Immunological mechanisms involved in the human response to a dog dander allergoid.

BACKGROUND: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. METHODS: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. RESULTS: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. CONCLUSION: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.

A new and simple scoring system to predict overall survival after irradiation for metastatic spinal cord compression.

PURPOSE: To develop a model that predicts survival in patients irradiated for metastatic spinal cord compression (MSCC), hence assisting in the decision between a short and a long-course radiotherapy (RT) regimen. METHODS: 138 patients diagnosed with MSCC and treated with RT alone were included. Based on a multivariate analysis, a scoring system was developed. It included four prognostic variables: age, number of vertebrae, ECOG and histology. Total scores ranged between 14 and 24 points and patients were divided into two groups. RESULTS: The 6-month survival rate was 22% for patients with a score of 14-18 points; and 69% for patients with a score of 19-24 points (P < 0.001). The system exhibits a high specificity and positive predictive value and an appropriate discriminative ability. CONCLUSIONS: Patients with scores between 19 and 24 points were found to survive longer, thus a long-course RT appears to be more appropriate.

[PSA bounce phenomenon after local treatment with radiation for prostate cancer]. / Fenómeno de rebote de PSA después de tratamiento local con radioterapia en el cáncer de próstata.

Radiotherapy is a curative treatment for localized prostate cancer in its modalities of brachytherapy (BT) and external beam radiotherapy (EBRT). A temporary increase in prostate-specific antigen (PSA) values following a radiotherapy treatment coupled with a decrease without therapeutic intervention may happen in 30% of the patients. This phenomenon is known as PSA bounce and lacks prognostic effect in relation to tumor control. Additionally, it produces anxiety in the patient because of the fear of failure, and in the physicists due to the uncertainty about the state of the tumor. The etiology and pathogenesis are still unknown. Several factors associated with the tumor and the treatments have been evaluated in the studies which analyze this phenomenon, the age is the only observed factor with the highest consistency as a bounce predictor. The definition of biologic failure (BF)after EBRT or BT with or without androgenic deprivation (ADT) according to Phoenix criteria, which considers an increase of at least 2 ng/ml over PSA nadir, enables better taking the bounce phenomenon into account, although is not free from false BF that may affect to the relapse-free survival in patients with follow-up shorter than 3 years.

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis.

Toxoplasma gondii infects a variety of vertebrate hosts, including humans. Transplacental passage of the parasite leads to congenital toxoplasmosis. A primary infection during the first weeks of gestation causes vertical transmission at low rate, although it causes major damage to the embryo. Transmission frequency increases to near 80% by the end of pregnancy, but the proportion of ill newborns is low. For transmission and pathogenesis, the parasite genetics is certainly important. Several host innate and adaptative immune response genes are induced during infection in adults, which control the rapidly replicating tachyzoite. The T helper 1 (Th1) response is protective, although it has to be modulated to avoid inflammatory damage. Paradoxical observations on this response pattern in congenital toxoplasmosis have been reported, as it may be protective or deleterious, inducing sterile abortion or favoring parasite transplacental passage. Regarding pregnancy, an early Th1 microenvironment is important for control of infectious diseases and successful implantation, although it has to be regulated to support trophoblast survival. Polymorphism of genes involved in these parallel phenomena, such as Toll-like receptors (TLRs), adhesins, cytokines, chemokines or their receptors, immunoglobulins or Fc receptors (FcRs), might be important in susceptibility for T. gondii vertical transmission, abortion or fetal pathology. In this study some examples are presented and discussed.

Evaluación prospectiva del tratamiento de brotes de sclerosis múltiple con megadosis oral de metilprednisolona: datos de respuesta y seguridad / Prospective assessment of the treatment of multiple sclerosis relapses with oral high-dose methylprednisolone: response and tolerability data

Objetivo. Evaluación de la respuesta y seguridad del tratamiento de brotes de esclerosis múltiple (EM) con dosis altas de metilprednisolona oral (MPO), y análisis de la correlación entre la escala de Kutzke (EDSS) y la escala funcional compuesta (EFC) en la evaluación de los cambios posbrote. Método. Se incluyeron consecutivamente pacientes diagnosticados de EM clínicamente definida con un brote de menos de 3 semanas de evolución. Los pacientes fueron evaluados y tratados con 1.000 mg de MPO en dosis única durante 3 días sin pauta de reducción. De todos disponíamos de una EDSS basal y al menos tres medidas de la EFC. Ambas escalas se completaron el día 0, antes del tratamiento, y las semanas 1, 4 y 12 después del mismo. Consideramos buena respuesta a la mejoría de al menos 1 punto en la EDSS respecto al día 0 o la recuperación de la EDSS basal. Resultados. Se trataron 21 brotes en 20 pacientes. EDSS basal media, 2,5; z-score de la EFC basal medio, 0,15; tiempo medio de evolución del brote, 6,8 días. Durante el brote la EDSS empeoró a 3,8 y el z-score a -0,57. Hubo buena respuesta en el 33,4 % de los brotes en la semana 1 y en el 85,7% en las semanas 4 y 12. Aunque ambas escalas mejoraron significativamente en la primera semana, la EDSS media no recuperó su valor basal hasta la semana 4 y la EFC lo hizo en la semana 12. Las escalas se correlacionaron en cada evaluación y respecto a los cambios debidos al brote (p<0,01). No se registraron acontecimientos adversos graves. Discusión. La megadosis de MPO es un tratamiento seguro y eficaz de los brotes de EM. EDSS y EFC son sensibles a los cambios posbrote, aunque su dinámica de recuperación es diferente, proporcionándonos cada una información complementaria (AU)

Objective: This study aims to assess the response and safety of the treatment of multiple sclerosis (MS) episodes with high oral doses of methylprednisolone (MP) and to investigate the correlation between expanded disability status scale (EDSS) and MS functional composite (MSFC) during recovery from relapses. Method: Patients consecutively diagnosed of clinically defined MS with an episode of less than three weeks course were included. They were evaluated and treated with a single dose of 1,000 mg of MP for three days without oral tapering. Baseline EDSS and at least three MSFC scale measurements were available. Patients were scored with EDSS and MSFC before the treatment and after 1, 4 and 12 weeks. Adverse events were also recorded. Response to treatment was defined as the recovery of at least 1 point in the EDSS or the return to baseline EDSS. Results: Twenty one episodes in 20 patients were treated. Mean baseline EDSS was, 2.5; mean baseline z-score was, 0.15, and mean relapse duration was, 6.8 days. During relapse, mean EDSS worsened to 3.8 and mean z-score to -0.57. At week 1, 33.4% of relapses had responded to treatment, and at weeks 4 and 12, 85.7% had responded. Although mean EDSS and mean z-score had already improved at week 1, mean EDSS did not reach baseline value until week 4 and mean z-score until week 12. EDSS correlated significantly to MSFC in each evaluation as well as to scale changes related to relapse (p;0.05). No serious adverse events were seen. Discussion: Oral high-dose of MP is a safe and effective therapy for MS relapses. Both EDSS and MSFC were sensitive to changes related to relapses although the dynamics of recovery was different, providing complementary information (AU)

Evaluation of response of multiple sclerosis (MS) relapse to oral high-dose methylprednisolone: usefulness of MS functional composite and Expanded Disability Status Scale.

To compare the usefulness of multiple sclerosis functional composite (MSFC) to the Expanded Disability Status Scale (EDSS) in assessing functional changes related to relapse. A prospective 12-week follow-up study after relapse was conducted among 14 multiple sclerosis (MS) patients treated with oral high-dose (1 g) methylprednisolone for 3 days. MSFC and the EDSS were assessed on day 0, before treatment and, 1, 4 and 12 weeks afterwards. In relapses, EDSS (2.5 +/- 1.2 to 3.8 +/- 1.0) and z-score of the MSFC (0.15 +/- 0.58 to -0.59 +/- 0.70) worsened. After 1 week of treatment, the EDSS improved (3.3 +/- 1.2; P = 0.002) while the MSFC did not change significantly. At week 4, EDSS improvement was maximal (2.8 +/- 1.3; P = 0.001). At week 12, EDSS remained stable whereas z-score continued improving (0.26 +/- 0.74). z-9peg-hole-test was the most sensitive subtest. There was correlation between baseline values of both scales (-0.620, P < 0.05) and between changes due to relapse (-0.535, P < 0.05). 78.5% of patients had improved at week 4 (35.7% at week 1). There were no serious adverse effects. MSFC and the EDSS were sensitive to changes due to relapses, although the dynamics for restoring baseline function were different. Our data support the usefulness of both scales in clinical trials, providing complementary information about outcome of MS patients with relapses.

[Prospective assessment of the treatment of multiple sclerosis relapses with oral high-dose methylprednisolone: response and tolerability data]. / Evaluación prospectiva del tratamiento de brotes de esclerosis múltiple con megadosis oral de metilprednisolona: datos de respuesta y seguridad.

OBJECTIVE: This study aims to assess the response and safety of the treatment of multiple sclerosis (MS) episodes with high oral doses of methylprednisolone (MP) and to investigate the correlation between expanded disability status scale (EDSS) and MS functional composite (MSFC) during recovery from relapses. METHOD: Patients consecutively diagnosed of clinically defined MS with an episode of less than three weeks course were included. They were evaluated and treated with a single dose of 1,000 mg of MP for three days without oral tapering. Baseline EDSS and at least three MSFC scale measurements were available. Patients were scored with EDSS and MSFC before the treatment and after 1, 4 and 12 weeks. Adverse events were also recorded. Response to treatment was defined as the recovery of at least 1 point in the EDSS or the return to baseline EDSS. RESULTS: Twenty one episodes in 20 patients were treated. Mean baseline EDSS was, 2.5; mean baseline z-score was, 0.15, and mean relapse duration was, 6.8 days. During relapse, mean EDSS worsened to 3.8 and mean z-score to -0.57. At week 1, 33.4% of relapses had responded to treatment, and at weeks 4 and 12, 85.7% had responded. Although mean EDSS and mean z-score had already improved at week 1, mean EDSS did not reach baseline value until week 4 and mean z-score until week 12. EDSS correlated significantly to MSFC in each evaluation as well as to scale changes related to relapse (p;0.05). No serious adverse events were seen. DISCUSSION: Oral high-dose of MP is a safe and effective therapy for MS relapses. Both EDSS and MSFC were sensitive to changes related to relapses although the dynamics of recovery was different, providing complementary information.

Tratamiento adyuvante y resultados / Adjuvant treatment and results

Aproximadamente el 50 per cent de los pacientes tratados con cirugía con intención curativa fallecerán por recurrencia del cáncer colorrectal. La quimioterapia (QT) adyuvante aumenta la supervivencia libre de enfermedad y la supervivencia global en el estadio III del cáncer de colon, y es controvertida en el estadio II, salvo en pacientes de alto riesgo. Actualmente el 5fluorouracilo (5-FU) y leucovorín (LV), administrado por vía intravenosa durante 6 meses, se considera el régimen más adecuado. No existe ninguna opción terapéutica estándar tras la resección de metástasis, pero en la práctica clínica diaria se suele emplear 5FU/LV durante 6 meses. En metástasis hepáticas irresecables de inicio, la QT neoadyuvante logra una reducción del tamaño del tumor y permite resecciones completas en casos seleccionados. Los pacientes ancianos con buen estado general pueden beneficiarse de la QT igual que los más jóvenes. En estadios II y III de cáncer de recto, la administración postoperatoria de radioterapia pélvica y quimioterapia basada en 5-FU disminuye la recidiva local y aumenta la supervivencia. La eficacia de nuevos citostáticos, como las fluoropirimidinas orales (UFT, capecitabina), raltitrexed, irinotecán y oxaliplatino, se está estudiando en ensayos clínicos aleatorizados. La identificación de nuevos factores pronósticos permitirá seleccionar a subgrupos de mayor riesgo que puedan necesitar terapias más agresivas (AU)