Challenging diagnosis of Plasmodium ovale malaria in a Colombian traveler: the importance of including P. ovale wallikeri in molecular screening.

This study reports a challenging diagnosis of Plasmodium ovale malaria in a Colombian citizen returning from Cameroon. Initial microscopy screenings conducted at two private hospitals yielded conflicting results, with the first showing negative smears and the second diagnosing P. vivax. Subsequent microscopy examinations at two government laboratories identified P. ovale, although the routine species-specific PCR strategy was negative. PCR confirmation was finally obtained when P. ovale wallikeri primers were used. Although P. ovale is not frequently found in Colombia, there is a clear need to include both P. ovale curtisi and P. ovale wallikeri in the molecular diagnostic strategy. Such need stems primarily from their extended latency period, which affects travelers, the increasing number of African migrants, and the importance of accurately mapping the distribution of Plasmodium species in Colombia.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Mediterranean Diet and its Effects on Silent Brain Infarcts in a Cohort of Patients With Atrial Fibrillation.

Background and Aims: The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients. Methods and Results: Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF. Conclusion: Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF.

Fitobezoar disuelto químicamente con coca-cola / Chemically dissolved phytobezoar with coca-cola

Los bezoares han estado presentes en la historia de la medicina desde sus inicios, si bien su incidencia es baja y suelen detectarse de manera incidental, es importante tener opciones menos invasivas para su tratamiento debido a que la endoscopia digestiva alta (EDA) no está siempre disponible en todos los centros y, además, muchas veces no logra ser resolutiva debido al tamaño y/o composición del bezoar. En este reporte se presenta el caso de una paciente que, en el contexto de un posible síndrome de CREST, presentó un fitobezoar que fue disuelto con Coca-Cola®, un elemento ampliamente disponible alrededor del mundo, por lo que podría incluso llegar a considerarse como primera línea dentro del manejo no invasivo.

Bezoars have been present in the history of medicine since its inception, although their incidence is low and they are usually detected incidentally, it is important to have less invasive options for their treatment because upper digestive endoscopy (EDA) is not always available in all centers and, moreover, often fails to resolve due to the size and/or composition of the bezoar. This report presents the case of a patient who, in the context of a possible CREST syndrome, presented a phytobezoar that was dissolved with Coca-Cola®, an element widely available around the world, for which reason it could even be considered as the first line of non-invasive management.

Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)'s 2013-2017 sample collection. METHODS: A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10®Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance (AMR), and AGROSAVIA. RESULTS: Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI > 99.9%). CONCLUSIONS: The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of sequence types (STs), MGE, and resistance and virulence genes.

Diet Quality, Food Groups and Nutrients Associated with the Gut Microbiota in a Nonwestern Population.

Diet plays an important role in shaping gut microbiota. However, much remains to be learned regarding this association. We analyzed dietary intake and gut microbiota in a community-dwelling cohort of 441 Colombians. Diet quality, intake of food groups and nutrient consumption were paired with microbial diversity and composition using linear regressions, Procrustes analyses and a random-forest machine-learning algorithm. Analyses were adjusted for potential confounders, including the five cities from where the participants originated, sex (male, female), age group (18-40 and 41-62 years), BMI (lean, overweight, obese) and socioeconomic status. Microbial diversity was higher in individuals with increased intake of nutrients obtained from plant-food sources, whereas the intake of food groups and nutrients correlated with microbiota structure. Random-forest regressions identified microbial communities associated with different diet components. Two remarkable results confirmed previous expectations regarding the link between diet and microbiota: communities composed of short-chain fatty acid (SCFA) producers were more prevalent in the microbiota of individuals consuming diets rich in fiber and plant-food sources, such as fruits, vegetables and beans. In contrast, an inflammatory microbiota composed of bile-tolerant and putrefactive microorganisms along with opportunistic pathogens thrived in individuals consuming diets enriched in animal-food sources and of low quality, i.e., enriched in ultraprocessed foods and depleted in dietary fiber. This study expands our understanding of the relationship between dietary intake and gut microbiota. We provide evidence that diet is strongly associated with the gut microbial community and highlight generalizable connections between them.

Adaptation of a mobile phone health survey for risk factors for noncommunicable diseases in Colombia: a qualitative study.

BACKGROUND: Data collection on noncommunicable disease (NCD) behavioral risk factors has traditionally been carried out through face-to-face surveys. However, its high costs and logistical difficulties can lead to lack of timely statistics for planning, particularly in low and middle-income countries. Mobile phone surveys (MPS) have the potential to fill these gaps. OBJECTIVE: This study explores perceptions, feasibility and strategies to increase the acceptability and response rate of health surveys administered through MPS using interactive voice response in Colombia. METHOD: A sequential multimodal exploratory design was used. We conducted key informant interviews (KII) with stakeholders from government and academia; focus group discussions (FGDs) and user-group tests (UGTs) with young adults and elderly people living in rural and urban settings (men and women). The KII and FGDs explored perceptions of using mobile phones for NCD surveys. In the UGTs, participants were administered an IVR survey, and they provided feedback on its usability and potential improvement. RESULTS: Between February and November 2017, we conducted 7 KII, 6 FGDs (n = 54) and 4 UGTs (n = 34). Most participants consider MPS is a novel way to explore risk factors in NCDs. They also recognize challenges for their implementation including security issues, technological literacy and telecommunications coverage, especially in rural areas. It was recommended to promote the survey using mass media before its deployment and stressing its objectives, responsible institution and data privacy safeguards. The preferences in the survey administration relate to factors such as skills in the use of mobile phones, age, availability of time and educational level. The participants recommend questionnaires shorter than 10 minutes. CONCLUSIONS: The possibility of obtaining data through MPS at a population level represents an opportunity to improve the availability of risk-factor data. Steps towards increasing the acceptability and overcoming technological and methodological challenges need to be taken.

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI.

BACKGROUND: Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI. OBJECTIVES: The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS2 and CHA2DS2VASc score. METHODS: Patients with a history of AF based on medical records who scored 0-1 in the CHADS2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms. RESULTS: 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA2DS2VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07-13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15-8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33-7.63). CONCLUSIONS: LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS2 and in the low-risk population according to CHA2DS2VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.

New variants in Spanish Niemann-Pick type c disease patients.

Niemann-Pick type C (NPC) disease is a rare inherited disease, with progressive neurodegeneration as the main symptom. It is a lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes, leading to a lysosomal cholesterol trafficking impairment. Disease indicators are the clinical suspicion and biomarker levels. However, a genetic study is mandatory for the diagnosis, which is complicated due to the different variants with unknown significance. The aim of this work was to identify the variants responsible for NPC in our pediatric population. Twenty-two samples from non-related infants believed to have NPC disease were analyzed during the last 3 years. Surrogate biomarkers of the disease were evaluated whenever possible. Sanger sequencing for both genes is reported for all samples. Complementary genetic studies were performed when necessary. NPC disease was confirmed in 31.8% of subjects due to homozygous or compound heterozygous genetic variants in NPC1. The following four novel variants were identified: a gross deletion variant composed of the gene promoter and the first exon, NM_000271.3:c.385delT, NM_000271.3:c.1553+1342_1655-291del, and NM_000271.3:c.1757delA. None had functional activity and all resulted in important structural changes in the protein.

Implicaciones anestésicas de las distrofias musculares / Anesthetic implications of muscular dystrophies

Abstract Introduction: Muscular dystrophies are a group of genetic diseases characterized by the compromised synthesis or regeneration of the muscle contractile proteins. Although they belong to the same group of diseases, they have different characteristics in their clinical presentation and in their genetic origin. These diseases are classified as orphan as they have a low incidence among the general population, but represent a huge anesthetic challenge, particularly among the pediatric population. Objective: To describe the main clinical aspects of muscular dystrophies, their etiology, anesthetic implications, and the major complications that may occur during the perioperative management. Methodology: A review article is discussed based on a systematic search of the literature to produce a descriptive review. The main source of information is case reports obtained from databases as PubMed, Google Scholar, and websites specialized in rare diseases, to describe the main anesthetic implications of muscular dystrophies. Results: A total of 65 references were identified by the authors in accordance with the relevance of the topic for the final review. Conclusion: Muscular dystrophies are a heterogeneous group of diseases that share a common etiology due to direct injury of the muscle fiber with a progressive and systemic compromise. Each type of muscular dystrophy is different in terms of its clinical presentation, genetic origin, and anesthetic risks which are mainly cardiovascular complications due to malignant arrhythmias, acute rhabdomyolysis triggered by drugs used in anesthesia, and perioperative respiratory failure.

Resumen Introducción: Las distrofias musculares son un grupo de enfermedades genéticas que se caracterizan por compromiso en la síntesis o regeneración de las proteínas contráctiles del musculo. Aunque pertenecen al mismo grupo de enfermedades tienen características muy diferentes en su presentación clínica y en su origen genético. Estas enfermedades se clasifican como huérfanas debido a que tienen una incidencia muy baja en la población general, pero representan un enorme reto anestésico, especialmente en la población pediátrica. Objetivo: Describir los principales aspectos clínicos de las distrofias musculares, su etiología, implicaciones anestésicas y principales complicaciones que pueden ocurrir durante el perioperatorio. Metodología: Se presenta un artículo de revisión basado en una búsqueda sistemática de la literatura para una revisión descriptiva, donde la principal fuente de información son los reportes de caso obtenidos en las bases de datos de pubmed, google académico y páginas web especializadas en enfermedades raras, con el propósito de describir las principales implicaciones anestésicas de este grupo de enfermedades. Resultados: Se obtuvo un total de 65 referencias bibliográficas las cuales fueron seleccionadas por los autores de acuerdo con la relevancia del tema para la revisión final. Conclusión: Las distrofias musculares son un grupo heterogéneo de enfermedades que comparten una etiología común que es la lesión directa en la fibra muscular con un compromiso sistémico progresivo. Se diferencian en su presentación clínica, origen genético y riesgos anestésicos que son principalmente complicaciones cardiovasculares por arritmias malignas, rabdomiolisis aguda desencadenada por fármacos utilizados en la anestesia y falla respiratoria perioperatoria.

Yield of atrial fibrillation detection with Textile Wearable Holter from the acute phase of stroke: Pilot study of Crypto-AF registry.

BACKGROUND: We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry. METHODS: We monitored cryptogenic stroke patients from stroke onset (<3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days). RESULTS: The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days). CONCLUSIONS: 28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF.

Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases.

Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection.

Relationship between vitamin intake and total antioxidant capacity in elderly adults / Relación entre ingesta de vitaminas y capacidad atnioxidante total en adultos mayores / Relação entre a ingestão de vitaminas e a capacidade antioxidante total em idosos

Abstract The consumption of foods high in natural antioxidants, like fruits and vegetables, is associated with a lower risk of oxidative stress-related diseases. The aim of this study was to establish the relationship between the plasma antioxidant capacity in adults over fifty and their intake of vitamin A, C, and E. We evaluated 118 24-hour recalls of intake of foods. The intake of vitamin A, C, and E was quantified using food composition tables. We quantified plasma phenols using the Folin-Ciocalteu method. The antioxidant capacity was determined using the Trolox Equivalent Antioxidant Capacity (TEAC) and Oxygen Radical Absorption Capacity (ORAC) methods. Correlation analyses were performed between the studied variables and a positive correlation was found in most cases. However, none of the correlations was statistically significant. In all cases p-value was >0.05. The quantification of nutrient intake is not an adequate predictor of plasma antioxidant capacity in individuals over fifty.

Resumen El consumo de alimentos ricos en antioxidantes naturales, como frutas y vegetales, está asociado con un menor riesgo de enfermedades relacionadas con el estrés oxidativo. El objetivo de este trabajo fue establecer la relación entre capacidad antioxidante del plasma en adultos mayores de cincuenta años y su consumo de vitamina A, C y E. Se evaluaron 118 recordatorios de ingesta de alimentos de 24 horas. La ingesta de vitamina A, C y E fue cuantificada usando tablas de composición de alimentos. Se cuantificaron los fenoles en plasma usando el método Folin-Ciocalteu, y la capacidad antioxidante se determinó con base en los métodos de Capacidad Antioxidante Equivalente a Trolox (TEAC) y de Capacidad de Absorción de Radicales de Oxígeno (ORAC). Se realizaron análisis de correlación entre las variables estudiadas y se encontró una correlación positiva en la mayoría de los casos. Sin embargo, ninguna de las correlaciones resultó estadísticamente significativa. En todos los casos, p > 0.05. La cuantificación de ingesta de nutrientes no es un predictor adecuado de la capacidad antioxidante del plasma en adultos mayores de 50 años.

Resumo O consumo de alimentos ricos em antioxidantes naturais, como frutas e vegetáis, é associado a um baixo risco de doenças relacionadas ao estresse oxidativo. O objetivo do trabalho foi determinar a relação entre a capacidade antioxidante plasmática em adultos acima de cinquenta anos e sua ingestão de vitamina A, C e E. Foram avaliados 118 lembretes de consumo de alimentos de 24 horas. A ingestão de vitamina A, C e E foi quantificada usando tabelas de composição de alimentos. Foram quantificados fenóis plasmáticos usando método Folin-Ciocalteu baseado na base de dados de um estúdio prévio e obtivemos a capacidade antioxidante utilizando os métodos de Capacidade Antioxidante Equivalente de Trolox (TEAC) e Capacidade de Absorção de Radical Oxigênio (ORAC). Análises de correlação foram realizadas para cada variável estudada e uma correlação positiva foi obtida na maioria dos casos. Entretanto, nenhuma das relações mostrou resultados estatisticamente significativos. Em todos os casos, o valor dep > 0,05. A quantificação da ingestão de nutrientes não é um preditor adequado da capacidade antioxidante plasmática em indivíduos acima de cinquenta anos.

Perfil clínico y parasitológico de la malaria por Plasmodium falciparum y Plasmodium vivax no complicada en Córdoba, Colombia / Clinical and parasitological profiles of patients with non-complicated Plasmodium falciparum and Plasmodium vivax malaria in northwestern Colombia

Antecedentes. En Colombia existen pocos estudios que buscan encontrar diferencias clínicas y parasitológicas en la malaria causada por Plasmodium falciparum y Plasmodium vivax. Objetivo. Describir el perfil clínico y parasitológico de las malarias por Plasmodium falciparum y Plasmodium vivax no complicadas en Tierralta, Córdoba, Colombia. Materiales y métodos. Se evaluaron pacientes con paludismo no complicado por Plasmodium falciparum y Plasmodium vivax según los protocolos estandarizados por la Organización Panamericana de la Salud y se recolectó información clínica y parasitológica. De igual forma, se utilizó análisis multivariado por correspondencias múltiples para describir diferentes perfiles de pacientes con paludismo no complicado por estas dos especies antes de recibir tratamiento. Resultados. Se evaluaron 112 pacientes con edad entre 6 y 64 años, 59 (52.7%) con Plasmodium falciparum y 53 (47.3%) con Plasmodium vivax. Los síntomas más frecuentes fueron fiebre en 111 pacientes (99.1%; IC 95%: 81.5-100), sudoración en 105 (93.8%; IC 95%: 76.7-100) y dolor osteomuscular en 105 (93.8%; IC 95%: 76.7-100). Se presentaron con mayor frecuencia, y con diferencia significativa, en las infecciones por Plasmodium falciparum: diarrea en 18 pacientes (30.5%; IC 95%: 18.1-48.2); decaimiento en 49 (83%; IC 95%: 61.4-109.8); palidez palmar en 39 (66.1%; IC 95%: 47-90.4) y sequedad de mucosas en 12 (20.3%; IC 95%: 10.5-35.5). El escalofrío se presentó con mayor frecuencia en Plasmodium vivax (98.1%; IC 95%: 73.4-128.1). El análisis multivariado agrupó las variables en cuatro perfiles distintos de presentaciones clínicas así: 1) síntomas clínicos y su relación con el recuento parasitario, 2) características clínicas en relación con la edad y sexo, 3) antecedentes de malaria en relación con características demográficas y clínicas y 4) especie del parásito en relación con antecedentes, clínica y variables demográficas. Conclusión. Se identificaron algunas diferencias clínicas entre los enfermos con Plasmodium vivax y los enfermos con Plasmodium falciparum, y las variables estudiadas se agruparon en cuatro perfiles que permiten una variedad de interpretaciones.

Background. There are few studies in Colombia that have aimed at finding clinical and parasitological differences between Plasmodium falciparum and Plasmodium vivax malaria. Objective. To describe the clinical and parasitological profile of non-complicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Tierralta, Cordoba, Colombia. Materials and Methods. Patients with non-complicated malaria caused by Plasmodium falciparum and Plasmodium vivax were evaluated according to standardized protocols recommended by the Pan American Health Organization. Both clinical and parasitological information was collected. A multiple correspondence multivariate analysis was used to describe the different profiles of patients suffering non-complicated malaria caused by these two species before the administration of the required treatment. Results. One hundred and twelve patients aged 6 to 64 were evaluated, 59 (52.7%) suffering Plasmodium falciparum malaria and 53 (47.3%), Plasmodium vivax malaria. The most frequent symptoms were fever in 111 (99.1%; 95% CI: 81.5- 100), sweating in 105 (93.8%; 95% CI: 76.7-100) and musculoskeletal pain in 105 (93.8%; IC 95%: 76.7-100). Regarding the Plasmodium falciparum infections there was a higher frequency, with significant difference, in the following clinical manifestations: diarrhea: 18 patients (30.5%; 95%: 18.1-48.2); asthenia: 49 patients (83%; 95% CI: 61.4-109.8); palmar pallor: 39 patients (66.1%; 95% CI: 47-90.4); mucosal dryness: 12 patients (20.3%; 95%CI: 10.5-35.5). The chills appeared with higher frequency in Plasmodium vivax malaria (98.1%; 95%CI: 73.4-128.1). The multivariate analysis grouped the variables into four different profiles of clinical presentations: Clinical symptoms and their relation to the parasite count; clinical characteristics in relation to age and sex; history of malaria regarding demographic and clinical characteristics; and parasite species in relation to historic, clinical and demographic variables. Conclusions. Some clinical differences between patients with Plasmodium vivax and patients with Plasmodium falciparum were identified and the studied variables were grouped into four profiles which allow for a variety of interpretations.

Liver transplantation for classical maple syrup urine disease: long-term follow-up.

OBJECTIVES: The aim of the study was to evaluate indications, results, and clinical and neurological evolution in children who have undergone liver transplantation for classical maple syrup urine disease (MSUD). METHODS: Descriptive study of liver transplantation for MSUD between 1991 and 2012. Eight patients were transplanted. RESULTS: Indications for transplant were poor metabolic control expressed as significant psychomotor disabilities (4 had psychomotor delays, 5 had spasticity, and 5 had epilepsy) and poor quality of life (mean number of acute metabolic decompensations and mean number of total hospitalizations before transplantation 5 and 12, respectively). Four required nasogastric tube, with a maximum 4 g/day protein-restricted diet in all of them. Seven sustained significant alterations in brain magnetic resonance imaging. Mean leucine and alloisoleucine levels were 608 (standard deviation [SD] 516) and 218 µmol/L (SD 216), respectively. All of the patients received transplants with deceased-donor livers, with ages between 1.5 and 2.5 years (mean 1.78 years). Mean posttransplantation follow-up period was 12.2 years (range 5-21 years). Final patient and graft survival was 87.5% and 75%, respectively. Following transplantation, none required hospitalization in the last 3 years nor did any have new acute metabolic decompensations following a normal diet. Five followed normal schooling, 2 had motor disabilities, and 2 had convulsive crises. Brain magnetic resonance imaging was taken in 4 patients, showing neuroimage improvement in 3 of them. Mean leucine levels were <350 µmol/L from the immediate posttransplantation period (mean 225 µmol/L, SD 78), with a maximum alloisoleucine level of 20 µmol/L. CONCLUSIONS: Liver transplantation is an effective treatment for classical MSUD that arrests brain damage, although it does not reverse the process.

Recurrence of bile salt export pump deficiency after liver transplantation.

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.

Efficacy and safety of valganciclovir in liver-transplanted children infected with Epstein-Barr virus.

Epstein-Barr virus (EBV) infection after liver transplantation (LT) is associated with increased risk of posttransplant lymphoproliferative disorder (PTLD). Lowering immunosuppression is the current method to prevent PTLD in LT children with a high viral load. The aim of this study was to assess the efficacy and safety of valganciclovir (VGCV) in children with EBV infection after LT. Forty-seven children showing detectable EBV-DNA (72% asymptomatic) were treated with VGCV (520 mg/sqm twice daily) with no immunosuppression decrease (except in 4 cases). VGCV treatment started 17 months (median) after the onset of EBV infection. A 30-day treatment applied to 26 patients led to undetectable EBV-DNA in 11/32 courses (34.3%), with 82% relapsing. A long VGCV treatment (median: 8 months) achieved undetectable EBV-DNA in 20/42 (47.6%), 60% of whom maintained response off therapy. There were no new PTLD cases. Symptoms worsened in 1 (2.1%) in whom PTLD was suspected but not confirmed in liver and jejunum biopsies. Factors associated with achievement of undetectable EBV-DNA were a longer time from LT and a lower rate of intervening infections in comparison with nonresponders. The safety profile for VGCV was excellent. Graft rejection occurred in 6%. In conclusion, in 47 LT children with a sustained increased EBV load treated with VGCV and unchanged immunosuppression, PTLD was suspected in 1 child (2.1%). A viral load decrease could be achieved as EBV-DNA was undetectable in 47% of patients under prolonged treatment.

Efficacy and safety of peginterferon-alpha2b and ribavirin combination therapy in children with chronic hepatitis C infection.

BACKGROUND: Interferon (IFN)-alpha2b plus ribavirin is approved for treatment of hepatitis C in children; however, little is known about efficacy and tolerability of pegylated IFN (PEG-IFN)-alpha2b in this population. The objective of this study was to test the efficacy and safety of PEG-IFN-alpha2b plus ribavirin in children with chronic hepatitis C. METHODS: Thirty children 3-16 years of age who had detectable hepatitis C virus (HCV) RNA for >or=3 years after exposure and elevated alanine aminotransferase values received PEG-IFN-alpha2b 1.0 microg/kg/wk plus ribavirin 15 mg/kg/d for 24 weeks (genotype 2/3) or 48 weeks (genotype 1/4). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) at week 24 of follow-up. RESULTS: SVR was achieved in 50% of patients (3/3 genotype 3; 12/27 genotype 1/4). At week 12, 52% of patients were HCV RNA negative and 72% had a >2 log10 decrease in viral load, compared with baseline; 87% and 71% of these patients, respectively, attained an SVR. Therapy was discontinued in 3 patients as a result of adverse events. No patient required ribavirin dose reduction; PEG-IFN-alpha2b dose was reduced in 23% of patients to manage neutropenia. CONCLUSIONS: Combination therapy with PEG-IFN-alpha2b and ribavirin treatment was effective in children with chronic hepatitis C. Virologic status at week 12 identified future responders and nonresponders. PEG-IFN-alpha2b and ribavirin were reasonably well tolerated, with no unexpected or permanent adverse effects. Further studies are needed to identify the optimum treatment regimen for this patient population.

Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1.

Farnesoid X receptor (FXR) is a transcription factor that controls bile acid homeostasis. The phenotype of Fxr null mice is characterized by hypercholanaemia, impaired secretion of bile acids and failure to thrive. Human disorders with these characteristics include FIC1 disease (caused by mutations in ATP8B1, which encodes a putative aminophospholipid translocase, FIC1, whose function in bile handling is unknown) and bile salt export pump (BSEP) disease (caused by mutation in ABCB11, which encodes BSEP, the primary canalicular bile salt export pump). We investigated the possibility of hepatic down-regulation of FXR in FIC1 disease and BSEP disease. Three siblings with this phenotype, born to consanguine parents, were initially studied. The children were demonstrated to be compound heterozygotes for missense and nonsense mutations in ATP8B1. Expression of specific genes in liver was analysed, comparing one of these siblings with a child homozygous for missense mutation in ABCB11, as well as with a child having idiopathic cholestatic liver disease, a child with extrahepatic biliary atresia and a normal organ donor. The expression of two main FXR isoforms was specifically decreased in the liver of the FIC1 disease patient. A consistent and concomitant reduction in messenger RNA levels of FXR targets, such as BSEP and small heterodimer partner, was also found. Gene-profiling experiments identified 163 transcripts whose expression changed significantly in FIC1-disease liver. Of note was that several genes involved in synthesis, conjugation and transport of bile acids were down-regulated. A cluster of genes involved in lipid metabolism was also differentially expressed. Our findings suggest that hepatic down-regulation of FXR contributes to the severe cholestasis of FIC1 disease.

Comportamiento de pacientes con maltrato infantil durante la consulta odontológica / Maltreated child patient's behavior during the clinical dental treatment

En el presente estudio de casos y controles se observaron las caracterísitcas del comportamiento de pacientes con síndrome del niño maltratado durante procedimientos no invasivos, y se compararon con las de niños sin el síndrome. Los sujetos del estudio, seleccionados intencionalmente, fueron niños entre 5 y 12 años, 48 con cualquier tipo de maltrato y 50 sin SNM. se observaron las características del comportamiento en los procedimientos de adapatación al consultorio, control de placa bacteriana, instrucción y motivación en higiene oral, profilaxis y flúor.