5-Year management and outcomes of penetrating neck injury in a trauma center. Penetrating neck injury / Manejo y resultados de trauma penetrante de cuello en 5 años dentro de un centro de urgencias. Trauma penetrante de cuello

Background Penetrating neck injuries represent 5–10% of all traumatic injuries, these bring with them a high rate of morbidity and mortality due to vital structures that could be injured in this area. The aim of this study was to determine the epidemiological and clinical characteristics of penetrating neck injuries. Methods This was a retrospective, unicentric and descriptive study that included all patients who underwent neck exploration surgery. Results A total of 70 neck exploration cases were reviewed, 34 (49%) didn’t had any injury. Thirty (43%) had at least one hard sign, 42 (60%) patients showed at least one soft sign. Statistical analysis showed only surgical time (252±199.5 vs. 155±76.4; p=0.020) and transfusions (1.87±3 vs. 0.4±0.856; p=0.013) were statistically significant. We report a mortality of 2 (3%) patients. Conclusions Our prevalence of neck surgical exploration without vascular injury was slightly higher (49% vs. 40%) than literature. We highlight the importance of not performing neck explorations in all patients who present a penetrating injury. We did not obtain differences between groups for hard signs and soft signs. We were not able to identify whether or not there would be an injury based on clinical characteristics. Imaging studies should be performed to avoid unnecessary neck explorations; however, depending on the clinical scenario some surgery cannot be avoided (AU)

Antecedentes Las lesiones penetrantes de cuello representan entre el 5-10% de todas las lesiones traumáticas, estas traen consigo una alta tasa de morbimortalidad por estructuras vitales que podrían lesionarse en esta área. El propósito de este estudio fue determinar las características epidemiológicas y clínicas del trauma penetrante de cuello. Métodos Estudio retrospectivo, unicéntrico y descriptivo que incluyó a todos los pacientes sometidos a cirugía de exploración de cuello. Resultados Se revisaron un total de 70 casos de exploración de cuello, 34 pacientes (49%) no presentaron ninguna lesión. Treinta pacientes (43%) tenían al menos un signo duro, 42 pacientes (60%) mostraron al menos un signo blando. El análisis estadístico mostró que solo el tiempo quirúrgico (252±199,5 vs. 155±76,4; p=0,020) y las transfusiones (1,87±3 vs, 0,4±0,856; p=0,013) fueron estadísticamente significativas. Reportamos la mortalidad de 2 pacientes (3%). Conclusiones Nuestra prevalencia de exploración quirúrgica de cuello sin lesión vascular fue ligeramente superior (49 vs. 40%) que la literatura. Destacamos la importancia de no realizar exploraciones de cuello en todos los pacientes que presentan una lesión penetrante. No obtuvimos diferencias entre grupos para signos duros y signos blandos. No pudimos identificar si hubiera o no una lesión en función de las características clínicas. Se deben realizar estudios de imagen para evitar exploraciones innecesarias del cuello; sin embargo, dependiendo del escenario clínico, no se pueden evitar algunas cirugías (AU)

Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies. / Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante.

BACKGROUND AND OBJECTIVE: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. MATERIALS AND METHOD: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. RESULTS: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. CONCLUSIONS: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease.

Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante / Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies

Antecedentes y objetivo: Para estimar la carga real del melanoma y el impacto de las nuevas terapias adyuvantes sobre las recaídas y la supervivencia, se precisa conocer con mayor exactitud la incidencia por estadios y analizar la transición entre ellos. Este estudio pretende estimar dicha incidencia y determinar el número de pacientes en estadio III que podrían beneficiarse del tratamiento sistémico adyuvante en España. Materiales y método: Se elaboró un modelo epidemiológico basado en datos de pacientes diagnosticados de melanoma o en recaída, recogidos prospectivamente durante 2012-2016 por cuatro unidades de melanoma de centros sanitarios públicos. Resultados: Las tasas brutas de incidencia estimadas para estadios I y II se situaron en 7 y 2,9 casos por 100.000 personas-año, respectivamente. Para estadio III se estimó en 1,9 (25,8% en IIIA, 47% en IIIB, y 27,3% en IIIC), siendo la de estadio IV de 1,3. La tasa de recaídas en estadio III se estimó en 1,1, siendo para estadio IV de 0,9. El 54% de recaídas a estadio III procedían de estadios I/II, mientras que el resto progresaban desde subestadios III. En estadio III, un 85% de nuevos diagnósticos y un 80% de recaídas fueron resecables, por tanto, candidatos a adyuvancia, de los cuales el 47% presentaba mutación en BRAF. Conclusiones: Estas estimaciones podrían tener un impacto importante en la planificación de los recursos sanitarios. La proyección en el número de potenciales candidatos a adyuvancia puede ayudar a decisores y clínicos a anticiparse a futuras necesidades en el manejo del melanoma (AU)

Background and objective: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. materials and method: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. Results: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. Conclusions: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease (AU)

[Translated article] Epidemiology of Melanoma in Spain: Estimation of Number of Patients With Stage III Disease Eligible for Adjuvant Therapies / Epidemiología del melanoma en España: estimación de los pacientes con melanoma con estadio III candidatos al tratamiento adyuvante

Background and objective: Accurate information on the incidence of melanoma by stage and a better understanding of transition between stages are important for determining the burden of disease and assessing the impact of new adjuvant therapies on recurrence and survival. The aim of this study was to estimate the incidence rates of the various stages of melanoma in Spain and to estimate the number of patients with stage III disease who are eligible for adjuvant systemic therapies. materials and method: We built an epidemiological model using prospectively collected data from patients diagnosed with de novo or recurrent melanoma between 2012 and 2016 in the melanoma units of 4 public hospitals. Results: The estimated crude incidence rates for stage I and II melanoma were 7 and 2.9 cases per 100,000 person-years, respectively. The corresponding rates for stage III and IV melanoma were 1.9 and 1.3 cases per 100,000 person-years; 25.8% of patients with stage III melanoma were stage IIIA, 47% were stage IIIB, and 27.3% were stage IIIC. The respective estimated incidence rates for recurrent stage III and IV melanoma were 1.1 and 0.9 cases per 100,000 person-years. Overall, 54% of patients with recurrent stage III melanoma had progressed from stage I or II; the other cases corresponded to changes in substage. Of the patients with stage III melanoma, 85% of those with a de novo diagnosis and 80% of those who had relapsed had resectable disease, meaning they were eligible for adjuvant therapy; 47% of these patients had a BRAF mutation. Conclusions: The above estimates could have a major impact on health care resource planning. Assessing the number of patients with melanoma who are eligible for adjuvant therapies in melanoma could help decision-makers and clinicians anticipate future needs for the management of this disease (AU)

Antecedentes y objetivo: Para estimar la carga real del melanoma y el impacto de las nuevas terapias adyuvantes sobre las recaídas y la supervivencia, se precisa conocer con mayor exactitud la incidencia por estadios y analizar la transición entre ellos. Este estudio pretende estimar dicha incidencia y determinar el número de pacientes en estadio III que podrían beneficiarse del tratamiento sistémico adyuvante en España. Materiales y método: Se elaboró un modelo epidemiológico basado en datos de pacientes diagnosticados de melanoma o en recaída, recogidos prospectivamente durante 2012-2016 por cuatro unidades de melanoma de centros sanitarios públicos. Resultados: Las tasas brutas de incidencia estimadas para estadios I y II se situaron en 7 y 2,9 casos por 100.000 personas-año, respectivamente. Para estadio III se estimó en 1,9 (25,8% en IIIA, 47% en IIIB, y 27,3% en IIIC), siendo la de estadio IV de 1,3. La tasa de recaídas en estadio III se estimó en 1,1, siendo para estadio IV de 0,9. El 54% de recaídas a estadio III procedían de estadios I/II, mientras que el resto progresaban desde subestadios III. En estadio III, un 85% de nuevos diagnósticos y un 80% de recaídas fueron resecables, por tanto, candidatos a adyuvancia, de los cuales el 47% presentaba mutación en BRAF. Conclusiones: Estas estimaciones podrían tener un impacto importante en la planificación de los recursos sanitarios. La proyección en el número de potenciales candidatos a adyuvancia puede ayudar a decisores y clínicos a anticiparse a futuras necesidades en el manejo del melanoma (AU)

Psychosocial repercussion of migraine: is it a stigmatized disease?

INTRODUCTION: Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient's internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. MATERIALS AND METHODS: The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. RESULTS: The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. CONCLUSIONS: There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

Epidemiología y evolución perioperatoria de lesión vascular periférica en civiles por trauma penetrante durante una década / Epidemiology and outcomes for civilian peripheral vascular injury in penetrating trauma during a decade

Introducción: Las lesiones causadas por trauma penetrante son una de las principales causas de morbimortalidad en todo el mundo. Para una gestión eficiente y un tratamiento adecuado, es esencial lograr una rápida detección, localización y caracterización de la lesión. Objetivo: Determinar la epidemiología y revisar el manejo perioperatorio de lesiones vasculares periféricas en extremidades durante una década. Material y métodos: Se utilizaron datos de 2006-2015 de un hospital universitario con pacientes con diagnóstico de lesión vascular en extremidades. Resultados: Se reportó un total de 110 casos. En 26 de los pacientes (23,6%) la lesión fue causada por una herida por arma punzo cortante y en 84 pacientes (76,4%) por proyectil de arma de fuego. El sitio lesionado más común fue la extremidad inferior. Veintiséis pacientes (23,6%) no mostraron lesión durante la angiografía. Se identificaron un total de 150 lesiones vasculares. Conclusiones: La arteria más comúnmente lesionada fue la femoral. Los factores predictivos de las lesiones estadísticamente significativos fueron la puntuación de la gravedad de la lesión, el grado de choque y los pacientes con lesiones múltiples. Seis amputaciones reportadas coinciden con un trauma severo. La ausencia de signos duros no descarta la posibilidad de lesión arterial. Se recomienda la reparación con injerto de safena invertido para las lesiones no reparables de manera primaria (AU)

Background: Penetrating trauma injuries are a leading cause of morbidity and mortality worldwide. For efficient management and appropriate treatment, the injuries need to be rapidly detected, located, and characterised. Objective: To describe the epidemiology and review the management of vascular injuries over a 10-year period. Material and methods: Data were used from patients with a diagnosis of vascular injury in extremities between 2006 and 2015 from a university hospital. Results: A total of 110 cases were reported. In 26 (23.6%) patients the injury was caused by a stab wound, and by a gunshot wound in 84 (76.4%) patients. The most common injury site was the lower limb. Twenty-six (23.6%) patients showed no injury in the angiography. A total of 150 vascular injuries were identified. Conclusion: The most commonly injured artery was the femoral. Statistically significant injury predictive factors were the injury severity score, the degree of shock, and patients with multiple injuries. Six amputations reported were associated with severe trauma. The absence of severe signs does not rule out the possibility of arterial injury. Inverted saphenous vein graft repair is recommended for non-repairable injuries (AU)

Candidiasis cutánea congénita, ¿una entidad poco frecuente o infradiagnosticada? / Congenital cutaneous candidiasis. An infrequent or underdiagnosed entity?

La candidiasis cutánea congénita es una infección poco frecuente, producida por Candida spp., que se desarrolla en la primera semana de vida. Su curso es habitualmente benigno y autolimitado, aunque existen casos graves de infección diseminada. Se presentan 2 casos de recién nacidos con eritema generalizado y rápida evolución a exantema papulopustular. En los cultivos de las lesiones se aisló Candida albicans. Ambos recibieron tratamiento tópico y presentaron una evolución favorable y sin complicaciones. Se revisan los factores de riesgo, la fisiopatología, las formas de presentación y la evolución de la candidiasis cutánea congénita (AU)

Congenital cutaneous candidiasis is an uncommon infection due to Candida spp. which develops within the first week of life. It has usually a benign and self-limited course although there are serious cases of systemic disease. We review the cases of two newborns with disseminate erythema present at birth. Both of them showed a rapid evolution to a papulo-pustular rash. Candida Albicans was isolated in cultures of the cutaneous lesions. After topical treatment, newborns presented a favourable outcome without any complications. Risk factors, physiopathology, clinical presentation and outcome of congenital cutaneous candidiasis are revised (AU)

The transfer of NIR calibrations for undried grass silage from the laboratory to on-site instruments: comparison of two approaches.

As a first step in a project whose aim is to implement near infrared (NIR) analysis of animal feed on the farm, the present work has examined the possibility of transferring undried grass silage calibrations for dry matter, crude protein, and neutral detergent fiber from a dispersive laboratory NIR instrument (Foss NIRSystem 6500) to a diode array on-site NIR instrument (Zeiss Corona 45 visNIR 1.7). Because the samples are complex and heterogeneous and have high humidity levels it is not easy to establish good calibrations, and it is even more of a challenge to transfer them. By cutting the spectral range to 1100-1650 nm and treating with first or second derivative followed by standard normal variate (SNV) scatter correction, it was possible to obtain very similar spectra from the two instruments. To make the transfer, two approaches were tried. Simply correcting the Corona spectra by subtracting the mean difference spectrum from a transfer set met with only limited success. Making a calibration on the Foss using a calibration set of 503 samples with spectra orthogonalized to the all the difference spectra in the transfer set of 10 samples resulted in a successful transfer for all three calibrations, as judged by performance on two prediction sets of size 22 and 29. Measuring 5 replicate subsamples with the Corona allows it to see a similar surface area to that of 3 replicates in the Foss transport cell, and it is suggested that this is an appropriate level of replication for the Corona.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) impairs the response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab in metastatic colorectal cancer patients.

BACKGROUND: The validation of KRAS mutations as a negative marker of response to anti-epidermal growth factor receptor (EGFR) antibodies has meant a seminal advance towards treatment individualisation of colorectal cancer (CRC) patients. However, as a KRAS wild-type status does not guarantee a response to anti-EGFR antibodies, a current challenge is the identification of other biomarkers of response. On the basis of pre-clinical evidence, we hypothesised that mitogen-activated protein kinase phosphatase-1 (MKP-1), a phosphatase that inactivates MAPKs, could be a mediator of resistance to anti-EGFR antibodies. METHODS: Tumour specimens from 48 metastatic CRC patients treated with cetuximab-based chemotherapy were evaluated for KRAS and BRAF mutational status and MKP-1 expression as assessed by immunohistochemistry. RESULTS: As expected, clinical benefit was confined to wild-type KRAS and BRAF patients. Mitogen-activated protein kinase phosphatase-1 was overexpressed in 16 patients (33%) and was not associated with patient baseline clinicopathological characteristics and KRAS mutational status. All patients with BRAF mutations (n=3) had MKP-1 overexpression. Among KRAS wild-type patients, MKP-1 overexpressors had a 7% response rate (RR), whereas patients not overexpressing MKP-1 had a 44% RR (P=0.03). Moreover, median time to progression was significantly longer in MKP-1 non-overexpressing patients (32 vs 13 weeks, P=0.009). CONCLUSION: These results support the concept of MKP-1 as a promising negative marker of response to cetuximab-based treatment in CRC patients with wild-type KRAS.

Trichinella: differential expression of angiogenic factors in macrophages stimulated with antigens from encapsulated and non-encapsulated species.

The newborn larval stage of Trichinella spiralis enters the host striated skeletal muscle cell resulting in the formation of the nurse cell. Vascular Endothelial Growth Factor (VEGF) was detected in cells in the area immediately surrounding the nurse cells. However, no data are available on the antigens involved, the role of other angiogenic factors or the relationship of angiogenesis with Nitric Oxide (NO) production. Using macrophage cell culture we study the effect of different Trichinella L1 antigens from one encapsulated (T. spiralis) and one non-encapsulated (Trichinellapseudospiralis) on the expression of VEGF and basic Fibroblast Growth Factor (FGF2). Also, we investigate the relationship between the production of NO and angiogenic mediators. The results show that encapsulated and non-encapsulated Trichinella species are different in their capacity to stimulate the expression of VEGF and FGF2 from host macrophages. Finally, there is no relationship between angiogenic factors and NO production by T. spiralis antigen.

Trichinellosis survey in the wild boar from the Toledo mountains in south-western Spain (2007-2008): molecular characterization of Trichinella isolates by ISSR-PCR.

In Spain, trichinellosis represents a public health problem, with an average of five outbreaks per year, wild boar meat being the main source of infection. A trichinellosis survey (2007-2008 hunting campaign) was carried out on wild boars in the Toledo Mountains (south-western Spain, EU) in the context of a surveillance programme on wildlife diseases. A total of 2216 wild boars from different locations of the region were examined. The examination was carried out by veterinarians in the local abattoir (Matadero Municipal de Toledo). The positive samples were sent to the Department of Parasitology (Facultad de Farmacia, UCM) for experimental isolation and specific identification by inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR). Using this technique we identified 17 isolates as Trichinella spiralis with an electrophoretic profile indistinguishable from the T. spiralis reference strain (ISS48). We confirmed that ISSR-PCR is a robust technique for the molecular identification of Trichinella isolates. According to our results, the prevalence of T. spiralis in wild boars from the Toledo Mountains (>800 m above sea level) during the hunting season was approximately 0.77%. The prevalence of T. spiralis (100% of our observations) is a good example of the persistence of this species in sylvatic conditions (coming from the domestic cycle), if a good wild host is abundant. Our observations confirm the major prevalence of T. spiralis over T. britovi in this region, as well as the risk to human health represented by the consumption of uninspected wild boar meat.

Identification of Spanish Trichinella isolates by ISSR-PCR: intra-specific variability of Trichinella britovi.

In the present work, we investigated genetic variability of the Spanish Trichinella isolates by ISSR-PCR (inter-simple sequence repeat polymerase chain reaction), a technique that is being successfully used to study diversity among related populations. We recovered a total of 43 isolates from different host and geographic localization and identified them by molecular techniques (RAPD and multiplex-PCR) and by Western blot with monoclonal antibodies US5 and US9. Nineteen (44.2%) out of 43 were identified as Trichinella spiralis and 24 (55.8%) as Trichinella britovi. When these samples were analysed by the ISSR technique, all the T. spiralis isolates presented a pattern similar to the T. spiralis ISS116. By contrast, the ISSR-PCR analysis of the isolates identified as T. britovi, showed two different banding profiles compatible with the European T. britovi isolate pattern (ISS2), and the autochthonous Spanish T. britovi isolate (ISS11). Three of these 43 isolates were involved in human outbreaks; the three were identified as T. britovi and showed a pattern similar to the European isolate ISS2. As conclusion, we highlight that an intra-species variability within the Spanish T. britovi isolates analysed was observed, with a predominant group similar to T. britovi ISS2, while T. spiralis group isolates were more homogeneous. No correlations were found between the different ISSR-PCR T. britovi types and the host/geographical origin of the isolates.

Prevalence of Trichinella spp. in North Spain wild fauna and new variety of Trichinella britovi identification.

Trichinella spiralis and Trichinella britovi live in apparent sympatry among wild fauna of the Iberian Peninsula. In the present study 105 Trichinella isolates from wild mammals were typed by inter-sequence simple repeat PCR (ISSR-PCR). All isolates identified as T. spiralis were indistinguishable from the ISS48 reference strain. Among those belonging to T. britovi, four variations were clearly distinguishable; two of them, ISS11 C-76 and ISS86 MON, had been previously detected while the ISS2 reference strain and Trichinella Rioja 3, (MVUL/SP/02/R3) had not been reported before. The newly distinguished genotype of T. britovi was analyzed by ISSR-PCR, multiplex-PCR, UARR sequencing, and single larva cross-breeding with the other T. britovi genotypes including Trichinella T8 (ISS49). Among all of them, the ISS11 and ISS2 isolates were found to be the most frequent. The uniformity found within T. spiralis isolates is consistent with its recent introduction in Iberian Peninsula, whereas the presence of four variations within T. britovi suggests that this species is an endemic species. Orographical diversity of the West-End of Eurasian Region could act to preserve population diversity observed within T. britovi.

The addition of a new immunomodulator with the adjuvant adaptation ADAD system using fatty acid binding proteins increases the protection against Fasciola hepatica.

Fatty acid binding proteins (FABP) have shown protective immune response against Fasciola hepatica infection. We evaluated the protection induced by the Fh12 FABP from F. hepatica (Fh12) combined with the new immunomodulator the lipidic aminoalcohol OA0012 in the ADAD system in mice and sheep. In this work we introduced a lipidic aminoalcohol OA0012 as immunomodulator alone or in combination with the hydroalcoholic extract of Phlebodium pseudoaureum; PAL. Mice vaccinated with ADAD containing OA0012+Fh12 or OA0012+Qs+Fh12 had survival rates of 40-50%. Sheep ADAD-vaccinated with OA0012+Qs+Fh12 showed lower fluke recovery, less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Sheep ADAD-vaccinated with OA0012 combined PAL and Qs+Fh12 showed lower fluke recovery (42%), lower adult worms count (57%) lower faecal egg count (38%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the addition of a new immunomodulator of synthesis to ADAD system with FABPs increased the protection against F. hepatica.

Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined. PATIENTS AND METHODS: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and fluorescence in situ hybridization (FISH) in tumor samples. RESULTS: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>15 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.22-6.50; P = 0.015] and overall survival (HR 3.24; 95% CI 1.38-7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 +/- 2.7 versus 30.5 +/- 24.8 ng/ml; P = 0.016). FISH was negative in all samples. CONCLUSIONS: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.

Pharmacological immunomodulation of surgical trauma.

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.

Genetic and immunological characterization of the 14-3-3xi molecule from Schistosoma bovis.

Currently available candidate vaccines against schistosomiasis elicit only partial protection. In addition, the type of immune response that could lead to the highest level of protection against schistosomes has not yet been described. Thus, efforts should be made in both the identification of novel proteins essential for the parasite cycle and in the modulation of immune responses against these novel candidates through the combined use of immunomodulatory molecules. Several parasites have 14-3-3 proteins, and these proteins are known to play a key role in parasite biology. In the present work, we report the isolation and characterization of a new 14-3-3 gene from Schistosoma bovis and offer new information regarding the genetic structure of the gene. In addition, we have produced the corresponding recombinant protein. Finally, we describe the immune responses elicited by this protein when combined with 4 different immunomodulators in immunized mice.

The Sb14-3-3zeta recombinant protein protects against Schistosoma bovis in BALB/c mice.

Schistosoma bovis is a trematode parasite mainly affecting cattle and sheep. Evidences about the arise of drug resistance and the high rates of re-infection of animals in endemic areas have pointed out the need of developing new control tools, e.g., effective vaccines. Schistosomes 14-3-3 proteins have been defined as vaccine candidates against respective infections. We have therefore investigated the protective capacity of the 14-3-3 protein from S. bovis - Sb14zeta - against S. bovis in mice. In addition, we have addressed the influence of the co-administration of four different immunomodulators with the 14-3-3 polypeptide. The values of protection against S. bovis were statistically significant when the Sb14zeta was combined in two independent experiments with the AA0029 (61.0% and 40.31%), AA2829 (49% and 36.3%) and PAL (49% and 40.075%) immunomodulatory molecules. Immune responses from vaccinated animals showed that the highest protection rates do not necessarily match with a dominant Th1-type response.

Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD.

Fatty acid binding proteins (FABP) have been designed as a potential vaccine against fasciolosis. In this work, the immunoprophylaxis of the recombinant Fh15 FABP from F. hepatica (Fh15) in adjuvant/immunomodulator ADAD system was evaluated using mice and sheep challenged with F. hepatica. The ADAD system combines the Fh15 antigen with an immunomodulator (hydroalcoholic extract of Polypodium leucotomos; PAL) and/or an adjuvant (saponins of Quillaja saponaria; Qs) in a water/oil emulsion (30/70) with a non-mineral oil (Montanide). All the infected control mice died by 41-48 days post-infection. The mice vaccinated with ADAD only with PAL+Fh15 present a survival rate of 40-50% and those vaccinated with ADAD containing PAL+Qs+Fh15 had a survival rate of 50-62.5%. IgG1 antibodies were lower in surviving mice in comparison with non-surviving mice. The sheep vaccinated with ADAD PAL+Qs+Fh15 showed lower fluke recovery (43%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the ADAD system using recombinant fatty acid binding proteins from F. hepatica could be a good option to develop vaccines against F. hepatica.

[Results the application of mitomicyn during endonasal and endocanalicular dacryocystorhinostomy by diode laser]. / Resultados de la aplicación de mitomicina en la dacriocistorrinostomía endonasal y endocanalicular con láser diodo.

AIM OF THE STUDY: To study the effects, secondary effects and security of the intrasurgical application of mitomicyn C during endonasal and endocanalicular dacryocystorhinostomy with diode laser (TLA-ELA DCR). METHODS: We carried out a randomized, prospective, interventional and double blind study in 200 patients: intrasurgical mitomicyn C was applied in 150 of then (0.4 mgr/0.2 ml) for 5 minutes by means of a polivinil acetate dressing over the osteotomy. In other 50 patients MMC was not used we followed up at 24 hours, 10 days and 1, 3 and 6 months after surgery. Endoscopic aspects and possible complications were valued. The results were compared using the Chi-squared test with the Yates correction. We looked for the presence or abscense of secondary effects in the application of mitomicyn C. RESULTS: The average follow up was 15.25 months (range 6 to 21 months). The percentages of alterations for excesive scarring were 21.77% in patients without and MAC 8.03% in the ones MMC. The difference was statisticaly significant (p = 0.02). We did not find secondary effects due to application of mitomcyn. CONCLUSIONS: Intrasurgical application of topical MMC during TLA-ENL DCR reduces the number of pathological findings due to scarring of the surrouding area of the new drainage without secondary effects.