Metabolic-associated fatty liver voxel-based quantification on CT images using a contrast adapted automatic tool.

BACKGROUND & AIMS: Metabolic-dysfunction associated fatty liver disease (MAFLD) is highly prevalent and can lead to liver complications and comorbidities, with non-invasive tests such as vibration-controlled transient elastography (VCTE) and invasive liver biopsies being used for diagnosis The aim of the present study was to develop a new fully automatized method for quantifying the percentage of fat in the liver based on a voxel analysis on computed tomography (CT) images to solve previously unconcluded diagnostic deficiencies either in contrast (CE) or non-contrast enhanced (NCE) assessments. METHODS: Liver and spleen were segmented using nn-UNet on CE- and NCE-CT images. Radiodensity values were obtained for both organs for defining the key benchmarks for fatty liver assessment: liver mean, liver-to-spleen ratio, liver-spleen difference, and their average. VCTE was used for validation. A classification task method was developed for detection of suitable patients to fulfill maximum reproducibility across cohorts and highlight subjects with other potential radiodensity-related diseases. RESULTS: Best accuracy was attained using the average of all proposed benchmarks being the liver-to-spleen ratio highly useful for CE and the liver-to-spleen difference for NCE. The proposed whole-organ automatic segmentation displayed superior potential when compared to the typically used manual region-of-interest drawing as it allows to accurately obtain the percent of fat in liver, among other improvements. Atypical patients were successfully stratified through a function based on biochemical data. CONCLUSIONS: The developed method tackles the current drawbacks including biopsy invasiveness, and CT-related weaknesses such as lack of automaticity, dependency on contrast agent, no quantification of the percentage of fat in liver, and limited information on region-to-organ affectation. We propose this tool as an alternative for individualized MAFLD evaluation by an early detection of abnormal CT patterns based in radiodensity whilst abording detection of non-suitable patients to avoid unnecessary exposure to CT radiation. Furthermore, this work presents a surrogate aid for assessing fatty liver at a primary assessment of MAFLD using elastography data.

Comparison of Extracellular Vesicle Isolation Methods for miRNA Sequencing.

MicroRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) are potential diagnostic and prognostic biomarkers. However, discrepancies in miRNA patterns and their validation are still frequent due to differences in sample origin, EV isolation, and miRNA sequencing methods. The aim of the present study is to find a reliable EV isolation method for miRNA sequencing, adequate for clinical application. To this aim, two comparative studies were performed in parallel with the same human plasma sample: (i) isolation and characterization of EVs obtained using three procedures: size exclusion chromatography (SEC), iodixanol gradient (GRAD), and its combination (SEC+GRAD) and (ii) evaluation of the yield of miRNA sequences obtained using NextSeq 500 (Illumina) and three miRNA library preparation protocols: NEBNext, NEXTFlex, and SMARTer smRNA-seq. The conclusion of comparison (i) is that recovery of the largest amount of EVs and reproducibility were attained with SEC, but GRAD and SEC+GRAD yielded purer EV preparations. The conclusion of (ii) is that the NEBNext library showed the highest reproducibility in the number of miRNAs recovered and the highest diversity of miRNAs. These results render the combination of GRAD EV isolation and NEBNext library preparation for miRNA retrieval as adequate for clinical applications using plasma samples.

Dasatinib-Induced Chylothorax: A Clinical Laboratory's Perspective.

Dasatinib is a tyrosine kinase inhibitor drug used for chronic myeloid leukaemia (CML) treatment. Chylothorax has been rarely reported as a secondary effect of dasatinib occurring especially in long-term treated patients, although its pathophysiology is not yet fully understood. Laboratory analysis of the pleural effusion is crucial for chylothorax diagnosis. We report a case of a 53-year-old male patient presenting a chylothorax after 14 years of dasatinib therapy where the clinical laboratory was key in the diagnosis.

Insights into Insulin Resistance and Calcification in the Myocardium in Type 2 Diabetes: A Coronary Artery Analysis.

Type 2 diabetes (T2D) is responsible for high incidence of cardiovascular (CV) complications leading to heart failure. Coronary artery region-specific metabolic and structural assessment could provide deeper insight into the extent of the disease and help prevent adverse cardiac events. Therefore, in this study, we aimed at investigating such myocardial dynamics for the first time in insulin-sensitive (mIS) and insulin-resistant (mIR) T2D patients. We targeted global and region-specific variations using insulin sensitivity (IS) and coronary artery calcifications (CACs) as CV risk factor in T2D patients. IS was computed using myocardial segmentation approaches at both baseline and after an hyperglycemic-insulinemic clamp (HEC) on [18F]FDG-PET images using the standardized uptake value (SUV) (ΔSUV = SUVHEC - SUVBASELINE) and calcifications using CT Calcium Scoring. Results suggest that some communicating pathways between response to insulin and calcification are present in the myocardium, whilst differences between coronary arteries were only observed in the mIS cohort. Risk indicators were mostly observed for mIR and highly calcified subjects, which supports previously stated findings that exhibit a distinguished exposure depending on the impairment of response to insulin, while projecting added potential complications due to arterial obstruction. Moreover, a pattern relating calcification and T2D phenotypes was observed suggesting the avoidance of insulin treatment in mIS but its endorsement in mIR subjects. The right coronary artery displayed more ΔSUV, whilst plaque was more present in the circumflex. However, differences between phenotypes, and therefore CV risk, were associated to left descending artery (LAD) translating into higher CACs regarding IR, which could explain why insulin treatment was effective for LAD at the expense of higher likelihood of plaque accumulation. Personalized approaches to assess T2D may lead to more efficient treatments and risk-prevention strategies.

Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice.

BACKGROUND: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. METHODS: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic-euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. RESULTS: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. CONCLUSIONS: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.

Niveles de PAPP-A y fßhCG en gestantes gemelares monocoriónicas y bicoriónicas espontáneas y sus implicaciones en el cálculo del riesgo del cribado prenatal del primer trimestre / Papp-a and ß - hCG levels in spontaneous monochorionic and dichorionic twin pregnancies and their implications in calculating the prenatal risk in first trimester screening

Objetivo: Evaluar los niveles de distribución de los valores bioquímicos de PAPP-A y fßhCG según su edad gestacional, en gestaciones gemelares monocoriónicas y bicoriónicas concebidas espontáneamente en nuestra población. Material y métodos: Se ha estudiado un grupo de 123 gestantes gemelares. Un subgrupo de 72 gestantes gemelares bicoriónicas, con una edad media de 32,1 años, y otro de 41 gestantes gemelares monocoriónicas, con una edad media de 31,1 años. Resultados: Las gestantes gemelares bicoriónicas presentan valores estadísticamente superiores a las monocoriónicas para los valores de las medias de PAPP-A (MoM) (2,55 versus 1,79; p < 0,001) y de fßhCG (MoM) (2,18 versus 1,70; p < 0,001), y no estadísticamente significativos en las medias de la translucencia nucal (Tn) (MoM) (0,96 versus 0,93; p = 0,3). Se analizan las diferentes distribuciones de las concentraciones de las curvas de normalidad de estos parámetros según edad gestacional y corionicidad. Conclusiones: Es necesario determinar ecográficamente si los gemelos son mono- o bicoriónicos ya que hemos comprobado que en nuestra población presentan curvas de normalidad diferenciadas para PAPP-A y fßhCG, utilizadas para el cálculo del riesgo de aneuploidías en el cribado prenatal de primer trimestre (AU)

Objective: To analyse the distribution of PAPP-A and fß-hCG levels in monochorionic and dichorionic twin pregnancies conceived spontaneously in our population. Materials and methods: One hundred twenty-three twin pregnancies were studied. A group of 72 dichorionic twin pregnancies, with an average age of 32.1 years, and another 32 monochorionic twin pregnancies, with an average age of 31.1 years. Results: Dichorionic twin pregnancies conceived spontaneously show values statistically higher than monochorionic of PAPP-A (MoM) (2.55 versus 1.79, P>.001) and fβHCG (MoM) (2.18 versus 1.70, P>.001). There were no significant differences in nuchal traslucency (NT) between both groups (MoM) (0.96 versus 0.93, P=.3). The distributions of PAPP-A and fßhCG levels according the gestation age and chorionic state have been studied. Conclusions: Ultrasound needs to be performed to determine whether twins are mono- or bichorionics as our population has different distribution curves for PAPP-A and fßhCG, which are used to calculate the first trimester prenatal risk (AU)

Niveles de PAPP-A y fßhCG en gestantes gemelares bicoriónicas concebidas por técnicas de reproducción asistida (FIV-IAH) y sus implicaciones en el cálculo del riesgo del cribado prenatal del primer trimestre / PAPP-A and fBhCG levels in dichorionic twin pregnancies conceveid by assisted reproductive technologies (IVF-AIH) and their implications to calculate the prenatal risk on first trimestry

Objetivo: Evaluar los niveles de proteína plasmática placentaria (PAPP-A) y fracción libre de la βhCG (fßhCG) en gestaciones gemelares bicoriónicas concebidas mediante técnicas de reproducción asistida tipo fertilización in vitro (FIV) o inseminación artificial (IA) en nuestra población. Posterior cálculo de los factores de corrección necesarios a aplicar para el screening de primer trimestre en gestantes gemelares concebidas mediante FIV. Población en estudio: Se han estudiado 171 gestantes gemelares. Un grupo compuesto por 71 gestaciones bicoriónicas concebidas mediante FIV, con una edad media de 36,3 años; un grupo control de 76 gestaciones bicoriónicas concebidas por gestación espontánea, con una edad media de 31,8 años; y un último grupo de 24 gestaciones bicoriónicas concebidas por IA, con una edad media de 32,9 años. Resultados: Las gestantes gemelares bicoriónicas concebidas mediante FIV respecto el grupo control, concebidas espontáneamente, presentan unos niveles estadísticamente inferiores de PAPP-A (2,17 MoM versus 2,41 MoM, p<0,008) y valores superiores no significativos de fßhCG (2,33 MoM versus 2,05 MoM, p=0,144). Las medias de la translucencia nucal (Tn) entre ambos grupos tampoco muestran diferencias significativas (p=0,178). Esta misma tendencia se observa en los valores de PAPPA y fßhCG para las gestaciones concebidas mediante IA, pero con un número menor de gestantes no significativo. Conclusiones: Las mujeres con gestaciones gemelares concebidas por técnicas de reproducción asistida han sido sometidas a tratamientos para la estimulación de la ovulación. Este hecho se ha postulado como una de las causas que podrían explicar la presencia de valores de PAPP-A significativamente inferiores y de fßhCG superiores, aunque no significativos, a las gestantes gemelares espontáneas. Por ello se aconseja la elaboración de curvas propias con gestantes gemelares FIV, o en su defecto, el empleo de factores de corrección para disminuir este efecto. Se comprueba que con la aplicación de estos factores de corrección la tasa de falsos positivos de los gemelares bicoriónicos concebidos por FIV baja de 4,22% a 1,41% en nuestra población, con la consecuente disminución de biopsias de corion que son especialmente complejas en gestaciones gemelares (AU)

Objective: Evaluation of levels of PAPP-A and fßhCG in dichorionic twin pregnancies conceived by Assisted Reproductive Technology, i.e. In Vitro Fertilization (IVF) and Artificicial Insemination (AI) in our population. Calculate the necessary correction factors for first trimester screening in pregnancies conceived by IVF. Study population: One hundred seventyone twin pregnancies were considered within this study. One group was composed by 71 dichorionic twin pregnancies conceived by IVF with an average maternal age of 36.6 years. The control group was composed by 76 dichorionic twin pregnancies conceived spontaneously with an average maternal age of 31.8. A third group was composed by 24 dichorionic twin pregnancies conceived by AI with an average maternal age of 32.9 years. Results: Dichorionic twin pregnancies conceived by IVF present statistically significant lower values for PAPP-A than the control group (2.17 MoM versus 2.41 MoM, p<0.008) and higher values of fßhCG though this difference is not significant (2.33 MoM versus 2.05 MoM, p=0.144). In the other hand, average nuchal translucency (NT) does not show statistical differences between these two groups (p=0.178). Twin pregnancies conceived by AI present these same results tendencies for PAPP-A, fßhCG, and NT, with a lower number of patients not significant. Conclusions: Women with twin pregnancies conceived by Assisted Reproductive Technology (ART) have undergone treatments to induce ovulation. These treatments are proposed as one of the causes that may justify lower PAPP-A values and higher (though not significant) fßhCG values, when twin pregnancies conceived by ART are compared to spontaneously conceived twin pregnancies. Construction of normality curves for twin pregnancies conceived by IVF or calculation of correction factors is advised, in order to decrease this effect in the studied biochemical parameters. Applying these correction factors to our population data, the rate of false positives in first trimester screenings in dichorionic twin pregnancies conceived by IVF is decreased from a 4.22% to a 1.41%; this consequently implies a reduction of chorion biopsies, which are specially complicated in twin pregnancies (AU)