Risk Factors in Serrated Pathway Lesions: N-Glycosylation Profile as a Potential Biomarker of Progression to Malignancy.

Introduction: The serrated pathway contributes to interval colorectal cancers, highlighting the need for new biomarkers to assess lesion progression risk. The ß1,6-GlcNAc branched N-glycans expression in CRC cells was associated with an invasive phenotype and with immune evasion. Therefore, this study aims to identify potential risk factors for progression of serrated lesions (SLs) to malignancy, analyzing the N-glycosylation profile of epithelial/infiltrating immune cells. Methods: A retrospective cohort study was performed with data from 53 colonoscopies (48 patients). Sixty-three serrated pathway lesions (SPLs) were characterized based on N-glycosylation profile (lectin histochemistry/flow cytometry) and MGAT5 expression. Statistical analysis was performed to search for associations between the glycoprofile and clinical variables from each patient. Results: Increased ß1,6-GlcNAc branched N-glycans expression in epithelial cells is found associated with age (p = 0.007 in SPL), smoking (p = 0.038 in SL), increased BMI (p = 0.036 in sessile serrated lesions [SSL]), and polyp dimensions ≥10 mm (p = 0.001 in SL), while increased expression of these structures on immune cells is associated with synchronous CA number (CD4+T cells: p = 0.016; CD8+T cells: p = 0.044 in SL) and female gender (p = 0.026 in SL). Moreover, a lower high-mannose N-glycans expression in immune cells is associated with smoking (p = 0.010 in SPL) and synchronous CA presence (p = 0.010 in SPL). Higher expression of these glycans is associated with female (p = 0.016 in SL) and male (p = 0.044 in SL) gender, left colon location (p = 0.028), dysplasia (p = 0.028), and adenocarcinoma (p = 0.010). Conclusions: We identified an association between an abnormal glycoprofile and several clinical risk factors, proposing the N-glycosylation profile as a potential biomarker of tumor progression in the serrated pathway. The N-glycosylation anatomopathological profile analysis could be further used to decide shorter interval follow-up in patients with SPL.

Introdução: A via serreada contribui para os cancros colorretais de intervalo, destacando a necessidade de novos biomarcadores para determinar o risco de progressão destas lesões. A expressão de ß1,6-GlcNAc N-glicanos ramificados foi associada a um fenótipo invasivo e a evasão imune. Assim, este estudo tem como objetivo identificar potenciais fatores de risco de progressão das lesões serreadas para malignidade, analisando o perfil de N-glicosilação das células epiteliais/células imunitárias. Métodos: Foi realizado um estudo retrospetivo com dados de 53 colonoscopias (48 doentes). 63 lesões da via serreada foram caracterizadas segundo o perfil de N-glicosilação (histoquímica de lectinas/citometria de fluxo) e expressão de MGAT5. A análise estatística foi realizada para encontrar associações entre o perfil de N-glicosilação e as variáveis clínicas de cada doente. Resultados: O aumento da expressão de ß1,6-GlcNAc N-glicanos ramificados nas células epiteliais encontra-se associado com a idade (p = 0.007 nas SPL), tabagismo (p = 0.038 nas SL), aumento do BMI (p = 0.036 nas SSL), e pólipos com dimensões ≥10 mm (p = 0.001 nas SL), enquanto que o aumento destas estruturas nas células imunitárias está associado com o número de CA síncronos (células TCD4+: p = 0.016; células TCD8+: p = 0.044 nas SL) e o género feminino (p = 0.026 nas SL). Além disso, uma diminuição da expressão de N-glicanos ricos em manose está associada ao tabagismo (p = 0.010 para SPL) e a presença de adenomas síncronos (p = 0.010 nas SPL). A expressão aumentada destas estruturas está associado com o género feminino (p = 0.016 nas SSL), género masculino (p = 0.044 nas SSL), localização no cólon esquerdo (p = 0.028), displasia (p = 0­028) e adenocarcinoma (p = 0.010). Discussão/Conclusão: Identificámos uma associação entre um perfil de glicosilação anormal e vários fatores de risco clínicos, propondo o perfil de N-glicosilação como um potencial biomarcador de progressão tumoral na via serreada. A análise anatomopatológica do perfil de N-glicosilação pode vir a ser usada para decidir intervalos de follow-up mais curtos em doentes com SPL.

The cross-sectional area of the median nerve: An independent prognostic biomarker in amyotrophic lateral sclerosis.

INTRODUCTION: Ultrasound changes in the cross-sectional area of the median nerve (CSAmn) could be of interest as biomarkers in patients with amyotrophic lateral sclerosis (ALS). METHODS: Eighty-four ALS patients (51 men [60.7%]; mean 62.0 [SD 11.46] years old) and forty-six controls (27 men [58.7%]; mean 59.9 [SD 8.08] years old) of two different cohorts were recruited between September 2013 and February 2018. The CSAmn was measured bilaterally in each cohort, by two different examiners with two different ultrasound machines (one in each cohort). Its association with clinical variables (disease duration, muscle strength, disability, progression rate and tracheostomy-free survival) was assessed. RESULTS: The CSAmn was smaller in patients than in controls, and the study cohort did not influence its values. A mild correlation between the strength of the wrist flexor and the CSAmn was found. In the multivariable analysis, the probability of this association being true was 90%. In the cox regression, both a faster progression rate and a larger CSAmn independently predicted poor survival (HR=4.29, [Cr.I95%: 2.71-6.80], p<0.001; and HR=1.14, [Cr.I95%: 1.03-1.25], p=0.01), after adjusting by age, body mass index, bulbar onset, and diagnostic delay. CONCLUSIONS: The CSAmn is an easy to assess biomarker that seems reliable and reproducible. Our data also suggest that it could act as a progression and prognostic biomarker in ALS patients. Longitudinal studies with repeated measures are warranted to confirm its usefulness in the clinical practice.

Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis.

INTRODUCTION: Despite the key role of the endothelium in atherosclerosis, there are no direct techniques for its analysis. The study of extracellular vesicles of endothelial origin (EEVs), might lead to the identification of molecular signatures and early biomarkers of atherosclerosis. The aim of this work was to set up the methods for EEVs separation and transcriptomic analysis. METHODS: We adapted an antibody-magnetic-bead based immunocapture protocol for plasma EEVs separation from control (G1), subclinical atherosclerosis (G2) and peripheral artery disease subjects (PAD) (G3), and modified an ultra-low input RNASeq method (n=5/group). By bioinformatics analysis we compared the transcriptome of plasma EEVs with that of human aortic endothelial cells (TeloHAECs), and then, searched for differentially expressed genes (DEG) among EEVs of G1, G2 and G3. From those DEG, UCP2 was selected for further validation in plasma EVs (qPCR), and in vitro, in stimulated TeloHAECs (IL-1ß, TNFα, oxLDL and hypoxia). RESULTS: The RNASeq analysis of plasma EEVs rendered 1667 genes enriched in transcripts expressed by TeloHAECs (NES: 1.93, p adjust=1.4e-73). One hundred seventy DEGs were identified between G2 vs G1, and 180 between G3 vs G1, of which 17 were similarly expressed in G2 and G3 vs control, including UCP2. IL-1ß and TNFα (10ng/mL, p<0.05), hypoxia (1% O2, p=0.05) and oxLDL (100µg/mL, p=0.055) reduced UCP2 expression in TeloHAECs. CONCLUSIONS: We set up a protocol for EEVs separation and sequencing that might be useful for the identification of early markers of endothelial dysfunction in atherosclerosis.

Effects of Bisphenol A on Male Gonadal Tissue of Viviparous Fish: Histopathological Evidence in Goodea atripinnis / Efectos del Bisfenol A en tejido Gonadal Masculino de Peces Vivíparos: Evidencia Histopatológica en Goodea atripinnis

SUMMARY: BPA is a multifunctional endocrine disruptor with ubiquitous presence in aquatic ecosystems. The Mexican Central Plateau is an area severely impacted by pollution, inhabited by endemic viviparous fish. However, efforts to understand the effects of BPA on native species such as Goodea atripinnis are non-existent. This study focused on providing in vivo evidence of alterations in the testes of G. atripinnis males due to acute exposure to BPA at test concentrations of 1 mg/L, 10 mg/L, and 50 mg/L for 96 h. BPA exposition 1 mg/L and 10 mg/L showed degeneration and disorganization in germinal tissue. Furthermore, there was a notable decrease in sperm within the seminiferous tubules of males exposed to 10 mg/L of BPA. In all treatments, somatic cells had alterations by connective tissue thickening and an increase in collagen fibers. Additionally, inflammation and bleeding occurred in the testes of males exposed to 1 and 10 mg/L BPA. The alterations in the testes of G. atripinnis are related to BPA toxicity, which can lead to apoptosis in germ cells increasing connective tissue. Finally, even though the changes produced by BPA became evident in acute exposure (96 h), its effects are probably irreversible, compromising the reproduction of G. atripinnis.

El BPA es un disruptor endocrino multifuncional con presencia ubicua en los ecosistemas acuáticos. La Meseta Central mexicana habitada por peces vivíparos endémicos, es una zona severamente impactada por la contaminación. Sin embargo, los esfuerzos por comprender los efectos del BPA en especies nativas como Goodea atripinnis son inexistentes. Este estudio se centró en proporcionar evidencia in vivo de alteraciones en los testículos de machos de G. atripinnis debido a la exposición aguda al BPA en concentraciones de prueba de 1 mg/L, 10 mg/L y 50 mg/L durante 96 h. La exposición a BPA 1 mg/L y 10 mg/L mostró degeneración y desorganización en el tejido germinal. Además, hubo una disminución notable de los espermatozoides dentro de los túbulos seminíferos de machos expuestos a 10 mg/L de BPA. En todos los tratamientos las células somáticas presentaron alteraciones por engrosamiento del tejido conectivo y aumento de las fibras de colágeno. Además, se produjo inflamación y sangrado en los testículos de machos expuestos a 1 y 10 mg/L de BPA. Las alteraciones en los testículos de G. atripinnis están relacionadas con la toxicidad del BPA, lo que puede provocar apoptosis en las células germinales aumentando el tejido conectivo. Finalmente, si bien los cambios producidos por el BPA se hicieron evidentes en la exposición aguda (96 h), sus efectos probablemente sean irreversibles, comprometiendo la reproducción de G. atripinnis.

Biomarkers: how to consolidate them in clinical practice.

An inadequate biomarker validation can affect many patients' diagnosis, treatment, and follow-up. Therefore, special interest should be placed on performing these analyses correctly so that biomarkers can be applicable to patients and evidence of their clinical usefulness can be generated. A methodological work on the concept of biomarkers is presented, as well as the difficulties associated with the methodological approach to their development, validation, and implementation in clinical practice.

[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.

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 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)

Use of Bladder Epicheck® in the follow-up of 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.

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)

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.

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.

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.

Duplicación interna en tándem del gen de la tirosina quinasa 3

Introducción: La reacción en cadena de la polimerasa requiere de varios procedimientos y controles para garantizar la eficacia del estudio. Se debe realizar un control de calidad a la reverso transcripción con el fin de determinar la efectividad del proceso y pasar a la siguiente etapa. Se comprueba con la amplificación de un gen normal, que se interpreta mediante electroforesis. Por dificultades en la importación de reactivos, se propuso sustituir este paso por la identificación del gen de la tirosina quinasa 3, que en la leucemia mieloide aguda puede afectarse por una mutación del tipo duplicación interna en tándem. Objetivo: Evaluar si el biomarcador duplicación interna en tándem del gen de la tirosina quinasa 3 es útil como control del proceso de reverso transcripción dentro de la técnica de reacción en cadena de la polimerasa para los estudios moleculares. Métodos: Se analizaron 235 muestras de aspirado medular de pacientes hematológicos, en el laboratorio de biología molecular del Instituto de Hematología e Inmunología entre junio de 2017 y junio de 2019. Resultados: El 85,53 % presentó solo una banda en la electroforesis capilar, correspondiente al alelo salvaje, y en el resto se observaron la banda normal y la correspondiente al alelo mutado. De esta forma, se comprobó la presencia de ADN complementario en todas las muestras. Conclusiones: La sustitución del control basado en un gen normal, por el biomarcador duplicación interna en tándem del gen de la tirosina quinasa 3 dentro de la técnica de reacción en cadena de la polimerasa, se realiza como parte del protocolo de laboratorio para el estudio de pacientes con enfermedades oncohematológicas.

Introduction: The polymerase chain reaction requires several procedures and controls to ensure the quality of the study. Quality control must be performed on the reverse transcript in order to determine the effectiveness of the process and move to the next step. It is checked with the amplification of a normal gene, which is interpreted by electrophoresis. Due to difficulties in importing reagents, it was proposed to replace this step with the identification of the tyrosine kinase 3 gene, which in acute myeloid leukemia can be affected by an internal tandem duplication type mutation. Objective: To evaluate whether the biomarker internal tandem duplication of the tyrosine kinase 3 gene is useful as a control of the reverse transcription process within the polymerase chain reaction technique for molecular studies. Methods: 235 bone marrow aspirate samples from hematological patients were analyzed in the molecular biology laboratory of the Institute of Hematology and Immunology between June 2017 and June 2019. Results: 85.53% presented only one band in capillary electrophoresis, corresponding to the wild-type allele, and in the rest, the normal band and the band corresponding to the mutated allele were observed. Thus, the presence of cDNA was verified in all samples. Conclusions: The substitution of the control based on a normal gene, by the biomarker internal tandem duplication of the tyrosine kinase 3 gene, within the polymerase chain reaction technique, is possible and, moreover, useful as part of the laboratory protocol for the study of patients with oncohematological diseases.

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)

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.