Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Management of postoperative pain in Spain: a nationwide survey of practice.

BACKGROUND: Although the need for structured assessment and management of acute postoperative pain has been recognized, practices and responsibilities vary between and within hospitals and countries. We sought to determine current pain management practices in Spanish hospitals with and without acute pain services (APSs) or acute pain management programmes (APMPs) and compare them to practices reported for 1997-1998. METHODS: Members of the Spanish Pain Society and APS/APMP heads were asked to respond to a survey. Responses were stratified by hospital size (< 200 or ≥ 200 beds) and APS/APMP presence or not. Categorical variables were described by percentages and the 95% confidence interval and continuous ones by the median and interquartile range. RESULTS: Responses were received from 42.4% of hospitals with ≥ 200 beds (vs. 9.6% of the smaller ones). We fully analysed only data for the larger hospitals, 57.7% of which had an APS or APMP. Full-time pain physicians were on staff in 28.6% of large hospitals; 25% had full-time nurses. Patients received written information about postoperative pain in 34.8% of APS/APMP hospitals, and 72% of them recorded pain assessments routinely. Protocols reflected interdepartmental consensus in 80.8%; training in postoperative pain was organised in 54%. Respondents thought pain was well or very well managed in 46.4%. In APS/APMP hospitals the following results had improved: provision of written information for patients (58.5% vs. 0%), the recording of pain assessments (93% vs. 43.8%), consensus on a pain scale (92.5% vs. 41.9%), use of protocols (99.7% vs. 55.2%), analysis of quality indicators (52.8% vs. 15.4%), training (73% vs. 26.9%), and respondents' satisfaction with pain management in their hospital (68.6% vs. 9.5%). CONCLUSIONS: The presence of an APS or APMP is associated with better results on indicators of quality of acute postoperative pain management.

Epigenetics in Non-tumor Immune-Mediated Skin Diseases.

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.

Flow injection photoinduced chemiluminescence determination of imazalil in water samples.

In this work, a fast, simple and economic method is proposed for the determination of imazalil in water samples by flow injection photoinduced chemiluminescence. In this method, imazalil degrades in basic media through the use of a photoreactor, and the resulting photofragments react with ferricyanide and generate the direct chemiluminescence signal. To the authors' knowledge, this is the first time that a chemiluminescence method has been proposed for the determination of this fungicide. All physical and chemical parameters in the flow injection chemiluminescence system were optimized in the experimental setting. In the absence of preconcentration, the linear dynamic range for imazalil was 0.75-5 mg L(-1) and the detection limit was 0.171 mg L(-1). The application of solid-phase extraction with C18 cartridges allowed the elimination of interference ions, the reduction of the linear dynamic range to 15-100 µg L(-1), and a detection limit of 3.4 µg L(-1). This detection limit is below the maximum concentration level established by the Regulations of the Hydraulic Public Domain for pesticide dumping. The sample throughput after solid-phase extraction of the analyte was 12 samples h(-1). The intraday and interday coefficients of variation were below 9.9% in all cases. This method was applied to the analysis of environmental water samples, and recoveries of between 95.7 and 110% were obtained.

Echinococcus granulosus: genomic and isoenzymatic study of Spanish strains isolated from different intermediate hosts.

The phenomenon on intraspecific variation in Echinococcus granulosus is already documented in Spain, where unilocular hydatidosis is an endemic disease. The first speciation studies, focused at a genomic level, showed the existence of three different strains: ovine-bovine-human, equine and swine-caprine. In the present study, the genomic identification, by random amplified polymorphic DNA technique (RAPD) of a larger number of Spanish E. granulosus isolates, using five different primers, showed the maintenance of these groups. Thus, some of these strains may not be infective for man. These conclusions were supported by a phenotypic characterization of the same isolates by zymodeme technique, showing the five isoenzyme systems used that Spanish E. granulosus strains can also be distinguished at a phenotypic level by isoenzymatic patterns. Both techniques (RAPD and zymodemes) were used for statistical analysis and for the construction of two dendrograms, which were slightly different. In addition, some intrastrain variation was detected with both techniques, a phenomenon that is directly related to the different speciation theories proposed for E. granulosus strains. The epidemiological implications of the results are discussed in the text.

[Evolution of drug-resistant Mycobacterium tuberculosis in the province of Castellón. 1992-1998]. / Evolución de las resistencias a Mycobacterium tuberculosis en la provincia de Castellón. Años 1992-1998.

OBJECTIVES: To determine the frequency of resistant Mycobacterium tuberculosis and the risk factors associated with resistance in the province of Castellón (Spain). MATERIAL AND METHODS: This prospective study of M. tuberculosis sensitivity applied Canetti's method of proportions to all strains isolated in Castellón (n = 532) from January 1992 through December 1998 (7 years); 461 cases were new. RESULTS: The overall frequency of resistant strains was 4.7% (25/532), of which 3.9% (18/461) were instances of primary resistance and 11.1% (7/63) were of secondary resistance. Three percent were resistant to isoniazid, 1.87% to rifampicin, 1.87% to streptomycin and 0.56% to ethambutol. Multiple drug resistance was found in 0.2% (1/461) of the new cases and 1.1% (6/532) overall. The presence of resistant M. tuberculosis was associated with a history of antituberculous treatment (OR = 3.14; p = 0.017) and the presence of one or more risk factors for tuberculosis (OR = 3.32; p = 0.066). CONCLUSIONS: The overall rates of resistant M. tuberculosis and multiple drug resistance are low in the province of Castellón; however resistance is associated with higher mortality such that controlling some preventable risk factors might reduce the frequency of resistance.

[Total intravenous anesthesia in general surgery]. / Anestesia total intravenosa en cirugía general.

To evaluate unwanted side effects expressed in hemodynamic parameters, postanesthetic recovery and quality of intravenous total anesthesia (IVTA) with propofol, fentanyl and atracurium. A prospective study in 292 patients undergoing general surgery. Fifty-three percent of the patients were ASA I, 32.2% were ASA II and 14.8% were ASA II, representing a wide range of ages, weights and heights. Mean time of anesthesia was 108.25 +/- 56.96 min. Anesthesia was achieved with propofol 0.108 +/- 0.027 mg/kg/min, fentanyl 0.093 +/- 0.035 microgram/kg/min and atracurium 0.011 +/- 0.0034 mg/kg/min. Slight pain was evident at injection in 1.7% of the patients. Greater hemodynamic instability was recorded at induction, with mean decreases in systolic and diastolic arterial pressures of 16% and 10%, respectively, with scarcely any response to intubation and extubation. Anesthetic recovery was recorded at 5.95 +/- 4.97 min, with surgical amnesia in 100% of the patients. Nausea was seen in 3.42% and vomiting in 1.7%. Patient evaluation of anesthetic technique was "good" in 60.3% and "excellent" in 39.7%. Propofol dose was significantly (p < 0.05) correlated with age (r = -0.33) and time of anesthesia (r = -0.4). IVTA with propofol and fentanyl in general surgery provides adequate maintenance of anesthesia for surgery and recovery, with good hemodynamic stability. In older patients and longer times of anesthesia, the total dose of propofol administered decreases, with negative effect on time and quality of recovery. Total dose of propofol administered is not significantly correlated with either time or quality of recovery.

[Cesarean section in a patient with a congenital deficit of antithrombin III: apropos of a case]. / Cesárea en una paciente con déficit congénito de antitrombina III: a propósito de un case.

Antithrombin III (AT III) is a physiological inhibitor of coagulation. AT III deficit, whether congenital or acquired, results in a state of hypercoagulability characterized by recurring instances of venous thrombosis in young people. Although AT III levels normally change little during pregnancy, a deficit can be associated to the appearance of recurring thromboembolism and the need to perform cesarean section increases the risk. We report a cesarean section under general anesthesia in a patient with congenital AT III, reviewing the etiology and pathophysiology of this entity as well as its treatment.

Respiratory system of vegetative and sporulating Bacillus cereus.

The composition and organization of the Bacillus cereus respiratory system were studied. The abolition of NADH-dependent respiration in vegetative and sporulating cell membranes by near-UV light (360 nm) indicated that electrons reduce oxygen only through a quinone-cytochrome pathway. Difference spectroscopy demonstrated the presence of cytochromes b555, c548, aa3, b562, and a2. This composition and studies with respiratory inhibitors suggested that cytochromes are organized in at least two branches, one being highly sensitive to cyanide.

Lesion of the internal carotid artery caused by a car safety belt.

A description is given of a case of complete obstruction of the internal carotid in a patient wearing a lap-shoulder belt. This was presumed due to direct contusion of the vessel at the C2 level.

Evolución de las resistencias a Mycobacterium tuberculosis en la provincia de Castellón. Años 1992-1998 / Evolution of resistant Mycobacterium tuberculosis in the province of Castellón (Spain): 1992 through 1998

Objetivos: Conocer la frecuencia de las resistencias a Mycobacterium tuberculosis y los factores de riesgo asociados a éstas en la provincia de Castellón. Material y métodos: Se ha realizado un estudio prospectivo de la sensibilidad a los tuberculostáticos, por el método de las proporciones de Canetti, de todas las cepas de M. tuberculosis aisladas en nuestra provincia (532) desde enero de 1992 a diciembre de 1998 (7 años), de las que 461 correspondían a casos nuevos. Resultados: Encontramos una tasa global de resistencias del 4,7 por ciento (25/532), de las cuales el 3,9 por ciento (18/461) fueron primarias y el 11,1 por ciento (7/63) secundarias. Por fármacos, el 3 por ciento eran resistentes a isoniacida, el 1,87 por ciento a rifampicina, el 1,87 por ciento a estreptomicina y el 0,56 por ciento a etambutol. La multirresistencia hallada ha sido del 0,2 por ciento (1/461) para los casos nuevos y del 1,1 por ciento (6/532) para el total. La presencia de resistencia de M. tuberculosis se asocia al antecedente de tratamiento antituberculoso previo (OR = 3,14; p = 0,017), y a la presencia de uno o más factores de riesgo para tuberculosis (OR = 3,32; p = 0,666). Conclusiones: La tasa global de resistencias de M. tuberculosis y la multirresistencia son bajas en la provincia de Castellón; sin embargo, se asocian a un aumento de la mortalidad, de manera que el control de algunos de estos factores de riesgo de tuberculosis prevenibles podría, tal vez, disminuir la frecuencia de resistencias. (AU)