Occurrence of Coxiella burnetii in wild lagomorphs and their ticks in Spanish Mediterranean ecosystems.

BACKGROUND: Coxiella burnetii, the causative agent of Q fever, is a zoonotic multi-host vector-borne pathogen of major public health importance. Although the European Food Safety Authority has recently made the monitoring of this bacterium in wildlife a priority, the role of wild lagomorphs in the transmission and maintenance of C. burnetii is poorly understood. AIMS: The aims of this study were to determine the prevalence and risk factors associated with C. burnetii circulation in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis) and to assess the presence of this pathogen in ticks that feed on them in Mediterranean ecosystems in Spain, the country with the highest number of reported cases of Q fever in Europe. METHODS: A total of 574 spleen samples were collected from 453 wild rabbits and 121 Iberian hares, and 513 ticks (processed in 120 pools) between the 2017/2018 and 2021/2022 hunting seasons. RESULTS: C. burnetii DNA was detected in 103 (17.9%; 95% CI: 14.8-21.1) of the 574 wild lagomorphs tested. By species, prevalence was 16.3% (74/453; 95% CI: 12.9-19.7) in the European wild rabbit and 24.0% (29/121; 95% CI: 16.4-31.6) in the Iberian hare. At least one positive lagomorph was found on 47.9% of the 96 hunting estates sampled and in every hunting season since 2018/2019. Two risk factors associated with C. burnetii infection were as follows: outbreak of myxomatosis on the hunting estate in the month prior to sampling and high tick abundance observed by gamekeepers on the hunting estate. C. burnetii DNA was also found in 33 of the 120 (27.5%; 95% CI: 19.5-35.5) tick pools tested. The pathogen was detected in 66.7% (4/6), 29.2% (26/89) and 21.4% (3/14) of Haemaphysalis hispanica, Rhipicephalus pusillus and Hyalomma lusitanicum pools respectively. CONCLUSIONS: This study provides new epidemiological data on C. burnetii in European wild rabbits and is the first survey on this zoonotic pathogen performed in Iberian hares. Our results indicate widespread endemic circulation of C. burnetii and highlight the importance of both wild lagomorph species as natural reservoirs of this zoonotic bacterium in Mediterranean ecosystems in southern Spain, which may be of public and animal health concern. The high prevalence and wide diversity of positive tick species suggest the possible role of ticks in the epidemiological cycle of C. burnetii, with the potential risk of transmission to sympatric species, including humans.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Evaluation of usability, adherence, and clinical efficacy of therapeutic footwear in persons with diabetes at moderate to high risk of diabetic foot ulcers: A multicenter prospective study.

OBJECTIVE: To evaluate therapeutic footwear expectations and usability of individuals with diabetes and foot complications. DESIGN: A prospective multicenter study was conducted on participants with a high risk of developing a diabetic foot ulcer. SETTING: Participants were enrolled in 11 different specialized diabetic foot units in Spain between March 2022 and June 2023. SUBJECTS: Patients with diabetes at moderate to high risk of foot ulceration receiving first therapeutic footwear prescription. INTERVENTIONS: All the patients included in the research were prescribed with their first pair of therapeutic footwear. MAIN MEASURES: Primary outcome measures were MOS-pre and MOS-post questionnaires evaluating use and usability of prescribed therapeutic footwear. Secondary outcome measures aimed to evaluate footwear clinical efficacy as ulceration rate and self-reported perceived walking distance per day. RESULTS: The use of therapeutic footwear exceeded the patient's pre-provision prediction of their anticipated use in 94% of people (n = 126). Based on the visual analogic satisfaction scale, the median satisfaction of daily wearing their therapeutic footwear was 7 points, Interquartile Range (IQR) [5-8.25]. During the follow-up period, 39 participants (29.1%) experienced diabetic foot ulcer. Perceived walking distance participants reported an improvement in their perceived walking ability during various daily life activities. CONCLUSIONS: Diabetes patients at moderate to high risk of diabetic foot ulcer improved their perception of walking ability after therapeutic footwear prescription. Adherence to the therapeutic footwear prescription resulted in less ulcerations.

Underground ibogaine use for the treatment of substance use disorders: A qualitative analysis of subjective experiences.

INTRODUCTION: Ibogaine is one of the alkaloids naturally found in plants such as Tabernanthe iboga, which has been traditionally used by members of the Bwiti culture. Since the discovery of its anti-addictive properties by Howard S. Lotsof in 1962, ibogaine has been used experimentally to treat substance use disorders (SUD), especially those involving opioids. We aim to provide a detailed understanding of the underlying psychological aspects of underground ibogaine use for the treatment of SUD. METHODS: Semi-structured interviews were carried out with 13 participants with SUD, which motivated their self-treatment with ibogaine. The data were analysed using the grounded theory approach and considered the context of the treatment, and the nature of the occurring hallucinogenic and cognitive phenomena during the treatment experience. RESULTS: We identified several psychological effects that the study respondents experienced, which seem to play a substantial role in the therapeutic process concerning SUD. The evoking of interpersonal and transpersonal experiences, autobiographical memories, and preparation, integration and motivation for a lifestyle change are important components that participants reported during and after ibogaine intake. DISCUSSION AND CONCLUSION: Ibogaine is increasingly being used for the treatment of SUD, due in part to the limited treatment options currently available. Its beneficial effects seem to be related not only to its complex pharmacology but also to the subjective experience that ibogaine induces. The main aspects of this experience are related to autobiographical memories and valuable personal insights, which together appear to help individuals cope with their SUD.

Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood-brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.

Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada / Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed

Objetivos: Analizar la probabilidad de PSA indetectable (< 0,01 ng/ml) tras disección ampliada de los ganglios linfáticos pélvicos (DGLP-ampliada) versus disección estándar de los ganglios linfáticos (GL) pélvicos (DGLP-estándar) en pacientes pN+. Materiales y métodos: Se realizó una investigación en la base de datos institucional de cáncer de próstata para obtener información sobre pacientes que se sometieron a prostatectomía radical (PR) con DGLP, con hallazgos de 3 o menos metástasis ganglionares entre 2007 y 2017. La DGLP ampliada se definió de acuerdo con el número de GL. Los pacientes con un percentil 75 o superior de ganglios linfáticos extraídos conformaron el grupo DGLPa; los pacientes con un percentil 25 o inferior se adjudicaron al grupo DGLPe (DGLP estándar). Se compararon las variables clínicas y patológicas entre ambos grupos. Se utilizaron la prueba de la t de Student para comparar las variables continuas y la prueba de la chi al cuadrado para las variables categóricas. La regresión logística multivariable evaluó la probabilidad de PSA indetectable al tercer mes desde la operación. El método de Kaplan-Meier estimó la probabilidad de recurrencia bioquímica. Las diferencias entre los grupos se compararon mediante la prueba de log-rank. Resultados: De 1.478 pacientes tratados en el periodo considerado, se seleccionó a 95 con 3 o menos metástasis en los ganglios linfáticos. Tras aplicar los criterios de inclusión, 23 pacientes con una mediana de 11 GL extraídos se incluyeron en el grupo PGLPe (percentil 25) y 23 pacientes con > 27 GL se incluyeron en el grupo PGLPa (percentil 75). El tiempo quirúrgico fue más largo para el grupo de DGLPa. Dieciséis pacientes (69,6%) tratados con DGLPa presentaron PSA indetectable tras la operación. En el análisis multivariable, la probabilidad de PSA indetectable a los 3 meses fue mayor en los pacientes tratados con DGLPa (HR = 5,18; IC del 95%, 1,16-23,11; p = 0,03). Conclusiones: Independientemente de las características de la enfermedad, la DGLPa tiene más probabilidades de predecir un PSA indetectable al tercer mes tras la PR

Objectives: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. Materials and methods: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. Results: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR = 5.18; IC 95% = 1.16-23.11; P = .03). Conclusions: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics

Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed. / Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada.

OBJECTIVES: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. MATERIALS AND METHODS: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. RESULTS: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16-23.11; P=.03). CONCLUSIONS: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

Early toll-like receptor 4 blockade reduces ROS and inflammation triggered by microglial pro-inflammatory phenotype in rodent and human brain ischaemia models.

BACKGROUND AND PURPOSE: Ischaemic stroke is a leading cause of death, disability, and a high unmet medical need. Post-reperfusion inflammation and an up-regulation of toll-like receptor 4 (TLR4), an upstream sensor of innate immunity, are associated with poor outcome in stroke patients. Here, we identified the therapeutic effect of targeting the LPS/TLR4 signal transduction pathway. EXPERIMENTAL APPROACH: We tested the effect of the TLR4 inhibitor, eritoran (E5564) in different in vitro ischaemia-related models: human organotypic cortex culture, rat organotypic hippocampal cultures, and primary mixed glia cultures. We explored the therapeutic window of E5564 in the transient middle cerebral artery occlusion model of cerebral ischaemia in mice. KEY RESULTS: In vivo, administration of E5564 1 and 4 hr post-ischaemia reduced the expression of different pro-inflammatory chemokines and cytokines, infarct volume, blood-brain barrier breakdown, and improved neuromotor function, an important clinically relevant outcome. In the human organotypic cortex culture, E5564 reduced the activation of microglia and ROS production evoked by LPS. CONCLUSION AND IMPLICATIONS: TLR4 signalling has a causal role in the inflammation associated with a poor post-stroke outcome. Importantly, its inhibition by eritoran (E5564) provides neuroprotection both in vitro and in vivo, including in human tissue, suggesting a promising new therapeutic approach for ischaemic stroke.

Birth weight and postnatal microbial exposures predict the distribution of peripheral blood leukocyte subsets in young adults in the Philippines.

The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=-0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.

Maternal pregnancy C-reactive protein predicts offspring birth size and body composition in metropolitan Cebu, Philippines.

The gestational milieu is an important influence on fetal development and long-term disease risk. Here we assess relationships between maternal pregnancy inflammation, indicated by C-reactive protein (CRP), and offspring anthropometric outcomes measured soon after birth. Data come from female participants (n=327, age 24.4-30.2 years) in a longitudinal study located in Metropolitan Cebu, Philippines. Between 2009 and 2014, pregnancy interviews (n=429) were conducted during which questionnaire and anthropometric data were obtained along with dried blood spot cards for CRP measurement. Offspring body weight, length, head circumference and five skinfold thickness measures were obtained soon after birth. Maternal pregnancy CRP was borderline (-1.11±0.64 days/log-mg/l; P<0.1) inversely related to gestational age at delivery, but did not increase the likelihood of preterm delivery. After adjusting for maternal pre-pregnancy body mass index, height, pregnancy adiposity, age, parity and other covariates, CRP was significantly, inversely related to offspring body weight (-0.047±0.017 kg/log-mg/l), length (-0.259±0.092 cm/log-mg/l) and sum of skinfolds (-0.520±0.190 mm/log-mg/l) (all P<0.05), and borderline inversely related to offspring head circumference (-0.102±0.068 cm/log-mg/l; P<0.1). Notably, relationships were continuous across the full CRP range, and not limited to unusually high levels of inflammation. These findings point to an important role of maternal non-specific immune activation as a predictor of offspring birth outcomes. In light of evidence that early life microbial, nutritional and stress experiences influence adult inflammatory regulation, these findings point to inflammation as a potential pathway for the intergenerational transmission of maternal experience to offspring health.

European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real-life clinical assessment.

BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal, web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified. RESULTS: A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) [95% confidence interval (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88], P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37], P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01). CONCLUSION: AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.

[Focal Laser Ablation and Photodynamic Vascular Therapy with soluble TOOKAD® in the treatment of low risk prostate cancer]. / Ablación Focal con Láser y Terapia Vascular Fotodinámica con TOOKAD® soluble, en el tratamiento del cáncer de próstata de bajo riesgo.

The increase of the diagnosis of low risk prostate cancer translates into a new clinical entity, for which active surveillance may not be always enough and conventional therapies are clearly overtreatment. Faced with the necessity of giving a therapeutic answer to these patients, and facilitated by the technological advances in the imaging field and new energy sources, the interest is centered in the clinical development of focal therapies as an alternative with minimal morbidity and oncologically safe. As a part of the review carried out in this monographic issue, this article focus on the features relative to the preclinical and clinical development of laser ablative therapy and the innovative photodynamic vascular therapy with soluble TOOKAD®. With this aim we performed an exhaustive bibliographic search, updated to February 2016, in the greater databases, including original articles and reviews in reference to the object of this review, without restrictions for year of publication. This article reviews the preclinical and clinical development of these innovative ablative techniques in the field of focal therapy for low risk prostate cancer.

The spatial distribution of overweight and obesity among a birth cohort of young adult Filipinos (Cebu Philippines, 2005): an application of the Kulldorff spatial scan statistic.

OBJECTIVES: The objectives of the study were to test for spatial clustering of obesity in a cohort of young adults in the Philippines, to estimate the locations of any clusters, and to relate these to neighborhood-level urbanicity and individual-level socioeconomic status (SES). SUBJECTS: Data are from a birth cohort of young adult (mean age 22 years) Filipino males (n=988) and females (n=820) enrolled in the Cebu Longitudinal Health and Nutrition Survey. METHODS: We used the Kulldorff spatial scan statistic to detect clusters associated with unusually low or high prevalences of overweight or obesity (defined using body mass index, waist circumference and body fat percentage). Cluster locations were compared to neighborhood-level urbanicity, which was measured with a previously validated scale. Individual-level SES was adjusted for using a principal components analysis of household assets. RESULTS: High-prevalence clusters were typically centered in urban areas, but often extended into peri-urban and even rural areas. There were also differences in clustering by both sex and the measure of obesity used. Evidence of clustering in males, but not females, was much weaker after adjustment for SES.

[Non-invasive diagnosis of prostate cancer: serum and urine markers]. / Diagnóstico no invasivo del cáncer de próstata; marcadores séricos y en orina.

The great number of biomarkers basic research is presenting in different clinical scenarios of prostate cancer demands the scientific community rigor in their molecular and clinical development for the selection of those which could supply diagnostic and prognostic information for the established nomograms of clinical-pathological factors. Prostate cancer, due to its prevalence and heterogeneity, needs a more directed diagnosis, characterization of malignant potential and monitoring of its multiple therapies. In this review article we try to go over the recent incorporation of new serum and urine markers in the clinical management of this tumor, emphasizing those with greater clinical development.

Diagnóstico no invasivo del cáncer de próstata: marcadores séricos y en orina / Non-invasive diagnosis of prostate cancer: serum and urine markers

El gran número de biomarcadores que la investigación básica plantea en distintos escenarios clínicos de cáncer de próstata (CaP) exige de la comunidad científica un rigor en su desarrollo molecular y clínico para la selección de aquellos que puedan aportar información diagnóstica o pronóstica a los nomogramas de factores clínico-patológicos establecidos. El CaP necesita por su prevalencia y heterogenicidad un diagnóstico más dirigido, la caracterización de su potencial maligno y la monitorización de sus múltiples tratamientos. En este artículo de revisión pretendemos repasar la reciente incorporación de nuevos biomarcadores séricos y en orina en el manejo clínico de este tumor, haciendo hincapié en aquellos con mayor desarrollo clínico (AU)

The great number of biomarkers basic research is presenting in different clinical scenarios of prostate cancer demands the scientific community rigor in their molecular and clinical development for the selection of those which could supply diagnostic and prognostic information for the established nomograms of clinical-pathological factors. Prostate cancer, due to its prevalence and heterogeneity, needs a more directed diagnosis, characterization of malignant potential and monitoring of its multiple therapies. In this review article we try to go over the recent incorporation of new serum and urine markers in the clinical management of this tumor, emphasizing those with greater clinical development (AU)

Oral rush desensitization to egg: efficacy and safety.

BACKGROUND: Current management of egg allergy relies on egg elimination from the diet. It does not protect patients from reactions after accidental ingestion of the food and it has a negative influence on quality of life. To solve these problems, some desensitization protocols have been described that are safe and effective, but only one study of a rush regimen for egg with a small patient sample has been published. OBJECTIVE: To evaluate the safety, efficacy and immunologic effects of an oral rush desensitization protocol for immediate egg allergy. METHODS: Subjects aged 5 years or older with symptomatic IgE-mediated allergy to hen's egg underwent a 5-day oral tolerance induction regimen and were subsequently maintained on a regular egg intake. The variables studied were the reactions that occurred during the induction regimen and follow-up and the duration of desensitization. Prick test weal size and egg white-specific IgE and IgG concentrations were monitored. RESULTS: Twenty-three patients between 5 and 17 years of age entered the protocol. Twenty (86.9%) achieved the daily intake of a whole cooked egg, 14 of them within the scheduled 5 days. One abandoned the protocol and two were changed to a slower regimen because of repeated reactions. Allergic reactions were frequent but in general were mild. No severe reactions occurred. During follow-up of at least 6 months, egg was well tolerated by all patients. Compared with baseline, skin prick test weal size and egg white-sIgE levels had fallen at 3 months, although the differences were only significant at 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: The rush protocol described is useful and safe for achieving tolerance to egg within a few days but it should always be performed in a highly supervised setting. A high proportion of patients allergic to egg can effectively be desensitized using the described schedule, with the advantage of shortening the time to become protected from reactions after inadvertent ingestion of egg, with no increase in the risk compared with the earlier reported slower protocols.

A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis.

BACKGROUND: With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment. OBJECTIVE: To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period. METHODS: A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) >or=45, nasal obstruction score or=2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS. RESULTS: In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo (n = 185), cetirizine (n = 175) and rupatadine (n = 183). Rupatadine (P = 0.008) but not cetirizine (P = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P = 0.013; cetirizine vs placebo, P = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated. CONCLUSION: Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.