Association between adipophilin expression and risk of dyslipidaemia in patients with granuloma annulare.

BACKGROUND: An association between granuloma annulare (GA) and dyslipidaemia has been reported. Adipophilin expression may play a plausible role as a cutaneous biomarker for dyslipidaemia in patients with GA; however, this potential link remains to be explored. METHODS: Patients with GA were identified at our hospital between January 1, 1990, and December 31, 2021, with a thorough review of their clinical and histological characteristics. Adipophilin staining was assessed in biopsies of GA lesions. RESULTS: A total of 107 patients with GA were included. The prevalence of dyslipidaemia in patients with positive adipophilin staining was clearly higher than in those with negative labelling (62.3% vs 13.3%). Relative to the dyslipidaemia risk for patients with negative adipophilin expression, the odds for patients with positive adipophilin expression were increased 10-fold (OR: 10.8; p-value<.01). We identified 23 incident cases of dyslipidaemia over a median follow-up period of 91 months among 54 patients with no history of dyslipidaemia. The patients with positive adipophilin expression showed a higher risk of developing dyslipidaemia (HR: 8.9; p-value<.01). CONCLUSIONS: Patients with positive adipophilin staining in their GA biopsies were found to be associated with a higher risk for both baseline and incident dyslipidaemia.

Value of the biomarker soluble tyrosine kinase 1 type fms (sFLT-1) in the diagnosis and prognosis of sepsis: a systematic review. / Valor del biomarcador tirosina quinasa 1 soluble tipo fms (sFLT-1) en el diagnóstico y pronóstico de la sepsis: una revisión sistemática.

INTRODUCTION: The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022. MATERIALS AND METHODS: A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry). RESULTS: The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction. CONCLUSIONS: It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.

Use of Bladder Epicheck® in the follow-up of high-risk non-muscle-invasive Bladder cancer: A systematic literature review.

INTRODUCTION: In recent years, different urinary markers such as the Bladder Epicheck® have been developed in an attempt to reduce the number of cystoscopies in the follow-up of non-muscle invasive bladder cancer (NMIBC). AIM: To provide a systematic review of Bladder Epicheck® and its current clinical utility in the follow-up and detection of recurrence of NMIBC. MATERIAL AND METHODS: Systematic review based on a literature search of PubMed, Web of Science and Scopus databases until October 2023, according to PRISMA and Quadas-2 criteria. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the marker were calculated. Diagnostic performance was evaluated by the area under the curve (AUC). RESULTS: Fifteen studies were analyzed (n = 3761) including 86.7% prospective studies. Of the patient series, 53.2% had received previous intravesical instillations. The mean Se of the biomarker in the detection of recurrence varied according to tumor grade (87.9%-high grade/HG vs. 44.9%-low grade/LG, respectively). Their weighted mean Se and Sp were 71.6% and 84.5%, respectively. The mean recurrence rate was 29.1%. The weighted mean PPV and NPV were 56.4% and 92.8% (97.7% non-LG), respectively. The mean AUC was 85.63%. CONCLUSION: Bladder Epicheck® is a useful urinary marker in the follow-up of NMIBC, with significantly high Se and NPV in the detection of recurrences, especially in cases of HG disease. Its use can reduce the number of cystoscopies required in the follow-up of NMIBC, improving the quality of life of patients and potentially increasing health economic savings.

Extracellular vesicles in atherosclerosis: Current and forthcoming impact?

Atherosclerosis is the main pathogenic substrate for cardiovascular diseases (CVDs). Initially categorized as a passive cholesterol storage disease, nowadays, it is considered an active process, identifying inflammation among the key players for its initiation and progression. Despite these advances, patients with CVDs are still at high risk of thrombotic events and death, urging to deepen into the molecular mechanisms underlying atherogenesis, and to identify novel diagnosis and prognosis biomarkers for their stratification. In this context, extracellular vesicles (EVs) have been postulated as an alternative in search of novel biomarkers in atherosclerotic diseases, as well as to investigate the crosstalk between the cells participating in the processes leading to arterial remodelling. EVs are nanosized lipidic particles released by most cell types in physiological and pathological conditions, that enclose lipids, proteins, and nucleic acids from parental cells reflecting their activation status. First considered cellular waste disposal systems, at present, EVs have been recognized as active effectors in a myriad of cellular processes, and as potential diagnosis and prognosis biomarkers also in CVDs. This review summarizes the role of EVs as potential biomarkers of CVDs, and their involvement into the processes leading to atherosclerosis.

Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma / El valor de ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico del glioma

Background: Glioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. Methods: The miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan–Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. Results: HAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis.Conclusions: Normal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients.(AU)

Introducción: Los gliomas presentan una alta incidencia y un mal pronóstico, por lo que es necesario un tratamiento más efectivo. Algunos estudios han confirmado que los ARN no codificantes de cadena larga (ARNncl) regulan diferentes enfermedades, entre las que se incluyen los gliomas. Se ha postulado que HAS2-AS1 actúa como un ARNncl, con un efecto oncogénico en diferentes tipos de cáncer. Este estudio tiene como objetivo analizar el valor del ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico de glioma. Métodos: Descargamos los datos clínicos y de expresión de micro-ARN de la base de datos del Atlas del Genoma del Cáncer (TCGA) para realizar el análisis diferencial y de supervivencia. También analizamos la expresión de HAS2-AS1 en muestras patológicas y muestras de tejido adyacente normal de 80 pacientes con glioma. Para analizar la capacidad diagnóstica y el valor pronóstico de HAS2-AS1 en el glioma, recurrimos a la curva ROC. También utilizamos curvas de Kaplan-Meier para evaluar la supervivencia de los pacientes con glioma con diferentes niveles de expresión de HAS2-AS1. Resultados: La expresión de HAS2-AS1 era significativamente mayor en las muestras patológicas que en el tejido normal. Las curvas de supervivencia demostraron que la sobreexpresión de HAS2-AS1 estaba relacionada con una menor supervivencia general y supervivencia libre de progresión. Algunos factores clínico-patológicos de los pacientes con glioma, como el tamaño del tumor y su grado, según la clasificación de la OMS, mostraron una correlación significativa con la expresión de HAS2-AS1 en los tejidos afectados. La curva ROC mostró un área bajo la curva de 0,863, lo que indica que la expresión de HAS2-AS1 posee un importante valor diagnóstico. El área bajo la curva de la supervivencia general estimada fue de 0,906; para la supervivencia libre de progresión estimada, de 0,88. Ambos valores muestran que la sobreexpresión de HAS2-AS1 se asocia con un mal pronóstico...(AU)

Hemoglobina reticulocitaria en el diagnóstico precoz de la anemia por deficiencia de hierro / Reticulocyte hemoglobin in the early diagnosis of iron deficiency anemia / Hemoglobina de reticulócitos no diagnóstico precoce da anemia por deficiência de ferro

La anemia por deficiencia de hierro es un problema prevalente a nivel global que aparece en niños, adolescentes y mujeres en edad fértil, son los más afectados. La hemoglobina reticulocitaria es un nuevo biomarcador prometedor para el diagnóstico temprano. Objetivo. Evaluar la hemoglobina reticulocitaria para el diagnóstico precoz de anemia por deficiencia de hierro. Metodología. Se realizó una revisión sistemática en bases de datos biomédicas como PubMed, Scielo, Researchgate, Base, Cochrane Library y DOAJ; se incluyeron 24 estudios observacionales (2018-2023) sobre el uso de la hemoglobina reticulocitaria en el diagnóstico de anemia por deficiencia de hierro; se extrajeron datos sobre las características de los estudios, los valores de sensibilidad y especificidad de este biomarcador. Resultados. La hemoglobina reticulocitaria presentó una sensibilidad agrupada de 90% y una especificidad de 89,5% en los estudios analizados. También mostró una diferencia de medias significativa de -2,88 (IC 95%: -3,36 a -2,40) entre grupos con y sin anemia por deficiencia de hierro. Se encontró una heterogeneidad sustancial entre los resultados de los diferentes estudios (I2=95%; p<0,00001). Conclusión. La hemoglobina reticulocitaria demostró elevada sensibilidad y especificidad, así como una diferencia significativa entre grupos con y sin la condición, lo que evidencia su utilidad como prueba para la detección temprana de la anemia por deficiencia de hierro.

Iron deficiency anemia is a prevalent global health problem that appears in children, adolescents and women of childbearing age, who are the most affected. Reticulocyte hemoglobin is a promising new biomarker for early diagnosis. Objective. To evaluate reticulocyte hemoglobin for the early diagnosis of iron deficiency anemia. Methodology. A systematic review was conducted searching biomedical databases including PubMed, Scielo, Researchgate, Base, Cochrane Library and DOAJ; 24 observational studies (2018-2023) were included on the use of reticulocyte hemoglobin in the diagnosis of iron deficiency anemia; data were extracted on the characteristics of the studies and the sensitivity and specificity values of this biomarker. Results. Reticulocyte hemoglobin showed a pooled sensitivity of 90% and a specificity of 89.5% in the studies analyzed. It also showed a significant mean difference of -2.88 (95% CI: -3.36 to -2.40) between groups with and without iron deficiency anemia. Substantial heterogeneity was found among the results of the different studies (I2=95%; p<0.00001). Conclusion. Reticulocyte hemoglobin demonstrated high sensitivity and specificity, as well as a significant difference between groups with and without the condition, which shows its usefulness as a test for the early detection of iron deficiency anemia.

A anemia por deficiência de ferro é um problema de saúde global prevalente que aparece em crianças, adolescentes e mulheres em idade fértil, sendo os mais afetados. A hemoglobina reticulocitária é um novo biomarcador promissor para o diagnóstico precoce. Objetivo. Avaliar a hemoglobina reticulocitária para o diagnóstico precoce da anemia por deficiência de ferro. Metodologia. Foi realizada uma revisão sistemática com busca em bases de dados biomédicas incluindo PubMed, Scielo, Researchgate, Base Cochrane Library e DOAJ; foram incluídos 24 estudos observacionais (2018-2023) sobre o uso da hemoglobina reticulocitária no diagnóstico de anemia por deficiência de ferro; foram extraídos dados sobre as características dos estudos e os valores de sensibilidade e especificidade deste biomarcador. Resultados. A hemoglobina reticulocitária apresentou sensibilidade agrupada de 90% e especificidade de 89,5% nos estudos analisados. Também mostrou uma diferença média significativa de -2,88 (IC 95%: -3,36 a -2,40) entre grupos com e sem anemia por deficiência de ferro. Encontrou-se heterogeneidade substancial entre os resultados dos diferentes estudos (I2=95%; p<0,00001). Conclusão. A hemoglobina reticulocitária demonstrou elevada sensibilidade e especificidade, bem como uma diferença significativa entre grupos com e sem a condição, o que evidencia a sua utilidade como teste para a detecção precoce da anemia por deficiência de ferro.

Presence of subfoveal hyperreflective dots as an anatomic and functional prognostic biomarker in macular holes.

OBJECTIVE: To evaluate the presence of subfoveal hyperreflective dots (SfHD) using optical coherence tomography (OCT) in macular holes (MH) and establish whether there is a relationship with postoperative anatomical and functional outcomes. METHODS: An observational cross-sectional study was conducted at the Dr. Elías Santana Hospital. Sixty-eight eyes of 67 patients with a tomographic diagnosis of full-thickness MH who underwent pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. Preoperative and postoperative measurements were obtained using radial macular scans and HD raster scans with Optovue and Cirrus 5000 (Zeiss) OCT machines. The main outcome measures were anatomical closure by OCT and functional outcome through best-corrected visual acuity (BCVA). RESULTS: The anatomical closure rate in our study was 63%. MHs that failed to achieve anatomical closure exhibited a higher number of hyperreflective dots and worse postoperative BCVA. A statistically significant association was found between exposed retinal pigment epithelium (RPE) in microns and the number of SfHD (P = .001). CONCLUSION: SfHD is a common tomographic finding in MH, and the presence of a higher number of these points is associated with poorer anatomical and functional outcomes. This imaging finding is a potential prognostic biomarker in this pathology.

Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma.

BACKGROUND: Glioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. METHODS: The miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan-Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. RESULTS: HAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis. CONCLUSIONS: Normal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients. Therefore, HAS2-AS1 could be used as a diagnostic and prognostic marker for glioma.

Capacidad pronóstica del PIV (pan-immune-inflammation value) en pacientes con carcinoma escamoso de cabeza y cuello / Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma

Introducción: El PIV (pan-immune-inflammation value), un índice que resulta del cociente (neutrófilos×monocitos×plaquetas) / linfocitos, ha sido propuesto como un biomarcador con capacidad pronóstica en diferentes modelos tumorales. El objetivo del presente estudio es analizar la capacidad pronóstica del PIV en pacientes con carcinoma escamoso de cabeza y cuello. Pacientes y métodos: Estudio retrospectivo de 1.187 pacientes con carcinoma escamoso de cabeza y cuello tratados en nuestro centro durante el periodo 2000-2017. Se obtuvo el valor del PIV a partir de un análisis realizado en un intervalo inferior a las 3 semanas previas al inicio del tratamiento. Resultados: El valor del PIV se relacionó de forma significativa con el consumo de tóxicos (p=0,001), la localización del tumor (0,0001), la extensión tumoral (0,0001), y el grado histológico (0,016). Mediante un análisis de partición recursiva se definieron 4 categorías en función del valor del PIV: categoría i: PIV<136,3 (n=118; 9,9%), categoría ii: PIV 136,3-451,1 (n=594, 50,0%); categoría iii: PIV 451,1-1.141,2 (n=357; 30,1%); categoría iv: PIV>1.141,2 (n=118; 9,9%). Se pudo observar una reducción ordenada y significativa de la supervivencia específica a medida que se incrementaba la categoría en el valor del PIV. Esta disminución en la supervivencia se produjo de forma independiente al tipo de tratamiento, la extensión del tumor, o la localización del tumor primario. La categoría en el valor del PIV se relacionó de forma significativa con la supervivencia específica en un estudio multivariable. Conclusiones: El PIV es un biomarcador con capacidad pronóstica en los pacientes con carcinoma escamoso de cabeza y cuello.(AU)

Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methods: Retrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. Results: PIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. Conclusions: PIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.(AU)

Biomarcadores sanguíneos, de orina y conductas autolesivas e intentos de suicidio repetidos en los adolescentes / Blood and urine biomarkers and repeated self-injurious behaviors and suicide attempts in adolescents

Hay evidencia parcial de que los niveles elevados de la β-endorfina sanguínea se asocian a la adicción suicida en los adultos, pero apenas hay datos sobre los adolescentes. La β-endorfina sanguínea, con un importante papel en los mecanismos de gestión de las adicciones, puede inducir euforia y felicidad, recompensar y reforzar el comportamiento suicida. Para probar si los grandes repetidores de intentos de suicidio (5 o más intentos de suicidio) y de conductas autolesivas (20 o más episodios de autolesiones) tienen unos niveles de biomarcadores más elevados, se selecciona una muestra de 43 pacientes de entre 12 y 17 años que acuden al Servicio de Urgencias Psiquiátricas en el Hospital Universitario Puerta de Hierro Majadahonda. Diez presentan 5 o más intentos de suicidio, 35 presentan 20 o más episodios autolesivos y 10 presentan ambas características, y la mayoría de los adolescentes cumplían criterios de adicción para autolesiones y suicidio. Los resultados sugieren que todos los pacientes que presentaban adicción al suicidio también presentaban adicción a la autolesión. Los niveles de ACTH, cortisol y β-endorfina sanguíneos y de cortisol en orina fueron muy elevados, pero no diferenciaban a los grandes repetidores del resto de adolescentes. (AU)

There is partial evidence that elevated levels of blood β-endorphin are associated with suicidal addiction in adults, but hardly any data on adolescents. Blood β-endorphin, with an important role in addiction management mechanisms, can induce euphoria and happiness, reward and reinforce suicidal behavior. To test whether high repeaters of suicide attempts (5 or more suicide attempts) and self-injurious behaviors (20 or more episodes of self-injury) have higher biomarker levels, a sample of 43 patients aged 12-17 years attending the Psychiatric Emergency Department at the Hospital Universitario Puerta de Hierro Majadahonda is recruited. Ten present 5 or more suicide attempts, 35 present 20 or more self-injurious episodes and 10 present both characteristics, and most of the adolescents meet addiction criteria for self-injury and suicide. The results suggest that all patients with addiction to suicide also had addiction to self-injury. Blood ACTH, cortisol and β-endorphin and urine cortisol levels were very elevated, but did not differentiate heavy repeaters from the rest of the adolescents. (AU)

Utilidad de la región medial de la pro-adrenomodulina para la detección de bacteriemia verdadera en pacientes mayores atendidos en urgencias por sospecha de infección / Utility of the medial region of pro-adrenomodulin for the detection of true bacteremia in elderly patients treated in the emergency department for suspected infection

Introducción. La predicción de bacteriemia en urgencias es importante para la toma de decisiones iniciales. La población mayor un reto diagnóstico. El objetivo fue evaluar la capacidad de la región medial de la pro-adrenomodulina (MR-proADM) para identificar bacteriemia verdadera (BV) en pacientes mayores atendidos en tres servicios de urgencias. Metodología. Estudio observacional incluyendo pacientes ≥75 años atendidos por sospecha de infección en los que se extrajo un hemocultivo (HC). Se recogieron variables sociodemográficas, comorbilidad, hemodinámicas, analíticas y biomarcadores [MR-proADM, procalcitonina (PCT), proteína C reactiva (PCR) y lactato]. La variable de resultado fue un verdadero positivo en el hemocultivo. Resultados. Se incluyeron 109 pacientes con edad media de 83 (DE 5,5) años. En 22 pacientes (20,2%) se obtuvo un diagnóstico final de BV. Las variables independientes para predecirla fueron PCT (OR13,9; IC95%: 2,702-71,703; p=0,002), MR-proADM (OR4,081; IC95%: 1,026-16,225; p=0,046) y temperatura (OR 2,171; IC95%: 1,109-4,248; p=0,024). Considerando el punto de corte con mayor rendimiento diagnóstico para el MR-proADM (2,13 mg/dl), se obtuvo una sensibilidad (Se) de 73%, una especificidad (E) de 71%, un valor predictivo positivo (VPP) de 39%, un valor predictivo negativo (VPN) de 91%, un coeficiente de verosimilitud positivo (LHR+) de 2,53 y un coeficiente de verosimilitud negativo (LHR-) de 0,38; para PCT (0,76 mg/dl) se obtuvo una Se de 90%, E de 65%, VPP de 40%, VPN de 96%, LHR+ 2,64 y un LHR– de 0,14. Al combinar ambos, se observó una Se de 69%, E de 84%, VPP de 52%, VPN de 91%, LHR+ de 4,24 y un LHR- de 0,38. Conclusión. Niveles elevados de PCT y MR-proADM se asocian a un riesgo incrementado de BV y la combinación de ambos mejora la capacidad para identificar estos pacientes. (AU)

Background. The prediction of bacteremia in the emergency department (ER) is important for initial decision-making. The elderly population is a diagnosis challenge. The objective was to evaluate the accuracy of mid regional pro-adrenomedullin (MR-proADM) to identify true bacteremia (BV) in elderly patients attended in 3 hospital emergency departments. Methods. Observational study including patients ≥75 years of age or older attended in the ER for suspected infection in whom a blood culture (BC) was extracted. Sociodemographic, comorbidity, hemodynamic and analytical variables, biomarkers [MR-proADM, procalcitonin (PCT), C-reactive protein (CRP) and lactate] and final diagnosis were collected. The primary outcome was a true positive on a blood culture. Results. A total of 109 patients with a mean age of 83 (SD: 5.5) years were included. A final diagnosis of BV was obtained in 22 patients (20.2%). The independent variables to predict it were PCT (OR: 13.9; CI95%: 2.702-71.703; p=0.002), MR-proADM (OR: 4.081; CI95%: 1.026-16.225; p=0.046) and temperature (OR: 2.171; CI95%: 1.109-4.248; p=0.024). Considering the cut-off point for MR-proADM (2.13 mg/dl), a sensitivity (Se) of 73%, specificity (E) of 71%, a positive predictive value (PPV) of 39%, a negative predictive value (NPV) of 91%, a positive likelihood ratio (LHR+) of 2.53 and a negative likelihood ratio (LHR-) of 0.38; for PCT (0.76 mg/dl) a Se of 90%, E of 65%, PPV of 40%, NPV of 96%, LHR+ 2,64 and a LHR- of 0.14 were obtained. When combining both, a Se of 69%, E of 84%, PPV of 52%, NPV of 91%, LHR+ of 4.24 and LHR- of 0.38 were observed. Conclusions. Elevated levels of PCT and MR-proADM were independently associated with an increased risk of BV and the combination of both improves the accuracy to identify these patients. (AU)

Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma.

INTRODUCTION: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils × monocytes × platelets)/lymphocytes, has been proposed as a prognostic biomarker in different tumour models. The aim of this study is to analyse the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Retrospective study of 1187 patients with HNSCC treated at our centre between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. RESULTS: PIV value was significantly associated with toxic consumption (0.001), tumour location (0.0001), tumour extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category I: PIV < 136.3 (n = 118, 9.9%), category II: PIV 136.3-451.1 (n = 594, 50.0%), category III: PIV 451.1-1,141.2 (n = 357, 30.1%), and category IV: PIV > 1141.2 (n = 118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumour extension, or location of the primary tumour. The PIV category was and independent prognostic factor of disease-specific survival in a multivariable study. CONCLUSIONS: PIV is a prognostic biomarker in patients with HNSCC.

Diagnostic Efficacy of Fecal Calprotectin in Inflammatory Bowel Disease: Systematic Literature Review

Introduction: Inflammatory bowel disease is a group of pathologies that include ulcerative colitis and Crohn's disease, which have similar manifestations. Currently, the diagnosis and monitoring of this disease rely mainly on endoscopic studies. Still, this method can hardly be applied to periodic disease monitoring as it is expensive, invasive, and not readily available. Fecal calprotectin is widely known, easy to use, and affordable, and it is currently the best-characterized biomarker for this pathology. Materials and methods: The research design is a systematic diagnostic test validation literature review. A search was conducted in different databases using the QUADAS-2 checklist to evaluate the methodological quality. Results: The initial search yielded 352,843 articles published chiefly in PubMed, followed by Scopus and Science Direct. After multiple filters, 221 papers were selected and wholly reviewed. They were evaluated with inclusion and exclusion criteria, with 18 articles being chosen. Conclusions: Fecal calprotectin is a reliable surrogate marker of endoscopic activity in IBD. However, there is a lack of consensus on delimiting a cut-off point and improving applicability and diagnostic accuracy. Colonoscopy remains the gold standard in all studies.

Introducción: La enfermedad inflamatoria intestinal es un conjunto de patologías entre las que están incluidas la colitis ulcerativa y la enfermedad de Crohn, las cuales tienen presentación similar. En la actualidad, el diagnóstico y seguimiento de dicha enfermedad se basa principalmente en estudios endoscópicos, pero este método difícilmente puede aplicarse a la monitorización periódica de la enfermedad al ser costoso, invasivo y con disponibilidad limitada. La calprotectina fecal cumple con ser ampliamente disponible, fácil de usar y de precio asequible, y actualmente es el biomarcador mejor caracterizado para el uso en esta patología. Metodología: Diseño de investigación tipo revisión sistemática de la literatura de validación de prueba diagnóstica. Se realizó una búsqueda en diferentes bases de datos y para la evaluación de la calidad metodológica se empleó la lista verificación QUADAS-2. Resultados: La búsqueda inicial para la selección de los artículos arrojó un total de 352.843 artículos publicados principalmente en PubMed seguido de Scopus y Science Direct. Después de múltiples filtros se logró elegir 221 artículos, los cuales se llevaron a revisión completa. Se valoraron con criterios de inclusión y exclusión, lo que determinó la elección final de 18 artículos. Conclusiones: La calprotectina fecal es un marcador sustituto fiable de la actividad endoscópica en la EII. Se evidencia la falta de consenso para delimitar un punto de corte y mejorar la aplicabilidad y la precisión diagnóstica. La colonoscopia sigue siendo en todos los estudios el estándar de oro.

Capacidad predictiva de la expresión transcripcional de FAT1 en pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia / Predictive capacity of FAT1 transcriptional expression in patients with head and neck squamous cell carcinomas treated with radiotherapy

Objetivo Analizar la capacidad predictiva de la respuesta a nivel local de la expresión transcripcional de FAT1 en pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia.Material y métodosLlevamos a cabo un estudio retrospectivo realizado a partir de biopsias de la localización primaria del tumor en 82 pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia. Se determinó la expresión transcripcional de FAT1 mediante RT-PCR. Se categorizó el nivel de expresión transcripcional de FAT1 en función del control local tras el tratamiento con radioterapia mediante un análisis de partición recursiva.ResultadosLa expresión transcripcional elevada de FAT1 se relacionó con un incremento en el riesgo de recidiva local tras el tratamiento con radioterapia. Los pacientes con unos niveles de expresión elevada de FAT1 (n=18; 22,0%) tuvieron una supervivencia libre de recidiva local a los 5 años del 42,1% (IC 95%: 18,6-65,6%), en tanto que para los pacientes con una expresión baja (n=64; 78,0%) fue del 72,4% (IC 95%: 61,5-83,3%) (p=0,002). De acuerdo con el resultado de un análisis multivariante, los pacientes con una categoría de expresión elevada de FAT1 tuvieron un riesgo 2,3 veces superior de recidiva local (IC 95%: 1,0-5,2; p=0,043).ConclusionesLa expresión transcripcional elevada de FAT1 se relacionó con un incremento significativo del riesgo de recidiva local en los pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia. (AU)

Objective To analyze the predictive capacity at the primary location of the tumor of the FAT1 transcriptional expression in patients with head and neck squamous cell carcinoma treated with radiotherapy.Material and methodsWe conducted a retrospective study from biopsies of the primary location of the tumor in 82 patients with head and neck squamous cell carcinoma treated with radiotherapy. The transcriptional expression of FAT1 was determined by RT-PCR. The level of FAT1 transcriptional expression was categorized according to the local control after radiotherapy using a recursive partitioning analysis.ResultsElevated FAT1 transcriptional expression was associated with an increased risk of local recurrence after radiotherapy. Patients with a high expression level of FAT1 (n=18; 22.0%) had a 5-year local recurrence-free survival of 42.1% (95% CI: 18.6–65.6%), whereas for patients with a low expression (n=64; 78.0%) it was 72.4% (95% CI: 61.5%–83.3%) (P=0.002). According to the result of a multivariate analysis, patients with a high FAT1 expression category had a 2.3-fold increased risk of local recurrence (95% CI: 1.0–5.2; P=0.043).ConclusionsElevated FAT1 transcriptional expression was associated with a significantly increased risk of local recurrence in patients with head and neck squamous cell carcinoma treated with radiotherapy. (AU)

Predictive capacity of FAT1 transcriptional expression in patients with head and neck squamous cell carcinomas treated with radiotherapy.

OBJECTIVE: To analyze the predictive capacity at the primary location of the tumor of the FAT1 transcriptional expression in patients with head and neck squamous cell carcinoma treated with radiotherapy. MATERIAL AND METHODS: We conducted a retrospective study from biopsies of the primary location of the tumor in 82 patients with head and neck squamous cell carcinoma treated with radiotherapy. The transcriptional expression of FAT1 was determined by RT-PCR. The level of FAT1 transcriptional expression was categorized according to the local control after radiotherapy using a recursive partitioning analysis. RESULTS: Elevated FAT1 transcriptional expression was associated with an increased risk of local recurrence after radiotherapy. Patients with a high expression level of FAT1 (n=18; 22.0%) had a 5-year local recurrence-free survival of 42.1% (95% CI: 18.6%-65.6%), whereas for patients with a low expression (n=64; 78.0%) it was 72.4% (95% CI: 61.5%-83.3%) (p=0.002). According to the result of a multivariate analysis, patients with a high FAT1 expression category had a 2.3-fold increased risk of local recurrence (95% CI: 1.0-5.2; p=0.043). CONCLUSIONS: Elevated FAT1 transcriptional expression was associated with a significantly increased risk of local recurrence in patients with head and neck squamous cell carcinoma treated with radiotherapy.

La proteína meteorin-like se asocia a un perfil de mayor riesgo y predice un peor pronóstico en pacientes con IAMCEST / Meteorin-like protein is associated with a higher risk profile and predicts a worse outcome in patients with STEMI

Introducción y objetivos: La proteína meteorin-like (Metrnl) es una citocina implicada en la atenuación de la inflamación asociada a mal pronóstico en la insuficiencia cardiaca. En este estudio se evalúan los niveles circulantes de Metrnl y su valor pronóstico en el infarto agudo de miocardio con elevación del segmento ST (IAMCEST).Métodos: Se incluyó a pacientes con IAMCEST tratados con angioplastia primaria. Se determinaron los niveles de Metrnl en sangre periférica a las 12 horas del inicio de los síntomas. El criterio de evaluación primario fue muerte por cualquier causa o infarto de miocardio no mortal a 3 años.Resultados: Se estudiaron 381 pacientes (edad media 61 años, 21% mujeres, 8% clase Killip III/IV). Los niveles de Metrnl se asociaron con la edad, los factores de riesgo cardiovascular y la extensión de la enfermedad coronaria, pero también con complicaciones del infarto, especialmente insuficiencia cardíaca y shock cardiogénico. En la regresión multivariante de Cox Metrnl fue un predictor independiente del criterio de evaluación combinado (HR = 1,86; IC95%, 1,23-2,81; p=0,003). Además, los pacientes en el tercil más alto (> 491,6 pg/ml) presentaron mayor riesgo que en los terciles inferiores (HR = 3,24; IC95%, 1,92-5,44; p <0,001), incluso después de ajustar por edad, diabetes, paro cardíaco, clase Killip-Kimball III/IV, fracción de eyección y aclaramiento de creatinina (HR = 1,90; IC95%, 1,10-3,29; p=0,021).Conclusiones: En los pacientes con IAMCEST, los niveles circulantes de Metrnl se asocian con las complicaciones durante la fase aguda y predicen de forma independiente un peor pronóstico.(AU)

Introduction and objectives: Meteorin-like protein (Metrnl) is a cytokine involved in the attenuation of inflammation. In patients with heart failure, high levels of this biomarker are associated with a worse outcome. In this study, we evaluated the circulating levels and prognostic value of Metrnl in patients with ST-segment elevation myocardial infarction (STEMI).Methods: We enrolled STEMI patients undergoing primary percutaneous coronary intervention. Circulating Metrnl levels were measured in peripheral blood 12hours after symptom onset. The primary endpoint was a composite of all-cause mortality or nonfatal myocardial infarction (MI) at 3 years.Results: We studied 381 patients (mean age 61 years, 21% female, 8% Killip class III/IV). Metrnl levels were associated with age, cardiovascular risk factors and the extent of coronary artery disease, as well as with STEMI complications, particularly heart failure and cardiogenic shock. Multivariable Cox regression analysis revealed that Metrnl independently predicted all-cause death or nonfatal MI at 3 years (HR, 1.86; 95%CI, 1.23-2.81; P=.003). Moreover, patients in the highest tertile (> 491.6 pg/mL) were at higher risk for the composite endpoint than those in the lowest tertiles (HR, 3.24; 95%CI, 1.92-5.44; P <.001), even after adjustment by age, diabetes mellitus, cardiac arrest, Killip-Kimball III/IV class, left ventricular ejection fraction, and creatinine clearance (HR, 1.90; 95%CI, 1.10-3.29; P=.021).Conclusions: Circulating Metrnl levels are associated with complications during the acute phase of STEMI and independently predict a worse outcome in these patients.(AU)

Una imagen PET amiloide estática del primer minuto (FMF) se correlaciona con [18F]FDG PET en pacientes con afasia progresiva primaria / Static first-minute-frame (FMF) PET imaging after 18F-labeled amyloid tracer injection is correlated to [18F]FDG PET in patients with primary progressive aphasia

Objetivo Estudiar la correlación entre una imagen PET estática del primer minuto (FMF) adquirida con radiotrazadores de amiloide marcados con flúor-18 y la PET cerebral con [18F]FDG en pacientes con afasia primaria progresiva (APP). Material y métodos La cohorte de estudio incluyó a 17 pacientes diagnosticados de APP con la siguiente distribución: 9APP variante no fluente, 4APP variante logopénica, 1APP variante semántica, 3APP inclasificables. Se extrajeron los SUVR regionales de las FMF y sus correspondientes imágenes PET con [18F]FDG y se calcularon los coeficientes de correlación de Pearson. Resultados Los SUVR de ambas imágenes mostraron patrones similares de alteración cerebral regional. Los análisis de correlación intrapaciente dieron como resultado un coeficiente medio de r=0,94 ±0,06. Los coeficientes de correlación regional entre pacientes de la cohorte del estudio fueron superiores a 0,81. Las subcohortes específicas según el radiotrazador y la variante de APP no mostraron diferencias en la similitud de las imágenes. Conclusiones La FMF estática podría ser una alternativa válida a la PET dinámica de amiloide en fase inicial propuesta en la literatura, así como un biomarcador de neurodegeneración para el diagnóstico y la clasificación de la APP en los estudios de PET amiloide (AU)

Objective To study the correlation between a static PET image of the first-minute-frame (FMF) acquired with 18F-labeled amyloid-binding radiotracers and brain [18F]FDG PET in patients with primary progressive aphasia (PPA). Material and methods The study cohort includes 17 patients diagnosed with PPA with the following distribution: 9nonfluent variant PPA, 4logopenic variant PPA, 1semantic variant PPA, 3unclassifiable PPA. Regional SUVRs are extracted from FMFs and their corresponding [18F]FDG PET images and Pearson's correlation coefficients are calculated. Results SUVRs of both images show similar patterns of regional cerebral alterations. Intrapatient correlation analyses result in a mean coefficient of r=.94 ±.06. Regional interpatient correlation coefficients of the study cohort are greater than 0.81. Radiotracer-specific and variant-specific subcohorts show no difference in the similarity between the images. Conclusions The static FMF could be a valid alternative to dynamic early-phase amyloid PET proposed in the literature, and a neurodegeneration biomarker for the diagnosis and classification of PPA in amyloid PET studies (AU)

Cortisol response to traumatic stress to predict PTSD symptom development - a systematic review and meta-analysis of experimental studies.

Background: Pre-and post-traumatic hypothalamic-pituitary-adrenal (HPA) axis markers have been studied to predict posttraumatic stress disorder (PTSD) risk, but its acute reactivity cannot be measured in real-life settings. Experimental paradigms can depict the cortisol response to stimuli that simulate traumatic events.Objective: To review experimental studies on the cortisol response to traumatic stimuli and the correlation between cortisol and PTSD symptoms.Method: Experimental, (un-)published studies in German or English from any year were eligible if they confronted non-traumatized humans with traumatic stimuli, assessed cortisol before, during or after stimulus presentation and subsequent PTSD symptoms. The literature was searched via PubMed, PubPsych, PsychINFO, PsycArticle, Web of Science, EMBASE, ProQuest and ClinicalTrials.gov up to 16th February 2021. Risk of bias was assessed with the Cortisol Assessment List. Multilevel-meta-analyses were conducted under the random effects model. The standardized mean change (dSMC) indicated the cortisol response. Coefficient r indicated the correlations between cortisol and PTSD symptoms.Results: 14 studies, investigating 1004 individuals, were included. A cortisol response was successfully induced between 21 and 40 min post-presentation onset (kobservations = 25, dSMC = 0.15 [.03; .26]). Cortisol was not associated with overall or cluster-level PTSD symptoms. On a symptom-level, higher pre-presentation onset cortisol was correlated with lower state tension (k = 8, r = -.18 [-.35; -.01]), higher state happiness (k = 8, r = -.34 [-.59; -.03], variable inverted) and lower state anger (k = 9, r = -.14 [-.26; -.01]). Higher post-presentation onset cortisol was correlated with higher state happiness (k = 16, r = -.20 [-.33; -.06]) and lower state sadness (k = 17, r = -.16 [-.25; -.05]), whereas cortisol response was positively correlated with state anxiety (k = 9, r = .16 [0.04; 0.27]).Conclusions: Experimental paradigms effectively induce a cortisol response. Higher basal cortisol, higher cortisol, as measured after traumatic stimulus presentation, and a lower cortisol response were associated with more adaptive emotional reactions. These markers did not predict longer-term PTSD symptoms.

Experimental trauma paradigms successfully induced a cortisol response.Cortisol was predictive for single state, emotion-related symptoms, but not overall PTSD symptoms.Trauma paradigms shed light into the immediate post-trauma period that is hard to capture in real life, but the gap between experimental and naturalistic settings is difficult to overcome.

Influencia de factores endógenos (edad y sexo) en los niveles de biomarcadores de estrés oxidativo en alcatraz (Morus bassanus) / Influence of endogenous factors (age and sex) on the levels of oxidative stress biomarkers in Northern gannet (Morus bassanus)

Las aves marinas pueden ser utilizadas como bioindicadoras de las alteraciones del ambiente en que residen, identificándose en ellas distintos biomarcadores, que no informen sobre los niveles cuantitativos de contaminantes sino sobre los efectos adversos subclínicos que dichos agentes pueden causar. En el presente trabajo se han analizado los niveles de Malondialdehído (MDA) y de actividad Glutatión-S-Transferasa (GST) en muestras de hígado y riñón de 30 alcatraces (Morus bassanus) procedentes de las costas de Galicia, como posibles indicadores de estrés oxidativo en las aves. Además, se ha determinado la influencia de dos factores endógenos (sexo y edad) sobre los niveles de estos biomarcadores. En hígado los valores medios de MDA obtenidos fueron de 0,508±0,502 nmol/mg proteína, mientras que en riñón fueron de 15,67±12,18 nmol/mg proteína. La actividad GST media en hígado fue de 10,93±7,067 nmol/min/mg proteína, mucho menor que la media de los valores en riñón, que fue 62,30±26,97 nmol/min/mg proteína. En cuanto a las variaciones respecto a la edad, solo se encontraron diferencias estadísticamente significativas en riñón en la actividad GST, siendo mayor la actividad de esta enzima en alcatraces adultos que en inmaduros. Por su parte, el factor sexo no influyó en los niveles de ninguno de los biomarcadores considerados. Los resultados obtenidos apuntan a que ambos biomarcadores podrían ser de utilidad en programas de biomonitorización de contaminación ambiental centrados en el alcatraz, aunque serían necesarios estudios que consideren un mayor número de animales, incorporando un abanico más amplio de biomarcadores. (AU)

Seabirds can be used as bioindicators of changes in the environment in which they live, identifying different biomarkers in them, which do not provide information on the quantitative levels of contaminants, but on the subclinical adverse effects that these agents can cause. At the present study, the levels of Malondialdehyde (MDA) and glutathione-S-transferase (GST) activity in liver and kidney samples of 30 gannets (Morus bassanus) from the coast of Galicia have been determined, as suitable biomarkers of oxidative stress on birds. In addition, the influence of two endogenous factors (sex and age) on the levels of these biomarkers has been determined. In the liver, the mean values of MDA were 0.508 ± 0.502 nmol/mg protein, while in kidney they were 15.67 ± 12.18 nmol/mg protein. On the other hand, mean GST activity in the liver was 10.93 ± 7.067 nmol/min/mg protein, much lower than the mean activity values found in kidney, which were 62.30 ± 26.97 nmol/min/mg protein. Regarding the variations with respect to age, statistically significant differences were only found in the kidney in GST activity, the activity of this enzyme being higher in adult gannets than in immature ones. Secondly, the gender factor did not influence the levels of any of the biomarkers considered. The obtained results indicate that both biomarkers could be useful in biomonitoring programs of environmental contamination focused on the gannet, although studies that consider a larger number of animals, incorporating a broader range of biomarkers, would be necessary. (AU)

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype.

BACKGROUND: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). CASE REPORT: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. CONCLUSIONS: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

INTRODUCCIÓN: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. CASO CLÍNICO: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. CONCLUSIONES: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.