Noninvasive Criteria Research Articles

DECISION MAKING FOR DEVICE CLOSURE IN ADULTS WITH ‘HYPERTENSIVE PDA’–NON-INVASIVE CRITERIA: IMMEDIATE RESULTS

Objective: To find the mean pulmonary artery pressures (PAP) in adults (>12 years) Patent Ductus Arteriosus (PDA) with ‘reversible pulmonary hypertension’ after the device closure. Residual PDA and immediate complications (embolization, pulse loss, obstruction in the aorta or pulmonary artery) are to be reported.
 Study Design: Retrospective study.
 Place and Duration of Study: Tertiary Care Referral Hospital, from Aug 2007 to Jun 2020.
 Methodology: This retrospective study is descriptive. Data collected by convenience sampling from 3 tertiary care referral hospital. 981 patients were undergone PDA device closure during the period from Aug 2007 to June 2020. After informed consent, an initial assessment was done by history, clinical examination, x-ray chest PA view, electrocardiography (ECG), and transthoracic echocardiography (TTE). Reversible pulmonary hypertension was labeled based on non-invasive criteria including room air saturation >93% and cardiomegaly on x-ray chest. Patients who had <93% and normal heart size on x-ray chest were excluded. The lower limit for age was 12 years.
 Results: Nine Hundred Eighty One patients had undergone PDA device closure. 32 (n=32/981 3.3%) had fulfilled our inclusion criteria. The mean age was 22 ± 9 (13–45) years. Mean weight was 41 ± 11 (25-66) kg. Successful device closure was done in 30 patients (93.7%). Mean diameter of PDA was 7 ± 0.1 (4.5-13 mm. Mean PAP decreased from 59 ± 13 mmHg to 38 ± 19 mmHg (p<0.05). Commonest device used was Shasma duct occluder (n=16/32 50%) followed by Occlutech Duct Occluder (n=7/32 21.9%), while 2 had muscular VSD device (n=5/32 15.6%). In 2 patients, there was an underestimation of the size of PDA so the device was retrieved and replaced with another larger one successfully. Two patients had the device fully dropped into the main pulmonary artery before it was released. Larger size device was not available at that time so the patients were referred for surgery. None of our patients had device embolization or residual shunt on echo performed next day to the procedure. Neither any patient had residual pulmonary hypertension on echocardiography. There was no significant obstruction in the aorta in any patients. Two patients had mild left pulmonary artery obstruction. There was no significant obstruction in the aorta in any of our patients. There was pulse loss in 3 patients which were treated successfully with heparin infusion with no residual damage.
 Conclusion: Device closure is a feasible option in adults with hypertensive PDA while the decision of reversibility is based on non-invasive criteria.

АЛГОРИТМ ДИАГНОСТИКИ И ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКИ ХРОНИЧЕСКИХ ДИФФУЗНЫХ ЗАБОЛЕВАНИЙ ПЕЧЕНИ (ХРОНИЧЕСКОГО ГЕПАТИТА И ЦИРРОЗА ПЕЧЕНИ) В ТРУДНЫХ КЛИНИЧЕСКИХ СИТУАЦИЯХ, ОСНОВАННЫЙ НА ОПРЕДЕЛЕНИИ ФЕРМЕНТАТИВНЫХ АКТИВНОСТЕЙ СЫВОРОТКИ КРОВИ

Background. The search for non-invasive criteria for differential diagnosis of chronic hepatitis and liver cirrhosis is one of the urgent tasks of hepatology. Aim. Development of an algorithm for the diagnosis and differential diagnosis of chronic diffuse liver diseases (chronic hepatitis and liver cirrhosis) in difficult clinical situations, namely in patients with questionable results of routine laboratory research. Materials and Methods. 55 patients were examined who had a characteristic clinical picture of chronic diffuse liver diseases, however, the levels of AST and ALT were close to normal values. Chronic hepatitis was confirmed in 14 patients (mean age 55.0±11.2 years), liver cirrhosis in 40 patients (mean age 55.0±9.9 years). The control group included 43 practically healthy individuals (mean age – 52.8±4.2 years). All patients underwent determination of the levels of hyaluronidase, elastase, trypsin-like and deoxyribonuclease serum activities, as well as levels of alpha-1-defensin and interleukin-13 in blood serum. Results. An algorithm for the differential diagnosis of chronic hepatitis and cirrhosis of the liver was developed, which makes it possible to identify liver disease with odds ratio of 988.0 [CI95%=31.3-31207.7]. Conclusion. The algorithm allows to optimize diagnostic measures in difficult clinical situations.

Validation and Diagnostic Performance of a CFD-Based Non-invasive Method for the Diagnosis of Aortic Coarctation.

Purpose: The clinical diagnosis of aorta coarctation (CoA) constitutes a challenge, which is usually tackled by applying the peak systolic pressure gradient (PSPG) method. Recent advances in computational fluid dynamics (CFD) have suggested that multi-detector computed tomography angiography (MDCTA)-based CFD can serve as a non-invasive PSPG measurement. The aim of this study was to validate a new CFD method that does not require any medical examination data other than MDCTA images for the diagnosis of CoA.Materials and methods: Our study included 65 pediatric patients (38 with CoA, and 27 without CoA). All patients underwent cardiac catheterization to confirm if they were suffering from CoA or any other congenital heart disease (CHD). A series of boundary conditions were specified and the simulated results were combined to obtain a stenosis pressure-flow curve. Subsequently, we built a prediction model and evaluated its predictive performance by considering the AUC of the ROC by 5-fold cross-validation.Results: The proposed MDCTA-based CFD method exhibited a good predictive performance in both the training and test sets (average AUC: 0.948 vs. 0.958; average accuracies: 0.881 vs. 0.877). It also had a higher predictive accuracy compared with the non-invasive criteria presented in the European Society of Cardiology (ESC) guidelines (average accuracies: 0.877 vs. 0.539).Conclusion: The new non-invasive CFD-based method presented in this work is a promising approach for the accurate diagnosis of CoA, and will likely benefit clinical decision-making.

Invasive exercise hemodynamics in patients with severe primary mitral regurgitation and preserved ejection fraction predicts future valve surgery

Abstract Background The role of invasive exercise hemodynamics in the management of asymptomatic patients with severe primary mitral regurgitation (MR) is unclear. Methods and results We compared the predictive power of parameters of invasive exercise testing for future valve surgery to guideline-defined non-invasive criteria. Maximal pulmonary capillary wedge pressure (PCWP), PCWP normalized to workload and weight (PCWL), and invasive maximal systolic pulmonary artery pressure (SPAP) were assessed in 113 asymptomatic patients with severe primary MR between 1996 and 2012. Mean age was 52±11 years, 16% were female, ejection fraction was ≥55% in all patients. During a median follow up of 4.5 years (IQR2.0; 8.3) 54 patients (48%) underwent valve surgery. In univariate analysis PCWP (P<0.001), PCWL (P<0.001), and maximal SPAP (P=0.009) were significantly associated with future mitral valve surgery. In multivariate analysis maximum PCWP and PCWL predicted future mitral valve surgery (HR 2.1 (1.44–3.10), P=0.005 and HR 1.31 (1.14–1.52), P<0.001, respectively) whereas SPAP did not. Adding maximum PCWP >25mmHg to a Cox regression model based on non-invasive guideline criteria resulted in a significant increase in the area under the curve (0.61 to 0.68, P=0.02). Conclusion In asymptomatic patients with severe primary mitral regurgitation and preserved left ventricular function invasive exercise hemodynamics improves information derived from current non-invasive guideline criteria. Figure 1 Funding Acknowledgement Type of funding source: None

Subcentimeter hepatocellular carcinoma in treatment-naïve patients: noninvasive diagnostic criteria and tumor staging on gadoxetic acid-enhanced MRI.

It is controversial to adopt non-invasive diagnostic criteria of hepatocellular carcinoma (HCC) in subcentimeter lesions. This study was aimed to define the optimal noninvasive diagnostic criteria of subcentimeter HCC and to evaluate the effect on tumor staging. We included 110 treatment-naïve patients at risk of HCC and eligible for curative treatment who had subcentimeter lesions (n = 136) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) performed between January 2013 and December 2013. Modified diagnostic criteria for subcentimeter HCC were developed using logistic regression analysis. Accuracies of MR staging with and without using the modified criteria were compared by generalized estimating equation test using pathologic staging as reference standards. Subgroup analysis was performed for patients with co-existing HCC ≥ 1 cm (co-HCC). The modified criteria (presence of co-HCC, arterial phase hyperenhancement, and hypointensity on transitional phase [TP]) showed 61.5% (95% CI, 41.6-78.2) of sensitivity and 98.2% (95% CI, 93.0-99.5) of specificity. Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001). Fifty percent of subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). In the subgroup with co-HCCs, the accuracy of MR staging with subcentimeter HCCs was improved from 69.0% to 92.8% (p = 0.001). Including subcentimeter HCCs based on the modified diagnostic criteria (co-existing HCC ≥ 1 cm, arterial phase hyperenhancement, and hypointensity on TP) improved MR staging accuracy. • Fifty percent of non-benign appearing subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). • Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001).

Diagnostic and economic efficiency of schemes for differential diagnosis of chronic hepatitis and liver cirrhosis, based on the determination of interleukin-13, alpha-1-defensin and enzymatic activities in serum

The search for non-invasive criteria for the differential diagnosis of chronic hepatitis and liver cirrhosis is one of the urgent tasks of hepatology. Purpose: to evaluate the diagnostic and economic efficiency of differential diagnostic schemes for the determination of chronic hepatitis and liver cirrhosis of alcoholic and unspecified etiology, based on the determination of interleukin-13, alpha-1-defensin and enzymatic activities in blood serum. Material and method: The study included 41 patients with chronic hepatitis, 102 patients with liver cirrhosis of alcoholic and unspecified etiology. The control group included 43 donors from the blood transfusion station. The levels of enzymatic activities, interleukin-13 and alpha-1-defensin of blood serum were determined. Results: Hyaluronidase and elastase activities, as well as serum interleukin-13 and alpha-1-defensin, showed high diagnostic efficiency in detecting chronic diffuse inflammatory liver diseases, and trypsin-like and deoxyribonuclease activities in differential diagnosis of chronic hepatitis and liver cirrhosis. The developed differential diagnostic schemes allow differentiating chronic hepatitis and liver cirrhosis with a high odds ratio and have a high economic effect in comparison with Fibrotest and liver biopsy. The inclusion of interleukin-13 and alpha-1-defensin in the examination scheme allows to increase the diagnostic efficiency. Conclusions: Schemes for the differential diagnosis of chronic hepatitis and liver cirrhosis based on enzymatic activity, interleukin-13 and alpha-1-defensin of blood serum allow to improve the results of diagnostic measures, and also have a high economic effect in comparison with Fibrotest and liver biopsy.

Interference experiment, anomalous weak value, and Leggett-Garg test of macrorealism

Macrorealism is a classical world view asserting that the properties of macro-objects exist independently and irrespective of observation. One practical approach to test this view in quantum theory is to observe the quantum coherence for a macro-object in an interference experiment. An elegant and conceptually appealing approach for testing the notion of macrorealism in quantum theory is through the violation of Leggett-Garg inequality. However, a conclusive Leggett-Garg test hinges on how the noninvasive measurability criteria are guaranteed in an experiment and remains a debated issue to date. In this work, we connect the practical and the conceptual approaches for testing the macrorealism through the weak value. We argue that whenever a quantum effect is observed in an interference experiment there is an existence of anomalous weak value. Further, we demonstrate that whenever such weak value exists, one obtains the violation of a Leggett-Garg inequality in any interference experiment. Since in a path-only interference experiment effectively no prior measurement is performed, the Leggett-Garg test of macrorealism presented here is without assuming the noninvasive measurability. We provide a rigorous discussion about the assumptions involved in the Leggett-Garg scenario and how our scheme fits into it. Further, we provide a simple argument about the macrorealistic understanding of our results by using the recently developed approach involving quasiprobability.

Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program.

Background & aimsGiven ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.MethodsMVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.ResultsAmong 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen’s kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.ConclusionsWe validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.

THU066 - Non-invasive criteria for diagnosis of alcoholic hepatitis: use in clinical practice and correlation with prognosis

THU066 - Non-invasive criteria for diagnosis of alcoholic hepatitis: use in clinical practice and correlation with prognosis

Evaluation of Primary Liver Cancers Using Hepatocyte-Specific Contrast-Enhanced MRI: Pitfalls and Potential Tips.

When radiologists interpret hepatic focal lesions seen on dynamic magnetic resonance imaging (MRI) scans, it is important not only to distinguish malignant lesions from benign ones but also to distinguish nonhepatocellular carcinoma (HCC) malignancies from HCCs. In addition, most major guidelines, including those of the American Association for the Study of Liver Disease, European Association for the Study of the Liver, and Korean Liver Cancer Association and National Cancer Center, allow for the noninvasive imaging diagnosis of HCC in at-risk patients. However, ~40% of HCC cases show atypical imaging features mimicking non-HCC malignancies. Furthermore, several benign and malignant lesions, such as flash-filling hemangioma and intrahepatic mass-forming cholangiocarcinoma, frequently look like HCC. In contrast, although multiparametric MRI options, including hepatobiliary phase and diffusion-weighted imaging, provide useful information that could help address these challenges, there remain several unresolved issues with regard to the noninvasive diagnostic criteria characterizing HCC. In this article, we discuss the typical imaging features and challenging situations related to primary liver cancers in MRI, while considering how to make a correct diagnosis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance.

Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

Beyond the vascular profile: conventional DWI, IVIM and kurtosis in the assessment of hepatocellular carcinoma.

To describe the role of the Diffusion Weighted Imaging (DWI) in the assessment of hepatocellular carcinoma (HCC). Several electronic databases were evaluated in the present review. The search included articles published from January 2010 to May 2019. The references of all articles were also evaluated. All titles and abstracts were assessed, and only the studies of DWI in patients with HCC were retained. HCC is the most common primitive hepatic cancer. The non-invasive radiological criteria for HCC diagnosis are based on the presence of the specific vascular profile characterized by contrast uptake during arterial phase, defined as arterial hyperenhancement, followed by washout in the venous/portal phase. However, arterial hyperenhancement and wash out appearance have a sensitivity rate of 50-60% in lesion smaller than 2 cm. Therefore, other functional parameters have been introduced in the detection and characterization of HCC nodules. DWI has been applied to liver imaging as an excellent tool for detection and characterization of focal liver lesions, increasing clinical confidence and decreasing false positives. The assessment of DW images can be done qualitatively and quantitatively, through the apparent diffusion coefficient (ADC) map. Intravoxel incoherent motion (IVIM) is a more sophisticated analysis, a biexponential model, to better defining the relationship between signal attenuation and increasing b value that separately reproduces tissue diffusivity and tissue perfusion. Traditionally DWI approach to analyze data is founded on the hypothesis that water molecules diffuse within a voxel following a single direction with a Gaussian behavior without any restriction. However, according to the presence of microstructures, water molecules within biologic tissues exhibits a non-Gaussian phenomena proposed by Jensen in 2005 called Diffusion Kurtosis Imaging (DKI). This approach assesses the kurtosis coefficient (K) that shows the deviance of diffusion from a Gaussian approach, and the diffusion coefficient (D) with the correction of non-Gaussian bias. DKI is an advanced DWI model that quantifies non-Gaussian behavior of diffusion and provides both a corrected ADC, as well as the excess kurtosis of tissue, a measure of the extent to which tissue diffusion deviates from a Gaussian pattern. It is believed that the DKI model is more sensitive to tissue microstructural complexity than standard DW. DWI should be an integral part of study protocol for HCC patients, considering the great advantages due to DWI and DWI-based approaches in detection and characterization of HCC.

Deciding Among Noninvasive Tools for Predicting Varices Needing Treatment in Chronic Liver Disease: An Analysis of Asian Cohort.

Both transient elastography (TE)-based and non-TE-based criteria exist for detection of varices needing treatment (VNT) in patients with asymptomatic advanced chronic liver disease (CLD). However, their performance in clinical settings at different risk thresholds of detection of VNT and in regions where elastography is not widely available is unknown. We aimed to validate existing noninvasive criteria in our patients with CLD and identify best TE- and non-TE-based criteria for VNT screening at usual risk thresholds. Patients with compensated advanced CLD (cACLD) who underwent esophagogastroduodenoscopy and TE within 3 months were included. Diagnostic performance of Baveno VI, expanded Baveno VI, platelet-model for end-stage liver disease, and platelet-albumin (Rete Sicilia Selezione Terapia-hepatitis C virus) criteria were estimated. Decision curve analysis was conducted for different predictors across range of threshold probabilities. A repeat analysis including all patients with compensated CLD (cACLD and non-cACLD) was performed to simulate absence of TE. A total of 1,657 patients (cACLD, 895; non-cACLD, 762) related to hepatitis B virus (38.2%), hepatitis C virus (33.4%), nonalcoholic steatohepatitis (14.7%), and alcohol (11.8%) were included. Baveno VI identified maximum VNT (97.3%) and had best negative predictive value (96.9%), followed by platelet-albumin criteria. Expanded Baveno VI and platelet-model for end-stage liver disease had intermediate performance. At threshold probability of 5%, Baveno VI criteria showed maximum net benefit, and platelet-albumin criteria was next best, with need for 95 additional elastographies to detect 1 additional VNT. Similar results were obtained on including all patients with compensated CLD irrespective of TE. Baveno VI criteria maximizes VNT yield at 5% threshold probability. An acceptable alternative is the platelet-albumin criteria in resource-limited settings.

Diagnostic and clinical significance of antigen-specific pancreatic antibodies in inflammatory bowel diseases: A meta-analysis.

BACKGROUNDNon-invasive criteria are needed for Crohn’s disease (CD) diagnosis, with several biomarkers being tested. Results of individual diagnostic test accuracy studies assessing the diagnostic value of pancreatic autoantibodies-to-glycoprotein-2 (anti-GP2) tests for the diagnosis of CD appear promising.AIMTo systematically review and meta-analyze evidence on the diagnostic accuracy of anti-GP2 tests in patients with suspected/confirmed CD.METHODSAn electronic search was conducted on PubMed, Cochrane-CENTRAL and grey literature (CRD42019125947). The structured research question in PICPTR format was “Population” including patients with symptoms akin to CD, the “Index test” being anti-GP2 testing, the “Comparator” involved standard CD diagnosis, the “Purpose of test” being diagnostic, “Target disorder” was CD, and the “Reference standard” included standard clinical, radiological, endoscopical, and histological CD diagnostic criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and hierarchical models were employed to synthesize the data.RESULTSOut of 722 studies retrieved, 15 were meta-analyzed. Thirteen studies had industry-related conflicts-of-interest, and most included healthy donors as controls (spectrum bias). For the combination of IgA and/or IgG anti-GP2 test, the summary sensitivity was 20% (95% confidence interval: 10%-29%) at a median specificity of 97%. If the test was applied in 10000 suspected patients, 9669 would be true negatives and in 26, the diagnosis would be missed. In this hypothetical cohort, the anti-GP2 would fail to produce a diagnosis for 81.3% of the positive cases. Low summary points of sensitivity and high specificity were estimated for the IgG or IgA anti-GP2 test. Analogous results were observed when the analyses were restricted using specific cut-offs, or when ulcerative colitis patients were used as comparators.CONCLUSIONAnti-GP2 tests demonstrate low sensitivity and high specificity. These results indicate that caution is required before relying on its diagnostic value. Additionally, the need for improving the methodology of diagnostic test accuracy studies is evident.

Biopsy for hepatocellular carcinoma: only occasionally.

We would like to highlight that the non-invasive criteria for HCC diagnosis, defined by the presence of hyperenhancement in the arterial phase (wash-in) followed by hypoenhancement (wash-out) in venous phases on MRI and/or CT, have been validated by multiple cohort studies and meta-analysis. These criteria are only applicable when the pre-test probability is high (lesions > 1 cm in patients diagnosed of liver cirrhosis or chronic hepatitis B). In addition, for an adequate use of these criteria, other processes such as active (or past) neoplasms must be ruled out. In this scenario, non-invasive criteria have repeatedly demonstrated a diagnostic specificity and positive predictive value close to 100 %. Moreover, we would like to remark the transversality in the consensus of the non-invasive diagnosis of HCC, since not only the hepatology societies recommend its use, but also the oncology and radiology ones.

Abstracts of the 24th Annual Congress of the SBRA, 2020 (Virtual Meeting).

Objective:Human embryos are affected by a high rate of aneuploidy, around 35% in natural conceptions and this prevalence is expected to be higher in pre-implantation embryos derived from in vitro fertilization (IVF). One of the most common alteration is the trisomy and preimplantation genetic testing for aneuploidies (PGT-A) is currently used in IVF to minimize the chances of transferring genetically abnormal embryos. The introduction of time-lapse monitoring (TLM) allowed additional noninvasive criteria to best embryo selection. Markers of embryonic kinetic from the first-cleavage onwards has been studied and applied in algorithms for best embryo choice. The aim of this study was to analyze the association of trisomy with the embryo morphokinetics in embryos derived from IVF and analyzed by PGT-A.Methods:This retrospective study included 509 embryos from 109 patients undergoing IVF between April/2018-September/2019. Mature oocytes were fertilized by ICSI and cultured in a TLM system (Embryoscope®). Blastocysts were biopsied for PGT-A and analyzed at Igenomix Brasil through Next Generation Sequencing (NGS). Twenty-seven embryos presenting trisomy of chromosomes 13, 15, 16, 18, 21 and 22 were selected and a matched analysis was performed, since a euploid embryo from the same patient was selected as a control for each trisomic embryo.Results:The women age was 38.0±3.0 years and euploid blastocyst rate was 36.3%. Two-way repeated measured ANOVA was performed based on times for achieving pronucleous-fade, two-cells, three-cells, four-cells, five-cells, eight-cells, nine-cells and blastocyst. Embryo morphokinetics significantly differed between euploid and trisomic embryos (p=0.052). The pairwise comparisons demonstrated significant difference on times between euploid and trisomic embryos from eight cells until blastocyst stage. The mean difference time between euploid and trisomic embryos to get the eight-cells stage was 5.1 hours (61.0±10.8x55.9±7.1, p=0.033) and to attain blastocyst stage was 6.2 hours (112.3±11.7x106.1±10.4, p=0.013).Conclusion:In this study, trisomic embryos showed a faster development than their paired euploid ones. Despite of this study have included a small number of embryos, the inclusion criteria was for each trisomic embryo there is an euploid embryo of the same patient, which exclude a number of confounders. The literature describes the association of accelerated embryonic development with lower success potential; however, the reason for that relationship is not clear. Our findings allow us to hypothesize that the decreased implantation potential of faster embryos could be due to chromosomal alteration, specifically trisomy, and to suggest that accelerated embryonic development may be an indication for genetic evaluation. These findings must be confirmed in a higher number of embryos and further studies are being conducted to investigate the association of genetic embryo alterations and embryo development.

Controlled attenuation parameter reflects steatosis in compensated advanced chronic liver disease.

Controlled attenuation parameter (CAP) for steatosis assessment has not been validated in compensated advanced chronic liver disease compensated advanced chronic liver disease (cACLD). We primarily aimed at assessing the accuracy of CAP for the diagnosis and quantification of steatosis in cACLD. Secondary aim: to assess the validity of non-invasive criteria for cACLD according to liver stiffness measurement (LSM). This is a single-centre retrospective study including patients with cACLD defined as LSM ≥10kPa, CAP measurement and liver biopsy (reference standard for steatosis and fibrosis) observed in 06/2015-06/2017. Steatosis was graded as S0 (<5%), S1 (5%-32%), S2 (33%-66%) and S3 (>66%). The diagnostic performance of CAP for any grade of steatosis and for high-grade steatosis (≥S2) was studied. Among 461 consecutive patients, 111 with LSM-based diagnosis of cACLD were included (63% male, median age 55years, median body mass index 28.1Kg/m2 , aetiology: 32% non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, 32% alcohol or viral+metabolic syndrome, 15% viral, 6% autoimmune, 4% alcohol, 11% others). Median LSM and CAP were 16.1kPa and 277dB/m respectively. On liver biopsy, steatosis was found in 88/111 patients (79%); 44 patients (43 with metabolic syndrome) had high-grade steatosis. CAP was accurate in identifying any grade of steatosis (area under the receiving operating characteristic curves 0.847; 95% CI 0.767-0.926, P<.0001), and ≥S2 steatosis (0.860; 95% CI 0.788-0.932, P<.0001). CAP performed similarly in patients with CAP- interquartile range (IQR) ≥ or <40dB/m. Steatosis is frequent in patients with cACLD and metabolic syndrome. CAP diagnostic accuracy for any steatosis and high-grade steatosis is good in this population. A CAP-IQR ≥40dB/m does not impair CAP diagnostic accuracy in cACLD.

Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

P897Diagnostic utility of tissue biopsy in transthyretin cardiac amyloidosis diagnosed by non-invasive diagnostic criteria

Abstract Background In the recent past, transthyretin cardiac amyloidosis (TTR-CA) is recognized as an important cause of heart failure with preserved ejection fraction, and diagnostic utility of 99mTc-pyrophosphate (99mTc-PYP) scintigraphy in TTR-CA has been established. However, pathological evaluation is still the basis to confirm diagnosis. Subcutaneous tissue and gastrointestinal tract biopsy are useful examinations alternative to endomyocardial biopsy. Nevertheless, the positive ratio of amyloid deposition in these organs is not fully evaluated based on recent non-invasive diagnostic criteria. Purpose Our aim was to evaluate the diagnostic sensitivity of tissue biopsy in TTR-CA patients diagnosed by 99mTc-PYP scintigraphy. Methods We retrospectively evaluated 124 consecutive TTR-CA patients [wild-type (ATTRwt): 90, hereditary (hATTR): 34] who were diagnosed by positive findings of 99mTc-PYP scintigraphy (visual score 2 or 3) between June 2002 and January 2019 at our institute. Results A total of 114 patients underwent tissue biopsy at least one organ. Amyloid was detected on Congo red staining of subcutaneous tissue (43/97: 44%), gastrointestinal tract (52/78: 67%) and heart (78/79: 99%), respectively. Among 70 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsy, amyloid was detected at least one specimen in 57/70 (81%). Compared to hATTR CA patients, ATTRwt CA patients had lower positive ratio of subcutaneous tissue (81% vs. 27%) and gastrointestinal tract (73% vs. 63%) biopsy. Conclusion Non-invasive diagnostic criteria of TTR-CA had excellent sensitivity of amyloid deposition in heart. The diagnostic sensitivity of subcutaneous tissue and gastrointestinal tract biopsy was lower in ATTRwt CA compared to hATTR CA. Combination of subcutaneous tissue and gastrointestinal tract biopsy was useful for pathological confirmation of amyloid deposition without endomyocardial biopsy.

Electrical properties of the myocardium in patients with arterial hypertension combined with subclinical hypothyroidism

Late atrial and ventricular potentials are non-invasive electrocardiographic criteria for presence of high arrhythmic readiness and risk of life-threatening arrhythmias. The electrical properties of the myocardium in patients with stage II arterial hypertension (AH) combined with subclinical hypothyroidism have not been studied previously.Aim. To study the changes of electrical properties of the atrial and ventricular myocardium in patients with AH combined with subclinical hypothyroidism.Materials and methods. The criteria for inclusion in the study were the presence of stage II AH without thyroid gland pathology and combined with subclinical hypothyroidism (SH) (for patients of the main group). Depending on the level of thyroid-stimulating hormone (TSH), the AH patients were divided into 2 groups – with normal (0.4–4.0 mU/ml) and moderately elevated level of TSH (4.0–15.6 mU/l, with normal levels of thyroid hormones).The group of patients with AH without SH included 92 patients (women – 81.52 % (75), men – 18.48 % (17)); the group of patients with AH with concomitant SH included 30 patients (women – 86.7% (26), men – 13.3 % (4)). All patients underwent 24-h BP monitoring and ECG (combined ECG and BP monitor “Kardiotechnica-04-AD-3”,St. Petersburg,Russia). A 40 Hz cutoff filter was used recording in the X, Y, Z orthogonal leads. Data were processed with the help of a program Statistica 6.0. Data were presented as the median and inter-quartile range of Me (25 %; 75 %).Results. In AH patients without concomitant subclinical hypothyroidism, unlike in relatively healthy patients, late atrial potential predominance was seen (63 % vs. 84 %; P = 0.0419) with a 16.4 times (P = 0.018) increase in the number of premature atrial contractions. Also, in patients with AH without concomitant subclinical hypothyroidism late ventricular potentials (LVPs) occurred 5.7 times more often (6 % vs. 34 %, P = 0.0302) and were associated with a significant (P = 0.004) increase in the number of premature ventricular contractions per day in this category of patients.In SH patients with a concomitant subclinical hypothyroidism, unlike in relatively healthy individuals, atrial ectopic activity was significantly more predominant (LAP was found in 87 %; versus 63 %, P = 0.0498), which was accompanied by a logical 27.2 times (P = 0.038) increase in the number of premature atrial contractions and ventricular ectopic activity. Changes in the electrical properties of the ventricles were accompanied by an increase in the percentage of detected LVPs (77 % versus 6 %, P = 0.0001), which was associated with a significant (P = 0.001) increase in the number of premature ventricular contractions per day in this category of patients (441.53 ± 1414.97 versus 0.00 ±0.00 inalmost healthy subjects, P = 0.001).AH patients with and without concomitant SH did not differ from each other in terms of indexes characterizing late atrial potentials. There was also no statistically significant difference in the number of premature atrial contractions (P = 0.527), paired premature atrial contractions (P = 0.449), salvos of atrial premature contractions (P = 0.314). However, in AH patients with concomitant SH there was a significant increase in the ectopic activity of the ventricles – LVPs were found in 77 % vs. 33 % in individuals without SH (P = 0.0001), changes in the electrical properties of ventricles in AH patients with concomitant SH were also associated with an increase in the number of premature ventricular contractions by 6.69 times (from 42.56 ± 36.96 to 441.53 ± 1414.97, P = 0.026) compared with the same index in patients with AH without concomitant SH, indicating the negative effect of SH on the electrical properties of the ventricles.Conclusions. In patients with stage II arterial hypertension in comparison to relatively healthy subjects, indicators that characterize the late potentials of the atria and ventricles are significantly changed, which is accompanied by an increase in the number of supraventricular and ventricular rhythm disorders. Subclinical hypothyroidism causes an additional pro-arrhythmic effect on the ventricular myocardium in arterial hypertension.