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BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

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Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.

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BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.

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Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Methods: Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Results: Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. Discussion: The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.

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INTRODUCTION: In 2020 the pandemic caused by SARS-COV-2 demanded an enormous number of healthcare resources in order to guarantee adequate treatment and support for those patients. This study aims to assess caloric and protein intake and evaluate its associations with relevant clinical outcomes in critically ill with coronavirus disease (COVID-19) patients. METHODS: A nationwide, multicentre prospective observational study including twelve Argentinian intensive care units (ICUs,) was conducted between March and October 2020. INCLUSION CRITERIA: Adult ICU patients>18 years admitted to the ICU with COVID-19 diagnosis and mechanical ventilation for at least 48h. Statistical analysis was carried out using IBM-SPSS© 24 programme. RESULTS: One hundred and eighty-five patients were included in the study. Those who died had lower protein intake (0.73g/kg/day (95% confidence interval (CI) 0.70-0.75 vs 0.97g/kg/day (CI 0.95-0.99), P<0.001), and lower caloric intake than those who survived (12.94kcal/kg/day (CI 12.48-13.39) vs 16.47kcal/kg/day (CI 16.09-16.8), P<0.001). A model was built, and logistic regression showed that factors associated with the probability of achieving caloric and protein intake, were the early start of nutritional support, modified NUTRIC score higher than five points, and undernutrition (Subjective Global Assessment B or C). The patients that underwent mechanical ventilation in a prone position present less caloric and protein intake, similar to those with APACHE II>18. CONCLUSIONS: Critically ill patients with COVID-19 associated respiratory failure requiring mechanical ventilation who died in ICU had less caloric and protein intake than those who survived. Early start on nutritional support and undernutrition increased the opportunity to achieve protein and caloric goals, whereas the severity of disease and mechanical ventilation in the prone position decreased the chance to reach caloric and protein targets.

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Introduction: In 2020 the pandemic caused by SARS-COV-2 demanded an enormous number of healthcare resources in order to guarantee adequate treatment and support for those patients. This study aims to assess caloric and protein intake and evaluate its associations with relevant clinical outcomes in critically ill with coronavirus disease (COVID-19) patients. Methods: A nationwide, multicentre prospective observational study including twelve Argentinian intensive care units (ICUs,) was conducted between March and October 2020. Inclusion criteria: Adult ICU patients > 18 years admitted to the ICU with COVID-19 diagnosis and mechanical ventilation for at least 48 h. Statistical analysis was carried out using IBM-SPSS© 24 programme. Results: One hundred and eighty-five patients were included in the study. Those who died had lower protein intake (0.73 g/kg/day (95% confidence interval (CI) 0.70-0.75 vs 0.97 g/kg/day (CI 0.95-0.99), P < 0.001), and lower caloric intake than those who survived (12.94 kcal/kg/day (CI 12.48-13.39) vs 16.47 kcal/kg/day (CI 16.09-16.8), P < 0.001).A model was built, and logistic regression showed that factors associated with the probability of achieving caloric and protein intake, were the early start of nutritional support, modified NUTRIC score higher than five points, and undernutrition (Subjective Global Assessment B or C). The patients that underwent mechanical ventilation in a prone position present less caloric and protein intake, similar to those with APACHE II > 18. Conclusions: Critically ill patients with COVID-19 associated respiratory failure requiring mechanical ventilation who died in ICU had less caloric and protein intake than those who survived. Early start on nutritional support and undernutrition increased the opportunity to achieve protein and caloric goals, whereas the severity of disease and mechanical ventilation in the prone position decreased the chance to reach caloric and protein targets.

Introducción: En 2020, la pandemia provocada por el SARS-COV-2 demandó una enorme cantidad de recursos sanitarios para garantizar el tratamiento y apoyo adecuado a estos pacientes. Este estudio tiene como objetivo evaluar la ingesta de calorías/proteínas y evaluar sus asociaciones con resultados clínicos relevantes en pacientes críticamente enfermos con enfermedad por coronavirus (COVID-19). Métodos: Se realizó un estudio observacional prospectivo multicéntrico a nivel nacional que incluyó 12 unidades de cuidados intensivos (UCI) argentinas entre marzo y octubre de 2020. Criterios de inclusión: pacientes adultos de la UCI > 18 años ingresados en la UCI con diagnóstico de COVID-19 y ventilación mecánica durante al menos 48 h. El análisis estadístico se realizó mediante el programa IBM-SPSS© 24. Resultados: En el presente estudio se incluyeron 185 pacientes. Entre los que fallecieron se observó un aporte proteico más bajo (0,73 g/kg/día [intervalo de confianza {IC} del 95% 0,70-0,75] vs. 0,97 g/kg/día [IC 0,95-0,99], p < 0,001), y menor aporte calórico que los que sobrevivieron (12,94 kcal/kg/día [IC 12,48-13,39] vs. 16,47 kcal/kg/día [IC 16,09-16,8], p < 0,001).Se construyó un modelo de regresión logística para analizar qué factores estaban asociados con la probabilidad de lograr los objetivos calóricos/proteicos. Se observó una mayor probabilidad de lograr dichos objetivos cuando el inicio del soporte nutricional era precoz, el puntaje NUTRIC modificado era superior a 5 puntos y el paciente tenía diagnóstico de desnutrición mediante la Evaluación Global Subjetiva(B o C). Por otra parte, en los pacientes que necesitaron ventilación mecánica en decúbito prono se observó menor aporte calórico y proteico, situación similar en aquellos con APACHE II > 18. Conclusiones: Los pacientes críticos con insuficiencia respiratoria asociada a la enfermedad por COVID-19 que requerían ventilación mecánica y que fallecieron en la UCI tuvieron una ingesta calórica y proteica menor que los que sobrevivieron. El inicio temprano del soporte nutricional y la desnutrición aumentaron la posibilidad de alcanzar los objetivos calóricos y proteicos, mientras que la gravedad de la enfermedad y la ventilación mecánica en decúbito prono disminuyeron la posibilidad de alcanzar los objetivos calóricos y proteicos.

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Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic-pituitary-adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.

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INTRODUCTION: Introduction: the COVID-19 pandemic put the world's population at risk. As the relationship between nutritional risk and clinical outcomes in critically ill patients with COVID-19 is still poorly understood, a multidisciplinary research team of the Argentine Society of Intensive Care (SATI) conducted a multicenter study aimed to define nutritional features, and to evaluate the relationship between nutritional risk and relevant clinical outcomes for COVID-19 patients in an intensive care unit (ICU). Methods: a multicenter, prospective, observational study including twelve Argentinian ICUs was conducted between March and October 2020. Inclusion criteria were: adult patients older than 18 years who were admitted to the ICU with a COVID-19 diagnosis were included. Clinical data included comorbidities scores, and nutritional screening tools such as the Subjective Global Assessment (SGA), the Nutritional Risk Screening (NRS) 2002, and the modified NUTRIC score (mNUTRIC SCORE) were used. In addition, clinical outcomes including overall mortality, mechanical ventilation (MV) days, and ICU and hospital length of stay (LOS) were recorded. Results: a total of 285 ICU patients met our inclusion criteria. Mean age was 61.24 (SD = 14.6) years; APACHE-II, 14.2 (SD = 6.6); Charlson Comorbidity Index (CCI), 2.3 (SD = 2.3). Most patients were admitted from the emergency room to the ICU. Hypertension, obesity, and diabetes were the most common comorbidities. Nutritional assessment showed that 36.9 % were SGA B+C, and 46 % were obese. Mean ICU LOS was 22.2 (SD = 19.5), and hospital LOS was 28.1 (SD = 21.9) days. Of all patients, 90.2 % underwent MV, and MV days were 20.6 (SD = 15.6). The univariate and multivariate analyses showed that risk factors for COVID-19 mortality were (odds ratio [95 % confidence interval]): SGA score of B or C: 2.13 [1.11-4.06], and NRS 2002 ≥ 3: 2.25 [1.01-5.01]. Conclusions: in the present study, nutritional status (SGA) and NRS 2002 were major mortality risk factors for CODIV-19 patients in the ICU.

INTRODUCCIÓN: Introducción: la pandemia de COVID-19 puso en riesgo a la población mundial. Dado que la relación entre el riesgo nutricional y los resultados clínicos en pacientes críticos con COVID-19 es aún poco conocida, un equipo de investigación multidisciplinario de la Sociedad Argentina de Cuidados Intensivos (SATI) realizó un estudio multicéntrico con el objetivo de definir las características nutricionales y evaluar la relación entre el riesgo nutricional y los resultados clínicos relevantes para los pacientes de la unidad de cuidados intensivos (UCI) de COVID-19. Métodos: entre marzo y octubre de 2020 se realizó un estudio observacional prospectivo y multicéntrico que incluyó 12 UCI argentinas. Criterios de inclusión: se incluyeron pacientes adultos mayores de 18 años que habían ingresado en la UCI con diagnóstico de COVID-19. Se utilizaron datos clínicos que incluían scores de comorbilidades, herramientas de cribado nutricional como la Evaluación Global Subjetiva (EGS) y el Cribado de Riesgo Nutricional (NRS) 2002, y la puntuación NUTRIC. Además. Se registraron los resultados clínicos, incluida la mortalidad, los días de ventilación mecánica (VM) y la duración de la estancia en la UCI y hospitalaria en general. Resultados: en total, 285 pacientes en UCI cumplieron nuestros criterios de inclusión. La edad media fue de 61,24 (DE = 14,6) años, la puntuación APACHE-II de 14,2 (DE = 6,6) y el índice de comorbilidad de Charlson (ICC) de 2,3 (DE = 2,3). La mayoría de los pacientes ingresaron desde la sala de emergencias a la UCI. La hipertensión, la obesidad y la diabetes fueron las comorbilidades más frecuentes. La evaluación nutricional mostró que el 36,9 % eran VGS B + C y el 46 % eran obesos. La estancia en la UCI fue de 22,2 (DE = 19,5) y la hospitalaria de 28,1 (DE = 21,9) días. El 90,2 % se sometieron a VM, siendo la media de días de VM de 20,6 (DE = 15,6). El análisis univariado y multivariado mostró que los factores de riesgo de mortalidad por COVID-19 eran (razón de posibilidades [intervalo de confianza del 95 %]): puntuación SGA de B o C: 2,13 [1,11-4,06], y NRS 2002 ≥ 3: 2,25 [1,01-5,01]. Conclusiones: en el presente estudio, el estado nutricional (EGS) y el NRS 2002 fueron los principales factores de riesgo de mortalidad para los pacientes con COVID-19 en la UCI.

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RESUMEN Las vacunas son productos biológicos que contienen antígenos que buscan generar protección contra a la exposición real de un agente patógeno. En cuanto a su importancia, hacen parte de las intervenciones más costo-efectivas en salud pública, siendo superadas únicamente por el agua potable. A grandes rasgos, podemos dividir las vacunas en vivas atenuadas e inactivadas; no obstante, el nuevo coronavirus ha producido la emergencia de plataformas innovadoras que utilizan mecanismos intracelulares y moleculares con el mismo objetivo de generar inmunidad. Se realizó una búsqueda sistemática de la literatura utilizando las bases de datos electrónicas Pubmed, Scopus y Web of Science. Todos los tipos de diseño de estudio fueron considerados, sin embargo, se prefierieron aquellos redactados en idioma inglés o español. Se hace una revisión de la literatura presente sobre las plataformas existentes para generar inmunidad frente al coronavirus SARS-CoV-2 y se desarrolla cada una según su ruta y forma de acción en aquellas basadas en subunidades proteicas, vector viral recombinante, ácidos nucleicos, virus inactivados, partículas virales y virus vivos atenuados. Los mecanismos por los cuales dichas vacunas generan inmunogenicidad son diferentes, no obstante, la constante inserción de mutaciones por parte del virus sigue siendo un objeto de interés y preocupación por los investigadores.

ABSTRACT Vaccines are biological products containing antigens that aim to generate protection against real exposure to an infectious pathogen. They constitute the most cost-effective interventions in public health, being surpassed only by drinking water. Generally speaking, we can divide the vaccines into live attenuated and inactive; However, the new coronavirus has produced innovative platforms that use intracellular and molecular mechanisms with the same objective of generating immunity. A systematic literature search was carried out using the PUBMED, SCOPUS, and Web of Science electronic databases. All types of study design were selected, those written in English or Spanish were prioritized. We reviewed the existing platforms to generate immunity against the SARS-CoV-2 coronavirus. Each one is developed according to its route and form of action, and can be classified as protein subunits, recombinant viral vector, nucleic acids, inactivated viruses, viral particles, and live attenuated viruses. The mechanisms by which these vaccines generate immunogenicity are different; however, the constant insertion of mutations by the virus remains an object of interest and concern for researchers.

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Resumen Objetivo: El propósito de este estudio es determinar la prevalencia de casos juveniles en una muestra de sujetos mexicanos con enfermedad de Huntington (EH) confirmada molecularmente. Métodos: Se incluyeron pacientes con inicio clínico antes de los 21 años de edad que acudieron a la clínica de trastornos del movimiento del Instituto Nacional de Neurología y Neurocirugía. La información demográfica y clínica se obtuvo de la revisión de expedientes. Resultados: Se revisaron un total de 198 casos de pacientes con diagnóstico de EH, de los cuales el 6.5% (n=13) correspondió a formas juveniles. La media de edad para el inicio de síntomas fue de 17.8 ± 3.9 años. La puntuación media del UHDRS-motor fue de 46.2 ± 17.4 puntos. El síntoma motor predominante fue corea en el 53.8% de los casos. El 84.6% de los afectados presentó al menos una alteración neuropsiquiátrica. Conclusión: Se detectó que el fenotipo motor de estos pacientes fue dominantemente corea, contrario a lo reportado mundialmente hasta ahora, es decir, nuestro grupo presentó clínica motora atípica de EHJ.

Abstract Objective: The purpose of this study is to know the prevalence of juvenile cases in a sample of mexican subjects with confirmed Huntington Disease (HD). Methods: Patients with clinical debut before 21 years of age were included who attended at movement disorders clinic of the National Institute of Neurology and Neurosurgery. The demographic and clinical information was obtained from the review of files. Results: A total of 198 cases of patients diagnosed with HD were reviewed, of which 6.5% (n = .13) corresponded to juvenile forms. The mean age for the onset of symptoms was 17.8 ± 3.9 years. The mean score of the UHDRS-motor was 46.2 ± 17.4 points. The predominant motor symptom was chorea in (53.8%) of the cases. 84.6% of those affected presented at least one neuropsychiatric disorder. Conclusion: It was detected that the dominant motor phenotype of these patients was chorea compared to the world reports until now, accordingly to that, our group of juvenile HD shows atypical motor clinical.