Selenium status in term neonates, according to birth weight and gestational age, in relation to maternal hypertensive pathology.

Background: Pregnancy represents a state of increased oxidative stress and antioxidants, in which selenium (Se) plays a pivotal role, contribute to maintain the oxidative balance. If antioxidant defenses are depleted, placental function is disrupted, resulting in pregnancy complications, including pregnancy-induced hypertension (PIH). Little is known about fetal selenium status in concomitant relation to maternal PIH, gestational age (GA) and birthweight (BW). Methods: We examined over a 3-year period the serum (SeS) and urine selenium (SeU) status in term neonates from normotensive (nonPIH) and hypertensive (PIH) mothers as clinical markers of oxidative stress. In this retrospective observational study, 72 neonates with maternal PIH were matched for GA and BW to 72 neonates of normotensive mothers. Four groups were obtained, based on maternal PIH and BW relative to GA (appropriate-for-gestational-age-AGA, small-for-gestational-age-SGA): nonPIH-AGA (control group), nonPIH-SGA, PIH-AGA, and PIH-SGA. Results: The results showed significant differences (p < 0.001) in selenium levels among the study groups: SeS - 44.85 ± 7.56 µg/L in nonPIH-AGA, 39.62 ± 11.42 µg/L in nonPIH-SGA, 40.01 ± 10.07 µg/L in PIH-AGA, and 25.39 ± 8.99 µg/L in PIH-SGA; SeU - 27.98 ± 7.99 µg/L in nonPIH-AGA, 22.85 ± 9.48 µg/L in nonPIH-SGA, 23.44 ± 6.73 µg/L in PIH-AGA, and 13.05 ± 5.86 µg/L in PIH-SGA. Selenium depletion was more common in neonates born from hypertensive mothers and those born small for gestational age. Though moderate in intensity, selenium levels were positively correlated with BW (0.319 for SeS, 0.397 for SeU) and negatively correlated with maternal systolic blood pressure (-0.313 for SeS, -0.324 for SeU). The main independent effects on SeS and SeU of each maternal blood pressure and birth weight turned out statistically significant. In interaction, a more pronounced effect was reached in PIH-SGA neonates. Conclusion: Selenium status seemed to reflect the negative impact that PIH exerts in neonates during intrauterine development. Clinical markers of selenium status could thus be of great value for tracking responses of individuals to selenium supplementation as part of health improvement and harm mitigation approaches.

Impact of COVID-19 on Patients with Decompensated Liver Cirrhosis.

The aim of this study was to assess the impact of COVID-19 infection on patients with decompensated liver cirrhosis (DLC) in terms of acute-on-chronic liver failure (ACLF), chronic liver failure acute decompensation (CLIF-AD), hospitalization, and mortality. In this retrospective study, we analyzed patients with known DLC who were admitted to the Gastroenterology Department with COVID-19. Clinical and biochemical data were obtained to compare the development of ACLF, CLIF-AD, days of hospitalization, and the presence of independent factors of mortality in comparison with a non-COVID-19 DLC group. All patients enrolled were not vaccinated for SARS-CoV-2. Variables used in statistical analyses were obtained at the time of hospital admission. A total of 145 subjects with previously diagnosed liver cirrhosis were included; 45/145 (31%) of the subjects were confirmed with COVID-19, among which 45% had pulmonary injury. The length of hospital stay (days) was significantly longer in patients with pulmonary injury compared to those without (p = 0.0159). In the group of patients with COVID-19 infection, the proportion of associated infections was significantly higher (p = 0.0041). Additionally, the mortality was 46.7% in comparison with only 15% in the non-COVID-19 group (p = 0.0001). Pulmonary injury was associated with death during admission in multivariate analysis in both the ACLF (p < 0.0001) and the non-ACLF (p = 0.0017) group. COVID-19 significantly influenced disease progression in patients with DLC in terms of associated infections, hospitalization length, and mortality.

Contrast-Enhanced Ultrasonography with Arrival Time Parametric Imaging as a Non-Invasive Diagnostic Tool for Liver Cirrhosis.

Liver biopsy is the gold standard method for staging liver fibrosis, but it is an invasive procedure that is associated with some complications. There are also non-invasive techniques for assessing liver fibrosis, such as elastography and biological tests, but these techniques can fail in detection or generate false measurements depending on the subject's condition. This study aimed to determine whether liver fibrosis can be evaluated using contrast-enhanced ultrasonography with arrival time parametric imaging using the ultrasound machine's parametric image software, the method being called (CEUS-PAT). CEUS-PAT was performed on each subject using SonoVue as a contrast agent, and images showing liver parenchyma and the right kidney on a single screen were used for analysis in parametric imaging, which was performed using the proprietary software of the ultrasound system. The ratio between the kidney and liver arrival times was calculated. The study included 64 predominantly male (56.3%) subjects, 37 cirrhotic patients, and 27 healthy volunteers, with a mean age of 58.98 ± 8.90 years. Significant differences were found between the liver cirrhosis and healthy groups regarding CEUS-PAT, 0.83 ± 0.09 vs. 0.49 ± 0.11, p < 0.0001. The correlation between CEUS-PAT and VCTE was r = 0.81. The optimal cut-off value for detecting liver cirrhosis was >0.7, with an AUC of 0.98, p < 0.001, Se = 89.19%, Sp = 100%, PPV = 100%, and NPV = 87.1%. We demonstrate that CEUS-PAT achieves excellent performance in diagnosing liver cirrhosis and is a fast method for diagnosing liver cirrhosis that can even be applied in situations where the use of other methods is excluded.

The role of elastography for liver fibrosis screening in alcoholic liver disease.

Non-invasive tests have been developed to determine the severity of liver disease in patients with alcohol use disorder (AUD). We aimed to assess the severity of liver steatosis and liver fibrosis (LF) in a cohort of patients with AUD using liver elastography and biological scores. MATERIALS AND METHODS: A prospective study was performed on 172 subjects, without previously known liver disease, with a positive AUDIT-C score, serum markers, and vibration-controlled transient elastography (VCTE) with Controlled Attenuation Parameter (CAP). RESULTS: From 172 subjects with positive AUDIT-C test, VCTE diagnosed advanced fibrosis (F3) in 13.9% (24/172) of the subjects and liver cirrhosis (F4) in 17.5% (30/172). Moderate and severe steatosis was found in 18.6% (32/172), respectively 52.3% (90/172). Significant correlations were found between liver stiffness and APRI (r=0.33, p=0.001), FIB-4(r=0.31, p=0.0012) and the age-platelet index (r=0.25, p=0.008). FIB-4 (p=0.01) and age-platelet index (p=0.03) were independently associated with the presence of advanced fibrosis. Age-platelet index (AUC- 0.82) performed significantly better than AST/ALT (AUC- 0.55) and APRI (AUC- 0.58) (p= 0.0001 and p= 0.0014, respectively), but no differences were found when compared to FIB-4 (AUC- 0.77) (p=0.35) for predicting advanced fibrosis. CONCLUSION: In conclusion, in a cohort of patients with AUD, 70.9% presented moderate and severe liver steatosis and 17.5% were newly diagnosed with liver cirrhosis.

Assessment of Renal Allograft Stiffness and Viscosity Using 2D SWE PLUS and Vi PLUS Measures-A Pilot Study.

Elastography is a useful noninvasive tool for the assessment of renal transplant recipients. 2D-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) have emerged as novel techniques that promise to offer improved renal stiffness and viscosity measures due to improved processing algorithms. Methods: We performed a cross-sectional study of 50 kidney transplanted patients (16 women, 34 men; mean age of 47.5 ± 12.5; mean estimated glomerular filtration rate (eGFR) estimated by Chronic Kidney Disease Epidemiology Collaboration formula: 52.19 ± 22.6 mL/min/1.73 m2; and a mean duration after transplant of 10.09 ± 5 years). For every patient, we obtained five valid measurements of renal stiffness (obtained from five different frames in the cortex of the renal graft), and also tissue viscosity, with a C6-1X convex transducer using the Ultra-Fast™ software available on the Aixplorer Mach 30 ultrasound system (Supersonic Imagine, Aix-en-Provence, France). The median values of elastographic and viscosity measures have been correlated with the patients' demographic, biological, and clinical parameters. Results: We obtained a cut-off value of renal cortical stiffness of <27.3 kiloPascal(kPa) for detection of eGFR < 60 mL/min/1.73 m2 with 80% sensitivity and 85% specificity (AUC = 0.811, p < 0.0001), a cut-off value of <26.9 kPa for detection of eGFR < 45 mL/min/1.73 m2 with 82.6% sensitivity and 74% specificity (AUC = 0.789, p < 0.0001), and a cut-off value of <23 kPa for detection of eGFR < 30 mL/min/1.73 m2 with 88.8% sensitivity and 75.6% specificity (AUC = 0.852, p < 0.0001). We found a positive correlation coefficient between eGFR and the median measure of renal cortical stiffness (r = 0.5699, p < 0.0001), between eGFR the median measure of viscosity (r = 0.3335, p = 0.0180), between median depth of measures and renal cortical stiffness (r = −0.2795, p = 0.0493), and between median depth of measures and body mass index (BMI) (r = 0.6574, p < 0.0001). Our study showed good intra-operator agreement for both 2D SWE PLUS measures­with an intraclass correlation coefficient (ICC) of 0.9548 and a 95% CI of 0.9315 to 0.9719­and Vi PLUS, with an ICC of 0.8323 and a 95% CI of 0.7457 to 0.8959. The multivariate regression model showed that 2D SWE PLUS values were associated with eGFR, Vi PLUS, and depth of measures. Conclusions: Assessment of renal allograft stiffness and viscosity may prove to be an effective method for identifying patients with chronic allograft injury and could prove to be a low-cost approach to provide additional diagnostic information of kidney transplanted patients.

Extreme Birth Weight and Metabolic Syndrome in Children.

Small and large birth weights (BWs) for gestational age (GA) represent extremes, but the correlation between extreme BW and metabolic syndrome (MetS) has not been fully elucidated. In this study, we examined this correlation in obese children based on changes in their metabolic profile from childhood to adolescence. A retrospective observational study was performed on 535 obese patients aged 0-18 years in the Clinical and Emergency Hospital for Children "Louis Turcanu" in Timisoara, Romania, based on clinical and biological data from January 2015 to December 2019. We emphasized the links between extreme BW and obesity, extreme BW and cardiometabolic risk, obesity and cardiometabolic risk, and extreme BW, obesity and MetS. Children born large for gestational age (LGA) predominated over those born small for gestational age (SGA). Our findings showed that BW has an independent effect on triglycerides and insulin resistance, whereas obesity had a direct influence on hypertension, impaired glucose metabolism and hypertriglyceridemia. The influences of BW and obesity on the development of MetS and its components are difficult to separate; therefore, large prospective studies in normal-weight patients are needed.

Multiparametric Ultrasound Approach Using a Tree-Based Decision Classifier for Inconclusive Focal Liver Lesions Evaluated by Contrast Enhanced Ultrasound.

BACKGROUND: Multiparametric ultrasound (MPUS) is a concept whereby the examiner is encouraged to use the latest features of an ultrasound machine. The aim of this study was to reanalyze inconclusive focal liver lesions (FLLs) that had been analyzed via contrast enhanced ultrasound (CEUS) using the MPUS approach with the help of a tree-based decision classifier. MATERIALS AND METHODS: We retrospectively analyzed FLLs that were inconclusive upon CEUS examination in our department, focusing our attention on samples taken over a period of two years (2017-2018). MPUS reanalysis followed a three-step algorithm, taking into account the liver stiffness measurement (LSM), time-intensity curve analysis (TIC), and parametric imaging (PI). After processing all steps of the algorithm, a binary decision tree classifier (BDTC) was used to achieve a software-assisted decision. RESULTS: Area was the only TIC-CEUS parameter that showed a significant difference between malign and benign lesions with a cutoff of >-19.3 dB for washout phenomena (AUROC = 0.58, Se = 74.0%, Sp = 45.7%). Using the binary decision tree classifier (BDTC) algorithm, we correctly classified 71 out of 91 lesions according to their malignant or benignant status, with an accuracy of 78.0% (sensitivity = 62%, specificity = 45%, and precision = 80%). CONCLUSIONS: By reevaluating inconclusive FLLs that had been analyzed via CEUS using MPUS, we managed to determine that 78% of the lesions were malignant and, in 28% of them, we established the lesion type.

Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis.

Lille score at Day 7 (LM7) helps to predict the outcome of patients with severe alcoholic hepatitis (sAH) undergoing corticotherapy. Several scores such as Maddrey's discriminant function (MDF), MELD, ABIC, and GAHS are used for a 28-day mortality prognosis. Our study aimed to evaluate if the assessment of the Lille score at 4 days (LM4) is as useful as the Lille score at Day 7 (LM7) to predict response to corticosteroids and 28-day mortality and evaluate the utility of severity scores at admission for predicting the prognosis of patients with liver cirrhosis (LC) and severe alcoholic hepatitis (sAH). A retrospective study was performed, and all consecutive patients with AH and MDF > 32 without contraindications to corticosteroids were included. Prognostic scores were evaluated at admission, and 28-day mortality was assessed. Response to corticotherapy was assessed by LM4 and LM7. Results: A total of 55/103 patients with sAH (51.5%) had MDF > 32 and received corticosteroids. There was no difference between the proportion of patients with a responder LM4 versus LM7 (27% vs. 36%, p = 0.31). The mean value for LM4 was 0.64 ± 0.3 versus 0.60 ± 0.3 for LM7 (p = 0.48). Precisely 90.3% of patients were correctly identified as responders or not by LM4 compared with LM7. The best model for predicting 28-day mortality was composed of MELD and LM4/LM7, with an accuracy of 0.90 for both combinations. Conclusion: LM4 could be used instead of LM7 for predicting response to corticosteroid therapy in patients with sAH and LC, as well as 28-day mortality. Using LM4, we could avoid prolonged use of this therapy and its complications.

Evaluation of Serum Selenium Status by Age and Gender: A Retrospective Observational Cohort Study in Western Romania.

Selenium, residing in a series of selenoproteins, plays an important role in both female and male reproductive function. Of particular significance for reproduction is the antioxidant glutathione peroxidase (GPx), a main selenoenzyme, whose level is regulated by the availability of Se in the body. We hypothesized that changes in Se status, closely related to GPx activity, would result in an increased risk of reproductive dysfunction in individuals. We retrospectively investigated the serum selenium (SeS) concentrations of 1264 apparently healthy people, aged 16-89 years, from Western Romania. The general analysis revealed a non-normal SeS distribution with a median SeS of 100.26 ± 18.32 µg/L and a significant difference in SeS levels between age groups. The analysis of the young group (16-35 years) revealed that up to 50% of individuals did not reach the SeS threshold corresponding to maximum GPx activity (80 µg/L), and a significant imbalance between the genders was apparent when looking at SeS values outside the range. Our results correlated with the general diminished reproductive ability registered in Romania during the last few years. Serum selenium content proves to offer a proper reflection of the fertility competence of the young population, and its monitoring is important for guiding dietary adjustments and attaining normal reproductive function.

Performance of a Noninvasive Time-Harmonic Elastography Technique for Liver Fibrosis Evaluation Using Vibration Controlled Transient Elastography as Reference Method.

AIM: This study aimed to evaluate the diagnosis performance of time-harmonic elastography (THE) technique in real life in assessing liver fibrosis, considering vibration-controlled transient elastography (VCTE) as a reference method. MATERIAL AND METHOD: We prospectively evaluated outpatients from the gastroenterology department. Liver stiffness (LS) was measured by the THE system by dedicated operators, and by VCTE by experienced operators. The diagnostic accuracy of THE in staging liver fibrosis was assessed. We also performed an intra- and interobserver reproducibility sub-analysis on a sub-group of 27 subjects, where liver stiffness measurements (LSM) were performed by a novice, an elastography expert, and an ultrasound expert. RESULTS: Of the 165 patients, using VCTE cut-off values, 49.6% were F0-F1, 15.7% were F2, 6.6% were F3, and 28.1% were F4. A direct, significant and strong correlation (r = 0.82) was observed between LSM assessed by VCTE and THE, p < 0.0001. The cut-off for ruling out liver cirrhosis (LC) by THE on our study group was <1.61 m/s (7.77 kPa)-AUROC = 0.90 [95% CI (0.82-0.93)], Se = 90.7%, Sp = 66.6%, PPV = 55.7%, NPV = 93.9%. The cut-off for ruling in LC by THE was >1.83 m/s (10 kPa)-AUROC = 0.90 [95% CI (0.82-0.93)], p < 0.0001, Se = 65.1%, Sp = 96.7%, PPV = 90.3%, NPV = 85.7%. The overall agreement between examiners was excellent: 0.94 (95% CI: 0.89-0.97); still, the ICCs were higher for the more experienced elastography examiner: 0.92 (95% CI: 0.82-0.96) vs. 0.94 (95% CI: 0.87-0.97) vs. 0.97 (95% CI: 0.95-0.99). CONCLUSIONS: THE is a feasible and reproducible elastography technique that can accurately rule in and rule out advanced liver disease.

Intra- and Inter-Observer Reproducibility of a 2-D Shear Wave Elastography Technique and the Impact of Ultrasound Experience in Achieving Reliable Data.

The aim of the study described here was to evaluate the reproducibility of a new shear-wave elastography (SWE) technique, 2-D SWE.GE, and the impact of ultrasound experience in acquiring reliable measurements, as no official recommendations are available for this system. Elastographic measurements (EMs) were obtained in 60 patients using 2-D-SWE with the GE Logiq E9. Three examiners with different levels of experience in ultrasound-based elastography performed 10 valid EMs on each subject: a novice (C.P.) who had no experience in liver elastography and had performed fewer than 50 ultrasound examinations; an elastography expert (A.M.S.) who had more than 1 y of liver elastographic experience in four elastographic methods and had performed more than 1000 ultrasonography examinations; and an ultrasound expert (T.M.) who had no experience in liver elastography and had performed more than 1000 ultrasound examinations. Medians and interquartile ranges were calculated (m/s). We used the inter-class correlation coefficient and Bland-Altman plots with 95% lower and upper limits of agreement to assess the inter- and intra-observer reproducibility of 2-D-SWE.GE measurements. The final study group included 60 patients, 56.7% women and 43.3% men, with a mean age of 33.08 ± 13.83 y and mean body mass index of 22.85 ± 4.04 kg/m2. In this group, 73.3% were healthy volunteers and 26.7% had compensated liver cirrhosis. We did not find significant differences between EMs taken by the examiners overall and across study groups. The overall agreement between examiners was excellent: 0.915 (95% confidence interval [CI]: 0.870-0.946). The agreement between the novice and the experienced examiners, respectively, was good to excellent (novice and ultrasound expert: 0.908, 95% CI: 0.846-0.945; novice and elastography expert: 0.885, 95% CI: 0.808-0.931). The intra-observer reproducibility for each of the examiners was excellent; however, the inter-class correlation coefficients were higher for the examiners more experienced in elastography: 0.936 (95% CI: 0.896-0.963) versus 0.966 (95% CI: 0.943-0.980) versus 0.984 (95% CI: 0. 973-0.991). The good ICCs for the median values indicate that 2-D-SWE.GE is a reproducible method. Ultrasound experience did not significantly influence the results.

Is Contrast Enhanced Ultrasonography a useful tool in a beginner's hand? How much can a Computer Assisted Diagnosis prototype help in characterizing the malignancy of focal liver lesions?

AIM: Contrast enhanced ultrasound (CEUS) improved the characterization of focal liver lesions (FLLs), but is an operatordependent method. The goal of this paper was to test a computer assisted diagnosis (CAD) prototype and to see its benefit in assisting a beginner in the evaluation of FLLs. MATERIAL AND METHOD: Our cohort included 97 good quality CEUS videos[34% hepatocellular carcinomas (HCC), 12.3% hypervascular metastases (HiperM), 11.3% hypovascular metastases (HipoM), 24.7% hemangiomas (HMG), 17.5% focal nodular hyperplasia (FNH)] that were used to develop a CAD prototype based on an algorithm that tested a binary decision based classifier. Two young medical doctors (1 year CEUS experience), two experts and the CAD prototype, reevaluated 50 FLLs CEUS videos (diagnosis of benign vs. malignant) first blinded to clinical data, in order to evaluate the diagnostic gap beginner vs. expert. RESULTS: The CAD classifier managed a 75.2% overall (benign vs. malignant) correct classification rate. The overall classification rates for the evaluators, before and after clinical data were: first beginner-78%; 94%; second beginner-82%; 96%; first expert-94%; 100%; second expert-96%; 98%. For both beginners, the malignant vs. benign diagnosis significantly improved after knowing the clinical data (p=0.005; p=0,008). The expert was better than the beginner (p=0.04) and better than the CAD (p=0.001). CAD in addition to the beginner can reach the expert diagnosis. CONCLUSIONS: The most frequent lesions misdiagnosed at CEUS were FNH and HCC. The CAD prototype is a good comparing tool for a beginner operator that can be developed to assist the diagnosis. In order to increase the classification rate, the CAD system for FLL in CEUS must integrate the clinical data.