Malnutrition, Functional Decline, and Institutionalization in Older Adults after Hospital Discharge Following Community-Acquired Pneumonia.

BACKGROUND AND AIMS: Community-acquired pneumonia (CAP) is a major threat to older adults, but mid-term implications are poorly described. The aim was to analyze functional decline, institutionalization, malnutrition, and risk factors after hospital admission for CAP. METHODS: This prospective observational study included patients over 65 years discharged after CAP between May 2019 and July 2021. We performed a comprehensive geriatric assessment and a general nutritional assessment 30-60 days after CAP. This included the MNA and blood test with trace elements and vitamins. The main outcomes were functional decline, institutionalization, and malnutrition. Multivariate logistic regression was used for the analyses. RESULTS: In total, 144 patients of 77.15 ± 7.91 years, 55.6% male, and 9% previously institutionalized were analyzed. At hospital admission, the Charlson Comorbidity Index (CCI) was 1.5 ± 1.6, the Pneumonia Severity Index was 98.1 ± 25.9, and the previous Barthel Index (BI) was 93.06 ± 17.13. Hospital stay was 9.72 ± 7.88 days. After 44.6 ± 14.4 days, 48.6% patients showed functional decline and 19.4% were institutionalized. Age (OR 1.17; CI 95% 1.09-1.26), previous institutionalization (29.1; 3.7-224.7), BI (1.09; 1.05-1.14), CCI (1.5; 1.1-2.1), and length of stay (1.1, 1.02-1.18) were independently associated with functional decline. The only predictors of new institutionalization were previous BI (0.96; 0.93-0.99) and length of stay (1.06; 1.00-1.13). The MNA indicated malnutrition in 28% of the community-dwelling patients and 67.9% of those institutionalized, with risk of malnutrition being 45.7% and 9.5%, respectively, after an average of 44.6 days of CAP diagnosis. The predictors of malnutrition were previous institutionalization (10.62; 2.20-51.21), BI (0.95; 0.92-0.98), and length of stay (1.12; 1.04-1.20). Micronutrient deficiencies were mainly zinc (61.8%), vitamin D (54.5%), and vitamin C (45.1%). An MNA score < 17 points or hypoalbuminemia showed good specificity to identify these deficiencies. CONCLUSIONS: After CAP admission, functional decline, institutionalization, and malnutrition rates were high. Longer hospital stay was a common risk factor for all outcomes. The presence of hypoalbuminemia or an MNA < 17 in older patients should prompt suspicion of deficiencies in micronutrients, such as vitamin D, C, and zinc.

Epidemiology of Fractures in Children Younger Than 12 Months.

OBJECTIVES: The aim of this study is to determine the prevalence and characteristics of fractures in young infants attended at the pediatric emergency department (PED). METHODS: This is a retrospective study for 2 years (2011-2012) of children younger than 12 months attended with a fracture at the PED. Age, sex, site and type of fracture, mechanism of injury, time interval before seeking medical attention, and management were analyzed. RESULTS: One hundred one patients were included. They represented 0.3% (95% confidence interval, 0.2%-0.4%) of all children younger than 12 months attended at the PED. The median age was 7.7 months (interquartile range, 5.2-10.1 months); 58 (57.4%) were boys. The most common fracture was skull fracture (58, 57.4%), mostly parietal, followed by long bone fractures (27, 26.7%); transverse and torus fractures were the most common types, located at the diaphysis and distal metaphysis, respectively. The principal mechanism reported was falling (83, 82.2%) mainly from furniture. Fifty-one patients (50.1%) were attended in the first 6 hours after injury. Sixty-five patients (64.4%) were admitted at the hospital and the other 9 (8.9%) were controlled in outpatient visits. One of them was injured because of negligence and another was diagnosed with osteoporosis. CONCLUSIONS: Fractures in young infants are uncommon at the PED, the skull fracture being the most common. Pediatricians should alert caretakers of the risks in normal development to prevent these injuries. Fractures caused by child abuse should always be discarded.

[Predictors of drug-resistant pathogens in community-onset pneumonia: Are factors considered in health-care-associated pneumonia useful in the emergency department?] / Predictores de patógenos resistentes en las neumonías procedentes de la comunidad: ¿es útil en urgencias el concepto de neumonía asociada a cuidados sanitarios?

OBJECTIVES: To analyze factors related to drug-resistant pathogens (DRPs) in community-onset pneumonia (COP) and whether previously suggested criteria are useful in our emergency-department. MATERIAL AND METHODS: Prospective 1-year study of adults coming to the emergency department for COP. We assessed the usefulness of criteria used in health-care-associated pneumonia (HCAP), as well the Shorr index, the Barthel index, and clinical suspicion of resistant pathogens. Data were analyzed by multiple logistic regression and the area under the receiver operating characteristic curve (AUC). RESULTS: We included 139 patients with a mean (SD) age of 75.9 (15.3) years; 63.3% were men. Forty-nine COP patients (35.2%) were at risk for DRP-caused pneumonia according to HCAP criteria; 43 (30.9%) according to the Shorr index, and 56 (40.3%) according to the Aliberti index. A score of less than 60 derived from the Barthel index was recorded for 25 patients (18%). Clinical suspicion of a DRP was recorded for 11 (7.9%). A DRP was isolated in 5 patients (3.6%) (3, Pseudomonas aeruginosa; 2, methicillin-resistant Staphylococcus aureus). Multiple logistic regression analysis identified 2 predictors of DRP-caused COP: hospital admission within the last 90 days (odds ratio [OR], 8.92; 95% CI, 1.92-41.45) and initial arterial blood oxygen saturation (OR, 0.85; 95% CI, 0.74-0.98). The AUC was 0.91 (95% CI, 0.85-0.98). The model identified 22 patients (16.8%) at risk for DRP-caused pneumonia. The positive and negative predictive values were 20% and 99.1%, respectively, for the model 90-day period (vs 8.7% and 98.9%, respectively, for criteria used in HCAP). CONCLUSION: Hospitalization within the 90-day period before a COP emergency and arterial blood oxygen saturation were good predictors of DRP in our setting. Criteria of DRP in HCAP, on the other hand, had lower ability to identify patients at risk in COP.

OBJETIVO: Analizar en las neumonías de la comunidad diagnosticados en nuestro centro los predictores de etiología por patógenos resistentes (PR) y evaluar la utilidad de distintos criterios de riesgo de PR previamente sugeridos. METODO: Se estudiaron prospectivamente durante 1 año los pacientes adultos procedentes de la comunidad atendidos en el servicio de urgencias (SU) por neumonía. Se evaluaron los criterios definitorios de neumonía asociada al cuidado sanitario (NACS), así como los índices de Shorr, Aliberti y Barthel y el juicio clínico de PR. Se realizó regresión logística múltiple y se calculó el área bajo la curva receptor-operador (ABC-ROC). RESULTADOS: Se incluyeron 139 pacientes con una edad media de 75 (DE: 15,3) años, el 63,3% varones. Tenían riesgo de PR según los criterios de NACS 49 (35,2%), según el índice de Shorr 43 (30,9%) y según índice de Aliberti 56 (40,3%). Se encontró un I. Barthel < 60 en 25 enfermos (18%) y juicio clínico de PR en 11 (7,9%). Se aisló PR en el 3,6% (3 Pseudomonas aeruginosa y 2 Staphylococcus aureus meticilin resistentes). En el análisis multivariado fueron predictores de PR el haber ingresado en los 90 días previos, con una odds ratio (OR) de 8,92 [intervalo de confianza (IC) 95%: 1,92-41,45], y la saturación inicial de oxígeno, con una OR de 0,85 [IC 95%: 0,74-0,98] con ABC-ROC de 0,91 (IC 95%: 0,85-0,98). Nuestro modelo identificó 22 pacientes (16,8%) con riesgo de PR, con valor predictivo positivo y negativo del 20% y 99,1%, respectivamente, frente a un 8,7% y 98,9%, respectivamente para NACS. CONCLUSIONES: En las neumonías de nuestro centro el antecedente de ingreso en los 90 días previos junto con la saturación de oxígeno fueron buenos predictores de PR, mientras que los criterios de NACS tuvieron menor capacidad de discriminación.

Predictores de patógenos resistentes en las neumonías procedentes de la comunidad: ¿es útil en urgencias el concepto de neumonía asociada a cuidados sanitarios? / Predictors of drug-resistant pathogens in community-onset pneumonia: Are factors considered in health-care-associated pneumonia useful in the emergency department?

Objetivos. Analizar en las neumonías de la comunidad diagnosticados en nuestro centro los predictores de etiología por patógenos resistentes (PR) y evaluar la utilidad de distintos criterios de riesgo de PR previamente sugeridos. Método. Se estudiaron prospectivamente durante 1 año los pacientes adultos procedentes de la comunidad atendidos en el servicio de urgencias (SU) por neumonía. Se evaluaron los criterios definitorios de neumonía asociada al cuidado sanitario (NACS), así como los índices de Shorr, Aliberti y Barthel y el juicio clínico de PR. Se realizó regresión logística múltiple y se calculó el área bajo la curva receptor-operador (ABC-ROC). Resultados. Se incluyeron 139 pacientes con una edad media de 75 (DE: 15,3) años, el 63,3% varones. Tenían riesgo de PR según los criterios de NACS 49 (35,2%), según el índice de Shorr 43 (30,9%) y según índice de Aliberti 56 (40,3%). Se encontró un I. Barthel < 60 en 25 enfermos (18%) y juicio clínico de PR en 11 (7,9%). Se aisló PR en el 3,6% (3 Pseudomonas aeruginosa y 2 Staphylococcus aureus meticilin resistentes). En el análisis multivariado fueron predictores de PR el haber ingresado en los 90 días previos, con una odds ratio (OR) de 8,92 [intervalo de confianza (IC) 95%: 1,92-41,45], y la saturación inicial de oxígeno, con una OR de 0,85 [IC 95%: 0,74-0,98] con ABC-ROC de 0,91 (IC 95%: 0,85-0,98). Nuestro modelo identificó 22 pacientes (16,8%) con riesgo de PR, con valor predictivo positivo y negativo del 20% y 99,1%, respectivamente, frente a un 8,7% y 98,9%, respectivamente para NACS. Conclusiones. En las neumonías de nuestro centro el antecedente de ingreso en los 90 días previos junto con la saturación de oxígeno fueron buenos predictores de PR, mientras que los criterios de NACS tuvieron menor capacidad de discriminación (AU)

Objectives. To analyze factors related to drug-resistant pathogens (DRPs) in community-onset pneumonia (COP) and whether previously suggested criteria are useful in our emergency-department. Methods. Prospective 1-year study of adults coming to the emergency department for COP. We assessed the usefulness of criteria used in health-care-associated pneumonia (HCAP), as well the Shorr index, the Barthel index, and clinical suspicion of resistant pathogens. Data were analyzed by multiple logistic regression and the area under the receiver operating characteristic curve (AUC). Results. We included 139 patients with a mean (SD) age of 75.9 (15.3) years; 63.3% were men. Forty-nine COP patients (35.2%) were at risk for DRP-caused pneumonia according to HCAP criteria; 43 (30.9%) according to the Shorr index, and 56 (40.3%) according to the Aliberti index. A score of less than 60 derived from the Barthel index was recorded for 25 patients (18%). Clinical suspicion of a DRP was recorded for 11 (7.9%). A DRP was isolated in 5 patients (3.6%) (3, Pseudomonas aeruginosa; 2, methicillin-resistant Staphylococcus aureus). Multiple logistic regression analysis identified 2 predictors of DRP-caused COP: hospital admission within the last 90 days (odds ratio [OR], 8.92; 95% CI, 1.92-41.45) and initial arterial blood oxygen saturation (OR, 0.85; 95% CI, 0.74-0.98). The AUC was 0.91 (95% CI, 0.85-0.98). The model identified 22 patients (16.8%) at risk for DRP-caused pneumonia. The positive and negative predictive values were 20% and 99.1%, respectively, for the model 90-day period (vs 8.7% and 98.9%, respectively, for criteria used in HCAP). Conclusions. Hospitalization within the 90-day period before a COP emergency and arterial blood oxygen saturation were good predictors of DRP in our setting. Criteria of DRP in HCAP, on the other hand, had lower ability to identify patients at risk in COP (AU)

Interaction of the LILRB1 inhibitory receptor with HLA class Ia dimers.

Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) has been reported to interact with a wide spectrum of HLA class I (HLA-I) molecules, albeit with different affinities determined by allelic polymorphisms and conformational features. HLA-G dimerization and the presence of intracellular Cys residues in HLA-B7 have been shown to be critical for their recognition by LILRB1. We hypothesized that dimerization of classical HLA class Ia molecules, previously detected in exosomes, might enhance their interaction with LILRB1. A soluble LILRB1-Fc fusion protein and a sensitive cellular reporter system expressing a LILRB1-ζ chimera were employed to assess receptor interaction with different HLA class Ia molecules transfected in the human lymphoblastoid 721.221 cell line. Under these conditions, intracellular Cys residues and HLA-I dimerization appeared associated with increased LILRB1 recognition. On the other hand, a marginal interaction of LILRB1 with primary monocytic cells, irrespective of their high HLA-I expression, was enhanced by type I interferon (IFN). This effect appeared disproportionate to the cytokine-induced increase of surface HLA-I expression and was accompanied by detection of HLA class Ia dimers. Altogether, the results support that a regulated assembly of these noncanonical HLA-I conformers during the immune response may enhance the avidity of their interaction with LILRB1.

Is pertussis in infants a potential cause of retinal haemorrhages?

AIM: To determine the prevalence of retinal haemorrhages in infants with pertussis infection with the purpose of clarifying the differential diagnosis of the cases of abusive head trauma. METHODS: Prospective study of children aged 15 days to 2 years admitted to our hospital with a diagnosis of pertussis over a period of 4 years (May 2004-May 2008). All children underwent one detailed ophthalmological examination within 72 h of admission. If retinal haemorrhages were detected, further investigation was undertaken to rule out systemic disorder or maltreatment. RESULTS: 35 children with pertussis infection were examined. None was found to have retinal haemorrhages. Therefore, applying Wilson's method, the data suggest with 95% confidence that the true effect estimate for retinal haemorrhage occurring due to symptomatic pertussis infection requiring admission to hospital is no higher than 9.9%. CONCLUSIONS: Pertussis infections are unlikely to cause retinal haemorrhages in children under 2 years of age.

Type II interleukin-1 receptor expression is reduced in monocytes/macrophages and atherosclerotic lesions.

Type II interleukin-1 receptor (IL-1R2) is a non-signaling decoy receptor that negatively regulates the activity of interleukin-1 (IL-1), a pro-inflammatory cytokine involved in atherogenesis. In this article we assessed the relevance of IL-1R2 in atherosclerosis by studying its expression in monocytes from hyperlipidemic patients, in THP-1 macrophages exposed to lipoproteins and in human atherosclerotic lesions. Our results showed that the mRNA and protein expression of IL-1R2 was reduced in monocytes from patients with familial combined hyperlipidemia (-30%, p<0.05). THP-1 macrophages incubated with increasing concentrations of acetylated low density (ac-LDL) and very low density (VLDL) lipoproteins also exhibit a decrease in IL-1R2 mRNA and protein levels. Pre-incubation with agents that block intracellular accumulation of lipids prevents the decrease in IL-1R2 mRNA caused by lipoproteins. Lipoproteins also prevented the increase in IL-1R1 and IL-1R2 caused by a 4-h stimulation with LPS and reduced protein expression of total and phosphorylated IL-1 receptor-associated kinase-1. Finally, IL-1R2 expression in human atherosclerotic vessels was markedly lower than in non-atherosclerotic arteries (-80%, p<0.0005). Overall, our results suggest that under atherogenic conditions, there is a decrease in IL-1R2 expression in monocytes/macrophages and in the vascular wall that may facilitate IL-1 signaling.

Tissue factor pathway inhibitor 2 is induced by thrombin in human macrophages.

Tissue factor pathway inhibitor 2 (TFPI2) is a serine protease inhibitor critical for the regulation of extracellular matrix remodeling and atherosclerotic plaque stability. Previously, we demonstrated that TFPI2 expression is increased in monocytes from patients with familial combined hyperlipidemia (FCH). To gain insight into the molecular mechanisms responsible for this upregulation, we examined TFPI2 expression in THP-1 macrophages exposed to lipoproteins and thrombin. Our results showed that TFPI2 expression was not affected by treatment with very low density lipoproteins (VLDL), but was induced by thrombin (10 U/ml) in THP-1 (1.9-fold increase, p<0.001) and human monocyte-derived macrophages (2.3-fold increase, p<0.005). The specificity of the inductive effect was demonstrated by preincubation with the thrombin inhibitors hirudin and PPACK, which ablated thrombin effects. TFPI2 induction was prevented by pre-incubation with MEK1/2 and JNK inhibitors, but not by the EGF receptor antagonist AG1478. In the presence of parthenolide, an inhibitor of NFκB, but not of SR-11302, a selective AP-1 inhibitor, thrombin-mediated TFPI2 induction was blunted. Our results also show that thrombin treatment increased ERK1/2, JNK and IκBα phosphorylation. Finally, we ruled out the possibility that TFPI2 induction by thrombin was mediated by COX-2, as preincubation with a selective COX-2 inhibitor did not prevent the inductive effect. In conclusion, thrombin induces TFPI2 expression by a mechanism involving ERK1/2 and JNK phosphorylation, leading finally to NFkB activation. In the context of atherosclerosis, thrombin-induced macrophage TFPI2 expression could represent a means of avoiding excessive activation of matrix metalloproteases at sites of inflammation.

Raquitisme, una malaltia del passat? / No disponible

No disponible

Retinal hemorrhages and apparent life-threatening events.

OBJECTIVE: To determine the prevalence of retinal hemorrhages in apparent life-threatening events (ALTEs) with the purpose of facilitating the differential diagnosis of the cases of nonaccidental head trauma. METHODS: Prospective study on children aged 15 days to 2 years admitted to our hospital with a diagnosis of an ALTE over a period of 2 years (May 2004-May 2006). All the children underwent detailed ophthalmologic examination within 72 hours of admission. If retinal hemorrhages were detected, further investigation was undertaken to rule out systemic disorder or maltreatment. RESULTS: One hundred eight children with an ALTE were examined. No patient was found to have retinal hemorrhages nor was any found to have experienced child abuse. Therefore, using the Hanley rule of 3, we can be confident to an upper limit of 95% that the chance of retinal hemorrhages occurring as a result of an ALTE alone is at the most 0.028. CONCLUSIONS: Apparent life-threatening events alone are unlikely to cause retinal hemorrhages in children younger than 2 years. Therefore, if retinal hemorrhages are detected, investigation into the possibility of nonaccidental injury is essential.

Minor head trauma and linear skull fracture in infants: cranial ultrasound or computed tomography?

OBJECTIVE: To determine the clinical evolution of children with skull fractures as a result of a minor head trauma from a witnessed accidental fall that have been studied by transfontanellar ultrasound (TFUS). METHODS: Observational study for 2 years (2004-2006) of children up to 1 year of age who suffered a skull fracture after minor head trauma and for whom a TFUS was carried out as the first neuroimaging test to rule out intracranial injuries. RESULTS: One hundred and twenty-three children were evaluated. The mean age was 5.7 months (SD 2.9) and the most common mechanism of injury was rolling off the bed. In seven (5.7%) patients, a computed tomography (CT) was eventually performed after TFUS; in two of these patients, this was because of the detection of possible intracranial alterations and in the others, it was because of a small fontanelle. Both patients with abnormal TFUS had a small epidural haematoma on the CT scan that did not need surgery. The clinical course for all patients was uneventful. CONCLUSION: TFUS is a valid and reliable alternative to CT for minor head trauma in infants with skull fractures. Its innocuousness and cost-effectiveness in comparison with CT makes it a good choice in this situation.

Ritonavir increases CD36, ABCA1 and CYP27 expression in THP-1 macrophages.

UNLABELLED: Ritonavir, a protease inhibitor used in combination antiretroviral therapy for HIV-1 infection, is associated with an increased risk of premature atherosclerosis. The aim of the present study was to assess the effects of ritonavir, in the absence of added lipoproteins, on the expression of genes that control cholesterol trafficking in human monocytes/macrophages. DESIGN: THP-1 cells were used to study the effects of ritonavir on the expression of CD36, ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1), scavenger receptor B class I (SR-BI), caveolin-1 and sterol 27-hydroxylase (CYP27). Exposure to ritonavir (2.5 mug/ml) increased CD36 protein (28%, P < 0.05) and mRNA (38%, P < 0.05) in differentiated THP-1 macrophages, but not in undifferentiated monocytes. This effect was not related to the increase in PPARgamma expression (51%, P < 0.05) caused by ritonavir. Ritonavir also reduced SR-BI protein levels (46%, P < 0.05) and increased CYP27 (43%, P < 0.05) and ABCA1 (49%, P < 0.05) mRNA expression. Liver X receptor alpha (LXRalpha) mRNA, protein and binding activity were also increased by ritonavir treatment. CONCLUSIONS: We propose that ritonavir induces ABCA1 expression in THP-1 macrophages through LXRalpha. The increase in ABCA1 and other cholesterol efflux mediators, such as CYP27, may compensate CD36 induction. Therefore, we suggest that the net effect of ritonavir on macrophages in the absence of lipoproteins is not clearly proatherogenic.

Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.

AIM: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH. METHODS: Fasting plasma for determination of lipid profiles, inflammatory molecules and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene-expression profiles were analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. RESULTS: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared with controls. Atorvastatin treatment modified the expression of 86 genes. Pathway analysis revealed the over-representation of the complement and coagulation cascades, the hematopoietic cell lineage and the arachidonic acid metabolism pathways. Changes in the expression of some genes, confirmed by real-time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen, tumor necrosis factor receptor superfamily, member 25, CD96 and lipoprotein lipase), may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. CONCLUSION: Our results show clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.

Estudio farmacogenómico mediante microarrays en monocitos de pacientes con hiperlipemia familiar combinada tratados con atorvastatina / Pharmacological study in monocytes of patients with familial combined hyperlipaemia treated with atorvastatin using microarrays

Introducción y objetivo. La hiperlipemia familiar combinada (HFC) es la hiperlipemia genética más común, y una causa frecuente de enfermedad cardiovascular prematura. Sin embargo, el origen genético de esta enfermedad todavía no se conoce totalmente. En el presente estudio, analizamos el perfil de expresión génica en monocitos de sangre periférica en un grupo de individuos control y en un grupo de pacientes con HFC antes y después del tratamiento con atorvastatina (ATV), con el objetivo de estudiar y profundizar en los mecanismos genéticos asociados a esta enfermedad, e identificar posibles dianas terapéuticas nuevas. Métodos y resultados. Se aislaron monocitos de sangre periférica de individuos control y de pacientes con HFC, del mismo sexo y edad, antes y después del tratamiento con ATV. El perfil de expresión génica se obtuvo usando los microarrays GeneChip Human Genome U133A de Affymetrix, y los cambios en la expresión de los genes seleccionados se validaron posteriormente con la técnica de retro-transcripción de la reacción en cadena de la polimerasa a tiempo real. Nuestros resultados mostraron cambios en la expresión de numerosos genes implicados en funciones clave del macrófago, especialmente en la respuesta inflamatoria (MNDA, IL1R2, ALCAM, LRIG1 y DR3), el control de la composición de la matriz extracelular (FN1, SDC2 y TFPI2) y el metabolismo lipídico (CD36). Conclusiones. Nuestros resultados indican que la HFC afecta de forma directa o indirecta al perfil de expresión génica en monocitos de sangre periférica. Los cambios en la expresión de algunos genes (MNDA, CD36, TFPI2, LRIG1 y DR3) podrían atribuirse al entorno proinflamatorio que rodea los monocitos en la HFC, que es parcialmente revertido por el tratamiento con ATV. Por otra parte, los cambios en la expresión génica que no revierten tras el tratamiento con ATV podrían relacionarse con anomalías metabólicas del tejido adiposo (valores bajos de adiponectina y elevación de ácidos grasos libres y triglicéridos) que no se corrigen con este tratamiento (AU)

Introduction and objective. The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used peripheral blood monocytes as a suitable target for differential gene expression assessment in FCH. Methods and results. Peripheral blood monocytes were isolated from male FCH patients basally and after atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Analysis of gene expression was performed using the GeneChip Human Genome U133A microarrays. Changes in the expression of selected genes were confirmed by real time RT-PCR. Our results showed the differential expression of genes involved in key macrophage functions, specially regarding the inflammatory response (MNDA, IL1R2, ALCAM, LRIG1 and DR3), extracellular matrix control (FN1, SDC2 and TFPI2) and lipid metabolism (CD36). Conclusions. Monocyte gene expression profiling can provide insight into the pathogenesis of FCH. The results suggest that alterations in the expression of some genes (MNDA, CD36, TFPI2, LRIG1 and DR3) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. However, metabolic dysfunction in adipose tissue may account for lower adiponectin and higher FFA and triglyceride plasma levels in FCH, which are not corrected by treatment. These abnormalites could also trigger changes in gene expression that atorvastatin cannot modify (AU)

Subdural haematomas and physical abuse in the first two years of life.

OBJECTIVE: To analyze our institution's work-up for patients with a diagnosis of subdural haematoma (SDH) in order to determine how many of them are secondary to child abuse, as well as to examine their final functional outcome. METHODS: Retrospective review of children under 2 years of age diagnosed as having SDH between 1995 and 2005. RESULTS: A total of 35 cases were identified. Fifteen patients that had underlying conditions that predispose them to bleed were excluded. Among the remaining 20 patients, seizures and head trauma were the main causes for consultation. All patients had a coagulation study and a head computed tomography carried out, 11 of these had a magnetic resonance imaging and 1 had a post-mortem examination. Bilateral SDHs in different stages of evolution was the most common pattern of intracranial haemorrhage. Fourteen infants had a skeletal survey, 4 had a bone scintigraphy and 19 had an ophthalmoscopic examination. Fractures were diagnosed in 7 patients and retinal haemorrhages in 11. The final diagnoses were: 10 shaken baby syndromes, 4 idiopathic SDH, 3 strokes, 2 coagulopathies and 1 accidental head injury. Upon follow-up, 1 patient had died and 9 had sustained permanent disabilities. CONCLUSIONS: Cases of infantile SDH are usually thoroughly investigated. In spite of this, sometimes it is not possible to determine the SDH aetiology. Nonetheless, shaken baby syndrome remains the most frequent cause of SDH in infants, and it carries a poor prognosis.

Ritonavir incrementa la expresión de CD36 y ABCA1 en macrófagos THP-1 / Ritonavir increases CD36 and ABCA1 expression in THP-1 macrophages

El ritonavir es uno de los inhibidores de las proteasas que se utilizan como parte del tratamiento antirretroviral de gran actividad (TARGA) para la infección por el virus de la inmunodeficiencia humana, y su uso se ha asociado a un aumento en el riesgo de aterosclerosis prematura. Se ha propuesto que el ritonavir favorece la formación de células espumosas, aunque los estudios previos realizados han mostrado efectos contradictorios de este fármaco sobre las concentraciones del receptor scavenger CD36 en monocitos y macrófagos. Nuestros resultados muestran que el tratamiento con ritonavir a concentraciones dentro del rango terapéutico produce un incremento en la expresión de proteína y ARNm de CD36 en macrófagos THP-1 diferenciados, pero no en monocitos de la misma línea celular. Estas diferencias se podrían deber a la activación de la proteincinasa C producida tras la diferenciación con el éster de forbol PMA y la consiguiente activación de proliferadores de peroxisomas g (PPARg). Este mecanismo también explicaría el incremento en la expresión de ABCA1 hallado en nuestro estudio, aunque no la reducción de las concentraciones de proteína SR-BI, que no parece ser un efecto de tipo transcripcional. Finalmente, la inducción de PPARg y CD36 causada por el ritonavir no se asocia a un incremento en las concentraciones de la forma madura de SREBP1 (AU)

Ritonavir, a protease inhibitor used in highly active antiretroviral therapy (HAART) for HIV-1 infection, is associated with an increased risk of premature atherosclerosis. It has been proposed that ritonavir facilitates foam cell formation from macrophages, but conflicting results on the effect of this drug on CD36 scavenger receptor expression in monocytes and macrophages have been published. Our results show that ritonavir exposure at concentrations within the therapeutic range cause an increase in CD36 protein and mRNA levels in differentiated THP-1 macrophages, but not in monocytes from the same cell line. Protein kinase C (PKC) activation by the differentiating agent PMA and subsequent peroxisome proliferator-activated receptor-g (PPARg) activation could account for these differences. This mechanism could also explain the increase in ABCA1 expression found in our study, but not the decrease in SR-BI protein, which does not seem to be a transcriptional effect. Finally, PPARg and CD36 up-regulation by ritonavir are not related to an increase in levels of mature SREBP1 (AU)

El monocito/macrófago como diana terapéutica en la aterosclerosis / Monocytes/macrophages as therapeutic targets in atherosclerosis

Monocitos y macrófagos son células que desempeñan un papel clave en todas las etapas del desarrollo de la aterosclerosis. Uno de los fenómenos iniciales en este proceso es la unión de monocitos circulantes al endotelio arterial mediante las moléculas de adhesión (MA), y la subsiguiente transmigración hacia la capa íntima bajo la influencia de quimiocinas como la proteína quimiotáctica de monocitos (MCP-1). En fases posteriores, los monocitos reclutados se diferencian a macrófagos, proceso que comporta el incremento de la expresión de receptores toll-like (TLR), implicados en la respuesta inmune innata, y receptores scavenger (SR). Los TLR activan la respuesta inflamatoria en los macrófagos, induciendo la expresión de citocinas como IL-6, IL-1b y factor de necrosis tumoral (TNF). Por otra parte, los SR (principalmente SR-A y CD36) captan lipoproteínas modificadas de forma no regulada por los valores intracelulares de esteroles. El colesterol que el macrófago ha captado a través de estos receptores es almacenado en forma de ésteres de colesterol tras su esterificación por la enzima acil-CoA:colesterol aciltransferasa (ACAT), conduciendo a la formación de células espumosas. Para mantener la homeostasis lipídica, el macrófago depende de la existencia de mecanismos de exportación de colesterol al espacio extracelular, incluyendo el transporte hacia las HDL maduras mediado por el receptor scavenger BI (SR-BI) y la transferencia de colesterol hacia la apolipoproteína AI a través del transportador ATP-binding cassette A1 (ABCA1). La modulación farmacológica de estas dianas (MA, quimiocinas, TLR, SR, ACAT y proteínas relacionadas con la exportación de colesterol), directa o indirectamente a través de factores de transcripción que controlan la expresión génica (receptor hepático X, factor nuclear kB), puede limitar el desarrollo de la aterosclerosis (AU)

Monocytes and macrophages play a key role in all stages of atherosclerosis development. One of the initial phenomena in this process is binding of circulating monocytes to the arterial endothelium through adhesion molecules (AM) and their subsequent transmigration toward the intimal layer under the influence of chemokines such as monocyte chemotactic protein-1 (MCP-1). In subsequent phases, the recruited monocytes differentiate into macrophages, a process that increases the expression of toll-like receptors (TLRs), which are implicated in innate immune response, and scavenger receptors (SRs). TLRs activate the inflammatory response in macrophages, inducing the expression of cytokines such as interleukin (IL)-6, IL-1b and tumor necrosis factor (TNF). SRs (mainly SR-A and CD36) are involved in the uptake of modified lipoproteins in a manner not regulated by intracellular sterol levels. The cholesterol taken up by macrophages through these receptors is stored in the form of cholesteryl esters after esterification by the enzyme acyl-CoA:cholesterol acyltransferase (ACAT), leading to the formation of foam cells. To maintain lipid homeostasis, macrophages depend on the existence of mechanisms of cholesterol export to the extracellular space, including transport to mature HDL mediated by the BI scavenger receptor (SR-BI) and transfer to apolipoprotein AI through the ATP-binding cassette transporter A1 (ABCA1). Pharmacological modulation of these targets (AM, cytokines, TLRs, SRs, ACAT and proteins related to cholesterol export) directly or indirectly through transcription factors controlling gene expression (liver X receptor, nuclear factor-kB) could limit the development of atherosclerosis

Úlceras genitales. Tres casos / Genital ulcers. A propos of three cases

consultan en nuestro Servicio de Urgencias por presentar lesiones ulcerosas en la zona vulvar. Se orientan clínicamente como lesiones de causa infecciosa, posiblemente herpética, y se recogen muestras para realizar la confirmación microbiológica. En dos casos se confirma la sospecha diagnóstica, siendo uno una primoinfección por virus herpes simple tipo 1 y el otro, una primoinfección por virus herpes simple tipo 2. El tercer caso se diagnostica de una infección por Streptococcus pyogenes. Se realiza tratamiento sintomático hasta la obtención de los resultados de la PCR para Herpes viridae y de los cultivos de las lesiones, y entonces se instaura el tratamiento etiológico adecuado. El caso de infección por virus herpes simple tipo 2 se remitió a la Unidad Funcional de Abuso al Menor de nuestro centro por sospecha de abuso sexual. Las úlceras genitales acostumbran a ser macroscópicamente muy similares, lo que implica que su diagnóstico etiológico sea difícil sólo con la observación de las lesiones. Las técnicas microbiológicas resultan imprescindibles, especialmente las de diagnóstico rápido como la PCR, para determinar el agente causal e instaurar el tratamiento correspondiente

We present the cases of three girls, aged 6 months, 4 and 5 years, who presented to our emergency department with vulvar ulcers. An infectious etiology was suspected and an infectious work-up was performed. In two cases, viral cultures and PCR showed Herpes simplex type 1 and type 2 primary infections, and in the third case, a streptococcus pyogenes infection was confirmed. Symptomatic treatment was initially given, followed by anti virals and antibiotics. The case of herpes simplex type 2 was referred to the Office for Childhood Protection due to the suspicion of sexual abuse. Genital ulcers are macroscopically very similar regardless of the etiology, which makes a clinical diagnosis difficult. Microbiological tools are very important, specially those that can yield rapid results such as PCR, in order to determine the infectious agent and implement the appropriate therapy