Neutrophils seeking new neighbors: radiotherapy affects the cellular framework and the spatial organization in a murine breast cancer model.

Neutrophils are known to contribute in many aspects of tumor progression and metastasis. The presence of neutrophils or neutrophil-derived mediators in the tumor microenvironment has been associated with poor prognosis in several types of solid tumors. However, the effects of classical cancer treatments such as radiation therapy on neutrophils are poorly understood. Furthermore, the cellular composition and distribution of immune cells in the tumor is of increasing interest in cancer research and new imaging technologies allow to perform more complex spatial analyses within tumor tissues. Therefore, we aim to offer novel insight into intra-tumoral formation of cellular neighborhoods and communities in murine breast cancer. To address this question, we performed image mass cytometry on tumors of the TS/A breast cancer tumor model, performed spatial neighborhood analyses of the tumor microenvironment and quantified neutrophil-extracellular trap degradation products in serum of the mice. We show that irradiation with 2 × 8 Gy significantly alters the cellular composition and spatial organization in the tumor, especially regarding neutrophils and other cells of the myeloid lineage. Locally applied radiotherapy further affects neutrophils in a systemic manner by decreasing the serum neutrophil extracellular trap concentrations which correlates positively with survival. In addition, the intercellular cohesion is maintained due to radiotherapy as shown by E-Cadherin expression. Radiotherapy, therefore, might affect the epithelial-mesenchymal plasticity in tumors and thus prevent metastasis. Our findings underscore the growing importance of the spatial organization of the tumor microenvironment, particularly with respect to radiotherapy, and provide insight into potential mechanisms by which radiotherapy affects epithelial-mesenchymal plasticity and tumor metastasis.

Modulatory role of α-MSH in hippocampal-dependent memory impairment, synaptic plasticity changes, oxidative stress, and astrocyte reactivity induced by short-term high-fat diet intake.

High-fat diet (HFD) consumption is associated with cognitive deficits and neurodegenerative diseases. Since the hippocampus is extremely sensitive to pathophysiological changes, neuroinflammation and the concomitant oxidative stress induced by HFD can significantly interfere with hippocampal-dependent functions related to learning and memory. The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) mediates neuroprotective actions in the central nervous system and can reverse the effects of neuroinflammation in cognitive functions that depend on the hippocampus. In this study, we used male Wistar rats to evaluate the effect of short-term HFD intake (5 days) plus a mild immune challenge, Lipopolysaccharide (LPS 10 µg/kg) on contextual fear, changes in structural plasticity, oxidative stress, and astrocyte reactivation in the hippocampus. We also determined the possible modulatory role of α-MSH. HFD consumption was associated with an increase in markers of oxidative stress (Advanced oxidation protein products and Malondialdehyde) in the dorsal hippocampus (DH). We also found changes in hippocampal structural synaptic plasticity, observing a decrease in total spine in the DH after HFD plus LPS. We observed astrocyte proliferation and a significant increase in the percentage of the area occupied by GFAP. Treatment with α-MSH (0.1 µg/0.25 µl) in the DH reversed the effect of short-term HFD plus LPS on contextual fear memory, oxidative stress, and spine density. α-MSH also reduced astrocyte proliferation. Our present results indicate that HFD consumption for a short period sensitizes the central nervous system (CNS) to a subsequent immune challenge and impairs contextual fear memory and that α-MSH could have a modulatory protective effect.

Culture-negative TB: clinical characteristics, risk factors and treatment outcomes.

BACKGROUND: Although culture remains the standard for TB diagnosis, 15-20% of patients diagnosed and treated for TB are culture-negative. We explored clinical characteristics, risk factors and treatment outcomes for culture-negative TB in a Peruvian cohort.METHODS: We recruited 4,500 index TB patients and 10,160 household contacts in Lima, Peru, and enrolled 692 secondary patients diagnosed with TB during follow-up of household contacts. We analyzed smear and culture status, sociodemographic factors, clinical characteristics and TB treatment outcomes to compare culture-negative and positive patients.RESULTS: Of the 4,880 adult patients, 915 (18.8%) were culture-negative. Culture-negative patients were less likely to report symptoms of TB disease and disease of longer duration. A multivariate analysis showed no statistically significant difference in loss to follow-up, treatment failure or recurrence between the culture-negative and -positive groups but a higher rate of death among culture-negative patients with an adjusted OR of 1.65 (95% CI 1.05-2.60). In a multivariate analysis of determinants of culture negativity, older age, substance use and being a secondary case were associated with culture status.CONCLUSIONS: More recognition and awareness of culture-negative TB is key for early and correct diagnosis to reduce transmission and improve treatment outcomes.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles / Evaluation of factors related to the occurrence of new fragility fractures: A case–control study

Introducción: Las fracturas por fragilidad (FF) son frecuentes en pacientes osteoporóticos. Existen una serie de factores de riesgo y variables clínicas, que podrían predecir su aparición. Material y método: Se realizó un estudio observacional retrospectivo de casos y controles. Los casos estuvieron definidos por la presencia de una FF (326 participantes) y los controles por pacientes de similares características sin FF (629 participantes). Resultados: Ciertos factores aumentan el riesgo de FF, como un diagnóstico previo de DM tipo 2 (OR: 2,001), las elevaciones de 1ng/mL del CTX (OR: 1,88), tener antecedentes parentales de fractura de cadera (OR: 1,667), el aumento en 5 años en la edad (OR: 1,39) y los incrementos de 1kg/m2 del IMC (OR: 1,041). Por el contrario, otros factores evaluados disminuyen ese riesgo, como mantener unos niveles de 25(OH)D≥30ng/mL (OR: 0,686) y una T-score≥−2,5 (OR: 0,642). Conclusiones: Niveles de 25(OH)D≥30ng/mL y una T-score en el cuello femoral≥−2,5 son factores protectores de las FF, mientras que el diagnóstico previo de DM tipo 2, un CTX elevado, el antecedente parental de fractura de cadera, un incremento de 1kg/m2 del IMC y el aumento de la edad en 5 años serían predisponentes a padecer FF.(AU)

Introduction: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. Material and method: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). Results: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥−2.5 (OR: 0.642). Conclusions: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥−2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.(AU)

[Translated article] Evaluation of factors related to the occurrence of new fragility fractures: A case–control study / Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles

Introduction: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. Material and method: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). Results: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥−2.5 (OR: 0.642). Conclusions: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥−2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.(AU)

Introducción: Las fracturas por fragilidad (FF) son frecuentes en pacientes osteoporóticos. Existen una serie de factores de riesgo y variables clínicas, que podrían predecir su aparición. Material y método: Se realizó un estudio observacional retrospectivo de casos y controles. Los casos estuvieron definidos por la presencia de una FF (326 participantes) y los controles por pacientes de similares características sin FF (629 participantes). Resultados: Ciertos factores aumentan el riesgo de FF, como un diagnóstico previo de DM tipo 2 (OR: 2,001), las elevaciones de 1ng/mL del CTX (OR: 1,88), tener antecedentes parentales de fractura de cadera (OR: 1,667), el aumento en 5 años en la edad (OR: 1,39) y los incrementos de 1kg/m2 del IMC (OR: 1,041). Por el contrario, otros factores evaluados disminuyen ese riesgo, como mantener unos niveles de 25(OH)D≥30ng/mL (OR: 0,686) y una T-score≥−2,5 (OR: 0,642). Conclusiones: Niveles de 25(OH)D≥30ng/mL y una T-score en el cuello femoral≥−2,5 son factores protectores de las FF, mientras que el diagnóstico previo de DM tipo 2, un CTX elevado, el antecedente parental de fractura de cadera, un incremento de 1kg/m2 del IMC y el aumento de la edad en 5 años serían predisponentes a padecer FF.(AU)

[Translated article] Evaluation of factors related to the occurrence of new fragility fractures: A case-control study.

INTRODUCTION: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. MATERIAL AND METHOD: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). RESULTS: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥-2.5 (OR: 0.642). CONCLUSIONS: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥-2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.

Evaluation of factors related to the occurrence of new fragility fractures: A case-control study. / Evaluación de los factores relacionados con la aparición de nuevas fracturas por fragilidad: un estudio de casos y controles.

INTRODUCTION: Fragility fractures (FF) are frequent in osteoporotic patients. There are a series of risk factors and clinical variables that could predict their appearance. MATERIAL AND METHOD: A retrospective observational study of cases and controls was carried out. Cases were defined by the presence of FF (326 participants) and controls by patients with similar characteristics without FF (629 participants). RESULTS: Certain factors increase the risk of FF, such as a previous diagnosis of type 2 DM (OR: 2.001), 1ng/mL elevations of CTX (OR: 1.88), having a parental history of hip fracture (OR: 1.667), 5-year increase in age (OR: 1.39), and 1kg/m2 increases in BMI (OR: 1.041). In contrast, other factors evaluated decreased this risk, such as maintaining 25(OH)D levels≥30ng/mL (OR: 0.686) and a T-score≥-2.5 (OR: 0.642). CONCLUSIONS: Levels of 25(OH)D≥30ng/mL and a T-score at the femoral neck≥-2.5 are protective factors for FF, while a previous diagnosis of type 2 DM, an elevated CTX, a parental history of hip fracture, an increase of 1kg/m2 in BMI and an increase in age by 5 years would be predisposing to FF.

Hemophilia and non-accidental head trauma in two siblings: lessons and legal implications.

Non-accidental head trauma (NAHT) is a common cause of traumatic brain injury in childhood, origin of profound and disabling neurological sequalae, and in the most disgraceful cases, ultimately death.Subdural hematoma (SDH) is the most common intracranial finding in NAHT. On the other hand, congenital bleeding disorders are a minor but a significant cause of ICH in the neonate and toddler. Not uncommonly, intracranial bleeding is the first sign of a severe inherited coagulation disorder. In the presence of an unexpected intracranial bleeding after a minor trauma or without a clear history of the related events, physicians and caregivers may be confronted to the dilemma of a possible child abuse. It must be bear in mind that physical abuse and bleeding disorders can co-exist in the same child.We report here the case of two siblings in whom a diagnosis of hemophilia coexisted with the presumption of a non-accidental head trauma. Child abuses were inflicted in both children with a spare time of 2 years. A diagnosis of mild hemophilia was prompted in the first sibling after initial NAHT, while inflicted trauma was evident in the second sibling after neuroimaging findings and concomitant lesions. Lessons from this case in co-existing bleeding disorders and inflicted trauma and legal implications derived will be discussed thereafter.The possibility of a bleeding disorder should be considered in all children presenting with unexplained bleeding at a critical site in the setting of suspected physical maltreatment, particularly intracranial hemorrhage (ICH).

Implementing 3HP vs. IPT as TB preventive treatment in Pakistan.

BACKGROUND: We assessed treatment uptake and completion for 6 months of isoniazid (6H) and 3 months of isoniazid plus rifapentine weekly (3HP) in a programmatic setting in Pakistan.METHODS: All household contacts were clinically evaluated to rule out TB disease. 6H was used for TB preventive treatment (TPT) from October 2016 to April 2017; from May to September 2017, 3HP was used for contacts aged ≥2 years. We compared clinical evaluation, TPT uptake and completion rates between contacts aged ≥2 years in the 6H period and in the 3HP period.RESULTS: We identified 3,442 contacts for the 6H regimen. After clinical evaluation, 744/1,036 (72%) started treatment, while 46% completed treatment. In contrast, 3,722 contacts were identified for 3HP. After clinical evaluation, 990/1,366 (72%) started treatment, while 67% completed treatment. Uptake of TPT did not differ significantly between the 6H and 3HP groups (OR 1.03, 95%CI 0.86-1.24). However, people who initiated 3HP had 2.3 times greater odds (95% CI 1.9-2.8) of completing treatment than those who initiated 6H after adjusting for age and sex.CONCLUSION: In programmatic settings in a high-burden country, household contacts of all ages were more likely to complete TPT with shorter weekly regimens, although treatment uptake rate for the two regimens was similar.

Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

A structured community engagement strategy to support uptake of TB active case-finding.

BACKGROUND: In Lima, Peru, a mobile TB screening program ("TB Móvil") was implemented in high TB prevalence districts to increase TB screening. Community engagement activities to promote TB Móvil were simultaneously conducted. OBJECTIVE: To describe a structured, theory-driven community engagement strategy to support the uptake of TB Móvil. METHODS: We adapted Popular Opinion Leader (POL), an evidence-based social networking intervention previously used in Peru to promote HIV testing, for TB Móvil. Community health workers, women who run soup kitchens, and motorcycle taxi drivers served as "popular opinion leaders" who disseminated information about TB Móvil in everyday conversations, aided by a multi-media campaign. Performance indicators of POL included the number/characteristics of persons screened; number of multimedia elements; and proportion of persons with abnormal radiographs hearing about TB Móvil before attending. RESULTS: Between February 2019 and January 2020, 63,899 people attended the TB Móvil program at 210 sites; 60.1% were female. The multimedia campaign included 36 videos, 16 audio vignettes, flyers, posters, community murals and "jingles." Among attendees receiving an abnormal chest X-ray suggestive of TB, 48% (6,935/14,563) reported hearing about TB Móvil before attending. CONCLUSIONS: POL promotes the uptake of TB Móvil and should be considered as a strategy for increasing TB screening uptake.

CONTEXTE: À Lima, Pérou, un programme mobile de dépistage de la TB (« TB Móvil ¼) a été mis en place dans les quartiers à forte prévalence de TB afin d'accroître le dépistage de la maladie. Des activités de mobilisation communautaire visant à promouvoir TB Móvil ont été menées en parallèle. L'objectif de ce rapport est de décrire une stratégie structurée de mobilisation communautaire, fondée sur des principes théoriques, afin de soutenir le recours au programme TB Móvil. MÉTHODES: Nous avons adapté à TB Móvil l'intervention factuelle de réseautage social appelée « Popular Opinion Leader (POL; leader d'opinion) ¼, précédemment utilisée au Pérou pour promouvoir le dépistage du VIH. Les agents de santé communautaires, les femmes responsables de la soupe populaire et les chauffeurs de mototaxis étaient des leaders d'opinion. Ils communiquaient des informations sur TB Móvil lors de leurs conversations quotidiennes, qui étaient étayées par une campagne multimédia. Les indicateurs de performance des POL comprenaient le nombre/les caractéristiques des personnes dépistées, le nombre d'éléments multimédias et le pourcentage de personnes avec cliché radiographique anormal qui avaient entendu parler de TB Móvil avant de se faire dépister. RÉSULTATS: Entre février 2019 et janvier 2020, 63 899 personnes ont pris part au programme TB Móvil dans 210 sites ; 60,1% étaient des femmes. La campagne multimédia reposait sur 36 vidéos, 16 vignettes audio, des prospectus, des posters, des peintures murales dans la communauté et des « jingles ¼. Parmi les personnes dont la radiographie pulmonaire était anormale et évocatrice de TB, 48% (6 935/14 563) ont rapporté avoir entendu parler de TB Móvil avant de venir consulter. CONCLUSIONS: L'intervention POL, qui semblait renforcer le recours au programme TB Móvil, peut donc servir d'une stratégie de promotion du dépistage de la TB.

Trastorno del Espectro Autista (TEA) en el primer nivel de atención: cómo estamos, dónde estamos? Relato de nuestra experiencia en el CESAC 5 / Autism Spectrum Disorder (ASD) in the first level of care: how are we, where are we? Report of our experience at CESAC 5

Los trastornos del desarrollo conforman la "nueva morbilidad" y su identificación oportuna facilita planear los apoyos específicos que pueden favorecer el pronóstico de estos pacientes. El objetivo de este proyecto es brindar información acerca del abordaje de los pacientes con diagnóstico de TEA en el primer nivel de atención, mediante la descripción de diferentes variables a través de la evaluación de sus historias clínicas. Se analizaron 35 historias clínicas y se obtuvieron los siguientes resultados. 85,7% sexo masculino con un promedio de edad de 8,1 años. El 48,57% poseían obra social. 14,29% fueron nacidos pretérmino. 8,57% presentaron síndrome genético/cromosómico asociado al autismo. 22.86% presentaban hermano con mismo diagnóstico. Retraso madurativo o discapacidad intelectual en el 22,8%. Edad de diagnóstico media de 45.05 meses, (DE 17.13). En el 65,71% de las HC no se consignaba si el familiar presentaba alguna preocupación con respecto al desarrollo. En el 40% de las HC figura alteración en la comunicación/ ausencia o retraso del lenguaje, como motivo de preocupación/ derivación. El 91,43% se realizó el diagnostico por el equipo especializado en el Hospital Garrahan. El 85,71% realiza o realizó tratamiento, 71,43% en un centro público. El 88,57% se encontraba escolarizado. 51,43% en escuela especial. El 68,57% tenían certificado de discapacidad. El 28,57% se encontraban en tratamiento psicofarmacológico. El análisis de las HC nos permitió acercarnos a describir nuestra población, con características de diagnóstico y seguimiento que se ajustan en mayor medida a la descripta en la bibliografía, pese a tratarse de una población con un bajo nivel socio económico (AU)

Developmental disorders are the "new morbidity" and their timely identification enhances the planning of specific support measures that may improve the prognosis of these patients. The aim of this project is to provide information on the approach of patients diagnosed with ASD at the first level of care, by describing different variables obtained from medical records (MR). Thirtyfive MR were analyzed and the following results were obtained: 85.7% were male and mean age was 8.1 years. Overall, 48.57% had a health insurance; 14.29% were born preterm; 8,57% had a genetic/chromosomal syndrome associated with autism; 22.86% had a sibling with the same diagnosis. Developmental delay or intellectual disability was observed in 22.8%. Mean age at diagnosis was 45.05 months (SD 17.13). In 65.71% of the MR it was not clear if the caregiver was worried about the development of the child. In 40% of the MR, communication disturbances or absence of language/language delay were mentioned as the reason for worry or referral. In 91.43% the diagnosis was made by the specialized team at Garrahan Hospital. Overall, 85.71% underwent or is undergoing treatment, of whom 71.43% at a public center. Of all the children, 88.57% was attending school, 51.43% of whom at a special school; 68.57% had a disability certificate; 28.57% received psychopharmacological treatment. Analysis of the MR allowed us to describe our population, with diagnostic and follow-up features that mostly agree with the findings reported in the literature, in spite of the low socio-economic level of the families (AU)

Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions.

The role of glycoprotein VI (GPVI) in platelets was investigated in 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to the transmembrane domain, leading to expression of a truncated protein in the cytoplasm devoid of the transmembrane region. Western blotting and flow cytometry of GP6hom (homozygous) platelets confirmed loss of the full protein. The level of the Fc receptor γ-chain, which associates with GPVI in the membrane, was partially reduced, but expression of other receptors and signaling proteins was not altered. Spreading of platelets on collagen and von Willebrand factor (which supports partial spreading) was abolished in GP6hom platelets, and spreading on uncoated glass was reduced. Anticoagulated whole blood flowed over immobilized collagen or a mixture of von Willebrand factor, laminin, and rhodocytin (noncollagen surface) generated stable platelet aggregates that express phosphatidylserine (PS). Both responses were blocked on the 2 surfaces in GP6hom individuals, but adhesion was not altered. Thrombin generation was partially reduced in GP6hom blood. The frequency of the GP6het (heterozygous) variant in a representative sample of the Chilean population (1212 donors) is 2.9%, indicating that there are ∼4000 GP6hom individuals in Chile. These results demonstrate that GPVI supports aggregation and PS exposure under flow on collagen and noncollagen surfaces, but not adhesion. The retention of adhesion may contribute to the mild bleeding diathesis of GP6hom patients and account for why so few of the estimated 4000 GP6hom individuals in Chile have been identified.

Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.