Differential effects of high dose omega-3 fatty acids on metabolism and inflammation in patients with obesity: eicosapentaenoic and docosahexaenoic acid supplementation.

Background: Obesity is complicated by low-grade chronic inflammation characterised by increases in inflammatory proteins and cells in peripheral blood. It has been known that omega-3 fatty acids (FA) like eicosapentaenoic (EPA) and docosahexaenoic (DHA) could modulate the inflammatory process and improve metabolic markers. Objective: This study aimed to determine the effect of high-dose omega-3 FA on metabolic and inflammatory markers among patients with obesity and healthy volunteers. Methods: This prospective study included 12 women with obesity (body mass index [BMI] ≥ 35.0 kg/m2) and 12 healthy women (BMI < 24.0 kg/m2) who were supplemented with a dose of 4.8 g/day (3.2 g EPA plus 1.6 g DHA) for 3 months followed by no treatment for 1 month. Plasma metabolic and inflammatory markers and levels of mRNA transcripts of CD4+ T lymphocyte subsets were determined monthly. Results: None of the participants exhibited changes in weight or body composition after study completion. EPA and DHA supplementation improved metabolic (insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], triglyceride [TG]/ high-density lipoprotein [HDL] ratio, TG, and arachidonic acid [AA]/EPA ratio) and tumor necrosis factor-alpha (TNF-α). Moreover, the levels of mRNA transcripts of T CD4+ lymphocyte subsets (TBX21, IFNG, GATA-3, interleukin [IL]-4, FOXP3, IL-10 IL-6, and TNF-α), were down-regulated during the intervention phase. After 1 month without supplementation, only insulin, HOMA-IR and the mRNA transcripts remained low, whereas all other markers returned to their levels before supplementation. Conclusion: Supplementation with high-dose omega-3 FAs could modulate metabolism and inflammation in patients with obesity without weight loss or changes in body composition. However, these modulatory effects were ephemeral and with clear differential effects: short-duration on metabolism and long-lasting on inflammation.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

Tinnitus distress: a paradoxical attention to the sound?

Tinnitus, the perception of sound in the absence of external stimuli, is often a disturbing symptom for which the underlying functional neuroanatomy still remains poorly understood. Most studies have focused solely on functional connectivity changes in the auditory cortex of tinnitus patients. The aim of this study was to investigate whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of five resting-state networks comprising the auditory, the default mode, the external control left and right, and the salience network. For this purpose, a large sample of one hundred and thirty-five subjects underwent resting-state functional magnetic resonance imaging and their behavioural scores were obtained using clinical evaluations. Networks were extracted using independent component analysis, and functional connectivity patterns in the extracted networks were evaluated by a graph theoretical approach. The effects of tinnitus for each network were investigated by correlating the graph strength of all the regions with the tinnitus behavioural scores using stepwise fit regression analysis. Results indicated that alterations of functional interactions between key neural circuits of the brain are not limited to one single network. In particular, tinnitus distress showed a strong correlation with the connectivity pattern within and between the right executive control network and the other four resting-state networks, indicating that tinnitus distress is probably the consequence of a hyperactive attention condition. Among the behavioural scores, the strongest correlation was observed between age and hearing loss, while the tinnitus objective loudness was not correlated with any behavioural scores.

Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial.

BACKGROUND: Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial. METHODS: Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6. RESULTS: Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels. CONCLUSIONS: Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Variability studies of allochthonous stone pine (Pinus pinea L.) plantations in Chile through nut protein profiling.

Stone pine (Pinus pinea) is characterized by low differentiation of growth parameters, high phenotypic plasticity and low genetic variability; detecting its diversity in introduced Chilean populations is therefore relevant for conservation and breeding programs. Here, variability among allochthonous Stone pine populations in Chile was explored using electrophoresis-based proteomic analysis of pine nuts. Cones from 30 populations distributed along a climatic gradient in Chile were surveyed and sampled, and proteins were extracted from seed flour using the TCA-acetone precipitation protocol. Extracts were subjected to SDS-PAGE and 2-DE for protein resolution, gel images captured, and spot or bands intensity quantified and subjected to statistical analysis (ANOVA, unsupervised Hierarchical Analysis Clustering and PLS regression). Protein yield ranged among populations from 161.7 (North populations) to 298.7 (South populations) mg/g dry weight. A total of 50 bands were resolved by SDS-PAGE in the 6.5-200 kDa Mr. range, of which 17 showed quantitative or qualitative differences, with 12 proteins identified. Pine nut extracts from the most distant populations were analyzed by 2-DE and a total of 129 differential spots were observed, out of which 13 were proposed as putative protein markers of variability. Out of the 129 spots, 118 proteins were identified after MALDI-TOF/TOF analysis. Identified proteins were classified into two principal categories: reserve and stress related. We provide the first protein map of P. pinea nuts. The use of a proteomic approach was useful to detect variability of Stone pine across three Chilean macrozones, with correlations between protein profiles and geoclimatic parameters, suggesting a new approach to study the variability of this species. BIOLOGICAL SIGNIFICANCE: This study presents the first protein map of Stone pine nuts, relevant for the advancement of protein characterization in pine nuts. Putative protein markers are proposed, evidencing that a proteomic approach may be useful to detect variability of Stone pine across Chilean macrozones, suggesting a new approach to study the variability of this species, which may also be extrapolated to other forest fruit species.

[Urological pathology of lymphatic origin]. / Patología urológica de origen linfático.

OBJECTIVES: Lymphatic disease is a rarely cause of some very unspecific genitourinary manifestations, assuming a diagnostic challenge in most cases. The aim of this paper is to warn about the possible etiology of these urological lymphatic presentations and discuss its management. METHODS: Retrospective review of clinical data in pediatric patients with urological pathology of lymphatic origin between 2008-2014. Three patients, two boys and a girl, were included. The complaints were: redundant prepuce, inguinal scrotal tumor and urinary incontinence. Clinical, diagnosis and treatment protocol is described. RESULTS: The first case is a male with genital lymphedema presented at birth as a redundant prepuce and the subsequent emergence of lower limb lymphedema, treated with compression bandages. The second case, a groin lymphangioma which debuted as a sudden painless inguinal tumor simulating a cord cyst, it was sclerosed and treated with OK- 432. Finally, a preteen who consulted for involuntary leakage of urine, genital lymphedema likely primary cause (lymphodisplasia) or malformation was diagnosed, which improved with two Lipiodol® embolization. CONCLUSIONS: Genitourinary manifestations can be the debut of more complex lymphatic pathology, so it is necessary to consider this cause, uncommon and nonspecific. Its management must be conservative initially by compression bandages, OK-432 or embolization with Lipiodol®.

OBJETIVOS: La patología linfática es infrecuente como causa de manifestaciones genitourinarias inespecíficas, suponiendo un reto diagnóstico en la mayoría de los casos. El objetivo de este trabajo es advertir sobre la posible etiología linfática de estas presentaciones urológicas y discutir su manejo. MATERIAL Y METODOS: Revisión retrospectiva de los datos clínicos de los pacientes pediátricos con patología urológica de origen linfático entre el año 2008-2014. Se incluyeron 3 pacientes, dos niños y una niña. Todos ellos se evaluaron para obtener un diagnóstico fiable. Los motivos de consulta fueron: prepucio redundante, tumoración inguino-escrotal e incontinencia urinaria. Se describe la clínica, el protocolo diagnóstico y el tratamiento de los mismos. CASOS CLINICOS: El primer caso se trata de un lactante varón con un linfedema genital que presentaba un prepucio redundante congénito y la aparición posterior de linfedema en el miembro inferior que es tratado con vendajes compresivos. El siguiente, un linfangioma inguinal que debutó con una tumoración inguinal indolora de aparición súbita simulando un quiste de cordón y tratado mediante esclerosis con OK-432. Por último, una preadolescente que consultó por escapes involuntarios de orina diagnosticada de linfedema genital de probable causa primaria (linfodisplasia) o malformativa que mejoró con dos embolizaciones de Lipiodol®. CONCLUSIONES: Las manifestaciones genitourinarias pueden ser el debut de una patología linfática más compleja, por ello es necesario tener presente esta etiología infrecuente e inespecífica. Su manejo inicialmente debe ser conservador, mediante vendajes compresivos, OK-432 o embolización con Lipiodol®.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Is the ISAC 112 microarray useful in the diagnosis of pollinosis in Spain?

Background: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. Methods: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. Results: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. Conclusions: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap (AU)

Introducción: La sensibilización a múltiples pólenes es frecuente entre los pacientes alérgicos a polen. El objetivo de este estudio fue determinar la exactitud diagnóstica de la micromatriz ImmunoCAP ISAC 112 (ISAC112) en alergia a polen de diversos taxones y su utilidad clínica en una población española. Métodos: Se determinó IgE específica mediante ISAC112 en 390 pacientes polínicos. Se calculó su exactitud diagnóstica (sensibilidad, especificidad, valores predictivos y área bajo la curva ROC) para el diagnóstico de alergia a polen de gramíneas (n=49), ciprés (n=75), olivo (n=33), plátano de sombra (n=63) y parietaria (n=17) y se comparó con la de ImmunoCAP monocomponente (CAP). Resultados: La sensibilidad de ISAC112 osciló entre 68,2% para alergia a polen de plátano de sombra y 93,9% a polen de gramíneas. La especificidad se situó por encima del 90% en todos los casos. El área bajo la curva (AUC) de la curva ROC para diagnóstico de alergia a polen de plátano fue de 0,798. El resto de AUC fueron ≥ 0,876. La exactitud diagnóstica de ISAC112 fue superior a la de CAP para la alergia a polen de plátano de sombra y similar para el resto de pólenes estudiados. La frecuencia de sensibilización a la mayoría de componentes alergénicos genuinos y a profilinas varió entre las diferentes zonas. El 73 % de los pacientes polínicos estaban sensibilizados a componentes genuinos de más de un tipo polínico. Conclusiones: ISAC112 es una herramienta exacta para el diagnóstico de alergia al polen de gramíneas, ciprés, olivo, plátano de sombra y parietaria, con prestaciones similares o superiores, en el caso de alergia a polen de plátano de sombra, a las de CAP. Es especialmente útil para el diagnóstico etiológico de la polinosis en pacientes con sensibilizaciones a múltiples pólenes con periodos de polinización solapados (AU)

Comprehensive nutritional status in sarco-osteoporotic older fallers.

OBJECTIVES: In older persons, the combination of osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of falls and fractures. However, the particular nutritional status of the sarco-osteoporotic (SOP) patients remains unknown. The goal of this study was to obtain a comprehensive picture of nutritional status in SOP patients. DESIGN: Cross-sectional study. SETTING: Falls and Fractures Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 680 subjects (mean age=79, 65% female) assessed between 2008-2013. MEASUREMENTS: Assessment included medical history, mini-nutritional assessment, physical examination, bone densitometry and body composition by DXA, and blood tests for nutritional status (albumin, creatinine, hemoglobin, vitamin D, vitamin B-12, calcium, phosphate and folate). Patients were divided in 4 groups: 1) osteopenia/osteoporosis (BMD<-1.0 SD); 2) sarcopenia; 3) SOP; and 4) normal (no sarcopenia/no osteoporosis). Difference between groups was assessed with one-way ANOVA and chi square analysis. Multivariable linear regression evaluated the association between the groups and measures of nutritional parameters. RESULTS: Sarcopenia was present in 47.4% of those with osteopenia (167/352) and 62.7% in those with osteoporosis (91/145). Mean age of the SOP was 80.4±7 years. SOP patients showed significantly higher prevalence of falls and fractures. Univariate analyses showed that SOP were more likely than normal to have a BMI< 25 (OR 2.42 95%CI 1.45-4.041, p<0.001), a MNA score <12 (OR 2.0, 95%CI 1.15-3.49, p<0.05), serum folate <20 nmol/L (OR 4.0 95%CI 1.35-11.87, p<0.01) and hemoglobin <120g/L (OR 2.0 95%CI 1.28-3.30, p<0.01). Multivariate analysis showed that a MNA score <12 was independently associated with SOP compared to normal when adjusted for age and gender. Hemoglobin <120g/L, BMI <25, and GDS >6 remained independently associated with SOP after adjustment for all variables including inflammatory conditions. Hypoalbuminemia (<35 g/L) was associated with just osteopenia/osteoporosis (OR: 2.03, 95%CI 1.08-3.81, p<0.01) and just sarcopenia (OR: 1.77, 95%CI 1.0-3.0, p<0.01) compared to normal. No differences in vitamin D, glomerular filtration rate, albumin, corrected calcium, phosphate, red blood cells folate or vitamin B12 levels were found between the subgroups. CONCLUSIONS: In approaching SOP patients, early prevention protocols directed to optimize their nutritional status would be a key strategy to prevent poor outcomes such as falls and fractures in this high risk population. Therefore, nutritional assessment and early nutritional supplementation should be essential domains in this strategy.

An independent SSVEP-based brain-computer interface in locked-in syndrome.

OBJECTIVE: Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use with severely disabled patients. Gaze-independent SSVEP-BCIs have been designed but have shown a drop in accuracy and have not been tested in brain-injured patients. In the present paper, we propose a novel independent SSVEP-BCI based on covert attention with an improved classification rate. We study the influence of feature extraction algorithms and the number of harmonics. Finally, we test online communication on healthy volunteers and patients with locked-in syndrome (LIS). APPROACH: Twenty-four healthy subjects and six LIS patients participated in this study. An independent covert two-class SSVEP paradigm was used with a newly developed portable light emitting diode-based 'interlaced squares' stimulation pattern. MAIN RESULTS: Mean offline and online accuracies on healthy subjects were respectively 85 ± 2% and 74 ± 13%, with eight out of twelve subjects succeeding to communicate efficiently with 80 ± 9% accuracy. Two out of six LIS patients reached an offline accuracy above the chance level, illustrating a response to a command. One out of four LIS patients could communicate online. SIGNIFICANCE: We have demonstrated the feasibility of online communication with a covert SSVEP paradigm that is truly independent of all neuromuscular functions. The potential clinical use of the presented BCI system as a diagnostic (i.e., detecting command-following) and communication tool for severely brain-injured patients will need to be further explored.

[Valorisation of brachytherapy and medico-economic considerations]. / Curiethérapie : valorisation et aspects médico-économiques.

Economic data in the literature for brachytherapy are still sparse and heterogeneous, with few controlled prospective studies and a perspective most often limited to those of the provider (health insurances). Moreover, these observation and conclusions are difficult to generalize in France. The prospective health economic studies performed in France in the framework of a national program to sustain innovative and costly therapies (STIC program) launched by the French cancer national institute are therefore of most importance. With the exception of prostate brachytherapy with permanent seeds, the valorisation of the brachytherapy activity by the French national health insurance does not take into account the degree of complexity and the real costs supported by health institutions (i.e. no specific valorisation for 3D image-based treatment planning and dose optimization and for the use of pulsed dose rate brachytherapy).

Transnodal lymphangiography in the diagnosis and treatment of genital lymphedema.

PURPOSE: To report the success of groin nodal lymphography in the diagnosis and treatment of genital lymphedema. METHODS AND MATERIALS: We present one female (8 years old [patient no. 1]) and two male (69 and [patient no. 2] 31 years old [patient no. 3], respectively) patients with genital lymphedema in whom conservative treatment failed. The girl also had lymphorrhagia. Genital lymphedema was caused by radical cystectomy (patient no. 2), lymphatic hyperplasia (patient no. 1), and idiopathic lymphangitis (patient no. 3). All of them underwent ultrasound-guided bilateral groin lymph node puncture. Afterward, 4-8 ml Lipiodol Ultra-Fluide (Guerbet) were injected at a rate of 0.2 ml/s. Lipiodol progression was assessed by fluoroscopy. Computed tomography scan of the abdomen and pelvis was performed immediately after and again at 24 h after the procedure to confirm the leak. The follow-up period was 15, 13, and 9 months, respectively. Technical success was considered as bilateral pelvic and abdominal filling of lymphatic vessels. Therapeutic success was considered as improvement or disappearance of genital lymphedema and/or lymphorrhagia. RESULTS: Lipiodol leak to the scrotum was observed in patients no. 2 and 3. Lymphaticopelvic fistula and genital lymphatic hyperplasia were seen in patient no. 1. Genital lymphedema diminished within 1 week and almost disappeared in two cases (patients no. 1 and 3) or significantly improved (patient no. 2). lymphorrhagia also resolved in patient no. 1. No recurrence or worsening was detected during follow-up. CONCLUSION: Therapeutic lymphangiography by lymph node injection seems to be effective to treat genital lymphedema. Lymph node puncture lymphangiography is feasible and less cumbersome than pedal lymphangiography.

[BIOBADADERM, the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology: first report]. / BIOBADADERM: registro español de acontecimientos adversos de terapias biológicas en Dermatología. Primer informe.

BACKGROUND AND OBJECTIVES: The Working Group on Psoriasis of the Spanish Academy of Dermatology and Venereology has initiated BIOBADADERM, a registry of patients with psoriasis receiving treatment with biologic drugs, in order to assess the long-term risk of adverse events (AEs). MATERIAL AND METHODS: A multicenter study was undertaken in 2 cohorts of patients with psoriasis: patients receiving biologic therapy and patients receiving nonbiologic systemic therapy other than phototherapy. Similar numbers of patients were included in each group. Information was recorded on demographic and clinical variables, treatment, and relevant AEs. The risk of specific AEs was determined by comparison of the frequencies for those events in the 2 cohorts. RESULTS: Data on the 2 cohorts were evaluated for the period from October, 2008 to November, 2009 alongside retrospective data on patients treated with biologics since 2005. Thirteen Spanish hospitals participated in the study. A total of 632 patients were included in the analysis: 417 treated with biologic drugs and 215 controls. Suspension of biologic therapy due to AEs was rare (72 cycles, 10%). A total of 232 AEs were reported in patients receiving biologic therapy. The majority were not serious. The most frequent AEs were infections (mostly upper respiratory tract infections and nasopharyngitis), followed by conditions affecting the skin or subcutaneous tissue. Forty-three AEs were reported in control subjects. The most frequent events were metabolic and nutritional abnormalities and abnormal transaminase levels. Comparison of the incidence of any AE in patients treated with biologics compared with control subjects revealed a relative risk of 2.2 (P<.001) The relative risks of infections or infestations and disorders of the skin or subcutaneous tissue in patients receiving biologic drugs were 23 (P<.01) and 4.9 (P<.05), respectively. CONCLUSIONS: Patients treated with biologic drugs had a greater number of AEs, particularly infections and skin conditions. Definitive conclusions, however, are difficult to draw due to the small number of patients included in the registry, particularly in the control cohort, and the short follow-up period. Differences in the percentages of events reported by the different hospitals reveal the difficulties associated with the concept of AEs in clinical practice and highlight the need to harmonize criteria in the future. Since the problems identified in this analysis should be overcome in future years, we expect BIOBADADERM to become an important source of information on the safety profile of biologic drugs in dermatology.

Tratamiento con Amisulpride de pacientes adictos a sustancias psicoactivas y síntomas psicóticos / Treatment with amisulpride of addicted patients to psychoactive substances and psychotic symptoms

Introducción. Cada vez disponemos de mayor información sobre la efectividad de los antipsicóticos de segunda generación en pacientes con síntomas psicóticos y trastorno por abuso de substancias. Amisulpride es un fármaco que por sus características puede considerarse una opción terapéutica válida en el manejo de estos pacientes. Objetivo. Evaluar la utilidad del Amisulpride en pacientes con Trastorno por Consumo de Sustancias y comorbilidad asociada. Método. Estudio experimental y prospectivo. Se reclutaron 97 pacientes ambulatorios que iniciaban y/o se encontraban en tratamiento en la Unidad de Conductas Adictivas de Paterna, Valencia (España). Los criterios de inclusión abarcaban a pacientes de ambos sexos con diagnostico de dependencia, según DSM-IV-TR, a una de las siguientes sustancias: alcohol, heroína, cocaína ó cannabis, que habiendo superado la fase de desintoxicación presentaban uno o varios de los síntomas siguientes: ideación paranoide, hostilidad, impulsividad ó irritabilidad marcada, sensibilidad interpersonal, alucinaciones auditivas, o alucinaciones visuales. Los pacientes que habían sido diagnosticados de dependencia a la heroína ya se encontraban en tratamiento de mantenimiento con metadona antes de ser incluidos en el estudio. Se pautó una dosis inicial de Amisulpride, estandarizada en dos rangos (100-300 mg y >/= 400 mg) que fue aumentándose paulatinamente según la respuesta clínica. El seguimiento fue de 9 meses y se realizaron 4 controles a los 3, 6 y 9 meses. Resultados. De un total de 97 pacientes seleccionados, 14 se excluyeron del análisis por violación del protocolo. Abandonaron el estudio 20 y finalizaron el seguimiento a los 9 meses un total de 63 casos. La dosis media de Amisulpride fue de 493,5±197,1 mg/día. En los pacientes que cumplieron el tratamiento, hubo mejoría global del distress psicológico, disminución del craving y mejoría de la funcionalidad psíquica y social. Conclusiones. El tratamiento con Amisulpride es efectivo en pacientes con dependencia a distintas sustancias y comorbilidad asociada, tanto a corto como a medio plazo (AU)

Introduction. There is ever more available information on the effectiveness of second-generation antipsychotic drugs used in addictive behaviour patients with psychotic symptoms. Due to its characteristics, Amisulpride is a medicine that can be considered as a valid therapeutic option to treat this group of patients. Objective. To assess the value of Amisulpride to treat patients with addictive behaviours, and the associated morbidity. Method. An experimental, prospective study was conducted. A total of 97 ambulatory patients, who were initiating, or already receiving, treatment at the Addictive Behaviours Unit in Paterna, Valencia (Spain), were selected to take part in the study. Inclusion criteria included female and male patients, diagnosed of miss using any of the following substances: alcohol, heroine, cocaine or cannabis, who having overcome the detoxification phase, presented one or more of the following symptoms: paranoidideas, hostility, severe irritative or impulsive behaviours, interpersonal sensitivity, and hearing or visual allucinations. An initial dose of Amisulpride, standardized in two ranges (100-300 mg y >/= 400 mg) was used. It was progressively increased according to the clinical response. Four assessments were conducted at months 0,3, 6 and 9. Results. Out of a total of 97 patients, 14 were excluded due to violation of the protocol. Twenty patients dropped out and 63 completed the follow-up period. Mean Amilsupride daily dose was 493.5 ± 197.1 mg In those patients who completed the treatment, an overall improvement in their psychological distress, a decreased in craving and an improvement in their psychological and social functioning were found. Conclusion. Treatment with Amisulpride seems to be effective in patients who are on different addictive substances, and its associated morbidity, both at a short and a medium period of time (AU)

Evaluación del contenido de esteviósido y rebaudiósido A en una población de Stevia rebaudiana Bertoni (kaâ heê) cultivada comercialmente: estudio preliminar / Evaluation of the content of stevioside and rebaudioside A in a population of Stevia rebaudiana Bertoni (kaâ heê) commercially cultivated: a preliminary study

Stevia rebaudiana Bertoni (kaâ heê) es un arbusto originario de la Región Oriental de Paraguay. Sus hojas contienen glucósidos diterpénicos que producen un sabor dulce, perosin valor calórico y son de 150 a 300 veces más dulces que la sacarosa (solución al 0,4%). Durante las temporadas agrícolas 1998 y 1999 se establecieron sembrados deselección individual, en el Instituto Agronómico Nacional (Caacupé, Paraguay). El objetivo de este trabajo fue determinar el contenido de esteviósido y rebaudiósido A en plantasseleccionadas en campo a fin de evaluar la variabilidad existente en la población e identificar clones con alto contenido de dichos glucósidos. De una población original de 2000 individuos, se seleccionaron fenotípicamente 140 plantas por características agronómicas superiores y se cosecharon en etapa de prefloración y libres de polinización.En los Laboratorios del Instituto Nacional de Tecnología Normalización y Metrología (INTN) fueron evaluados los contenidos de esteviósido y rebaudiósido A por detección por cromatografía liquida de alta resolución. El contenido de esteviósido fluctuó entre 0 y 21 % concentrándose el 92 % de la población entre valores del 5 al 15 % .En cuanto al contenido de rebaudiósido A se obtuvieron valores entre 0 y 12 % correspondiendo al 68% de la población un contenido entre 3 y 9 %. La demanda actual de stevia se halla en creciente aumento, por lo que las acciones orientadas a establecer líneas clonales con alto contenido de principios edulcorantes permitirá a los productores primarios la obtención decultivos más productivos e incrementara el rendimiento de obtención de glucósidos.

Stevia rebaudiana Bertoni (kaâ heê) is a bush native to the Eastern Region of Paraguay. Its leaves contain diterpene glycosides that produce a sweet taste but without any caloric value and are 150 to 300 times sweeter than sacharose (0, 4% solution). During 1998 and 1999 agricultural seasons, individual selection sown fields were established in the National Agronomical Institute (Caacupé, Paraguay). The objective of this work was todetermine the content of stevioside and rebaudioside A in these selected plants in the field in order to evaluate the variability existent in the population and identify clones with high content of those glycosides. Of an original population of 2,000 specimens, 140 plants were selected phenotipically by the superior agronomical characteristics and they were harvested in the period of pre-flowering and were pollination free. The content of stevioside and rebaudioside A were evaluated in the laboratories of the National Instituteof Technology, Standardization and Metrology (INTN in Spanish) by high resolution liquid chromatography. The content of stevioside ranged from 0 to 21% concentrating the 92% of the population between 5 to 15%. In relation to rebaudioside A, values between 0 and 12% were obtained being 68% of the population between a content of 3 to 9%. As the current demand of Stevia is increasingly rising, the actions oriented to establish clonallines with high content of sweetener principles will allow primary producers to obtain more productive cultivations and increase the output of glycoside obtainment.

Treatment with amisulpride of addicted patients to psychoactive substances and psychotic symptoms.

INTRODUCTION: There is ever more available information on the effectiveness of second-generation antipsychotic drugs used in addictive behaviour patients with psychotic symptoms. Due to its characteristics, Amisulpride is a medicine that can be considered as a valid therapeutic option to treat this group of patients. OBJECTIVE: To assess the value of Amisulpride to treat patients with addictive behaviours, and the associated morbidity. METHOD: An experimental, prospective study was conducted. A total of 97 ambulatory patients, who were initiating, or already receiving, treatment at the Addictive Behaviours Unit in Paterna, Valencia (Spain), were selected to take part in the study. Inclusion criteria included female and male patients, diagnosed of missusing any of the following substances: alcohol, heroine, cocaine or cannabis, who having overcome the detoxification phase, presented one or more of the following symptoms: paranoid ideas, hostility, severe irritative or impulsive behaviours, interpersonal sensitivity, and hearing or visual allucinations. An initial dose of Amisulpride, standardized in two ranges (100-300 mg y >/= 400 mg) was used. It was progressively increased according to the clinical response. Four assessments were conducted at months 0, 3, 6 and 9. RESULTS: Out of a total of 97 patients, 14 were excluded due to violation of the protocol. Twenty patients dropped out and 63 completed the follow-up period. Mean Amilsupride daily dose was 493.5 ± 197.1 mg In those patients who completed the treatment, an overall improvement in their psychological distress, a decreased in craving and an improvement in their psychological and social functioning were found. CONCLUSION: Treatment with Amisulpride seems to be effective in patients who are on different addictive substances, and its associated morbidity, both at a short and a medium period of time.

Tratamiento psicológico para dependientes a la cocaína en la red sanitaria pública / Psychological treatment for cocaine addicts in public health services

Objetivos. Se presenta un estudio en el que se plantearon como objetivos el comprobar la viabilidad y la efectividad en nuestro medio de un programa de intervención que ha ofrecido buenos resultados fuera de nuestro país; el enfoque de refuerzo comunitario (CRA). Se valoraron las tasas de retención y el consumo de cocaína, y se analizaron las variables que mejor predecían la retención en el tratamiento a las doce semanas. Material y métodos. La muestra del estudio estuvo compuesta por 41 pacientes que cumplían criterios de dependencia de la cocaína, y que fueron asignados aleatoriamente a un grupo de tratamiento CRA (n = 21 grupo experimental) y a un grupo de tratamiento estándar (n = 20 grupo control). Se administraron a los participantes al inicio del tratamiento los siguientes instrumentos de evaluación: EuropASI, MAST, SCL-90-R y BECK. Todos los pacientes realizaban dos controles analíticos semanales para disponer de datos objetivos sobre la abstinencia. Las medidas de resultado se obtuvieron a las doce semanas de tratamiento. Resultados. En el seguimiento a tres meses, el grupo de tratamiento CRA obtuvo mejores tasas de retención (80,9% frente al 65%) y de abstinencia continuada (55% frente al 42,8%). Las variables que mejor predecían la retención en el tratamiento fueron la abstinencia continuada de la cocaína en los primeros dos meses y no ser consumidor de cannabis. Conclusiones. Los resultados de retención y abstinencia son similares a los obtenidos con otros estudios en los que se utiliza este programa. Se sugiere la posible efectividad y viabilidad del programa CRA en un contexto de tratamiento como el nuestro, aunque se precisa de estudios adicionales que permitan generalizar los resultados

Objectives. We report a study thatexpounded as objectives to verify the viability andeffectiveness in our environment, of an interventionprogram that has worked well outside our country;the Community Reinforcement Approach (CRA).Retention rates and consumption of cocaine wereevaluated. Variables that best predicted retention intreatment were analyzed at the twelve weeks.Materials and methods. The study sample wascomposed by 41 patients who were fulfilling criteriaof cocaine dependence, and were randomly assignedto a treatment group CRA (n = 21 experimentalgroup) and a group of standard therapy (n = 20 controlgroup). The following instruments of evaluationwere administered to participants at the beginningof treatment: EuropASI, MAST, SCL-90-R andBECK. All patients realized two analytical weeklycontrols to provide objective data on the abstinence.Outcome measures were obtained at the twelve weeksof treatment. Results. In the follow-up at three months, the treatment group CRA obtained better retention rates(80,9% vs 65%) and continuous abstinence (55% vs42,8%). The variables that predicted better retentionin the treatment were to maintain continuousabstinence in the first two months, and not to be aconsumer of cannabis. Conclusions. The results of retention and abstinence are similar to those obtained with other studies that analyzed this program. It suggests possible effectiveness and viability of the CRA program in a context of treatment like ours, although further studies are needed to confirm the results

Infiltrating ductal carcinoma and synchronous malignant phyllodes tumour. Diagnostic and therapeutic approaches

Simultaneous presentation of breast cancer and malignant phyllodes tumour is rare. A female patient presented with a nodule in her left breast (infiltrating ductal carcinoma). On magnetic nuclear resonance another suspicious lesion (malignant phyllodes) was found in the right breast. Bilateral mastectomy was performed. Thirty two months later the patient is still free of disease. The approach to dealing with synchronous breast tumours should be the same as that normally used (AU)

[Functional constipation: prospective study and treatment response]. / Estreñimiento funcional: estudio prospectivo y respuesta al tratamiento.

OBJECTIVE: To assess the prevalence of functional constipation (FC) with and without encopresis, the factors involved in its onset, and treatment response. PATIENTS AND METHODS: A prospective study of 62 children was performed using a standard questionnaire (onset-age, regular toilet use, encopresis, complications, dietary habits and environmental and psychological factors) and physical and anthropometric assessment. FC was defined as a stool frequency of less than 3 bowel movements/week, with passage of large or scybalous stools, with or without 2 or more soiling episodes per week, without underlying disease. Treatment included demystification, behavioral modification and drugs (mineral oil and senna). Each child was periodically re-evaluated, and treatment was considered successful when the defecation rate was 3 or more bowel movements/week, discomfort was absent, and fecal soiling frequency was 2 or fewer episodes/ month. RESULTS AND CONCLUSIONS: FC accounted for 13 % of all first consultations (60 % boys, 40 % girls; mean age at diagnosis 6.1 years). The most frequent manifestations were painful defecation (60 %), rectorrhagia (42 %), obstructive episodes (34 %) and anal fissure or hemorrhoids (17 %); 19 patients (31 %) had encopresis. Nutritional assessment revealed that 84 % of the patients was well nourished and 16 % was overweight. Fiber intake was deficient in more than 60 %. Sixteen (26 %) patients underwent successful relief of impaction with senna (20-30 mg/dose) combined with mineral oil. Maintenance treatment included mineral oil (15-30 ml/day) and senna at the minimum effective dose (5-15 mg/day). Satisfactory results were achieved 1 month later in 32 % of the children, 3-6 months later in 71 %, and 6-12 months later in 85 %; successful response was closely related to regular toilet habits, dietary modification and a shift in the family's attitude.

Estreñimiento funcional: estudio prospectivo y respuesta al tratamiento / Functional constipation: prospective study and treatment response

Objetivo: Analizar la prevalencia del estreñimiento funcional asociado o no a encopresis, los factores implicados en su desarrollo y la respuesta al tratamiento. Pacientes y métodos: Estudio prospectivo de 62 niños en el que se incluyó cuestionario estándar (edad de comienzo, hábito higiénico, encopresis, complicaciones, encuesta dietética y factores psicológico-ambientales) y exploraciones clínica y antropométrica. Se definió estreñimiento funcional a la frecuencia de defecación inferior a 3 veces/semana con heces voluminosas o escíbalos, acompañado o no de 2 manchados/semana, sin causa orgánica. El tratamiento incluyó desmitificación, corrección de hábitos y fármacos (lubricantes y senósidos). Se reevaluaron periódicamente considerándose respuesta positiva si la defecación fue igual a 3 veces/semana, sin molestias y menos de 2 manchados/mes. Resultados y conclusiones: El estreñimiento funcional supuso el 13 % de las primeras consultas, siendo el 60 % niños y el 40 % niñas, con edad promedio de 6,1 años. Las principales manifestaciones fueron dolor a la defecación (60 %), rectorragia (42 %), episodios obstructivos (32 %) y fisuras y/o hemorroides (18 %); en 19 casos (31 %) se asoció encopresis. El 84 % estaba normonutrido y el 16 % tenían sobrepeso, siendo la alimentación deficitaria en fibra en más del 60 %. Requirieron desimpactación 16 niños con la combinación de senósidos (20-30 mg/dosis) y aceite de parafina, con total eficacia. El tratamiento de mantenimiento incluyó lubricantes (15-30 ml/día) y senósidos en la dosis mínima eficaz (media: 5-15 mg/día). La respuesta al mes fue positiva en el 32 %, a los 3-6 meses en el 71 % y a los 6-12 meses en el 85 % y se relacionó de forma estrecha con la modificación de los hábitos higiénico-dietéticos y el cambio en la actitud familiar

Objective To assess the prevalence of functional constipation (FC) with and without encopresis, the factors involved in its onset, and treatment response. Patients and methods A prospective study of 62 children was performed using a standard questionnaire (onset-age, regular toilet use, encopresis, complications, dietary habits and environmental and psychological factors) and physical and anthropometric assessment. FC was defined as a stool frequency of less than 3 bowel movements/week, with passage of large or scybalous stools, with or without 2 or more soiling episodes per week, without underlying disease. Treatment included demystification, behavioral modification and drugs (mineral oil and senna). Each child was periodically re-evaluated, and treatment was considered successful when the defecation rate was 3 or more bowel movements/week, discomfort was absent, and fecal soiling frequency was 2 or fewer episodes/ month. Results and conclusions FC accounted for 13 % of all first consultations (60 % boys, 40 % girls; mean age at diagnosis 6.1 years). The most frequent manifestations were painful defecation (60 %), rectorrhagia (42 %), obstructive episodes (34 %) and anal fissure or hemorrhoids (17 %); 19 patients (31 %) had encopresis. Nutritional assessment revealed that 84 % of the patients was well nourished and 16 % was overweight. Fiber intake was deficient in more than 60 %. Sixteen (26 %) patients underwent successful relief of impaction with senna (20-30 mg/dose) combined with mineral oil. Maintenance treatment included mineral oil (15-30 ml/day) and senna at the minimum effective dose (5-15 mg/day). Satisfactory results were achieved 1 month later in 32 % of the children, 3-6 months later in 71 %, and 6-12 months later in 85 %; successful response was closely related to regular toilet habits, dietary modification and a shift in the family's attitude