Encefalopatía inducida por disulfiram intranasal: resultados clínicos y de neuroimagen / Intranasal disulfiram-induced encephalopathy: clinical and neuroimage findings

Introducción: La encefalopatía inducida por disulfiram es una complicación rara que se ha descrito en adultos, generalmente en intoxicaciones agudas, aunque también se ha comunicado en forma de encefalopatía de aparición tardía. Su mecanismo fisiopatológico se desconoce con exactitud, pero se atribuye a un posible papel en la inhibición de la dopamina beta-hidroxilasa mediada por metabolitos tóxicos del disulfiram. El objetivo de este trabajo fue describir los hallazgos clínicos y en la neuroimagen en un caso inusual de encefalopatía aguda tóxica inducida por un consumo intranasal crónico de disulfiram. Caso clínico: Paciente de 48 años con enolismo crónico que refirió el uso inhalado por vía intranasal de una dosis muy elevada de disulfiram sin ingesta simultánea de alcohol desarrolló una encefalopatía aguda con insuficiencia respiratoria rápidamente progresiva. La neuroimagen reveló una extensa afectación simétrica bilateral de ambos núcleos pálidos, un hallazgo característico en esta intoxicación. La recuperación neurológica fue lenta. Dos meses después de la intoxicación, el paciente presentaba un ligero temblor intencional residual y una resonancia magnética mostró una evolución de las áreas simétricas de edema citotóxico a necrosis. Conclusión: La neurotoxicidad inducida por disulfiram debe sospecharse durante el tratamiento crónico con disulfiram o después de una ingesta aguda de dosis elevadas. La presencia de síntomas como una neuropatía sensitivomotora simétrica, confusión, catatonía, parkinsonismo, ataxia, coreoatetosis, convulsiones y encefalopatía nos debe obligar a descartar este trastorno. La neuroimagen debe considerarse en este escenario, ya que se ha descrito una afectación característica de ambos núcleos pálidos.(AU)

Introduction: Disulfiram-induced-encephalopathy is a rare complication that has been well described in adults. Although it usually occurs in acute intoxication with high doses of disulfiram, late onset encephalopathy has also been reported. Some authors propose the inhibition of dopamine beta-hydroxylase mediated by toxic metabolites of disulfiram as the main responsible, but the exact mechanism remains unclear. The aim of this report was to describe the clinical and neuroimaging findings in an unusual case of acute encephalitis due to disulfiram toxicity associated to chronic intranasal consume. Case report: A chronic alcoholic who referred snorted use of a very high dose of disulfiram without simultaneous alcohol intake developed an acute encephalopathy with a rapidly progressive respiratory failure. A characteristic neuroimage finding consisting in extensive bilateral symmetric involvement of both pallidal nuclei was described. Recovery and neurologic improvement were slow. Two months after the intoxication, the patient still had slight intentional tremor and a scheduled magnetic resonance imaging. showed evolution of symmetrical areas of cytotoxic edema to necrosis.  Conclusion: Disulfiram-induced neurotoxicity must be suspect during chronic therapy with disulfiram or after acute ingestion of high doses. Symptoms such as symmetric sensory and motor neuropathy, confusion, catatonia, parkinsonism, ataxia, choreoathetosis, seizures and encephalopathy should make us rule out this disorder. A brain imaging test should be performed in these patients since a characteristic involvement of both nuclei pallidus has been described, but it is not present in all patients.(AU)

Intranasal disulfiram-induced encephalopathy: clinical and neuroimage findings. / Encefalopatía inducida por disulfiram intranasal: resultados clínicos y de neuroimagen.

INTRODUCTION: Disulfiram-induced-encephalopathy is a rare complication that has been well described in adults. Although it usually occurs in acute intoxication with high doses of disulfiram, late onset encephalopathy has also been reported. Some authors propose the inhibition of dopamine beta-hydroxylase mediated by toxic metabolites of disulfiram as the main responsible, but the exact mechanism remains unclear. The aim of this report was to describe the clinical and neuroimaging findings in an unusual case of acute encephalitis due to disulfiram toxicity associated to chronic intranasal consume. CASE REPORT: A chronic alcoholic who referred snorted use of a very high dose of disulfiram without simultaneous alcohol intake developed an acute encephalopathy with a rapidly progressive respiratory failure. A characteristic neuroimage finding consisting in extensive bilateral symmetric involvement of both pallidal nuclei was described. Recovery and neurologic improvement were slow. Two months after the intoxication, the patient still had slight intentional tremor and a scheduled magnetic resonance imaging. showed evolution of symmetrical areas of cytotoxic edema to necrosis. CONCLUSION: Disulfiram-induced neurotoxicity must be suspect during chronic therapy with disulfiram or after acute ingestion of high doses. Symptoms such as symmetric sensory and motor neuropathy, confusion, catatonia, parkinsonism, ataxia, choreoathetosis, seizures and encephalopathy should make us rule out this disorder. A brain imaging test should be performed in these patients since a characteristic involvement of both nuclei pallidus has been described, but it is not present in all patients.

TITLE: Encefalopatía inducida por disulfiram intranasal: resultados clínicos y de neuroimagen.Introducción. La encefalopatía inducida por disulfiram es una complicación rara que se ha descrito en adultos, generalmente en intoxicaciones agudas, aunque también se ha comunicado en forma de encefalopatía de aparición tardía. Su mecanismo fisiopatológico se desconoce con exactitud, pero se atribuye a un posible papel en la inhibición de la dopamina beta-hidroxilasa mediada por metabolitos tóxicos del disulfiram. El objetivo de este trabajo fue describir los hallazgos clínicos y en la neuroimagen en un caso inusual de encefalopatía aguda tóxica inducida por un consumo intranasal crónico de disulfiram. Caso clínico. Paciente de 48 años con enolismo crónico que refirió el uso inhalado por vía intranasal de una dosis muy elevada de disulfiram sin ingesta simultánea de alcohol desarrolló una encefalopatía aguda con insuficiencia respiratoria rápidamente progresiva. La neuroimagen reveló una extensa afectación simétrica bilateral de ambos núcleos pálidos, un hallazgo característico en esta intoxicación. La recuperación neurológica fue lenta. Dos meses después de la intoxicación, el paciente presentaba un ligero temblor intencional residual y una resonancia magnética mostró una evolución de las áreas simétricas de edema citotóxico a necrosis. Conclusión. La neurotoxicidad inducida por disulfiram debe sospecharse durante el tratamiento crónico con disulfiram o después de una ingesta aguda de dosis elevadas. La presencia de síntomas como una neuropatía sensitivomotora simétrica, confusión, catatonía, parkinsonismo, ataxia, coreoatetosis, convulsiones y encefalopatía nos debe obligar a descartar este trastorno. La neuroimagen debe considerarse en este escenario, ya que se ha descrito una afectación característica de ambos núcleos pálidos.

Factores clínico-radiológicos asociados con muerte encefálica precoz / Clinico-radiological related to early brain death factors

Objective: To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 h. Design A retrospective cohort study was made covering the period 2015−2017. Setting An adult Intensive Care Unit (ICU).Patients/methodsEpidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD. Results A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD > 24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD > 24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD > 24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups.ConclusionsEarly BD (>24 h) was associated to GCS < 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation (AU)

Objetivo: Identificar los factores clínico-radiológicos que se asocian a evolución precoz a muerte encefálica (ME), definida esta como la ocurrida en ≤24 horas Diseño Estudio de cohortes retrospectivo desde 2015 hasta 2017, ambos incluidos. Ámbito Servicio de Medicina Intensiva (SMI) de adultos.Pacientes y métodoAnálisis de variables clínico-epidemiológicas y de la TC craneal de ingreso en pacientes con evolución a ME. Resultados Se analizaron 166 ME, 86 varones, edad media 62,7 años, 42,8% hemorragia intracerebral, 18,7% HSA, 17,5% TCE, 7,8% ictus isquémico, 9% anoxia y 4,2% otras causas; 50% HTA, 34% dislipemia, 33% tabaquismo, 21% antiagregación, 19% enolismo. El 15% anticoagulación, 15% diabetes. El GCS fue tres en el 68,8% en ME precoz frente 38,2% en ME >24 h (p 0,0001); 85 hematoma supratentorial (90,9 mL en ME precoz vs. 82,7 mL ME tardía, p 0,54); 12 hematoma infratentorial. Desplazamiento medio de línea media 10,7 mm en ME precoz vs. 7,8 mm en ME tardía (p 0,045); 91 pacientes ventriculomegalia y 38 trasudado periependimario (p 0,021). Borramiento completo de cisternas basales 36 en ME precoz frente a 24 en ME tardía (p 0,005), borramiento de surcos (p 0,013), pérdida de diferenciación córtico-subcortical (p 0,0001) y ausencia de cisterna supraselar (p 0,005). La medición de la vaina del nervio óptico no mostró diferencias significativas entre los dos grupos.ConclusionesSe asoció con ME ≤ 24 horas el GCS < 5, el desplazamiento de línea media, la pérdida de diferenciación córtico-subcortical, el borramiento de surcos, el borramiento completo de cisternas basales, de la cisterna supraselar y la presencia de trasudado periependimario (AU)

Clinico-radiological related to early brain death factors.

OBJECTIVE: To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 h. DESIGN: A retrospective cohort study was made covering the period 2015-2017. SETTING: An adult Intensive Care Unit (ICU). PATIENTS/METHODS: Epidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD. RESULTS: A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD > 24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD > 24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD > 24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups. CONCLUSIONS: Early BD (>24 h) was associated to GCS < 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation.

Early standardized clinical judgement for syncope diagnosis in the emergency department.

BACKGROUND: The diagnosis of cardiac syncope remains a challenge in the emergency department (ED). OBJECTIVE: Assessing the diagnostic accuracy of the early standardized clinical judgement (ESCJ) including a standardized syncope-specific case report form (CRF) in comparison with a recommended multivariable diagnostic score. METHODS: In a prospective international observational multicentre study, diagnostic accuracy for cardiac syncope of ESCJ by the ED physician amongst patients ≥ 40 years presenting with syncope to the ED was directly compared with that of the Evaluation of Guidelines in Syncope Study (EGSYS) diagnostic score. Cardiac syncope was centrally adjudicated independently of the ESCJ or conducted workup by two ED specialists based on all information available up to 1-year follow-up. Secondary aims included direct comparison with high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) concentrations and a Lasso regression to identify variables contributing most to ESCJ. RESULTS: Cardiac syncope was adjudicated in 252/1494 patients (15.2%). The diagnostic accuracy of ESCJ for cardiac syncope as quantified by the area under the curve (AUC) was 0.87 (95% CI: 0.84-0.89), and higher compared with the EGSYS diagnostic score (0.73 (95% CI: 0.70-0.76)), hs-cTnI (0.77 (95% CI: 0.73-0.80)) and BNP (0.77 (95% CI: 0.74-0.80)), all P < 0.001. Both biomarkers (alone or in combination) on top of the ESCJ significantly improved diagnostic accuracy. CONCLUSION: ESCJ including a standardized syncope-specific CRF has very high diagnostic accuracy and outperforms the EGSYS score, hs-cTnI and BNP.

Clinico-radiological related to early brain death factors. / Factores clínico-radiológicos asociados con muerte encefálica precoz.

OBJECTIVE: To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 hours. DESIGN: A retrospective cohort study was made covering the period 2015-2017. SETTING: An adult Intensive Care Unit (ICU). PATIENTS/METHODS: Epidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD. RESULTS: A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD >24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD >24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD >24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups. CONCLUSIONS: Early BD (>24 h) was associated to GCS < 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation.

Quality of life in elderly breast cancer patients with localized disease receiving endocrine treatment: a prospective study.

PURPOSE: In this paper we study the quality of life (QoL) of elderly breast cancer patients receiving endocrine treatment (ET). More QoL data on elderly patients treated with ET are needed. Our aims are to study QoL in early-stage breast cancer patients throughout the treatment period and compare the QoL of ET groups. METHODS: 148 patients > 65 years who began ET with either tamoxifen or aromatase inhibitor (AI) completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) questionnaires three times over 3 years of ET. Linear mixed-effect models were used to evaluate longitudinal QoL changes. ET group comparisons were conducted after 3 years of treatment via ANCOVA adjusted by basal QoL. RESULTS: QoL scores were high (> 80/100 points) in most QoL areas, with moderate limitations (> 30) in sexual functioning and enjoyment and in future perspective. After 3 years of ET, four QoL areas improved (< 6 points) compared to baseline and 3-month assessments. Hot flushes worsened (8 points) at the 3-month assessment but by 3 years had recovered. AI patients showed more hot flushes, pain and diarrhea and less sexual enjoyment than tamoxifen patients after 3 years of ET (differences 3-12 points). CONCLUSIONS: Results indicate that elderly early-stage breast cancer patients adapted well to their disease and ET treatment over the 3 years. Few QoL differences were observed between ET groups.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years) ±â€¯S.D. at diagnosis was 14.2 ±â€¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ±â€¯S.D. was 1.27 ±â€¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

Balance hídrico y carga de cloro en las primeras 24h de ingreso en UCI y su relación con las terapias de reemplazo renal mediante un estudio multicéntrico, retrospectivo, de casos y controles emparejados por APACHE-II / Fluid balance and chloride load in the first 24h of ICU admission and its relation with renal replacement therapies through a multicentre, retrospective, case-control study paired by APACHE-II

Objetivo. Analizar la asociación entre el balance hídrico durante las primeras 24h de ingreso en UCI y las variables relacionadas con los valores de cloro (carga de cloro, tipo de fluido administrado, hipercloremia), con el empleo de técnicas de reemplazo renal secundarias a insuficiencia renal aguda (IRA-TRR) durante el posterior ingreso en UCI de los enfermos. Pacientes y métodos. Estudio multicéntrico de casos y controles, de base hospitalaria y ámbito nacional, llevado a cabo en 6 UCI. Los casos fueron pacientes mayores de 18 años que desarrollaron una IRA-TRR. Los controles fueron pacientes mayores de 18 años, ingresados en el mismo periodo y centro que los casos, que no desarrollaron IRA-TRR durante su ingreso en UCI. Se realizó emparejamiento por APACHE-II. Se llevó a cabo un análisis de regresión logística no condicional ajustada por edad, sexo, APACHE-II. Las variables de interés principales fueron: balance hídrico, carga de cloro administrada, e IRA-TRR. Resultados. Se han analizado las variables de 310 enfermos. Se evidenció un aumento del 10% en la posibilidad de desarrollar IRA-TRR por cada 500ml de balance hídrico positivo (OR: 1,09 [IC 95%:1,05-1,14]; p<0,001). El estudio de los valores medios de carga administrada no evidenció diferencias entre el grupo de casos y de controles (299,35±254,91 frente a 301,67±234,63; p=0,92). Conclusiones. El balance hídrico en las primeras 24h de ingreso en UCI se relaciona con el desarrollo de IRA-TRR, independientemente de la cloremia (AU)

Objective. To analyse the association between water balance during the first 24h of admission to ICU and the variables related to chloride levels (chloride loading, type of fluid administered, hyperchloraemia), with the development of acute kidney injury renal replacement therapy (AKI-RRT) during patients’ admission to ICU. Patients and methods. Multicentre case-control study. Hospital-based, national, carried out in 6 ICUs. Cases were patients older than 18 years who developed an AKI-RRT. Controls were patients older than 18 years admitted to the same institutions during the study period, who did not develop AKI-RRT during ICU admission. Pairing was done by APACHE-II. An analysis of unconditional logistic regression adjusted for age, sex, APACHE-II and water balance (in evaluating the type of fluid). Results. We analysed the variables of 430 patients: 215 cases and 215 controls. An increase of 10% of the possibility of developing AKI-RRT per 500ml of positive water balance was evident (OR: 1.09 [95% CI: 1.05 to 1.14]; P<.001). The study of mean values of chloride load administered did not show differences between the group of cases and controls (299.35±254.91 vs. 301.67±234.63; P=.92). Conclusions. The water balance in the first 24h of ICU admission relates to the development of IRA-TRR, regardless of chloraemia (AU)

Fluid balance and chloride load in the first 24h of ICU admission and its relation with renal replacement therapies through a multicentre, retrospective, case-control study paired by APACHE-II. / Balance hídrico y carga de cloro en las primeras 24h de ingreso en UCI y su relación con las terapias de reemplazo renal mediante un estudio multicéntrico, retrospectivo, de casos y controles emparejados por APACHE-II.

OBJECTIVE: To analyse the association between water balance during the first 24h of admission to ICU and the variables related to chloride levels (chloride loading, type of fluid administered, hyperchloraemia), with the development of acute kidney injury renal replacement therapy (AKI-RRT) during patients' admission to ICU. PATIENTS AND METHODS: Multicentre case-control study. Hospital-based, national, carried out in 6 ICUs. Cases were patients older than 18 years who developed an AKI-RRT. Controls were patients older than 18 years admitted to the same institutions during the study period, who did not develop AKI-RRT during ICU admission. Pairing was done by APACHE-II. An analysis of unconditional logistic regression adjusted for age, sex, APACHE-II and water balance (in evaluating the type of fluid). RESULTS: We analysed the variables of 430 patients: 215 cases and 215 controls. An increase of 10% of the possibility of developing AKI-RRT per 500ml of positive water balance was evident (OR: 1.09 [95% CI: 1.05 to 1.14]; P<.001). The study of mean values of chloride load administered did not show differences between the group of cases and controls (299.35±254.91 vs. 301.67±234.63; P=.92). CONCLUSIONS: The water balance in the first 24h of ICU admission relates to the development of IRA-TRR, regardless of chloraemia.

Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment.

BACKGROUND AND AIMS: Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. METHODS: In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. RESULTS: We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. CONCLUSIONS: Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe.

Erratum:Quality of life in long-term premenopausal early-stage breast cancer survivors from Spain. Effects of surgery and time since surgery.

In this article published in Volume 21, issue 5, the authors' names were incorrectly stated in the Pubmed abstract as: "Ignacio Arraras J(1), Juan Illarramendi J, de la Cruz S, Asin G, Manterola A, Ibanez B, Salgado E, Cambra K, Zarandona U, Angel Dominguez M, Vera R.". The correct authors' names are: "Arraras JI(1), Illarramendi JJ, de la Cruz S, Asin G, Manterola A, Ibanez B, Salgado E, Cambra K, Zarandona U, Dominguez MA, Vera R.". This error appeared only in the PubMed database and not in the print form of the Journal.

CARACTERIZACIÓN ALERGÉNICA Y POTENCIAL IMPORTANCIA DEL LUPINO EN ALERGIA ALIMENTARIA ARTÍCULO DE REVISIÓN / Allergen characterization of lupine and its potential importance in food allergy: review article

El lupino pertenece al género de las leguminosas, junto con el maní, las arvejas, las lentejas y los garbanzos. La harina de lupino ha sido ampliamente utilizada en algunos países por sus propiedades nutritivas y funcionales, destacando entre ellas su gran aporte proteico, adecuada proporción de fi bras, carbohidratos y bajo contenido graso, constituyendo para algunos grupos la "nueva soja". En relación al progresivo aumento en su consumo, han aumentado los reportes de reacciones adversas, destacando entre ellas las correspondientes a alergia alimentaria, que pueden ir desde el síndrome de alergia oral hasta la anafi laxia. Clínicamente la reacción cruzada más relevante se produciría con el consumo de maní y de almendra. En la actualidad existen pocos estudios acerca de la sensibilización a lupino en la población general, en la población atópica y conocemos parcialmente sus alérgenos. Ello, más la falta de incorporación de lupino en el etiquetado de los alimentos, son elementos que difi cultan conocer el real impacto que este alérgeno alimentario emergente cumple en el desarrollo de alergias alimentarias.(AU)

Lupine belongs to the leguminous family, along with peanut, peas, chickpeas and lentils. Lupine fl our has been widely used in some countries for its nutritional and functional properties, outstanding among them its great proteic value, appropriate proportion of fi ber and carbohydrate content, and its low percentage of fat, thus it has been named by some as the "new soy bean". As its consumption has increased, there has also been a raise in the report of adverse reactions, such as food allergy, that range from oral allergy syndrome to anaphylaxis. The most relevant clinical cross-reaction occurs with peanut and almond consumption. Now days there are few studies on general and on atopic population regarding lupine sensitization, furthermore, we hardly know its allergens. The lack of brand identifi cation of lupine in foods is a relevant fact that makes even more diffi cult to have a realistic knowledge of this emerging food allergen and its role in the production of food allergies(AU)

Effectiveness of the E2-classical swine fever virus recombinant vaccine produced and formulated within whey from genetically transformed goats.

Subunit recombinant vaccines against classical swine fever virus (CSFV) are a promising alternative to overcome practical and biosafety issues with inactivated vaccines. One of the strategies in evaluation under field conditions is the use of a new marker E2-based vaccine produced in the milk of adenovirally transduced goats. Previously we had demonstrated the efficacy of this antigen, which conferred early protection and long-lasting immunity in swine against CSFV infection. Here, we have used a simpler downstream process to obtain and formulate the recombinant E2 glycoprotein expressed in the mammary gland. The expression levels reached approximately 1.7 mg/ml, and instead of chromatographic separation of the antigen, we utilized a clarification process that eliminates the fat content, retains a minor amount of caseins, and includes an adenoviral inactivation step that improves the biosafety of the final formulation. In a vaccination and challenge experiment in swine, different doses of the E2 antigen contained within the clarified whey generated an effective immune response of neutralizing antibodies that protected all of the animals against a lethal challenge with CSFV. During the immunization and after challenge, the swine were monitored for adverse reactions related to the vaccine or symptoms of CSF, respectively. No adverse reactions or clinical signs of disease were observed in vaccinated animals, in which no replication of CSFV could be detected after challenge. Overall, we consider that the simplicity of the procedures proposed here is a further step toward the introduction and implementation of a commercial subunit vaccine against CSF.

Controlled continuous bio-hydrogen production using different biogas release strategies.

Dark fermentation for bio-hydrogen (bio-H2) production is an easily operated and environmentally friendly technology. However, low bio-H2 production yield has been reported as its main drawback. Two strategies have been followed in the past to improve this fact: genetic modifications and adjusting the reaction conditions. In this paper, the second one is followed to regulate the bio-H2 release from the reactor. This operating condition alters the metabolic pathways and increased the bio-H2 production twice. Gas release was forced in the continuous culture to study the equilibrium in the mass transfer between the gaseous and liquid phases. This equilibrium depends on the H2, CO2, and volatile fatty acids production. The effect of reducing the bio-H2 partial pressure (bio-H2 pp) to enhance bio-H2 production was evaluated in a 30 L continuous stirred tank reactor. Three bio-H2 release strategies were followed: uncontrolled, intermittent, and constant. In the so called uncontrolled fermentation, without bio-H2 pp control, a bio-H2 molar yield of 1.2 mol/mol glucose was obtained. A sustained low bio-H2 pp of 0.06 atm increased the bio-H2 production rate from 16.1 to 108 mL/L/h with a stable bio-H2 percentage of 55% (v/v) and a molar yield of 1.9 mol/mol glucose. Biogas release enhanced bio-H2 production because lower bio-H2 pp, CO2 concentration, and reduced volatile fatty acids accumulation prevented the associated inhibitions and bio-H2 consumption.

Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RA) have recently been introduced for the treatment of immune thrombocytopenia (ITP), an anti-platelet-antibodies autoimmune disease. The observation of a low frequency of bleeding episodes despite their thrombocytopenia suggests the existence of a compensatory mechanism. This study aimed to evaluate the effect of TPO-RA treatment on platelet function and on the procoagulant state in ITP patients before (ITP-bR) and after responding (ITP-aR) to treatment. Plasma- and microparticle (MP)-associated procoagulant capacity from ITP patients was similar before and after responding to the TPO-RA regimen but higher than the healthy control values. High MP-associated procoagulant activity did not seem to be due to increased platelet activation, since platelet stimulation by agonists was reduced in ITP-bR and ITP-aR patients. It could be related to increased platelet apoptosis, evaluated in terms of surface phosphatidylserine (PS), observed in both ITP groups. In summary, TPO-RA treatment increased platelet count but did not ameliorate their function and did not change plasma- and MP-associated procoagulant state of ITP patient responders to this therapy.

Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected.

Risk factors associated with hepatitis C virus infection in an urban population of the State of Mexico.

The aim of this study was to determine the seroprevalence anti-hepatitis C virus (HCV) antibodies and risk factors associated with patients attending primary-care clinics in the State of Mexico. A cross-sectional, prospective study was conducted on 10,524 consenting patients with history of at least one risk factor for HCV. Antibodies were detected by immunoassay, third-generation ELISA; RT-PCR was carried out to confirm HCV infection. The seroprevalence of HCV antibodies was 1.2% (128). The most common risk factor was blood transfusion prior to 1993 (56.3%), followed by family history of cirrhosis 29 (22.7%); tattoos and/or piercings, 28 (21.9%); high-risk sexual practices, 4 (3.1%); healthcare work, 8 (6.3%); and intravenous drug use, 1 (8%). RT-PCR was performed on samples from 83 patients. Forty-five were considered positive. Genotype 1a was the most prevalent (37.7%).

[Health-related quality of life in the oncology departments of the hospital of Navarra. The EORTC Quality of Life Group]. / Calidad de vida relacionada con la salud en los servicios de Oncología del Hospital de Navarra. Grupo de Calidad de Vida de la.

Quality of life assessment is one of the key elements of the care that is offered to cancer patients. The aim of this work is to present the research line on quality of life that has been carried out since 1992 in the Oncology Departments of the Hospital de Navarra. These departments actively collaborate with the European Organisation of Research and Treatment of Cancer - EORTC - Quality of Life Group in creating questionnaires and also in other projects of this group. Our institution has coordinated the development process of the EORTC information module. Different EORTC questionnaires have been validated for use in our country. Quality of life studies have been carried out in the main tumour sites and in other areas, such as patients' satisfaction with care. This research line has a direct benefit on the attention that patients receive.