Unravelling Receptor and RGD Motif Dependence of Retargeted Adenoviral Vectors using Advanced Tumor Model Systems.

Recent advances in engineering adenoviruses are paving the way for new therapeutic gene delivery approaches in cancer. However, there is limited knowledge regarding the impact of adenoviral retargeting on transduction efficiency in more complex tumor architectures, and the role of the RGD loop at the penton base in retargeting is unclear. To address this gap, we used tumor models of increasing complexity to study the role of the receptor and the RGD motif. Employing tumor-fibroblast co-culture models, we demonstrate the importance of the RGD motif for efficient transduction in 2D through the epithelial cell adhesion molecule (EpCAM), but not the epidermal growth factor receptor (EGFR). Via optical clearing of co-culture spheroids, we show that the RGD motif is required for transduction via both receptors in 3D tumor architectures. We subsequently employed a custom-designed microfluidic model containing collagen-embedded tumor spheroids, mimicking the interplay between interstitial flow, extracellular matrix and adenoviral transduction. Image analysis of on-chip cleared spheroids indicated the importance of the RGD motif for on-chip adenoviral transduction. Together, our results show the interrelationship between receptor characteristics, the RGD motif, the 3D tumor architecture and retargeted adenoviral transduction efficiency. The findings are important for the rational design of next-generation therapeutic adenoviruses.

Is self-injectable epinephrine being used by children with food allergy?

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Social Media as a Tool for the Management of Food Allergy in Children.

BACKGROUND: Food allergy markedly impairs quality of life, and avoiding the offending food requires extensive patient education. Social media have been proven a useful source of information for other chronic conditions. Our aim was to describe how pediatric patients with food allergy and their families are using social media. METHODS: We performed a cross-sectional study in the pediatric allergy unit of a tertiary hospital. Patients with food allergy were questioned about their disease and their use of social media. The survey was completed by the patients themselves in the case of those aged over 13 years and by parents or guardians in the case of younger patients. RESULTS: We included 193 patients (162 guardians, 31 adolescents). Social media were used by 109 guardians (67.3%) and 29 adolescents (90.3%), of whom 30.3% and 6.9%, respectively, used them for food allergy-related purposes. The most popular websites were Facebook for guardians (52.2%) and YouTube for teenagers (80.6%). Having cow's milk and/or egg allergy was the only feature related to using social media for food allergy. Using social media for information on food allergy did not correlate with the frequency of recent reactions, self-scored knowledge about food allergy, or opinion on evidence-based or alternative therapies for the disease. CONCLUSIONS: Most patients and guardians of patients with food allergy used social media. However, only a small portion accessed used them to increase their knowledge of the disease.

Food protein-induced enterocolitis syndrome by fish: Not necessarily a restricted diet.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Recent researches show that fish is 1 of the most important triggers of FPIES in the Mediterranean countries. Due to the risk of multiple-food FPIES, avoiding foods in the same category or that often occur together may be reasonable. The aim of this study was to evaluate the evolution and follow-up of FPIES related to fish over a period of 20 years. We describe the clinical features of our population, discuss different approaches to oral food challenges, and analyze the possibility of introducing the culprit fish or other nonrelated fish to avoid unnecessary restricted diets.

Social media as a tool for the management of food allergy in children

Background: Food allergy markedly impairs quality of life, and avoiding the offending food requires extensive patient education. Social media have been proven a useful source of information for other chronic conditions. Our aim was to describe how pediatric patients with food allergy and their families are using social media. Methods: We performed a cross-sectional study in the pediatric allergy unit of a tertiary hospital. Patients with food allergy were questioned about their disease and their use of social media. The survey was completed by the patients themselves in the case of those aged over 13 years and by parents or guardians in the case of younger patients. Results: We included 193 patients (162 guardians, 31 adolescents). Social media were used by 109 guardians (67.3%) and 29 adolescents (90.3%), of whom 30.3% and 6.9%, respectively, used them for food allergy-related purposes. The most popular websites were Facebook for guardians (52.2%) and YouTube for teenagers (80.6%). Having cow's milk and/or egg allergy was the only feature related to using social media for food allergy. Using social media for information on food allergy did not correlate with the frequency of recent reactions, self-scored knowledge about food allergy, or opinion on evidence-based or alternative therapies for the disease. Conclusions: Most patients and guardians of patients with food allergy used social media. However, only a small portion accessed used them to increase their knowledge of the disease

Introducción: La alergia alimentaria afecta a la calidad de vida de quienes la sufren. La evitación de los alimentos que la producen exige la educación de los pacientes. Las redes sociales han demostrado ser una fuente útil de información acerca de otras enfermedades crónicas. El objetivo de este estudio fue describir el uso de las redes sociales por parte de los pacientes en edad pediátrica con alergia alimentaria, así como el de sus familias. Métodos: Se realizó un estudio transversal en la Unidad de Alergia Infantil de un hospital de tercer nivel. Se encuestó a pacientes diagnosticados de alergia alimentaria, acerca de su enfermedad, así como de su uso de las redes sociales. La encuesta fue cumplimentada por los propios pacientes a partir de los 13 años de edad, mientras que los tutores lo hicieron en los casos de pacientes menores. Resultados: Se incluyeron 193 pacientes (162 tutores y 31 adolescentes). Las redes sociales eran utilizadas por 109 tutores (67,3%) y 29 adolescentes (90,3%), de los que el 30,3% y el 6,9%, respectivamente, lo hacían en relación con la alergia alimentaria. Las páginas web más frecuentes eran Facebook(TM) en el caso de los tutores (52,2%) y YouTube(TM) entre los adolescentes (80,6%). Ser alérgico a la leche y/o al huevo era la única característica que se relacionó con el uso de redes sociales en relación a la alergia alimentaria. El uso de las redes sociales para informarse acerca de la alergia a los alimentos no se correlacionó con la frecuencia de reacciones, la percepción del conocimiento propio acerca de la alergia alimentaria o la opinión sobre terapias científicas y alternativas para su enfermedad. Conclusiones: La mayoría de los pacientes con alergia alimentaria y sus tutores son usuarios de las redes sociales. Sin embargo, sólo una pequeña porción las utiliza para formarse acerca de su enfermedad

Do Skin Prick Test and In Vitro Techniques Diagnose Sensitization to Peach Lipid Transfer Protein and Profilin Equally Well in Allergy to Plant Food and Pollen?

OBJECTIVE: To compare the skin prick test (SPT) with in vitro techniques (single and multiplex fluorescence enzyme-immunoassay [FEIA]) for detecting sensitization to profilin and lipid transfer protein (LTP). METHODS: We retrospectively studied 181 patients with pollen and/or plant food allergy and 61 controls. SPT was performed with date palm profilin (Pho d 2) and peach LTP (Pru p 3), and specific IgE (sIgE) to Phl p 12 and Pru p 3 was analyzed using single FEIA and microarray. RESULTS: Fifteen of 201 patients with negative results for LTP in the SPT were sensitized to this allergen in the in vitro tests, and 18 of 41 patients with positive results for LTP in the SPT were not sensitized according to the in vitro tests. Seventeen of 186 patients with negative results for profilin in the SPT were sensitized to Phl p 12 by serum sIgE, and 30 out of 56 patients with positive results for profilin in SPT were not sensitized to Phl p 12 according to the other tests. Moderate agreement was observed between the 3 techniques studied. CONCLUSIONS: SPT is a sensitive technique for detecting sensitization to LTP and profilin. Its results are similar to those of in vitro techniques, especially in patients with negative SPT results for peach LTP and palm tree profilin.

Do skin prick test and in vitro techniques diagnose sensitization to peach lipid transfer protein and profilin equally well in allergy to plant food and pollen?

Objetivo: Comparar las pruebas cutáneas prick (PC) con técnicas in vitro (fluoro enzimoinmunoensayo –FEIA- en detección única y múltiple) para detectar sensibilización a profilina y a LTP. Métodos: Se estudiaron retrospectivamente 181 pacientes con alergia a polen y a alimentos vegetales y 61 controles. Se realizaron PC frente a profilina de palmera (Pho d 2) y LTP de melocotón (Pru p 3) y se analizó la IgE específica a Phl p 12 y Pru p 3 por FEIA y por micromatriz de proteínas alergénicas. Resultados: Quince de los 201 sujetos con PC negativa a LTP mostraron ensibilización a este alérgeno mediante IgE específica sérica y en 18 de 41 con PC positivas a LTP no se observó esta sensibilización por otras técnicas. Diecisiete de los 186 sujetos con PC negativa a profilina detectaron IgE específica sérica frente a Phl p 12 y en 30 de los 56 con PC positiva a profilina no se objetivó sensibilización a Phl p 12 en suero. Se observó un acuerdo moderado entre las tres técnicas estudiadas. Conclusiones: La PC frente e a LTP y profilina es un método sensible detectando estas sensibilizaciones y muestra un acuerdo aceptable con las técnicas in vitro, especialmente en los pacientes con negatividad de la PC frente a LTP y a profilina (AU)

Objective: To compare the skin prick test (SPT) with in vitro techniques (single and multiplex fluorescence enzyme-immunoassay [FEIA]) for detecting sensitization to profilin and lipid transfer protein (LTP). Methods: We retrospectively studied 181 patients with pollen and/or plant food allergy and 61 controls. SPT was performed with date palm profilin (Pho d 2) and peach LTP (Pru p 3), and specific IgE (sIgE) to Phl p 12 and Pru p 3 was analyzed using single FEIA and microarray. Results: Fifteen of 201 patients with negative results for LTP in the SPT were sensitized to this allergen in the in vitro tests, and 18 of 41 patients with positive results for LTP in the SPT were not sensitized according to the in vitro tests. Seventeen of 186 patients with negative results for profilin in the SPT were sensitized to Phl p 12 by serum sIgE, and 30 out of 56 patients with positive results for profilin in SPT were not sensitized to Phl p 12 according to the other tests. Moderate agreement was observed between the 3 techniques studied. Conclusions: SPT is a sensitive technique for detecting sensitization to LTP and profilin. Its results are similar to those of in vitro techniques, especially in patients with negative SPT results for peach LTP and palm tree profiling (AU)

Early skin testing is effective for diagnosis of hypersensitivity reactions occurring during anesthesia.

Allergic skin tests have to be performed 4-6 weeks after an allergic anesthetic reaction. Patients with allergic reactions during anesthesia were prospectively included (n = 44). Skin tests were performed in two stages: (i) Stage 1 (S1), 0-4 days after the reaction; and (ii) Stage 2 (S2), 4-8 weeks after. Five (11.5%) surgical procedures were suspended due to the reaction. Positive skin tests were obtained in 25/44 patients (57%). Allergic diagnosis was carried out at S1 in 15/25 (60%) and at S2 in 10/25 (40%). Three patients resulted positive only in S1. Overall agreement among S1 and S2 skin tests was 70.45%. The kappa statistic was 0.41 (P-value = 0.002). Odds ratio of obtaining a false negative in S1 (compared with S2) was 3.33. Early allergological study is useful, could minimize false negatives, but should be considered as a complement to late skin tests.

[The rational preoperative diagnosis of ovarian tumors - imaging techniques and tumor biomarkers (review)]. / Racionální predoperacní diagnostika benigních a maligních ovariálních nádoru - zobrazovací metody, nádorové markery.

The majority of patients who suffer from an early-stage or advanced-stage of ovarian cancer complain about symptoms, mainly gastrointestinal ones. The pelvic examination in ovarian cancer detection is limited by the adnexal position in the pelvis and frequent extraovarian spread of disease. Recently, any reliable tumor biomarker (CA 125 and/or HE4), which can be used in differential diagnosis between benign and malignant ovarian tumors, does not exist. According the results of the largest multicenter International Ovarian Trial Analysis (IOTA), ultrasound if performed by an experienced sonologist is an ideal diagnostic method in differential diagnosis between benign and malignant ovarian tumors. The experienced examiner is also able to detect extraovarian tumor spread and to assess tumor operability. Magnetic resonance imaging (MRI) is used only to complement ultrasound in cases when high tissue resolution is needed. Computed tomography (CT) is a useful method for detection of extraovarian spread, especially in cases when an ultrasound examiner experienced in abdominal scanning is not available. Similarly, fusion of positron emission tomography with CT (PET/CT) is a highly accurate method for the detection of abdominal and extraabdominal tumor spread, but its use is limited by cost and the low availability of this method. On the other hand, PET/CT is not recommended for primary ovarian cancer detection because of its lower sensitivity in comparison to ultrasound and its high false positive rates as well.

[Follow-up after the treatment of ovarian cancer - really without Ca 125?]. / Follow-up po lécbe karcinomu ovaria -opravdu bez Ca 125?

Results of study MRC OV05 and EORTC/GCCG 55955 (Rustin et al.) have raised a considerable interest and controversy by questioning the early beginning of recurrent ovarian cancer treatment and the role of Ca 125 monitoring in the follow-up of ovarian cancer patients. Main pitfalls and limitations of this study are introduced in a survey. On their basis an author's opinion on the continuing role of Ca 125 monitoring is expressed with a possible benefit for the subgroup of patients with a solitary or operable relaps or those with new treatment possibilities or with inclusion to new clinical studies.

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells.

OBJECTIVES: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. METHODS: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC-NOS), five favour neoplasia (AGC-FN) and one adenocarcinoma in situ (AIS). Thirty-one with high-grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC-NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC-FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow-up controls were carried out every 8-12 weeks and, if there were no signs of progression, revaluation was scheduled 6-8 weeks after delivery. RESULTS: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. CONCLUSIONS: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre-cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC-FN or AIS. Triage of persistent AGC-NOS with HPV testing is useful in distinguishing significant underlying lesions.