancer set 7·00 [95% CI 1·27-51·44], p=0·025; OR for community type O for BRCA1 mutation carriers aged <35 years in the BRCA set 4·40 [1·14-24·36], p=0·031). INTERPRETATION: The presence of ovarian cancer, or factors known to affect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with having a community type O cervicovaginal microbiota. Whether re-instatement of a community type L microbiome by using, for example, vaginal suppositories containing live lactobacilli, would alter the microbiomial composition higher up in the female genital tract and in the fallopian tubes (the site of origin of high-grade serous ovarian cancer), and whether such changes could translate into a reduced incidence of ovarian cancer, needs to be investigated. FUNDING: EU Horizon 2020 Research and Innovation Programme, EU Horizon 2020 European Research Council Programme, and The Eve Appeal.


Asunto(s)
Carcinoma Epitelial de Ovario/microbiología , Cuello del Útero/microbiología , Neoplasias Ováricas/microbiología , Vagina/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Carcinoma Epitelial de Ovario/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Microbiota , Persona de Mediana Edad , Neoplasias Ováricas/genética , Factores de Riesgo , Adulto Joven
15.
Mol Microbiol ; 109(4): 509-527, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29923643

RESUMEN

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems.


Asunto(s)
Antibacterianos/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Escherichia coli/metabolismo , Secuencia de Aminoácidos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , ARN de Transferencia/metabolismo , Análisis de Secuencia de Proteína
16.
Transfusion ; 59(8): 2699-2708, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31050809

RESUMEN

BACKGROUND: The mortality of trauma patients requiring massive transfusion to treat hemorrhagic shock approaches 17% at 24 hours and 26% at 30 days. The use of stored RBCs is limited to less than 42 days, so older RBCs are delivered first to rapidly bleeding trauma patients. Patients who receive a greater quantity of older RBCs may have a higher risk for mortality. METHODS AND MATERIALS: Characterizing blood age exposure requires accounting for the age of each RBC unit and the quantity of transfused units. To address this challenge, a novel Scalar Age of Blood Index (SBI) that represents the relative distribution of RBCs received is introduced and applied to a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial (NCT01545232, https://clinicaltrials.gov/ct2/show/NCT01545232). The effect of the SBI is assessed on the primary PROPPR outcome, 24-hour and 30-day mortality. RESULTS: The distributions of blood storage ages successfully maps to a parameter (SBI) that fully defines the blood age curve for each patient. SBI was a significant predictor of 24-hour and 30-day mortality in an adjusted model that had strong predictive ability (odds ratio, 1.15 [1.01-1.29], p = 0.029, C-statistic, 0.81; odds ratio, 1.14 [1.02-1.28], p = 0.019, C-statistic, 0.88, respectively). CONCLUSION: SBI is a simple scalar metric of blood age that accounts for the relative distribution of RBCs among age categories. Transfusion of older RBCs is associated with 24-hour and 30-day mortality, after adjustment for total units and clinical covariates.


Asunto(s)
Conservación de la Sangre , Transfusión de Eritrocitos , Eritrocitos , Choque Hemorrágico , Heridas y Lesiones , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Choque Hemorrágico/sangre , Choque Hemorrágico/mortalidad , Choque Hemorrágico/terapia , Tasa de Supervivencia , Factores de Tiempo , Heridas y Lesiones/sangre , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapia
17.
Ann Emerg Med ; 73(6): 650-661, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30447946

RESUMEN

STUDY OBJECTIVE: The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. METHODS: We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. RESULTS: The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. CONCLUSION: Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.


Asunto(s)
Conservación de la Sangre/normas , Transfusión Sanguínea/mortalidad , Enfermedad Crítica/terapia , Centros Traumatológicos , Adulto , Conservación de la Sangre/estadística & datos numéricos , Enfermedad Crítica/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa
18.
Am J Dermatopathol ; 41(12): 924-926, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31389806

RESUMEN

The Treponema pallidum antibody immunohistochemical (IHC) stain has improved our ability to detect the organism histologically. We present a case of a man with genital condyloma acuminatum with a positive T. pallidum IHC stain but negative T. pallidum serologies and no syphilitic symptoms. It has been shown that the T. pallidum antibody IHC can cross-react, staining other spirochetes, including Borrelia burgdorferi and the Brachyspira family of intestinal spirochetes. Because of the proximity of our patient's lesions to the anus, and the persistently negative T. pallidum serologies, we believe nontreponemal spirochetes colonized the condyloma, giving a false-positive T. pallidum IHC. This cross-reactivity is a potential diagnostic pitfall and is important for the dermatopathologist to recognize, thereby avoiding false diagnosis of syphilis.


Asunto(s)
Anticuerpos/inmunología , Condiloma Acuminado/diagnóstico , Enfermedades de los Genitales Masculinos/diagnóstico , Inmunohistoquímica , Sífilis/diagnóstico , Treponema pallidum/inmunología , Adulto , Especificidad de Anticuerpos , Biopsia , Condiloma Acuminado/inmunología , Condiloma Acuminado/microbiología , Reacciones Falso Positivas , Enfermedades de los Genitales Masculinos/inmunología , Enfermedades de los Genitales Masculinos/microbiología , Humanos , Masculino , Valor Predictivo de las Pruebas , Sífilis/inmunología , Sífilis/microbiología , Serodiagnóstico de la Sífilis
19.
Public Health Nurs ; 36(5): 660-666, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31294864

RESUMEN

OBJECTIVES: To evaluate "Stop the Bleed" (STB) training among/K12 personnel in an Alabama school system, and to assess participants' perceived readiness to train peers in STB methods. DESIGN AND SAMPLE: We performed a cross-sectional observational study with a convenience, nonprobability sample of 466 full-time personnel who received STB training. Data were collected using an anonymous online survey. MEASUREMENTS: We asked participants to recall feelings related to STB both prior to and after completing training using a 5-point Likert scale (5 = "Strongly Disagree", 1 = "Strongly Agree"). We used logistic regression to evaluate the association among posttraining feelings and perceived preparedness to train others in STB. RESULTS: Participants were primarily female (78%), aged 41 ± 10 years, who held faculty positions (94%). Results revealed increased knowledge of (4 [IQR 2-4] vs. 2 [1-2], p < .001) and comfort with (4 [2-5] vs. 2 [1-2], p < .001) STB skills. Participants felt more empowered to organize STB training (4 [3-5] vs. 3 [2-4], p < .001); those who felt empowered to organize STB training were eight times more likely to feel capable of teaching STB. CONCLUSIONS: After STB training, K-12 personnel felt empowered to organize additional STB trainings and capable of teaching STB methods to others.


Asunto(s)
Docentes/estadística & datos numéricos , Primeros Auxilios/estadística & datos numéricos , Educación en Salud/estadística & datos numéricos , Heridas y Lesiones/terapia , Adulto , Alabama , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
20.
Ethn Health ; 23(3): 307-320, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-27897049

RESUMEN

OBJECTIVES: African-Americans are vulnerable to both cancer and cardiovascular disease (CVD) due to intricately connected risk factors. Use of text messages is an innovative method to provide health information to reduce these risks. The aim of this study was to test the feasibility and acceptability of a text messaging intervention to reduce CVD and cancer risk factors in African-Americans. DESIGN: We developed an intervention using text messages culturally tailored for African-Americans over age 50 who were at risk (one or more modifiable risk factors) for CVD and/or cancer. Sociodemographic data, biologic measures, cancer screening practices, and general health status were assessed. Group interviews were conducted to assess feasibility and acceptability. RESULTS: Participants were primarily female (69%), aged 58 ± 5 years, who were married (59%) and worked full time (56%). In terms of feasibility and acceptability, themes of encouragement through text messages received and a desire for a longer study period emerged from group interviews with participants. Participants experienced significant decreases in waist circumference (41 ± 5 vs 40 ± 5, p = .002), systolic blood pressure (147 ± 25 mmHg vs 138 ± 20 mmHg, p = .009), diastolic blood pressure (87 ± 16 mmHg vs 82 ± 10 mmHg, p = .02), total cholesterol (194 ± 35 mg/dL vs 173 ± 32 mg/dL, p < .001), and low-density lipoprotein levels (100 ± 32 mg/dL vs 86 ± 29 mg/dL, p = .015). Five participants had colorectal cancer screening, two had prostate cancer screening, and four had mammograms. CONCLUSIONS: Use of text messages was widely accepted among participants. Significant CVD risk reductions and increased cancer screenings were noted. Future studies should incorporate innovative strategies such as text messaging in promoting health in vulnerable populations.


Asunto(s)
Negro o Afroamericano , Enfermedades Cardiovasculares/diagnóstico , Detección Precoz del Cáncer/métodos , Promoción de la Salud/métodos , Envío de Mensajes de Texto , Anciano , Presión Sanguínea , Pesos y Medidas Corporales , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etnología , Enfermedades Cardiovasculares/etnología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/etnología , Competencia Cultural , Femenino , Hemoglobina Glucada , Conductas Relacionadas con la Salud/etnología , Estado de Salud , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/etnología , Factores de Riesgo , Factores Socioeconómicos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA