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INTRODUCTION@#Increased healthcare demands due to the COVID-19 pandemic have overwhelmed nurses worldwide. Resilience of nurses has been impacted due to many factors (e.g., longer work shifts) causing psychological distress. The study aimed to determine the correlation of burnout, compassion fatigue, and moral injury with resilience among nurses assigned in COVID-19 wards.@*METHODS@#Virtual survey tools were sent to nurses of a public hospital to obtain data. Data were analyzed using JAMOVI and SPSS.@*RESULTS@#Levels of burnout showed moderate burnout in personal burnout (f=44) (65.7%); Moderate burnout in work-telated burnout (f=36) (53.7%); no/low level of burnout in client-related burnout (f=48) (71.6%). Level of compassion fatigue showed job burnout (f=59) (88.1%). Level of moral injury indicated “requiring clinical attention” (f=52) (77.6%). Level of resilience showed medium resilience (f=45) (67.2%). Correlation between burnout and resilience yielded negligible negative correlations between personal burnout and resilience (r=-0.160, p=0.031), work-related burnout and resilience (r=-0.222, p=0.008), and client-related burnout and resilience (r=-0.120, p=0.741). Correlation yielded weak negative correlations between compassion fatigue and resilience (r=-0.254, p=0.038) and between moral injury and resilience (r=-0.318, p=0.009). The linear regression showed no significant correlations between personal burnout and resilience (p=0.063), work-related burnout and resilience (p=0.070), client-related burnout and resilience (p=0.331), compassion fatigue and resilience (p=0.080), moral injury and resilience (p=0.227).@*CONCLUSION@#The findings showed significant correlations between personal burnout and resilience, work- related burnout and resilience, compassion fatigue and resilience, and moral injury and resilience. There were no significant correlations between client-related burnout and resilience. Multiple linear regression indicated burnout, compassion fatigue, and moral injury are not predictive factors for resilience.
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Resiliencia Psicológica , Agotamiento Profesional , Desgaste por Empatía , Trastornos por Estrés PostraumáticoRESUMEN
We report a phenomenon manifesting itself as brief flashes of light on the snow's surface near a lidar beam. The flashes are imaged and interpreted as specular reflection patterns from individual ice particles. Such patterns have a two-dimensional structure and are similar to those previously observed in forward scattering. Patterns are easiest to capture from particles with well-defined horizontal facets, such as near-horizontally aligned plates. The patterns and their position can be used to determine properties such as ice particle shape, size, roughness, alignment, and altitude. Data obtained at Summit in Greenland show the presence of regular hexagonal and scalene plates, columns, and rounded plates of various sizes, among others.
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The optimal management of resectable oesophageal adenocarcinoma is controversial, with many centres using neoadjuvant chemotherapy following the Medical Research Council (MRC) oesophageal working group (OE02) trial and the MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. The more intensive MAGIC regimen is used primarily in gastric cancer but some also use it for oesophageal cancer. A database of cancer resections (2001-2013) provided information on survival of patients following either OE02 or MAGIC-type treatment. The data were compared using Kaplan-Meier analysis. Straight-to-surgery patients were also reviewed and divided into an 'early' cohort (2001-2006, OE02 era) and a 'late' cohort (2006-2013, MAGIC era) to estimate changes in survival over time. Subgroup analysis was performed for responders (tumour regression grade [TRG] 1-3) versus non-responders (TRG 4 and 5) and for anatomical site (gastro-oesophageal junction [GOJ] vs oesophagus). An OE02 regimen was used for 97 patients and 275 received a MAGIC regimen. Those in the MAGIC group were of a similar age to those undergoing OE02 chemotherapy but the proportion of oesophageal cancers was higher among MAGIC patients than among those receiving OE02 treatment. MAGIC patients had a significantly lower stage following chemotherapy than OE02 patients and a higher median overall survival although TRG was similar. On subgroup analysis, this survival benefit was maintained for GOJ and oesophageal cancer patients as well as non-responders. Analysis of responders showed no difference between regimens. 'Late' group straight-to-surgery patients were significantly older than those in the 'early' group. Survival, however, was not significantly different for these two cohorts. Although the original MAGIC trial comprised few oesophageal cancer cases, our patients had better survival with MAGIC than with OE02 chemotherapy in all anatomical subgroups, even though there was no significant change in operative survival over the time period in which these patients were treated. The use of the MAGIC regimen should therefore be encouraged in cases of operable oesophagogastric adenocarcinoma.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Terapia Neoadyuvante/mortalidad , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Estudios de Cohortes , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del TumorRESUMEN
This tutorial promotes good practice for exploring the rationale of systems pharmacology models. A safety systems engineering inspired notation approach provides much needed rigor and transparency in development and application of models for therapeutic discovery and design of intervention strategies. Structured arguments over a model's development, underpinning biological knowledge, and analyses of model behaviors are constructed to determine the confidence that a model is fit for the purpose for which it will be applied.
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Ingeniería Biomédica/métodos , Modelos Biológicos , Biología de Sistemas/métodos , Animales , Antiprotozoarios/inmunología , Antiprotozoarios/uso terapéutico , Ingeniería Biomédica/tendencias , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/terapia , Biología de Sistemas/tendenciasRESUMEN
OBJECTIVE: This study aimed to examine the performance of head and neck cytology at Nottingham University Hospitals between 2009 and 2010. METHODS: Cases were extracted from the Winpath pathology reporting system and correlations were investigated between results and the histological and clinical outcomes. Specimen adequacy and the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the cytology tests were calculated. RESULTS: In all, 19.7 per cent of aspirates were judged to be inadequate. The absolute and relative sensitivities of head and neck cytology were 87.0 per cent and 89.0 per cent, respectively, and the absolute and relative specificities were 99.0 per cent and 97.0 per cent, respectively. The positive predictive values were 99.0 per cent and 96.0 per cent and the negative predictive values were 92.0 per cent and 92.0 per cent for a diagnostic accuracy of 94.5 per cent and 93.0 per cent. The performance was consistent with previous reports and superior to that of a recent UK series. The high rate of inadequate samples is, however, a concern. CONCLUSION: Head and neck cytology is a robust technique at our institution, although there are certain problem areas. There is room for improvement in the technical quality of fine needle aspiration.
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Biopsia con Aguja Fina/normas , Neoplasias de Cabeza y Cuello/diagnóstico , Branquioma/diagnóstico , Pruebas Diagnósticas de Rutina/normas , Enfermedades Hematológicas/diagnóstico , Humanos , Linfoma/diagnóstico , Valor Predictivo de las Pruebas , Enfermedades de las Glándulas Salivales/diagnóstico , Sensibilidad y Especificidad , Reino UnidoRESUMEN
Lymphovascular invasion (LVI) in T1 esophagogastric adenocarcinoma may predict risk of recurrence despite definitive treatment with surgery or endoscopic resection. Podoplanin and CD34 are emerging biomarkers of lymphatic and blood vessel invasion, respectively, and could be adopted to refine LVI assessment. A consecutive series of 65 patients with T1 adenocarcinomas diagnosed at Nottingham University Hospitals were investigated. T1 tumors from 43/65 patients who received primary surgery only were suitable for LVI evaluation by hematoxylin and eosin (H&E) staining as well as by CD34 and Podoplanin immunohistochemistry. LVI was correlated to clinicopathological features and recurrence free survival. H&E staining detected LVI in 11.6% (5/43) of T1 tumors. CD34 and Podoplanin immunohistochemistry significantly improved LVI detection to 25.6% (11/43). Compared with LVI by H&E, immunohistochemical evaluation of blood vessel invasion (CD34) or lymphatic vessel invasion (Podoplanin) was significantly associated with higher grade (P = 0.005), submucosal invasion (T1b) (P = 0.018), lymph node positivity (N1) (P = 0.029) and poor recurrence free survival (P = 0.0003). Our study provides evidence that CD34 and Podoplanin immunohistochemistry could improve LVI detection and allow better prognostication of patients and optimum selection of definitive treatment. Larger multicenter studies are required for further validation that could have significant clinical implications.
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Adenocarcinoma/patología , Antígenos CD34/análisis , Vasos Sanguíneos/patología , Neoplasias Esofágicas/patología , Vasos Linfáticos/patología , Glicoproteínas de Membrana/análisis , Neoplasias Gástricas/patología , Anciano , Biomarcadores/análisis , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia , PronósticoRESUMEN
In Barrett's esophagus (BE), the normal squamous lining of the esophagus is replaced by specialized columnar epithelium. Endoscopic surveillance with autofluorescence imaging (AFI) and molecular biomarkers have been studied separately to detect early neoplasia (EN) in BE. The combination of advanced-imaging modalities and biomarkers has not been investigated; AFI may help detecting biomarkers as a risk-stratification tool. We retrospectively evaluated a cohort of patients undergoing endoscopy for EN in BE with AFI and correlated five biomarkers (HPP1, RUNX3, p16, cyclin A, and p53) in tissue samples with AFI and dysplasia status. Fifty-eight samples from a previous prospective study were selected: 15 true-positive (TP: AFI-positive, EN), 21 false-positive (FP: AFI-positive, no EN), 12 true-negative (TN1; AFI-negative, no EN in sample), 10 true-negative (TN2: AFI-negative, no EN in esophagus). Methylation-specific RT-PCR was performed for HPP1, RUNX3, p16, and immunohistochemistry for cyclin A, p53. P < 0.05 was considered statistically significant. Bonferroni correction was used for multiple comparisons. P16, cyclin A, p53 correlated with dysplasia (P < 0.01, P = 0.003, P < 0.001, respectively). Increased p16 methylation was observed between TP versus TN2 (P = 0.003) and TN1 versus TN2 (P = 0.04) subgroups, suggesting a field defect. Only p53 correlated with AFI-status (P = 0.003). After exclusion of EN samples, significance was lost. Although correlation with dysplasia status was confirmed for p16, cyclin A and p53, underlining the importance of these biomarkers as an early event in neoplastic progression, none of the investigated biomarkers correlated with AFI status. A larger prospective study is needed to assess the combination of AFI and a larger panel of biomarkers to improve risk stratification in BE.
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Esófago de Barrett/patología , Neoplasias Esofágicas/diagnóstico , Esofagoscopía , Imagen Óptica/métodos , Lesiones Precancerosas/patología , Anciano , Biomarcadores/metabolismo , Transformación Celular Neoplásica/patología , Estudios de Cohortes , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Ciclina A/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Metilación de ADN , Detección Precoz del Cáncer , Neoplasias Esofágicas/metabolismo , Estudios de Factibilidad , Femenino , Genes p53 , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Reacción en Cadena de la Polimerasa , Estudios RetrospectivosRESUMEN
Zebu (Bos indicus) crossbred beef cows (Droughtmaster) were maintained long-term (16 months) on standard nutrition (SN) or improved nutrition (IN). Cows on IN had better body condition and greater (P<0.05) circulating concentrations of leptin than cows on SN (0.7±0.1n/ml and 1.7±0.1n/ml, respectively). There were no outstanding differences between SN and IN cows in basal number of ovarian follicles (≤4mm, 5-8mm, and ≥9mm) and there were also no differences in number of oocytes recovered by oocyte pick-up. Cows on IN had a greater (P<0.05) number of total follicles after stimulation with FSH than cows on SN. Oocytes from cows on IN had greater (P<0.05) lipid content than cows on SN (-0.23±0.16 and 0.20±0.18 arbitrary units, respectively) and oocytes of the former cows also tended to have more active mitochondria, although this was not significant. Cows on IN showed a positive relationship (R(2)=0.31, P<0.05) between plasma leptin and oocyte lipid content. Lipids are utilized by oocytes during high energy consumptive processes including fertilization and early cleavage. The greater lipid content of oocytes from IN cows could therefore confer a reproductive advantage. The present study has shown relationships between nutrition, body condition, circulating leptin, and oocyte lipid content, but a clear cause-and-effect requires further investigation in the cow.
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Bovinos/fisiología , Dieta/veterinaria , Leptina/sangre , Oocitos/fisiología , Folículo Ovárico/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Femenino , Modelos Lineales , Metabolismo de los Lípidos , Microscopía Confocal/veterinaria , Mitocondrias/fisiología , Oocitos/metabolismo , QueenslandRESUMEN
BACKGROUND: Not all NAFLD patients are obese and many obese patients do not have NAFLD. Impaired peripheral fat storage may increase the delivery of lipids to the liver and facilitate NAFLD progression. AIM: To assess the association of anthropometric measures of regional adiposity including arm fat index (AFI) (upper body fat), waist circumference (visceral fat) and body mass index (total body fat) on liver injury and fibrosis in NAFLD. METHODS: One hundred and forty-one patients with histological evidence of NAFLD were included in this study. Multivariate logistic regression models examined the contribution of age, sex, body mass index, AFI, triceps fold thickness (TST), waist and hip circumference to the odds of liver injury (NAS scores ≥3) and fibrosis (fibrosis scores ≥2) by liver biopsy. RESULTS: Arm fat index (OR: 0.82, 95% CI: 0.59-0.91) and TST (OR: 0.13, 95% CI: 0.04-0.42) were negatively correlated with NAFLD histological severity. In women, waist circumference was positively correlated with NAFLD severity (OR: 1.21(1.02-1.44). Age (OR: 1.05, 95% CI: 1.01-1.0) and waist circumference (OR: 1.07, 95% CI: 1.00-1.15) were significantly associated with fibrosis risk. In women, AFI (OR: 0.87, 95% CI: 0.76-0.99) and TST (OR: 0.22, 95% CI: 0.05-0.95) were negatively associated with fibrosis risk. CONCLUSIONS: Regional anthropometric measures are associated with severity of NAFLD in a sex-specific manner. Men and women with lower arm fat depots and women with bigger waist circumference have a greater likelihood of liver injury. Age and waist circumference seem to be associated with liver fibrosis. Simple anthropometric measurements of peripheral fat deposits may help stratify significant liver injury risk.
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Antropometría , Hígado Graso/diagnóstico , Cirrosis Hepática/diagnóstico , Adulto , Pesos y Medidas Corporales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Valor Predictivo de las Pruebas , Análisis de Regresión , Factores de Riesgo , Índice de Severidad de la Enfermedad , Grasa SubcutáneaRESUMEN
BACKGROUND: Autofluorescence imaging (AFI), which is a "red flag" technique during Barrett's surveillance, is associated with significant false positive results. The aim of this study was to assess the inter-observer agreement (IOA) in identifying AFI-positive lesions and to assess the overall accuracy of AFI. METHODS: Anonymized AFI and high resolution white light (HRE) images were prospectively collected. The AFI images were presented in random order, followed by corresponding AFI + HRE images. Three AFI experts and 3 AFI non-experts scored images after a training presentation. The IOA was calculated using kappa and accuracy was calculated with histology as gold standard. RESULTS: Seventy-four sets of images were prospectively collected from 63 patients (48 males, mean age 69 years). The IOA for number of AF positive lesions was fair when AFI images were presented. This improved to moderate with corresponding AFI and HRE images [experts 0.57 (0.44-0.70), non-experts 0.47 (0.35-0.62)]. The IOA for the site of AF lesion was moderate for experts and fair for non-experts using AF images, which improved to substantial for experts [κ = 0.62 (0.50-0.72)] but remained at fair for non-experts [κ = 0.28 (0.18-0.37)] with AFI + HRE. Among experts, the accuracy of identifying dysplasia was 0.76 (0.7-0.81) using AFI images and 0.85 (0.79-0.89) using AFI + HRE images. The accuracy was 0.69 (0.62-0.74) with AFI images alone and 0.75 (0.70-0.80) using AFI + HRE among non-experts. CONCLUSION: The IOA for AF positive lesions is fair to moderate using AFI images which improved with addition of HRE. The overall accuracy of identifying dysplasia was modest, and was better when AFI and HRE images were combined.
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Esófago de Barrett/diagnóstico , Endoscopía del Sistema Digestivo/normas , Gastroenterología/normas , Imagen Óptica/normas , Lesiones Precancerosas/diagnóstico , Anciano , Endoscopía del Sistema Digestivo/métodos , Endoscopía del Sistema Digestivo/estadística & datos numéricos , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Imagen Óptica/métodos , Imagen Óptica/estadística & datos numéricos , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND AIMS: Establishing the presence of fibrosis and cirrhosis is an essential step in the management of patients with chronic liver diseases (CLD). Liver stiffness measurement (LSM) based on transient elastography (TE) correlates well with the stages of liver fibrosis and has been developed as a non-invasive alternative to liver biopsy. The studies performed to date have used physician operators. With the potential use of TE for screening of community-based populations for liver disease, we aimed to evaluate the performance of nurse operators. DESIGN: Retrospective analysis. METHODS: We reviewed the reliability and accuracy of LSMs performed by the nurse-led TE service at Queen's Medical Centre, Nottingham between May 2009 and January 2011. Consecutive patients with suspected CLD who underwent LSM were included. RESULTS: Over the study period 585 LSMs were performed. Analysis was performed on the 208 patients where LSM could be compared with liver biopsy findings. Of these 11 (5.3%) had unreliable LSM results (less than 10 valid shots or success rate <60%). There were no LSM failures. Inadequate liver biopsy specimen led to exclusion in 26 (12.5%) patients. For the detection of significant fibrosis (Ishak stage >2), a sensitivity of 0.78 and specificity of 0.81 was obtained, with a cut-off value of 8 kPa. Using a cut-off value of 13 kPa for detection of cirrhosis, a sensitivity and specificity of 0.8 and 0.92 was obtained. CONCLUSION: We have demonstrated that a nurse-led TE service can produce a low level of unreliable results and LSM failures, with comparable sensitivity and specificity for detecting significant fibrosis and cirrhosis to those reported in the literature. The demands on the use of TE could potentially be eased through the introduction of nurse-led service delivery.
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Diagnóstico por Imagen de Elasticidad/enfermería , Cirrosis Hepática/enfermería , Hígado/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Enfermedad Crónica , Elasticidad , Femenino , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease.
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Leishmania/patogenicidad , Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis Visceral/inmunología , Animales , Antígenos de Protozoos/inmunología , Citocinas/inmunología , Perros , Descubrimiento de Drogas , Epítopos/inmunología , Humanos , Inmunidad Celular , Leishmania/inmunología , Vacunas contra la Leishmaniasis/economía , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/terapia , Psychodidae/parasitología , VacunaciónRESUMEN
AIMS: Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response. METHODS AND RESULTS: Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040). CONCLUSIONS: We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.
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Adenocarcinoma/diagnóstico , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Neoplasias Esofágicas/diagnóstico , Neoplasias Gástricas/diagnóstico , Carga Tumoral/fisiología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/metabolismo , Núcleo Celular/metabolismo , Proliferación Celular , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos de Platino/administración & dosificación , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Análisis de Matrices Tisulares , Resultado del TratamientoRESUMEN
BACKGROUND: Endoscopic ultrasound (EUS) is useful for detecting depth of invasion and nodal involvement in patients with early Barrett's neoplasia (EBN), precluding endoscopic management. This study aimed to determine whether the lesion morphology of the EBN shown on high-resolution endoscopy predicts EUS and histologic tumor stage. METHODS: Retrospective series from two tertiary referral centers were studied. Patients with EBN referred for EUS evaluation before treatment were identified, and data were collected from endoscopies, a database, and case notes. All patients had high-resolution endoscopy followed by radial EUS. RESULTS: This study included 50 patients (22 men) with a median age of 69 years (interquartile range, 60-79 years). Visible lesions in the Barrett's segment were described as Paris types 0-1 (n = 9), 0-IIb (n = 12), 0-IIa (n = 12), 0-IIa + IIc (n = 6), and 0-IIc (n = 5). Of the 50 patients, 46 (92%) had either EMR (n = 17), esophagectomy (n = 23), or both (n = 6). All 12 patients (100%) with Paris 0-IIb lesions had T0/T1 m staging on EUS confirmed with resection histology. The sensitivity for EUS T-staging for Paris classification was 71.4% for type 0-I, 100% for type 0-IIb, 83% for type 0-IIa, 66.7% for type 0-IIa + IIc, and 66.7% for type IIc. Overall, 8 (17%) of the 46 patients were understaged and 2 (4%) were overstaged. For detecting submucosal invasion, EUS had a sensitivity of 66%, a specificity of 93%, a negative predictive value of 85%, and a diagnostic accuracy of 84.4%. CONCLUSION: Submucosal invasion is detected by EUS for 26% of patients with EBN. The value of EUS staging before resection for type 0-IIb early Barrett's cancer (flat lesions) is limited because 100% of these lesions are limited to the mucosa. For the management algorithm in this selected cohort, the use of EUS should be reconsidered.
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Esófago de Barrett/diagnóstico , Endoscopía Gastrointestinal/métodos , Endosonografía/métodos , Neoplasias Esofágicas/diagnóstico , Procesamiento de Imagen Asistido por Computador/métodos , Anciano , Esófago de Barrett/complicaciones , Esófago de Barrett/cirugía , Diagnóstico Diferencial , Diagnóstico Precoz , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Estudios de Seguimiento , Humanos , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Parental psychiatric disorder, especially depression, personality disorder and deliberate self-harm, is known to put children at greater risk of mental illness, neglect or physical, emotional and sexual abuse. Without a reliable procedure to identify children of parents presenting with these mental health problems, children at high risk of significant harm can be easily overlooked. Although deliberate self-harm constitutes a significant proportion of emergency presentations, there are no guidelines which address the emergency physician's role in identifying and assessing risk to children of these patients. METHODS: A robust system was jointly developed with the local social services child protection team to identify and risk-stratify children of parents with mental illness. This allows us to intervene when we identify children at immediate risk of harm and to ensure that social services are aware of potential risk to all children in this group. The referral process was audited repeatedly to refine the agreed protocol. RESULTS: The proportion of patients asked by the emergency department personnel about dependent children increased and the quality of information received by the social services child protection team improved. CONCLUSIONS: All emergency departments should acknowledge the inadequacy of information available to them regarding patients' children and consider a policy of referral to social services for all children of parents with mental health presentations. This process can only be developed through close liaison within the multidisciplinary child protection team.
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Maltrato a los Niños/prevención & control , Protección a la Infancia , Hijo de Padres Discapacitados , Servicio de Urgencia en Hospital/organización & administración , Trastornos Mentales , Adolescente , Adulto , Niño , Inglaterra , Femenino , Hospitales de Práctica de Grupo , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Biomolecular reagents that enable the specific molecular recognition of proteins play a crucial role in basic research as well as medicine. Up to now, antibodies (immunoglobulins) have been widely used for this purpose. Their predominant feature is the vast repertoire of antigen-binding sites that arise from a set of 6 hypervariable loops. However, antibodies suffer from practical disadvantages because of their complicated architecture, large size, and multiple functions. The lipocalins, on the other hand, have evolved as a protein family that primarily serves for the binding of small molecules. Here, we show that an engineered lipocalin, derived from human Lcn2, can specifically bind the T cell coreceptor CTLA-4 as a prescribed protein target with subnanomolar affinity. Crystallographic analysis reveals that its reshaped cup-like binding site, which is formed by 4 variable loops, provides perfect structural complementarity with this "antigen." Furthermore, comparison with the crystal structure of the uncomplexed engineered lipocalin indicates a pronounced induced-fit mechanism, a phenomenon so far considered typical for antibodies. By recognizing the same epitope on CTLA-4 that interacts with the counterreceptors B7.1/B7.2 on antigen-presenting cells the engineered Lcn2 exhibits strong, cross-species antagonistic activity, as evidenced by biological effects comparable with a CTLA-4-specific antibody. With its proven stimulatory activity on T cells in vivo, the CTLA-4 blocking lipocalin offers potential for immunotherapy of cancer and infectious disease. Beyond that, lipocalins with engineered antigen-binding sites, so-called Anticalins, provide a class of small ( approximately 180 residues), structurally simple, and robust binding proteins with applications in the life sciences in general.
Asunto(s)
Antígenos CD/metabolismo , Epítopos , Lipocalinas/metabolismo , Ingeniería de Proteínas , Proteínas de Fase Aguda/genética , Anticuerpos/química , Antígenos CD/química , Sitios de Unión , Antígeno CTLA-4 , Cristalografía por Rayos X , Humanos , Indicadores y Reactivos/síntesis química , Indicadores y Reactivos/química , Lipocalina 2 , Lipocalinas/química , Lipocalinas/genética , Unión Proteica , Conformación Proteica , Proteínas Proto-Oncogénicas/genéticaRESUMEN
BACKGROUND AND AIMS: Esophageal and/or gastric wall thickening raises the possibility of malignancy. Endoscopic-ultrasound-(EUS-)guided targeted biopsy of the thickened wall is possible. We aimed to evaluate the efficacy and safety of EUS-guided mural trucut biopsies (TCB) in detecting underlying malignancy in patients with thickened esophagogastric wall and negative mucosal biopsies. METHODS: Patients with alarm symptoms referred for EUS-guided sampling after negative endoscopy and mucosal biopsy were included in the study. All patients had radial EUS reporting abnormal thickening of the esophageal/gastric wall. A linear-array echoendoscope and a 19-gauge trucut needle were used for sampling. Clinical and investigatory data were collected prospectively between 2004 and 2008. RESULTS: Thirty-one patients (20 men) aged 60 - 74 years (median 67 years) were included. All patients had thickened esophageal wall (n = 10), gastric wall (n = 21), or both on radial EUS. Prior to EUS, patients had undergone 1 - 5 endoscopies (median 1.2) and 2 - 8 mucosal biopsies (median 4). The median esophageal and gastric wall thicknesses were 12 and 18 mm respectively. During sampling 1 - 5 needle punctures (median 3) were made. On EUS-TCB, an adequate specimen for histology was obtained in 28/31 patients (90 %). The size of the tissue cores was 4 - 10 mm (median 6mm). Malignancy was confirmed in 16/31 patients (54 %) on histology, and in 11/31 patients (35.4 %) an underlying malignancy was excluded. There was no significant correlation between wall thickness and biopsy size (rho = 0.11, 95 %CI- 0.25 to - 0.45, two-sided P = 0.53). EUS-TCB had sensitivity, specificity, and positive and negative predictive values of 85 %, 100 %, 100 %, and 74 % respectively. There were no immediate or late complications. CONCLUSIONS: EUS-guided mural TCB is a safe and effective technique in the investigation of esophagogastric wall thickening in patients with alarm symptoms and has high sensitivity and specificity for the diagnosis of a cancer.