[Review of a series of cases of Creutzfeldt-Jakob disease in a tertiary care hospital]. / Revisión de una serie de casos de enfermedad de Creutzfeldt-Jakob en un hospital de tercer nivel.

INTRODUCTION: We analysed a series of patients with sporadic Creutzfeldt-Jakob disease in our setting. AIM: The aim of this study is to describe the characteristics of our sample using the new diagnostic tools based on the most recently published criteria. MATERIAL AND METHODS: A descriptive, retrospective study was conducted using a digitalised hospital register. We identified 20 cases of the sporadic type, in the period 2012-2022: eight with a pathological diagnosis and 12 with high probability. The variables sex, age at onset, time of evolution, clinical phenotype, magnetic resonance imaging (MRI) findings, 14.3.3 protein, electroencephalogram (EEG), real-time quaking-induced prion protein conversion (RT-QuIC), autopsy, pathological phenotype and genetic diagnosis were recorded. RESULTS: Of those affected, 50% were men and 50%, women, with an age at onset of 67 years (30-83) and a mean survival time of eight months (1-11 months). Cognitive impairment was the most frequent onset symptom, followed by gait ataxia. All MRI scans with long time-lapse sequences (FLAIR and DWI) were pathological, and the pattern of diffuse cortical and basal ganglia involvement was the most frequent. Altogether, 55% of the sample had an EEG with characteristic triphasic complexes. Sixty-five per cent were positive for 14.3.3 protein in cerebrospinal fluid. Four RT QuIC studies were carried out (in 2020) and all were positive. In 40% of them a confirmatory autopsy was performed, with the MM/MV1 pattern being the most frequent. CONCLUSIONS: MRI with DWI sequences is a particularly sensitive test for the diagnosis of the disease, although its sensitivity decreases in the early stages. The high specificity and sensitivity of RT-QuIC, together with a characteristic clinical diagnosis and radiological pattern, are proposed as an alternative to the pathological definitive diagnosis.

TITLE: Revisión de una serie de casos de enfermedad de Creutzfeldt-Jakob en un hospital de tercer nivel.Introducción. Analizamos en nuestro medio una serie de pacientes con enfermedad de Creutzfeldt-Jakob esporádica. Objetivo. Describir las características de nuestra muestra haciendo uso de las nuevas herramientas diagnósticas según los últimos criterios publicados. Material y métodos. Realizamos un estudio descriptivo y retrospectivo mediante registro hospitalario digitalizado. Identificamos 20 casos del tipo esporádico, en el período 2012-2022, ocho con diagnóstico anatomopatológico y 12 con alta probabilidad. Se registraron las variables sexo, edad de inicio, tiempo de evolución, fenotipo clínico, hallazgos en la resonancia magnética (RM), proteína 14.3.3, electroencefalograma (EEG), conversión de proteína priónica inducida por agitación en tiempo real (RT-QuIC), autopsia, fenotipo anatomopatológico y diagnóstico genético. Resultados. Registramos un 50% de hombres y un 50% de mujeres afectos, con una edad de inicio de 67 años (30-83) y un tiempo de supervivencia medio de ocho meses (1-11 meses). El deterioro cognitivo fue el síntoma de inicio más frecuente, seguido de la ataxia de la marcha. Todas las RM con secuencias de tiempo de repetición largo (FLAIR y DWI) fueron patológicas, y el patrón de afectación cortical difusa y de los ganglios basales fue el más frecuente. El 55% de la muestra tuvo un EEG con complejos trifásicos característicos. El 65% mostró positiva la proteína 14.3.3 en el líquido cefalorraquídeo. Se realizaron cuatro estudios de RT-QuIC (en 2020) y todos fueron positivos. En un 40% se realizó una autopsia confirmatoria, con el patrón MM/MV1 como el más frecuente. Conclusiones. La RM con secuencias de DWI constituye una prueba especialmente sensible para el diagnóstico de la enfermedad, aunque su sensibilidad disminuye en estadios precoces. La alta especificidad y la alta sensibilidad de la RT-QuIC, junto con un diagnóstico clínico y patrón radiológico característico, se plantean como alternativa al diagnóstico de certeza anatomopatológico.

Revisión de una serie de casos de enfermedad de Creutzfeldt-Jakob en un hospital de tercer nivel / Review of a series of cases of Creutzfeldt-Jakob disease in a tertiary care hospital

Introducción Analizamos en nuestro medio una serie de pacientes con enfermedad de Creutzfeldt-Jakob esporádica. Objetivo Describir las características de nuestra muestra haciendo uso de las nuevas herramientas diagnósticas según los últimos criterios publicados. Material y métodos. Realizamos un estudio descriptivo y retrospectivo mediante registro hospitalario digitalizado. Identificamos 20 casos del tipo esporádico, en el período 2012-2022, ocho con diagnóstico anatomopatológico y 12 con alta probabilidad. Se registraron las variables sexo, edad de inicio, tiempo de evolución, fenotipo clínico, hallazgos en la resonancia magnética (RM), proteína 14.3.3, electroencefalograma (EEG), conversión de proteína priónica inducida por agitación en tiempo real (RT-QuIC), autopsia, fenotipo anatomopatológico y diagnóstico genético. Resultados Registramos un 50% de hombres y un 50% de mujeres afectos, con una edad de inicio de 67 años (30-83) y un tiempo de supervivencia medio de ocho meses (1-11 meses). El deterioro cognitivo fue el síntoma de inicio más frecuente, seguido de la ataxia de la marcha. Todas las RM con secuencias de tiempo de repetición largo (FLAIR y DWI) fueron patológicas, y el patrón de afectación cortical difusa y de los ganglios basales fue el más frecuente. El 55% de la muestra tuvo un EEG con complejos trifásicos característicos. El 65% mostró positiva la proteína 14.3.3 en el líquido cefalorraquídeo. Se realizaron cuatro estudios de RT-QuIC (en 2020) y todos fueron positivos. En un 40% se realizó una autopsia confirmatoria, con el patrón MM/MV1 como el más frecuente. Conclusiones La RM con secuencias de DWI constituye una prueba especialmente sensible para el diagnóstico de la enfermedad, aunque su sensibilidad disminuye en estadios precoces. La alta especificidad y la alta sensibilidad de la RT-QuIC, junto con un diagnóstico clínico y patrón radiológico característico, se plantean como alternativa al diagnóstico de certeza anatomopatológico. (AU)

INTRODUCTION We analysed a series of patients with sporadic Creutzfeldt-Jakob disease in our setting. AIM The aim of this study is to describe the characteristics of our sample using the new diagnostic tools based on the most recently published criteria. Material and methods. A descriptive, retrospective study was conducted using a digitalised hospital register. We identified 20 cases of the sporadic type, in the period 2012-2022: eight with a pathological diagnosis and 12 with high probability. The variables sex, age at onset, time of evolution, clinical phenotype, magnetic resonance imaging (MRI) findings, 14.3.3 protein, electroencephalogram (EEG), real-time quaking-induced prion protein conversion (RT-QuIC), autopsy, pathological phenotype and genetic diagnosis were recorded. RESULTS Of those affected, 50% were men and 50%, women, with an age at onset of 67 years (30-83) and a mean survival time of eight months (1-11 months). Cognitive impairment was the most frequent onset symptom, followed by gait ataxia. All MRI scans with long time-lapse sequences (FLAIR and DWI) were pathological, and the pattern of diffuse cortical and basal ganglia involvement was the most frequent. Altogether, 55% of the sample had an EEG with characteristic triphasic complexes. Sixty-five per cent were positive for 14.3.3 protein in cerebrospinal fluid. Four RT QuIC studies were carried out (in 2020) and all were positive. In 40% of them a confirmatory autopsy was performed, with the MM/MV1 pattern being the most frequent. CONCLUSIONS MRI with DWI sequences is a particularly sensitive test for the diagnosis of the disease, although its sensitivity decreases in the early stages. The high specificity and sensitivity of RT-QuIC, together with a characteristic clinical diagnosis and radiological pattern, are proposed as an alternative to the pathological definitive diagnosis. (AU)

Preliminary analysis of a shortened picture version of the Free and Cued Selective Reminding Test.

INTRODUCTION: A picture version of the Free and Cued Selective Reminding Test (FCSRT) would assist in the assessment of memory function in patients with low levels of schooling. A shortened version would improve the test's applicability. OBJECTIVES: To analyse the diagnostic usefulness of a shortened picture version of the FCSRT for distinguishing patients with amnestic mild cognitive impairment (aMCI) from controls, without excluding participants with a low level of schooling. METHODS: Phase I study of a diagnostic evaluation (convenience sampling; pre-test prevalence 50%). A blinded researcher independently administered the FCSRT to 30 patients with aMCI and 30 controls matched for age, sex, level of schooling and literacy, using images and omitting the usual 30-minutes delayed recall item. Three variables were recorded: free recall, total recall, and cue efficiency. Diagnostic accuracy was calculated using receiver operating characteristic curves and the area under the curve. The Youden index was used to identify optimal cut-off points. RESULTS: Of all participants, 41.7% had not completed primary education. There were no differences between groups as regards sociodemographic variables. Area under the curve was excellent for free recall (0.99), total recall (0.95), and cue efficiency (0.93). The optimal cut-off points were 21/22, 43/44, and < 0.77, respectively. CONCLUSIONS: This preliminary analysis shows that a shortened picture version of the FCSRT may be useful and applicable for the diagnosis of aMCI without excluding individuals with a low level of schooling.

High level of medication regimen complexity index correlate with worse quality of life in people living with HIV.

OBJECTIVE: People living with HIV (PLWHIV) have now a near-normal life expectancy and thus, a higher risk of polypharmacy. The main objective was to assess the correlation between medication regimen complexity index (MRCI) and quality of life (EQ-5D) and health utilities among PLWHIV patients on ART. METHODS: Observational prospective single-center study including adult PLWHIV on ART from January to March-2020 attended at hospital pharmacy outpatient service according to a Capacity-Motivation-Opportunity (CMO) pharmaceutical care model. RESULTS: A total of 428 patients were included, mean age of 50 ± 10.9 years, 82.2% males. Negative correlation (r2=-0.147; p= 0.0002) between MRCI and EQ-5D was found. Relationship between the comorbidity pattern and quality of life, was also observed. Regarding MRCI, Anxiety/Depression, Pain/discomfort and Self-Care were the dimensions with the worst assessment. CONCLUSIONS: A new multidimensional revised care plan for PLWHIV focussed on optimising overall patient care, not limited to viral load goal achievement alone but also in their pharmacotherapeutic complexity and quality of life is needed.

A Comprehensive Prospective Study of the Costs Associated With Evaluation of ß-Lactam Allergy.

BACKGROUND AND OBJECTIVE: Being labeled as allergic to penicillin (unverified ß-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. Objective: We aimed to evaluate the real costs of evaluating ß-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected ß-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were €28 176.70, with a mean (SD) cost of €95.19 (37.20). Direct nonhealth costs reached €6551.73, that is, €22.13 (40.44) per patient. Indirect health costs reached €20 769.20, with a mean of €70.17 (127.40). In summary, the total cost was €55 497.63, that is, a cost per patient of €187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of ß-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics.

Prevalence of prescription of the Top-10 drug classes to avoid in elderly people living with HIV in a real practice cohort.

OBJECTIVE: We assessed the prevalence of potentially inappropriate prescriptions (PIP) among older (≥ 65 years) people living with HIV (PLWHIV). Additionally, the secondary objective was to analyse the relationship between pharmacotherapeutic complexity and compliance with STOPP-Beers criteria associated with Top-10 drugs classes to avoid (TOP-10-A) of European AIDS Clinical Society (EACS) guidelines. METHODS: This was a cross-sectional observational single-centre study. PLWHIV aged 65 years-old or over on ART attending at hospital pharmacy outpatient service from December-2019 to March-2020 were included. Patients were classified by age group: 65-69, 70-75 and more than 75 years. Moreover, was analysed the relationship between pharmacotherapeutic complexity and compliance with STOPP-Beers Criteria associated with Top-10-A drugs. RESULTS: A total of 19 individuals were included. Overall polypharmacy was observed in 16 PLWHIV (84.2%). A PIP included Top-10-A was identified in 9 (47.4%) PLWHIV. Benzodiazepines were the most prevalent group of prescribed drugs in 6 patients (30.0%). Complex patients were observed in 57.9% (MRCI index value greater than 11.25). Similarly, the sum of criteria STOPP-Beers was higher in older patients. Student's t test showed the existence of a statistically significant relationship between pharmacotherapeutic complexity and sum of STOPP-Beers Criteria (p <0.05) in elderly PLWHIV. CONCLUSIONS: Prescription of PIPs is highly prevalent in older PLWHIV. Consistent with data, presence of PIPs were associated a presence of higher pharmacotherapeutic complexity and sum of STOPP-Beers Criteria. The basis for a new revised care plan for PLWHIV focussed on optimising overall patient care pharmacotherapeutic complexity and its possible consequences.

Experiencia del paciente en tratamiento con inhibidores de PCSK9 con el modelo de atención farmacéutica Capacidad-Motivación-Oportunidad (CMO) / Patient experience in treatment with PCSK9 inhibitors based on the pharmaceutical care model Capacity-Motivation-Oportunity (CMO)

Objetivo: Evaluar la experiencia del paciente crónico tratado con inhibidores de PCSK9 de una cohorte de práctica clínica real según el modelo de atención farmacéutica (AF) basado en el concepto Capacidad-Motivación-Oportunidad (CMO). Métodos: Estudio unicéntrico, transversal, que incluyó pacientes adultos con hipercolesterolemia en tratamiento con cualquier inhibidor PCSK9 que llevaran, al menos, 6 meses de tratamiento y acudieron a seguimiento en consultas externas de AF durante el mes de abril de 2019. Se recogieron variables demográficas (sexo y edad), clínicas (niveles de colesterol total y c-LDL), farmacoterapéuticas (número de medicamentos concomitantes prescritos y tipo de anti-PCSK9) y relacionadas con AF (nivel de estratificación según Modelo de Selección y Atención Farmacéutica de Pacientes Crónicos de la Sociedad Española de Farmacia Hospitalaria). La valoración de la experiencia del paciente se realizó mediante el cuestionario IEXPAC vía telefónica, por un farmacéutico diferente al que realizaba el seguimiento. Resultados: Se incluyeron 28 pacientes (67,9% varones), con una mediana de edad de 63 años (RIQ: 54-72). Los datos farmacacoterapéuticos muestran una población polimedicada. El 80,7% estaba en tratamiento con alirocumab y el 19,3% evolocumab. Mediante el concepto de Capacidad se estratificó la población en estudio resultando un 57,2% de nivel 3, mientras que un 21,4% pertenecían a los niveles 1 y 2 respectivamente. El cuestionario IEXPAC nos arrojó una puntuación global elevada (6,9±1,6). Conclusiones: La evaluación de la atención farmacéutica basada en la metodología CMO en pacientes crónicos en tratamiento con inhibidores PCSK9 cumple una alta expectativa en cada punto de interacción identificado. (AU)

Objective: To evaluate the experience of the chronic patient treated with PCSK9 inhibitors of a cohort of real clinical practice according to the pharmaceutical care model (AF) based on the concept Capacity-Motivation-Opportunity (CMO).Methods: One-way cross-sectional study that included adult patients with hypercholesterolemia in treatment with any PCSK9 inhibitor who took at least 6 months of treatment and who followed up in external AF consultations during the month of April 2019. Demographic variables (sex and age), clinics (levels of total cholesterol and LDL-c), pharmacotherapeutic (number of prescribed concomitant medications and type of anti-PCSK9) and related to AF (level of stratification according to the Chronic Patient’s Selection and Pharmaceutical Care Model Spanish Pharmacy Hospital). The assessment of the patient’s experience was carried out through the IEXPAC questionnaire via telephone, by a pharmacist different from the one who followed up.Results: 28 patients (67.9% male) were included, with a middle age of 63 (IQR: 54-72). Pharmaco-therapeutic data show a polymedicated population. 80.7% were treated with alirocumab and 19.3% evolocumab. Through the concept of Capacity, the study population was stratified resulting in 57.2% of level 3, while 21.4% belonged to levels 1 and 2 respectively. The IEXPAC questionnaire gave us a high overall score (6.9±1.6).Conclusions: The evaluation of pharmaceutical care based on the CMO methodology in chronic patients treated with PCSK9 inhibitors meets a high expectation level at each identified interaction point. (AU)

A Comprehensive Prospective Study of the Costs Associated With Evaluation of beta-Lactam Allergy

BACKGROUND: Being labeled as allergic to penicillin (unverified beta-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. OBJECTIVE: We aimed to evaluate the real costs of evaluating beta-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected beta-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to beta-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were (Euro)28 176.70, with a mean (SD) cost of (Euro)95.19 (37.20). Direct nonhealth costs reached (Euro)6551.73, that is, (Euro)22.13 (40.44) per patient. Indirect health costs reached (Euro)20 769.20, with a mean of (Euro)70.17 (127.40). In summary, the total cost was (Euro)55 497.63, that is, a cost per patient of (Euro)187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of beta-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics

INTRODUCCIÓN: Un diagnóstico no verificado de alergia a la penicilina o a los betalactámicos (BL) conlleva que los pacientes reciban antibióticos de amplio espectro, que pueden ser más tóxicos, menos efectivos, y/o de mayor coste. OBJETIVO: Evaluar los costes reales de un estudio de alergia a los betalactámicos. MÉTODOS: Se diseñó un estudio observacional prospectivo en condiciones de práctica clínica habitual en el que se evaluaron todos los pacientes adultos que consultaron por sospecha de alergia a BL durante un año. Los costes directos e indirectos se recogieron sistemáticamente. Los costes directos sanitarios se calcularon teniendo en cuenta el número de visitas y todas las pruebas diagnósticas realizadas; en los costes directos no sanitarios se consideraron el número de visitas y los kilómetros desde el domicilio hasta el Servicio de Alergología; en los costes indirectos se evaluó el absentismo. RESULTADOS: Se evaluaron 296 pacientes remitidos desde el 1 de junio de 2017 hasta el 31 de mayo de 2018. Los costes directos totales sanitarios fueron 28.176,70 (Euro): coste medio (desviación estándar, DS) de 95,19 (Euro) (37,20). Los costes directos no sanitarios alcanzaron, 6.551,73: coste medio 22,13 (40,44). Los costes indirectos fueron 20.769,20 (Euro): coste medio (DS) 70,17 (127,40). En resumen, la cantidad total fue de 55.497,63 (Euro), lo que supone un coste medio de 187,49 (Euro) (148,14). CONCLUSIONES: Considerando todos los costes posibles, la evaluación de la alergia a betalactámicos no es cara y puede ahorrar gastos futuros debido a una utilización innecesaria de antibióticos más caros y menos efectivos

Recomendaciones Rama de Dermatología Pediátrica, Sociedad Chilena de Pediatría. Pandemia COVID-19 / Recommendations Pediatric Dermatology Branch, Chilean Society of Pediatrics. COVID-19 pandemic

Resumen: La actual pandemia por Covid-19 (SARS-CoV-2) corresponde a una zoonosis viral altamente con tagiosa que ha requerido extremar las medidas de protección personal con el fin de disminuir la transmisión del virus, tanto en ambientes hospitalarios como fuera de ellos, siendo necesaria la adopción de estrictos métodos de aislamiento tanto de contacto como aerosoles. Esto ha reque rido la adopción de múltiples equipos de protección personal, dentro de los que se encuentran la protección ocular, mascarillas, escudo de protección facial, gorros, guantes, etcétera. Lo anterior ha generado un aumento en el daño de la barrera cutánea y, por lo tanto, la aparición de diversas dermatosis dentro de las que se encuentran dermatitis de contacto irritativa o alérgica, reaccio nes acneiformes, agravamiento de dermatosis previas, entre otras, cobrando así vital importancia el cuidado y restablecimiento de la barrera cutánea con medidas esenciales como aplicación de productos humectantes o emolientes y el correcto uso de los equipos en mención. No obstante, no solo se generan dermatosis derivadas del uso de equipos de protección personal, sino que tam bién, dentro del amplio espectro de manifestaciones dermatológicas que puede generar la enfer medad por Covid-19 propiamente tal, incluyendo compromiso cutáneo, piloso (efluvio telógeno) o ungueal (onicomadesis). Por otro lado pero no motivo de este artículo, el compromiso cutáneo puede corresponder a la primera expresión clínica de la enfermedad o ser un predictor de su evolu ción. Dentro de lo anterior encontramos la urticaria aguda, exantema maculo-papular, exantema varicela-like, erupción petequial, perniosis-like y lívedo reticularis como las principales formas de afección cutánea hasta el momento.

Abstract: The current Covid-19 pandemic (SARS-CoV-2) corresponds to a highly contagious viral zoonosis that has required to extreme measures in order to decrease the transmission of the virus in hospi tal settings and outside of them, requiring adoption of strict isolation methods, both contact and aerosols. This has required the adoption of multiple personal protective equipment, including eye protection, masks, face shield, medical caps, gloves, etc. The aforementioned has generated an in crease in the damage of the skin barrier, and therefore, the appearance of various dermatoses, among which are irritative o alergic contact dermatitis, acneiform reactions, aggravation of previous der matoses, and others, thus becoming vital protection and restoration of the skin barrier with mea sures such as the application of moisturizing or emollient products and the correct use of personal protection equipment. However, not only dermatoses are generated derived from the use of perso nal protection equipment, but also, within the wide spectrum of dermatological manifestations that Covid-19 disease itself can generate, including cutaneous, hairy involvement (telogen effluvium) or nail (onychomadesis). Cutaneous involvement may correspond to the first clinical expression of the disease or be a predictor of its evolution. Among the above we find acute urticaria, maculo-papular rash, chickenpox-like rash, petechial rash, perniosis-like, and livedo reticularis as the main forms of skin condition to date.

Preliminary analysis of a shortened picture version of the Free and Cued Selective Reminding Test. / Evaluación preliminar de una versión pictórica y abreviada del Free and Cued Selective Reminding Test.

INTRODUCTION: A picture version of the Free and Cued Selective Reminding Test (FCSRT) would assist in the assessment of memory function in patients with low levels of schooling. A shortened version would improve the test's applicability. OBJECTIVES: To analyse the diagnostic usefulness of a shortened picture version of the FCSRT for distinguishing patients with amnestic mild cognitive impairment (aMCI) from controls, without excluding participants with a low level of schooling. METHODS: Phase I study of a diagnostic evaluation (convenience sampling; pre-test prevalence 50%). A blinded researcher independently administered the FCSRT to 30 patients with aMCI and 30 controls matched for age, sex, level of schooling and literacy, using images and omitting the usual 30-minute delayed recall item. Three variables were recorded: free recall, total recall, and cue efficiency. Diagnostic accuracy was calculated using receiver operating characteristic curves and the area under the curve. The Youden index was used to identify optimal cut-off points. RESULTS: Of all participants, 41.7% had not completed primary education. There were no differences between groups as regards sociodemographic variables. Area under the curve was excellent for free recall (0.99), total recall (0.95), and cue efficiecy (0.93). The optimal cut-off points were 21/22, 43/44, and < 0.77, respectively. CONCLUSIONS: This preliminary analysis shows that a shortened picture version of the FCSRT may be useful and applicable for the diagnosis of aMCI without excluding individuals with a low level of schooling.

Impact of carbohydrate restriction in the context of obesity on prostate tumor growth in the Hi-Myc transgenic mouse model.

BACKGROUND: Previously, we showed that carbohydrate restriction with calorie restriction slowed tumor growth in xenograft mouse prostate cancer models. Herein, we examined the impact of carbohydrate restriction without calorie restriction on tumor development within the context of diet-induced obesity in the Hi-Myc transgenic mouse model of prostate cancer. METHODS: Mice were randomized at 5 weeks of age to ad libitum western diet (WD; 40% fat, 42% carbohydrate; n=39) or ad libitum no carbohydrate ketogenic diet (NCKD; 82% fat, 1% carbohydrate; n=44). At age 3 or 6 months, mice were killed, prostates weighed and prostate histology, proliferation, apoptosis and macrophage infiltration evaluated by hematoxylin and eosin, Ki67, TUNEL and F4/80 staining, respectively. Body composition was assessed by DEXA, serum cytokines measured using multiplex, and Akt/mTOR signaling assessed by Western. RESULTS: Caloric intake was higher in the NCKD group, resulting in elevated body weights at 6 months of age, relative to the WD group (45 g vs 38g; P=0.008). Despite elevated body weights, serum monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-1α levels were lower in NCKD versus WD mice (P=0.046 and P=0.118, respectively), and macrophage infiltration was reduced in prostates of NCKD versus WD mice (P=0.028). Relative Akt phosphorylation and phospho-S6 ribosomal protein levels were reduced in prostates of NCKD versus WD mice. However, while mice randomized to NCKD had smaller prostates after adjustment for body weight at 3 and 6 months (P=0.004 and P=0.002, respectively), NCKD mice had higher rates of adenocarcinoma at 6 months compared to WD mice (100 vs 80%, P=0.04). CONCLUSIONS: Despite higher caloric intake and elevated body weights, carbohydrate restriction lowered serum MCP-1 levels, reduced prostate macrophage infiltration, reduced prostate weight, but failed to slow adenocarcinoma development. Together, these data suggest that although carbohydrate restriction within the context of obesity may reduce obesity-associated systemic inflammation and perhaps slow tumor growth, it is not sufficient to counteract obesity-associated tumor development.

Performance in real life of the European Network on Drug Allergy algorithm in immediate reactions to beta-lactam antibiotics.

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta-lactam (BL) allergy. We evaluated its performance in real life. During 1994-2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re-evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present.

Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy?

BACKGROUND: Early and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. METHODS: The clinical profile of five patients with a predominantly 'non-visual' posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). RESULTS: PCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. CONCLUSIONS: Our sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent 'non-visual' posterior dysfunction should be potentially considered in clinical and research contexts.

Dermoscopy and direct immunofluorescence findings of elastosis perforans serpiginosa.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS.

Improving the performance of dairy cattle with a xylanase-rich exogenous enzyme preparation.

The objective of this experiment was to examine effects of adding 2 exogenous fibrolytic enzymes (EFE) to the total mixed ration (TMR) on the performance of lactating dairy cows (experiment 1) and the kinetics of ruminal degradation of the diet (experiment 2). Twelve EFE had been screened in a series of in vitro assays that identified the most potent EFE and their optimal doses for increasing the digestibility of bermudagrass. In experiment 1, 66 Holstein cows (21±5 d in milk) were grouped by previous milk production and parity (45 multiparous and 21 primiparous) and assigned randomly to 1 of the following 3 treatments: (1) control (CON, untreated), (2) Xylanase Plus [2A, 1mL/kg of TMR dry matter (DM); Dyadic International, Jupiter, FL], and (3) a 75:25 (vol/vol) mixture of Cellulase Plus and Xylanase Plus EFE (3A, 3.4mL/kg of TMR DM; Dyadic International). The EFE were sprayed twice daily onto a TMR (10% bermudagrass silage, 35% corn silage, 5% alfalfa-orchardgrass hay mixture, and 50% concentrates; DM basis) and fed for a 14-d training and covariate period and a 70-d measurement period. Experiment 2 aimed to examine the in situ DM ruminal degradability and ruminal fermentation measurements of the diets fed in experiment 1. Three ruminally fistulated lactating Holstein cows were assigned to the diets. The experiment had a 3×3 Latin square design with 23-d periods. In experiment 1, application of 2A increased intakes (kg/d) of DM (23.5 vs. 22.6), organic matter (21.9 vs. 20.9), and crude protein (3.9 vs. 3.7) and tended to increase yields (kg/d) of fat-corrected milk (41.8 vs. 40.7) and milk fat (1.48 vs. 1.44). In particular, 2A increased milk yield (kg/d) during wk 3 (41.2 vs. 39.8, tendency), 6 (41.9 vs. 40.1), and 7 (42.1 vs. 40.4), whereas 3A increased milk yield (kg/d) during wk 6 (41.5 vs. 40.1, tendency), 8 (41.8 vs. 40.0), and 9 (40.9 vs. 39.5, tendency). In experiment 2, EFE treatment did not affect ruminal DM degradation kinetics or ruminal pH, ammonia-N, and volatile fatty acid concentration. Application of 2A to the bermudagrass-based TMR increased DM intake and milk production, implying that this EFE could be used to increase the performance of lactating dairy cows fed diets containing up to 10% bermudagrass.