Bone marrow mesenchymal/fibroblastic stromal cells induce a distinctive EMT-like phenotype in AML cells.

The development of epithelial-to-mesenchymal transition (EMT) like features is emerging as a critical factor involved in the pathogenesis of acute myeloid leukaemia (AML). However, the extracellular signals and the signalling pathways in AML that may regulate EMT remain largely unstudied. We found that the bone marrow (BM) mesenchymal/fibroblastic cell line HS5 induces an EMT-like migratory phenotype in AML cells. AML cells underwent a strong increase of vimentin (VIM) levels that was not mirrored to the same extent by changes of expression of the other EMT core proteins SNAI1 and SNAI2. We validated these particular pattern of co-expression of core-EMT markers in AML cells by performing an in silico analysis using datasets of human tumours. Our data showed that in AML the expression levels of VIM does not completely correlate with the co-expression of core EMT markers observed in epithelial tumours. We also found that vs epithelial tumours, AML cells display a distinct patterns of co-expression of VIM and the actin binding and adhesion regulatory proteins that regulate F-actin dynamics and integrin-mediated adhesions involved in the invasive migration in cells undergoing EMT. We conclude that the BM stroma induces an EMT related pattern of migration in AML cells in a process involving a distinctive regulation of EMT markers and of regulators of cell adhesion and actin dynamics that should be further investigated. Understanding the tumour specific signalling pathways associated with the EMT process may contribute to the development of new tailored therapies for AML as well as in different types of cancers.

Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

OBJECTIVE: We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS: DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS: The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS: In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02431702.

Experiencia en el tratamiento de la enfermedad de Dupuytren con ondas de choque radiales: estudio de caso / Experience in the treatment of Dupuytren's disease with radial extracorporeal shockwave therapy: A case report

Introducción y objetivos La enfermedad de Dupuytren (ED) es un trastorno proliferativo benigno que afecta a la aponeurosis palmar y dedos en la mano. Los tratamientos propuestos son en su mayoría invasivos y presentan recurrencias. Se ha postulado la utilización de ondas de choque para el manejo de esta enfermedad dado su bajo costo, además de ser una técnica no invasiva. El objetivo de este trabajo es describir una experiencia terapéutica en el manejo de la ED utilizando ondas de choque radiales (OCr). Material y métod Mujer de 72 años, presenta tejido fibroso retráctil en la palma de ambas manos asociado al dedo meñique, manifestando dolor a la presión y limitación severa de la movilidad en extensión. Se evaluó la intensidad de dolor al reposo y al movimiento, umbral de dolor a la presión, movilidad, fuerza prensil, discapacidad y severidad de la ED. Se realizaron 6 sesiones de OCr distribuidas en 4 semanas, utilizando 2000 pulsos a 14Hz y 1,4bar, para luego seguir con 2000 pulsos a 6Hz y 3,4bar. Resultados: Se evidenciaron mínimas mejorías en todas las variables evaluadas. Estas no generaron una diferencia mínima clínicamente importante. Conclusión Basado en esta experiencia, las OCr no produjeron un cambio clínico relevante en el tratamiento de la ED en estadio avanzado. Es necesario profundizar en la eficacia de esta técnica considerando el tipo de ondas de choque que se utiliza, así como una estadificación variada que permita evidenciar los efectos según la severidad de la ED (AU)

Background and objectives Dupuytren's disease (DD) is a benign proliferative disorder that affects the palmar aponeurosis and fingers. Current treatments are mostly invasive and have recurrences. Extracorporeal shockwave therapy has been proposed for the management of this disease, given its low cost, in addition to being a non-invasive technique. The aim of this study is present a therapeutic experience in DD using radial extracorporeal shockwave therapy (rESWT). Material and method A 72-year-old woman presented in both hands a band of palmar fibrous tissue associated with the little finger, manifesting pain on pressure and severe limitation of extension. Pain intensity at rest and movement, pressure pain threshold, mobility, grip strength, disability, and severity of DD were evaluated. Six sessions of rESWT were performed distributed over 4 weeks using 2000 pulses at 14Hz and 1.4bar followed by 2000 pulses at 6Hz and 3.4bar. Results Minimal improvements were evidenced in all the variables evaluated. The effect of the intervention was not sufficient to generate a minimal clinically important difference. Conclusion Based on this experience, rESWT did not generate a relevant clinical change in the treatment of advanced-stage DD. It is necessary to inquire into the efficacy of this technique considering the type of extracorporeal shockwave used, as well as a varied staging that allows evidence the effects of radial shockwaves according to the severity of disease (AU)

Instrucciones con foco atencional durante el ejercicio terapéutico en personas con trastornos musculoesqueléticos. Una revisión de alcance / Attentional focus instructions for therapeutic exercise in people with musculoskeletal disorders. A scoping review

Las instrucciones con foco atencional son estrategias verbales que podrían maximizar los efectos del ejercicio. El objetivo de esta revisión fue explorar y sintetizar la evidencia sobre la incorporación de instrucciones con foco atencional al ejercicio terapéutico de personas con trastornos musculoesqueléticos. Se realizó una búsqueda en 11 bases de datos hasta octubre de 2020. De 4.227 estudios identificados en las búsquedas, 15 fueron incluidos. Los estudios presentaron deficiencia en la conceptualización y definición de instrucciones con foco atencional. La evidencia disponible indica que el foco externo es efectivo para mejorar el aprendizaje motor y la función. Sin embargo, limitaciones metodológicas, la heterogeneidad clínica, el reducido número de artículos incluidos y los nuevos estudios experimentales desafían las conclusiones de las revisiones sistemáticas disponibles a la fecha. Las instrucciones con foco atencional en los trastornos musculoesqueléticos es un campo emergente y requiere más investigación. Esta revisión es una guía para futuros estudios.(AU)

Attentional focus instructions are verbal strategies that could maximize the effects of exercise. The objective of this review was to explore and synthesize the available evidence on the incorporation of attentional focus instruction in the exercise of people with musculoskeletal disorders. A search of 11 databases was carried out until October 2020. Of 4,227 studies identified in the searches, 15 were included. The studies showed deficiencies in the conceptualization and definition of attentional focus instructions. The available evidence indicates that external focus is effective in improving motor learning and function. However, methodological limitations, clinical heterogeneity, the small number of articles included, and new experimental studies challenge the conclusions of the systematic reviews available to date. Attentional focus instructions in musculoskeletal disorders is an emerging field and requires further research. This review is a guide for future studies.(AU)

[Attentional focus instructions for therapeutic exercise in people with musculoskeletal disorders. A scoping review]. / Instrucciones con foco atencional durante el ejercicio terapéutico en personas con trastornos musculoesqueléticos. Una revisión de alcance.

Attentional focus instructions are verbal strategies that could maximize the effects of exercise. The objective of this review was to explore and synthesize the available evidence on the incorporation of attentional focus instruction in the exercise of people with musculoskeletal disorders. A search of 11 databases was carried out until October 2020. Of 4,227 studies identified in the searches, 15 were included. The studies showed deficiencies in the conceptualization and definition of attentional focus instructions. The available evidence indicates that external focus is effective in improving motor learning and function. However, methodological limitations, clinical heterogeneity, the small number of articles included, and new experimental studies challenge the conclusions of the systematic reviews available to date. Attentional focus instructions in musculoskeletal disorders is an emerging field and requires further research. This review is a guide for future studies.

Asociación entre la dependencia funcional, capacidad funcional y dolor, en personas mayores con artrosis severa de cadera / Association between functional dependence, functional capacity, and pain in older people with severe osteoarthritis of the hip

Antecedentes y objetivo: Determinar si existe asociación entre dependencia funcional, capacidad funcional e intensidad del dolor en personas mayores con artrosis de cadera. Materiales y métodos: Estudio transversal-analítico con reclutamiento consecutivo de 85 individuos. Se evaluó dependencia funcional (índice de Barthel), capacidad funcional (WOMAC) y dolor (escala numérica del dolor). Se determinaron diferencias en capacidad funcional y dolor, según la condición de dependencia funcional. Además, se analizó la correlación entre estas variables. Todos los análisis consideraron un nivel de significación de p<0,05. Resultados: Ochenta y cinco participantes (72,26±5,69 años de edad; 54,12% mujeres) fueron incluidos en el estudio. Los promedios para el índice de Barthel, WOMAC e intensidad del dolor fueron 94,00±9,35; 44,49±17,08 y 6,09±3,12 respectivamente. Del total de participantes 46 fueron clasificados como independientes. El análisis demostró que los participantes clasificados como dependientes presentaron un mayor puntaje en WOMAC-total (p=0,001), WOMAC-dolor (p=0,037), WOMAC-función (p<0,001) y dolor (p=0,010), con tamaños de efecto entre medio y grande. No se encontró diferencias en WOMAC-rigidez (p=0,184). Se encontró una correlación inversa, moderada y significativa entre los puntajes de WOMAC-total (p<0,001), WOMAC-dolor (p=0,007), WOMAC-función (p<0,001) e intensidad del dolor (p=0,002) con el puntaje de dependencia funcional de Barthel, pero no con WOMAC-rigidez (p=0,141). Conclusiones: Los individuos con artrosis de cadera avanzada dependientes funcionalmente tienen una capacidad funcional menor y una intensidad del dolor mayor que los clasificados como independientes. Esta información provee un insumo valioso para clínicos y para la planificación de estrategias de salud.

Background and aim: To determine the association between functional dependence, functional capacity, and pain intensity in older adults with hip osteoarthritis. Methods: Cross-sectional study with a consecutive sampling of 85 participants. Functional dependence (Barthel Index), functional capacity (WOMAC questionnaire), and pain (Numerical Rating Scale) were measured. Differences between functional capacity and pain, depending on functional dependence status were determined. Moreover, correlation analyses were performed between these outcomes. All analyses considered a significance level of p<.05. Results: 85 participants (72.26±5.69 years old; 54.12% women) were included. Mean values for Barthel Index, WOMAC, and pain intensity were 94.00±9.35; 44.49±17.08 and 6.09±3.12, respectively. Of the total participants, 46 were classified as independent. The analysis showed that participants classified as dependent exhibited a higher score in WOMAC-total (p=.001), WOMAC-pain (p=.037), WOMAC-function (p<.001), and pain intensity (p=.01), with medium to high effect sizes. No differences were seen in WOMAC-stiffness (p=.184). An inversed, moderate correlation between the Barthel Index and WOMAC-total (p<.001), WOMAC-pain (p=.007), WOMAC-function (p<.001) and pain intensity (p=.002) were seen, but not in WOMAC-stiffness (p = .141). Conclusion: Functionally dependent older adults with advanced hip osteoarthritis have lower functional capacity and higher pain intensity than those classified as functionally independent. This information provides a valuable insight for clinicians to plan future health strategies.

Axonal quantification of the white matter association fasciculi in cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus).

BACKGROUND: Cerebral white matter consists mainly of axons surrounded by myelin sheaths, which are grouped to form association, commissural, and projection fasciculi. The aim of our work was to quantify and compare under the microscope the axons of the white matter association fasciculi in the cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) indirectly by identification of their myelin sheaths. MATERIALS AND METHODS: The samples were taken from 30 cerebral hemispheres: 10 cow, 10 pig and 10 rabbit (15 right and 15 left). They were obtained following a protocol based on the Talairach-Tournoux coordinate system for human and primate brains. The slides were stained with Luxol Fast Blue, observed by optical microscopy, and photographed at 600×. Samples were also prepared for observation in scanning transmission electron microscopy with osmium tetroxide. The myelin sheaths/axons were counted with the ImageJ software. RESULTS: Statistically significant differences in the number of myelin sheaths per 410 µm² were found in the inferior and superior longitudinal fasciculi between the left and right hemispheres of cows, with predominance of the right hemisphere; and in the inferior occipitofrontal fasciculus of the rabbit with predominance of the left hemisphere. CONCLUSIONS: The use of animal models for experiments in the cerebral fasciculi, especially pig, could give us a greater understanding of the behaviour of demyelinating and neurodegenerative diseases in humans.

[Antimicrobials in neonatology. Part II: Recommendations for the dilution and administration of antimicrobials in the newborn]. / Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido.

Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

Antimicrobianos en neonatología. Parte II: Recomendaciones para la dilución y administración de antimicrobianos utilizados en el recién nacido / Antimicrobials in neonatology. Part II: Recommendations for the dilution and administration of antimicrobials in the newborn

Resumen Los antimicrobianos corresponden al grupo de medicamentos más utilizados en Unidades de Cuidados Intensivos Neonatales; no obstante, su uso ha sido asociado a constantes errores de medicación en la práctica clínica. Paradojalmente, aún no existe consenso en torno a la administración adecuada de estos medicamentos y existen importantes brechas de conocimiento en torno a los procesos de dosificación, administración y manipulación de antimicrobianos en esta población. Con el fin de mejorar el uso de antimicrobianos, disminuir errores y optimizar los resultados clínicos en el recién nacido, la presente revisión tiene por objetivo entregar recomendaciones y servir de guía para la correcta preparación de aquellos antimicrobianos de mayor relevancia en neonatología.

Abstract Antimicrobials are among the most commonly prescribed classes of medications in Neonatal Intensive Care Units; however, its use has been constantly associated with a number of medication errors in clinical practice. In contrast to this situation, there is no common agreement when it comes to determining the right dosing, administration, or handling of antibiotics in this population. In order to help improve the use of antibiotics, decrease the rate of medication errors and optimize clinical results in the newborn, this review aims to provide recommendations to support and guide the correct preparation of some of the most relevant antibiotics used in neonatal wards.

Prognostic value of molecular biomarkers in patients with metastatic colorectal cancer: a real-world study

Purpose Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. Methods We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan–Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. Results Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. Conclusions This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population (AU)

Prognostic value of molecular biomarkers in patients with metastatic colorectal cancer: a real-world study.

PURPOSE: Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. METHODS: We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan-Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. RESULTS: Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. CONCLUSIONS: This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population.

Effect of maternal nutrient restriction on expression of glucose transporters (SLC2A4 and SLC2A1) and insulin signaling in skeletal muscle of SGA and Non-SGA sheep fetuses.

Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.

Caracterización clínico-epidemiológica de las enterocolitis necrosantes neonatales de siete hospitales públicos

Resumen Introducción: Enterocolitis necrosante (ECN) representa una elevada mortalidad y morbilidad post-quirúrgica, gastrointestinal y del neuro-desarrollo. Existe limitada información en Chile. Objetivo: Describir el comportamiento clínico/epidemiológico de recién nacidos que cursaron con ECN. Pacientes y Métodos: Estudio multicéntrico descriptivo de pacientes con ECN de siete hospitales de Santiago, Chile, durante el 2016. Se realizó estadística descriptiva y análisis univariable/multivariable (software SPSS v22). Resultados: Se recolectaron 75 casos. Mediana de edad al diagnóstico fue 11 días, el promedio de edad gestacional 29 semanas y peso de nacimiento 1.285 g. La incidencia fue 2,6 por 1.000/recién nacidos vivos y letalidad de 18,6%, mayor en ≤ 750 g, ≤ 25 semanas y ECN quirúrgica. Hubo aislamiento microbiológico en 45,3% y se utilizaron 19 distintos esquemas antimicrobianos empíricos para el tratamiento de ECN. El análisis multivariable mostró tendencia a que la ECN fuese quirúrgica en usuarios de catéter umbilical arterial, PCR > 10 mg/L y aislamiento microbiológico, y hubo tendencia a fallecer en usuarios de catéter umbilical arterial. Discusión: Es el primer estudio multicéntrico que recopila información de datos locales. La incidencia fue similar a la descrita en la literatura médica, en cambio la letalidad fue algo menor. No existen consensos del tratamiento antimicrobiano a utilizar. Con estos resultados esperamos avanzar en mejorar el diagnóstico y unificar tratamientos antimicrobianos, para reducir cifras de morbimortalidad.

Abstract Background: Necrotizing enterocolitis (NEC) presents high mortality and postoperative, gastrointestinal and neurodevelopmental morbidity. There is limited information about NEC in Chile. Aim: To describe the clinical/epidemiological behavior of newborns who underwent NEC. Methods: Multicenter descriptive study of patients with NEC from seven hospitals of Santiago, Chile, during 2016. Descriptive statistics and univariate/multivariate analysis were performed (SPSS v22 software). Results: 75 cases were collected. Median days of life at diagnosis was 11, gestational age was 29 weeks, birth weight 1,114 g. The incidence was 2.6 per 1,000 live newborns and mortality was 18.6%, higher in ≤ 750 g, ≤ 25 weeks and surgical NEC. There was 45.3% microbiological isolation and 19 different empirical antibiotic schemes were used for the treatment of NEC. The multivariate analysis showed a higher risk of surgery in umbilical arterial catheter users, CRP > 10 mg/L and positive microbiological isolation. The highest risk of death was in umbilical arterial catheter users. Discussion: This ie the first multicenter study that collects local data information. The incidence was similar to that found in medical reports but with a lower mortality. There is no consensus of antibiotic treatment to use. With these results we hope to advance in improving the diagnosis and unify antimicrobial treatments, to reduce morbidity and mortality figures.

Antimicrobianos en neonatología. Parte I: Recomendaciones de dosificaciones basadas, en la más reciente evidencia en recién nacidos Comité Consultivo de Infecciones Neonatales, Sociedad Chilena de Infectología / Antibiotics in neonatology. Part I: Dosage recommendations based on the most recent evidence in newborns Advisory Committee on Neonatal Infections, Chilean Society of Infectious Diseases

Resumen Los antimicrobianos son los medicamentos más utilizados en los neonatos durante su primer mes de vida cuando se encuentran en unidades neonatales, principalmente por el alto riesgo que presentan de adquirir infecciones graves como la sepsis. La mayoría de estos antimicrobianos se utilizan con dosis extrapoladas en base a las recomendaciones en población adulta y niños mayores, a pesar de que la fisiopatología en los recién nacidos es absolutamente diferente. Lo anterior lleva a un mayor riesgo a que ocurran más efectos adversos los que pueden conducir a una mayor toxicidad y a fallas terapéuticas, entre otros. En la última década se han realizado mayores estudios farmacocinéticos de antimicrobianos en neonatos; esta reciente evidencia ha permitido nuevas recomendaciones de dosificación considerando el peso y la edad gestacional del recién nacido, entre otras variables, de acuerdo al antimicrobiano estudiado. En base a una mayor evidencia sobre el comportamiento farmacocinético de los antimicrobianos en neonatos, se ha elaborado este documento para así facilitar y promover su correcto uso en las unidades neonatales.

Abstract Antibiotics are the most widely used medications in neonates during their first month of life in neonatal units, mainly due to the high risk they present of acquiring serious infections such as sepsis. Most of these antibiotics are used with extrapolated doses based on the suggestions in the adult population and older children, despite the fact that the pathophysiology in newborns is absolutely different. This leads to a higher risk of more adverse effects occurring, which can lead to greater toxicity and therapeutic failures, among others. In the last decade more and more pharmacokinetic studies of antibiotics have been carried out in neonates, this recent evidence has led to new dosage recommendations taking into account the weight and gestational age of the newborn, among other variables, in agreement to the antibiotic studied. Therefore, based on the need to order and summarize the most up-to-date and most evidence-based information on antibiotics in neonates, this document was prepared to facilitate and promote its correct use in neonatal units.

Efectos del ejercicio de flexión cráneo-cervical y movilización manual vertebral en pacientes con cervicalgia crónica: serie de casos / Effects of cranio-cervical flexion and manual spinal mobilisation in patients with chronic neck pain: Case series

ANTECEDENTES: La cervicalgia crónica (CC) es una afección frecuente, siendo una de las principales causas de discapacidad. Dentro de los tratamientos fisioterapéuticos más utilizados se encuentran el ejercicio y la movilización manual vertebral (MMV). No obstante, la aplicación de MMV se basa en fundamentos artrocinemáticos y no en el propósito directo de favorecer la ejecución de un ejercicio específico. OBJETIVO: Describir el efecto de un programa de fisioterapia a corto y medio plazo basado en MMV destinada a favorecer el ejercicio de flexión cráneo-cervical (EFCC). Descripción de los casos: Se evaluaron la intensidad de dolor, el umbral de dolor a la presión, el rango de movimiento, el control neuromuscular y la discapacidad cervical en 12 mujeres con CC al inicio, al término y a 3 meses de finalizada la intervención. Intervención: Se ejecutó un programa de 10 sesiones de tratamiento basadas en EFCC y MMV. RESULTADOS: Todas las participantes experimentaron una mejoría clínicamente relevante de su condición a corto plazo, la que se mantuvo 3 meses postintervención. CONCLUSIÓN: El EFCC sumado a una técnica de MMV que busca potenciar la ejecución del ejercicio presentó resultados positivos en mujeres con CC a corto y medio plazo

BACKGROUND: Chronic neck pain is a frequent condition, considered one of the main causes of disability. Among the most used physiotherapeutic treatments are exercise and vertebral manual mobilisation (VMM). However, the application of VMM is based on arthrokinematic fundamentals and not on directly favouring the execution of a specific exercise. OBJECTIVE: to describe the effect of a short- and medium-term physiotherapy programme based on VMM aimed at promoting the exercise of cranio-cervical flexion (CCFE). Cases description: Pain intensity, pressure pain threshold, range of motion, neuromuscular control and cervical disability were evaluated in 12 women with chronic neck pain at the beginning, end and 3 months after the intervention. Intervention: A programme of 10 treatment sessions based on CCFE and VMM was executed. RESULTS: all participants experienced a clinically relevant improvement of their condition in the short term, which remained 3 months post-intervention. CONCLUSION: The CCFE added to a VMM, which seeks to enhance the execution of the exercise, presented positive results in women with chronic neck pain in the short and medium term

Myocardial Inflammatory Changes Before and After Antiretroviral Therapy Initiation in People With Advanced Human Immunodeficiency Virus Disease.

Because of the high frequency of late presentation of human immunodeficiency virus (HIV) disease in our population, we decided to explore the presence of myocarditis among people with HIV infection and advanced immunosuppression (less than 200 CD4+ cells/µL) and to describe the inflammatory changes observed after combined antiretroviral therapy initiation in an observational, longitudinal, prospective cohort. We performed both cardiovascular magnetic resonance imaging and doppler transthoracic echocardiogram.

[Empiric vancomycin dosing in neonates: relationship between initial dose and 24 h area under the curve/minimum inhibitory concentration ratio]. / Dosificación empírica de vancomicina en neonatos: relación entre recomendación de dosis iniciales y relación área bajo la curva en 24 h/concentración inhibitoria mínima.

BACKGROUND: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. AIM: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. METHODS: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. RESULTS: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. CONCLUSIONS: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

Dosificación empírica de vancomicina en neonatos: relación entre recomendación de dosis iniciales y relación área bajo la curva en 24 h/concentración inhibitoria mínima / Empiric vancomycin dosing in neonates: relationship between initial dose and 24 h area under the curve/minimum inhibitory concentration ratio

Resumen Introducción: Vancomicina es un antimicrobiano ampliamente utilizado para infecciones por Staphylococcus coagulasa negativa en neonatos; sin embargo, no existe claridad sobre la dosis empírica que asegure su eficacia terapéutica. Objetivo: Evaluar la relación entre las dosis iniciales de vancomicina utilizadas en una Unidad de Cuidado Intensivo Neonatal (UCIN) con la eventualidad de alcanzar el objetivo terapéutico de área bajo la curva sobre concentración inhibitoria mínima (ABC/CIM) mayor a 400 µg/h/mL. Materiales y Método: Estudio descriptivo y retrospectivo, realizado entre febrero 2016 y marzo 2018. Se incluyeron neonatos en tratamiento con vancomicina por sospecha/confirmación de infección por cocáceas grampositivas y medición de concentraciones plasmáticas de vancomicina al inicio del tratamiento. La probabilidad de alcanzar el objetivo terapéutico se evaluó mediante re-muestreo de valores de ABC y CIM. Resultados: Se incluyeron 38 pacientes con 49 concentraciones plasmáticas de vancomicina. Los aislados microbiológicos se confirmaron en 94,7% de los pacientes (n = 36). Los valores de ABC/CIM en dos grupos (según niveles valle de vancomicina < 10 µg/mL y ≥ 10 µg/mL), fueron de una mediana de 327 (IQ 25-75 = 174-395) y 494 (IQ 25-75 = 318-631), respectivamente (p = 0,035). Las dosis empíricas utilizadas logran logran un objetivo terapéutico (ABC/CIM > 400) de sólo 47,7% considerando CIMs en nuestra institución. Conclusiones: Teniendo en cuenta las sensibilidades institucionales, no es posible asegurar alcanzar ABC/CIM > 400 µg/h/mL. Se debe seguir investigando para replantear las actuales estrategias de dosificación y así determinar la más apropiada para neonatos.

Abstract Background: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. Aim: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. Methods: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. Results: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. Conclusions: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

Effect of maternal nutrient restriction on skeletal muscle mass and associated molecular pathways in SGA and Non-SGA sheep fetuses.

Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences.

[Clinical-epidemiological characterization of neonatal necrotizing enterocolitis of seven public hospitals]. / Caracterización clínico-epidemiológica de las enterocolitis necrosantes neonatales de siete hospitales públicos.

BACKGROUND: Necrotizing enterocolitis (NEC) presents high mortality and postoperative, gastrointestinal and neurodevelopmental morbidity. There is limited information about NEC in Chile. AIM: To describe the clinical/epidemiological behavior of newborns who underwent NEC. METHODS: Multicenter descriptive study of patients with NEC from seven hospitals of Santiago, Chile, during 2016. Descriptive statistics and univariate/multivariate analysis were performed (SPSS v22 software). RESULTS: 75 cases were collected. Median days of life at diagnosis was 11, gestational age was 29 weeks, birth weight 1,114 g. The incidence was 2.6 per 1,000 live newborns and mortality was 18.6%, higher in ≤ 750 g, ≤ 25 weeks and surgical NEC. There was 45.3% microbiological isolation and 19 different empirical antibiotic schemes were used for the treatment of NEC. The multivariate analysis showed a higher risk of surgery in umbilical arterial catheter users, CRP > 10 mg/L and positive microbiological isolation. The highest risk of death was in umbilical arterial catheter users. DISCUSSION: This ie the first multicenter study that collects local data information. The incidence was similar to that found in medical reports but with a lower mortality. There is no consensus of antibiotic treatment to use. With these results we hope to advance in improving the diagnosis and unify antimicrobial treatments, to reduce morbidity and mortality figures.