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1.
HNO ; 68(12): 899-904, 2020 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-32995896

RESUMEN

BACKGROUND: Clinical application of immune checkpoint inhibitors (ICI), whether as monotherapy or in combination with established methods, is revolutionizing treatment of head and neck cancer. However, this change in therapeutic concepts requires reevaluation and further development of predictive and prognostic markers, since the survival rates for advanced and particularly human papillomavirus (HPV)-negative disease remain poor. MATERIALS AND METHODS: A selective literature review was performed in PubMed. Literature found with the keywords "cytodiagnostics, circulating tumor cells, liquid biopsy, cfDNA, exosomes" in combination with "head and neck cancer" and/or "immune checkpoint inhibitor therapy" published until March 2020 was included. The articles were selected for their relevance for the current study by the authors. RESULTS: This work provides a review of the current literature and indicates possible applications in the field of head and neck cancers. Liquid biopsy refers to the analysis of circulating tumor cells or of tumor genetic material in body fluids. This minimally invasive analysis can support therapeutic decisions and enable a personalized approach to treating head and neck cancer. DISCUSSION: Before any of these approaches can be established in clinical routine, long-term data and standardization of the methods for isolating and analyzing the markers are needed.


Asunto(s)
Neoplasias de Cabeza y Cuello , Células Neoplásicas Circulantes , Biomarcadores de Tumor , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Humanos , Biopsia Líquida , Oncología Médica
2.
Int J Oral Maxillofac Surg ; 49(12): 1611-1617, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32475707

RESUMEN

The aim of this study was to examine the lateral pterygoid muscle (LPM) parenchyma, myotendinous junction, and tendon in temporomandibular disorder (TMD) patients using 3T magnetic resonance imaging (MRI). Results were compared with findings reported in the literature, in which the LPM has been attributed a major role in triggering TMD. 3T MRI was used for temporomandibular joint (TMJ) imaging. The MRI images of 63 patients were analysed for muscle contracture and atrophy, tendon rupture, signal alterations of the tendon, tendon contrast enhancement, and peritendinous fluid collection. Descriptive statistics and the coefficient estimate method were used for statistical analysis. Focus was placed on the association between LPM tendon pathology and TMJ lesions like osteoarthritis and disc displacement. Severe lesions of the LPM tendon and muscle parenchyma, like rupture or fibrosis, were detected in very few cases. Only moderate signs of tendinosis were found in TMD patients. In contrast, there was a clear correlation between tendon lesions and osteoarthritis or anterior disc displacement. These results indicate the need to discuss and question the role of the LPM and its tendon in TMD. Data suggest that LPM and tendon lesions are part of complex degenerative changes of the TMJ, and it seems less likely that a LPM disorder is causative in TMD.


Asunto(s)
Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Luxaciones Articulares/diagnóstico por imagen , Imagen por Resonancia Magnética , Músculos Pterigoideos/diagnóstico por imagen , Articulación Temporomandibular/diagnóstico por imagen , Disco de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen
3.
Br J Surg ; 107(7): 801-811, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32227483

RESUMEN

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.


ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.


Asunto(s)
Trasplante de Riñón/efectos adversos , Enfermedades Linfáticas/etiología , Humanos , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/patología , Índice de Severidad de la Enfermedad , Terminología como Asunto
4.
J Nutr Health Aging ; 23(4): 323-329, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30932130

RESUMEN

OBJECTIVE: This study aimed to investigate the association between dietary inflammation, pre-frailty and frailty among older US adults. Additionally, effect modification of gender on the association between dietary inflammation and frailty was assessed. DESIGN: Study data came from the National Health and Nutrition Examination Survey (2007-2014) - a nationally representative, cross-sectional study of adults. PARTICIPANTS: The analytic sample included adults ≥60 years (n=7,182). MEASUREMENTS: Dietary Inflammatory Index (DII®) scores were calculated from 24-hour dietary recalls; DII was categorized into quintiles from Quintile 1 (Q1) (least inflammatory) to Q5 (most inflammatory). Frailty was assessed by four criteria: exhaustion, weakness, low body mass, and low physical activity. Individuals were then categorized into robust (0 criteria), pre-frail (1-2 criteria), or frail (3-4 criteria). Multinomial logistic regression was used to examine the odds of frailty categories (pre-frail vs. robust; frail vs. robust). RESULTS: After adjusting for potential confounders, individuals in DII quintile 5 (vs Q1) were more likely to be pre-frail (OR = 1.71; 95% CI: 1.36-2.15) and frail (OR = 1.70; 95% CI: 1.02-2.85). Individuals in Q4 had greater odds of frailty only (OR = 1.82; 95% CI: 1.13, 2.93). No evidence of effect modification by gender on the association of DII and frailty was found. CONCLUSION: This study expands upon previous evidence of a relationship between dietary inflammation and frailty. When designing nutrition-based frailty interventions, inflammatory properties of diets should be considered.


Asunto(s)
Dieta , Anciano Frágil/estadística & datos numéricos , Fragilidad/fisiopatología , Estado de Salud , Encuestas Nutricionales/estadística & datos numéricos , Anciano , Estudios Transversales , Femenino , Humanos , Inflamación/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad
6.
Acta Paediatr ; 108(6): 1049-1054, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30461053

RESUMEN

AIM: We evaluated the weight, insulin-like growth factor-1, neonatal, retinopathy of prematurity (WINROP) algorithm for very premature infants. METHOD: Infants born before 32 weeks who had undergone fundus examinations in the neonatal intensive care unit at the University Hospital of Nancy were included in this French retrospective cohort study from July 2012 to July 2016. We evaluated how well the WINROP software predicted threshold retinopathy of prematurity (ROP). RESULTS: We studied 570 infants with a mean gestational age of 28.7 ± 1.8 weeks and a mean birth weight of 1110 ± 297 g: 28.1% had ROP and 1.2% had threshold ROP. The overall WINROP sensitivity was 57.1%, specificity was 46.0%, predictive positive value was 1.3% and predictive negative value was 98.9%. At more than 30 weeks of gestation or 1250 g, these figures rose to a respective specificity of 100% and 95.7% and respective predictive negative value of 100% and 100%. There were independent associations between the severity of ROP and the Apgar score at five minutes, the duration of oxygen therapy and non-invasive ventilation. CONCLUSION: WINROP worked better on preterm infants born from 31 weeks onwards or weighing over 1250 g. Fundus examinations remain necessary for infants born earlier or lighter.


Asunto(s)
Algoritmos , Fondo de Ojo , Examen Físico , Retinopatía de la Prematuridad/diagnóstico , Peso al Nacer , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Valor Predictivo de las Pruebas , Retinopatía de la Prematuridad/sangre , Estudios Retrospectivos
7.
Eur Arch Otorhinolaryngol ; 275(7): 1767-1773, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29721614

RESUMEN

PURPOSE: Acute edema of the head and neck region may lead to life-threatening dyspnea and require quick and targeted treatment. They can be subdivided in bradykinin- and histamine-mediated swellings, which require treatment with different classes of pharmaceuticals. Clinical pathways for differential diagnoses do not exist so far, although it is known that early treatment is decisive for faster symptom relief and reduced expression of the swellings. Aim of the study was the creation of a clinical algorithm for identification of bradykinin-mediated angioedema. METHODS: 188 patients that presented to our outpatient department between 2010 and 2016 with an acute, non-inflammatory swelling of the head and neck region were included in our retrospective study. All available anamnestic and clinical parameters were obtained from patient files. Parameters showing significant differences between the two groups were included in our score. Utilization of the Youden's index allowed determination of an optimal cut-off value. RESULTS: 76 patients could be assigned to the histamine and 112 patients to bradykinin group. The following parameters were included in our score: age, dyspnea, itching or erythema, glucocorticoid response and intake of ACEi/AT-II blockers. The cut-off value is set at three points. The proposed score yielded a sensitivity for identification of bradykinin-mediated angioedema of 96%, a specificity of 84%, a positive predictive value of 91% and a negative predictive value of 93%. CONCLUSIONS: Utilization of the proposed score allows quick and reliable assignment of patients to the correct subgroup and thereby reduces time for treatment.


Asunto(s)
Angioedema/diagnóstico , Angioedema/etiología , Bradiquinina , Cabeza , Histamina , Cuello , Adulto , Anciano , Anciano de 80 o más Años , Angioedema/terapia , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
8.
Urologe A ; 57(5): 568-576, 2018 May.
Artículo en Alemán | MEDLINE | ID: mdl-29500474

RESUMEN

Adjuvant therapy with different bacillus Calmette-Guérin (BCG) preparations is a well-established guideline-endorsed treatment for nonmuscle invasive bladder cancer (NMIBC). Our observational study demonstrates equality between BCG and mitomycin C (MMC) treatment based on the oncological outcome. However, there were significant toxicity differences with higher rates in the BCG treatment group. The potential adverse effects of BCG in terms of a BCGitis are controversially discussed regarding their occurrence. As such, we sought to retrospectively evaluate the incidence in 106 consecutive patients. The BCG group demonstrated minor adverse effects in 78.4% and major adverse effects in 43.3%-partially coincident. Moreover, the parallel MMC group showed in 34.7% respectively 1.4% adverse events-as expected distinctly lower. In the context of this clinical discussion, we refer to alternative treatment concepts. Our data show a high clinical relevance of the patient's primary comorbidity.


Asunto(s)
Antibióticos Antineoplásicos , Vacuna BCG , Mitomicina , Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Antibióticos Antineoplásicos/uso terapéutico , Vacuna BCG/uso terapéutico , Humanos , Mitomicina/uso terapéutico , Invasividad Neoplásica , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
9.
J Prev Alzheimers Dis ; 5(1): 26-30, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29405229

RESUMEN

Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment. This randomized, placebo-controlled, double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment. In thirteen patients (omega:n=5; placebo:n=8) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging. There was a medium effect of intervention on cerebral blood flow (η2=0.122) and blood volume (η2=0.098). The omega group showed an increase in blood flow (mean difference: 0.02 [corresponds to 26.1%], 95% confidence interval:0.00-0.05) and blood volume (mean difference: 0.08 [corresponds to 18.5%], 95% confidence interval:0.01-0.15), which was not observed in the placebo group. These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment.Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia.


Asunto(s)
Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Ácidos Grasos Omega-3/administración & dosificación , Anciano , Anciano de 80 o más Años , Encéfalo/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Disfunción Cognitiva/fisiopatología , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
10.
Pediatr Obes ; 13(5): 292-300, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28493362

RESUMEN

BACKGROUND: Limited information exists regarding the association between early-life diet and cardiometabolic risk. OBJECTIVES: Examine associations of dietary inflammatory index (DII) in pregnancy and early childhood (3-5 years) with adiposity, blood pressure and metabolic markers in mid-childhood (6-10 years). METHODS: Among 992 mother-child pairs from Project Viva, a pre-birth cohort, we examined associations of DII scores with outcomes using multivariable linear regression adjusted for child age and sex and maternal age, BMI, education, parity, smoking, race and income. RESULTS: Mean (SD) maternal DII in pregnancy was -2.6(1.4) units and in child DII in early childhood was 0.3(0.7). Mean mid-childhood BMI z-score was 0.40(0.98) units. In boys only, DII in early childhood was associated with higher BMIz (adjusted ß = 0.16 units per unit DII, 95%CI 0.02, 0.29), waist circumference (0.93 cm; -0.07, 1.92) and skin fold thicknesses (1.12 mm; 0.01, 2.23). Dietary inflammatory index in the highest quartiles during both pregnancy and in early childhood, compared to the lowest quartiles, was associated with higher waist circumference (2.4 cm; 0.14, 4.6) in all children, and BMIz in boys (0.78 units; 0.34, 1.22). Associations with BP and metabolic markers were null. CONCLUSIONS: A pro-inflammatory diet in pregnancy and early childhood may promote the development of adiposity.


Asunto(s)
Adiposidad/fisiología , Presión Sanguínea/fisiología , Conducta Alimentaria/fisiología , Inflamación/complicaciones , Obesidad Infantil/etiología , Adulto , Antropometría/métodos , Niño , Preescolar , Dieta/efectos adversos , Dieta/métodos , Femenino , Humanos , Estudios Longitudinales , Masculino , Fenómenos Fisiológicos de la Nutrición , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Factores de Riesgo
11.
Eur J Clin Nutr ; 71(11): 1273-1277, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29019343

RESUMEN

BACKGROUND/OBJECTIVES: To examine the associations of dietary inflammatory index (DII) with bone mineral density (BMD) and fracture risk in adult Americans.Subjects/Method:The United States National Health and Nutrition Examination Survey participants during 2005-2010 were included if they had measured data on dietary intake and BMD. DII scores were calculated from estimated micro- and macronutrients from a single 24-h dietary recall. BMD was measured using dual-energy X-ray absorptiometry densitometers. Risk of fractures was obtained from participant self-report (ever) based on doctor information. Analyze of covariance and χ2-tests were employed, while accounting for the complex survey design. RESULTS: A total of 18 318 participants were included, with 51.3% (9397) being men. Age, sex, race, physical activity, smoking, C-reactive protein and body mass index-adjusted mean BMD (g/cm2) in different bodily sites significantly decreased across increasing quarters of the DII (all P<0.001). After further adjustment for calcium intake, the trend in BMD across DII quarters remained significant for total femur, femoral neck, trochanter and intertrochanter BMD (all P<0.001). Across increasing quarters of the DII, the proportion of fractures ranged from 1.1 to 1.5% for hip fracture (P=0.02), from 7.9 to 10.5% for wrist fracture (P<0.001) and from 2.2 to 2.7% for spine fracture (P=0.002. Prevalent wrist fractures significantly differed across DII quarters (P<0.0001), driven by high prevalence in the top quarter, while hip and spine fractures' prevalence did not vary significantly. CONCLUSIONS: The current study provides evidence suggesting a potential adverse effect of pro-inflammatory diet on bone health; which may have implications for dietary approaches for those with history of abnormal bone health complications.


Asunto(s)
Fracturas Osteoporóticas/epidemiología , Absorciometría de Fotón , Adulto , Factores de Edad , Densidad Ósea , Dieta , Etnicidad , Femenino , Fracturas del Fémur/epidemiología , Fracturas del Fémur/etiología , Fracturas del Fémur/prevención & control , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Factores de Riesgo , Factores Sexuales , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/prevención & control , Estados Unidos/epidemiología , Articulación de la Muñeca
12.
World J Urol ; 35(12): 1891-1897, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28836063

RESUMEN

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Nefrectomía , Medición de Riesgo/métodos , Anciano , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Europa (Continente)/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/diagnóstico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Mortalidad , Clasificación del Tumor , Estadificación de Neoplasias , Nefrectomía/efectos adversos , Nefrectomía/métodos , América del Norte/epidemiología , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
13.
J Nutr Health Aging ; 21(5): 487-491, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28448077

RESUMEN

OBJECTIVE: Chronic inflammation is linked to many chronic conditions. One of the strongest modulators of chronic inflammation is diet. The Dietary Inflammatory Index (DII) measures dietary inflammatory potential and has been validated previously, but not among African Americans (AAs). DESIGN: Cross-sectional analysis using baseline data from the Healthy Eating and Active Living in the Spirit (HEALS) intervention study. SETTING: Baseline data collection occurred between 2009 and 2012 in or near Columbia, SC. PARTICIPANTS: African-American churchgoers. MEASUREMENTS: Baseline data collection included c-reactive protein (CRP) and interleukin-6 from blood draws, anthropometric measures, and numerous questionnaires. The questionnaires included a food frequency questionnaire which was used for DII calculation. The main analyses were performed using quantile regression. RESULTS: Subjects in the highest DII quartile (i.e., more pro-inflammatory) were younger, more likely to be married, and had less education and greater BMI. Individuals in DII quartile 4 had statistically significantly greater CRP at the 75th and 90th percentiles of CRP versus those in quartile 1 (i.e., more anti-inflammatory). CONCLUSION: Construct validation provides support for using the DII in research among AA populations. Future research should explore avenues to promote more anti-inflammatory diets, with use of the DII, among AA populations to reduce risk of chronic disease.


Asunto(s)
Negro o Afroamericano , Proteína C-Reactiva/metabolismo , Dieta/efectos adversos , Conducta Alimentaria , Inflamación/etiología , Adulto , Anciano , Enfermedad Crónica , Estudios Transversales , Encuestas sobre Dietas , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas y Cuestionarios
15.
Eur J Pharm Biopharm ; 115: 131-139, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28237713

RESUMEN

In the management of bladder cancer, surgical resection of the tumour is usually followed by intravesical instillation of immunomodulatives and/or chemotherapeutics. The purpose of this local intravesical therapy is to eliminate residual malignant cells after surgical intervention. The main limitation of a localised adjuvant therapy is the insufficient concentration of the active pharmaceutical ingredient (API) in malignant cells due to the unique structure of the human urothelium making it an exclusively hard to overcome barrier in the human body. Different strategies such as electromotive drug administration or local hyperthermia are employed to ameliorate intravesical drug uptake. Previous studies on biorecognitive targeting showed promising results for lectin-, especially wheat germ agglutinin (WGA), mediated drug delivery. Here, we present a targeted conjugate that provides enough binding sites for a possible API as well as high cytoadhesive and cytoinvasive potential. The conjugate should comprise the following components: First WGA, as the targeting moiety, second poly-l-glutamic acid (PGA) as a polymeric backbone providing more than 300 possible binding sites for an API and third fluorescein cadaverine (Fc), a fluorescent dye we coupled to PGA rendering the conjugate traceable. After purification via size exclusion chromatography (SEC) the WGA containing and therefore binding conjugate was isolated from the reaction mix. In flow-cytometric and fluorimetric experiments with single cells and cell monolayers, respectively, binding and internalisation of the conjugate representing a high molecular weight (>100kDa) could be demonstrated. Fluorescent PGA without the WGA component showed neither binding nor internalisation potential. Microscopic colocalization studies with cell monolayers and single cells confirmed the cytoadhesive and cytoinvasive potential of the WGA containing conjugate. In accordance with the results of specificity studies the interaction between the conjugate and the cell surface depended solely on the WGA component of the conjugate. With the help of this targeted drug delivery system limiting factors of intravesical adjuvant therapy could eventually be overcome and thereby treatment efficacy of instillative chemotherapy could be improved. In addition, traceable drug conjugates might bear interesting advantages for theranostic purposes in the treatment of bladder cancer.


Asunto(s)
Ácido Glutámico/química , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/química , Polímeros/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Aglutininas del Germen de Trigo/química , Administración Intravesical , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Humanos , Lectinas/química , Vejiga Urinaria/efectos de los fármacos , Urotelio/efectos de los fármacos
16.
Nutr Cancer ; 69(2): 238-247, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28094571

RESUMEN

No studies have evaluated the association between the dietary inflammatory index (DII) and colorectal adenoma recurrence. DII scores were calculated from a baseline food frequency questionnaire. Participants (n = 1727) were 40-80 years of age, enrolled in two Phase III clinical trials, who had ≥1 colorectal adenoma(s) removed within 6 months of study registration, and a follow-up colonoscopy during the trial. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations were found between DII and odds of colorectal adenoma recurrence [ORs (95% CIs) = 0.93 (0.73, 1.18) and 0.95 (0.73, 1.22)] for subjects in the second and third DII tertiles, respectively, compared to those in the lowest tertile (Ptrend = 0.72). No associations were found for recurrent colorectal adenoma characteristics, including advanced recurrent adenomas, large size, villous histology, or anatomic location. While our study did not support an association between a proinflammatory diet and colorectal adenoma recurrence, future studies are warranted to elucidate the role of a proinflammatory diet on the early stages of colorectal carcinogenesis.


Asunto(s)
Adenoma/etiología , Neoplasias Colorrectales/etiología , Dieta/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Inflamación/etiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Oncogene ; 36(13): 1804-1815, 2017 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-27721407

RESUMEN

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Genes p53 , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 2/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Animales , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 2/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ratones , Ratones Noqueados , Mutación , Neoplasias Pancreáticas/patología , Regiones Promotoras Genéticas , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/genética
18.
Arch Pediatr ; 24(1): 36-40, 2017 Jan.
Artículo en Francés | MEDLINE | ID: mdl-27887956

RESUMEN

Ophthalmologic involvement in Sturge-Weber-Krabbe syndrome (SWKS) is present in 30-70% of cases and needs to be reviewed because of its impact on visual development. We report a case of a newborn for whom SSWK with ophthalmologic involvement was suspected. She had a right segmental plane angioma associated with right congenital glaucoma and suspected right pial angioma. Ophthalmic involvement in SWKS may be nonocular: iatrogenic by treatment-associated complications and central by leptomeningeal damage. Ophthalmologic involvement can occur throughout childhood and is mainly represented by glaucoma and diffuse choroidal hemangioma and then conjunctival hemangioma, retinal detachment, and iris heterochromia. SWKS requires multidisciplinary care with eye examination and prolonged follow-up as soon as clinical suspicion arises.


Asunto(s)
Glaucoma/complicaciones , Hemangioma/complicaciones , Neoplasias Meníngeas/complicaciones , Síndrome de Sturge-Weber/complicaciones , Femenino , Glaucoma/congénito , Humanos , Recién Nacido , Piamadre/diagnóstico por imagen
19.
Prostate Cancer Prostatic Dis ; 20(1): 61-66, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27618951

RESUMEN

BACKGROUND: Current guidelines do not recommend a preferred treatment modality for locally advanced prostate cancer. The aim of the study was to compare treatment patterns found in the USA and Germany and to analyze possible trends over time. METHODS: We compared 'Surveillance Epidemiology and End Results' (SEER) data (USA) with reports from four German federal epidemiological cancer registries (Eastern Germany, Bavaria, Rhineland-Palatinate, Schleswig-Holstein), both from 2004 to 2012. We defined locally advanced prostate cancer as clinical stage T3 or T4. Exclusion criteria were metastatic disease and age over 79 years. RESULTS: We identified 9127 (USA) and 11 051 (Germany) patients with locally advanced prostate cancer. The share was 2.1% in the USA compared with 6.0% in Germany (P<0.001). In the United States, the utilization of radiotherapy (RT) and radical prostatectomy (RP) was comparably high with 42.0% (RT) and 42.8% (RP). In Germany, the major treatment option was RP with 36.7% followed by RT with 22.1%. During the study period, the use of RP increased in both countries (USA P=0.001 and Germany P=0.003), whereas RT numbers declined (USA P=0.003 and Germany P=0.002). The share of adjuvant RT (aRT) was similar in both countries (USA 21.7% vs Germany 20.7%). CONCLUSION: We found distinctive differences in treating locally advanced prostate cancer between USA and Germany, but similar trends over time. In the last decade, a growing number of patients underwent RP as a possible first step within a multimodal concept.


Asunto(s)
Pautas de la Práctica en Medicina , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vigilancia de la Población , Prostatectomía/métodos , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/diagnóstico , Sistema de Registros , Programa de VERF , Estados Unidos/epidemiología
20.
Urologe A ; 55(12): 1586-1594, 2016 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-27826660

RESUMEN

BACKGROUND: The decision aid "Entscheidungshilfe Prostatakrebs" is available online free of charge since June 2016. It is designed to support patients with their treatment decision-making and to lighten the burden on their treating urologists. This study evaluates usage data from the first 3 months. MATERIALS AND METHODS: The ICHOM standard set was applied to allow a personalised presentation and to collect relevant data for subsequent counselling. Additionally, personal preferences and psychological burden were assessed amongst others. We collected anonymous data. A multivariate model evaluated predictors for high user satisfaction. RESULTS: From June through August 2016 a total of 319 patients used the decision aid, showing a continuous monthly increase in the number of users. There were n = 219 (68.7%) complete questionnaires. Median age was 66.1 ± 8.0 years. The oncological risk was low in 30.3%, intermediate in 43.6% and high in 26.1%. A majority of 57.5% used the decision aid together with their partner, 35.1% alone and 5.5% with their children. In all, 54.8% were "very satisfied" and 32.0% were "satisfied" with the decision aid for a total satisfaction rate of about 87%. The only predictors of total satisfaction were the usage mode and reported distress level. CONCLUSIONS: As shown by the continuously increasing number of users this decision aid is becoming well established in German urology. Patients' overall ratings are very positive. The majority of patients use the decision aid with their partner. This represents a significant advantage of a multimedia approach compared to print media.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas/estadística & datos numéricos , Educación del Paciente como Asunto/estadística & datos numéricos , Participación del Paciente/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Neoplasias de la Próstata/psicología , Neoplasias de la Próstata/terapia , Anciano , Alemania/epidemiología , Humanos , Masculino , Sistemas en Línea , Participación del Paciente/psicología , Atención Dirigida al Paciente/estadística & datos numéricos , Proyectos Piloto , Neoplasias de la Próstata/epidemiología , Revisión de Utilización de Recursos
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