Morphological assessment of oocyte quality during assisted reproductive technology cycle.

Following the advancement of medically assisted reproduction (MAR) technology, and the rationale to extend the culture to the blastocyst stage, performing elective single embryo transfer (eSET), gamete quality and assessment have acquired large relevance in ART. Embryo quality is strictly correlated with gametes quality and culture conditions. Oocyte maturity assessment is therefore imperative for fertilization and embryo evolution. Mature oocytes at the metaphase II stage result in a higher fertilization rate compared to immature oocytes. Indeed, oocyte morphology evaluation represents an important and challenging task that may serve as a valuable prognostic tool for future embryo development and implantation potential. Different grading systems have been reported to assess human embryos, however, in many cases, it is still a major challenge to select the single embryo to transfer with the highest implantation potential. Further, eSET has conferred a challenge to embryologists, who must try to enhance embryo culture and selection to provide an adequate success rate, whilst reducing the overall number of embryos transferred. Above the standard morphological assessment, there are several invasive or non-invasive approaches for embryo selection such as preimplantation genetic testing, time-lapse technology, proteomics and metabolomics, as well as oxygen utilization and analysis of oxidative stress in culture medium. This short review is not designed to be a comprehensive review of all possible features that may influence oocyte quality. It does give, however, a brief overview and describes the prognostic value of the morphological characteristics of human oocytes on their developmental capacity following ART treatments.

Enhancing the Diagnosis of Lateral Ankle Sprains: The Role of MSK Diagnostic Ultrasound in Evaluating ATFL and CFL.

Lateral ankle sprains, predominantly involving the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), constitute a significant portion of sports-related injuries, with a notable rate of recurrence and progression to chronic instability. Precise diagnosis and effective treatment of the ATFL and CFL injuries are crucial in preventing long-term complications. Musculoskeletal (MSK) diagnostic ultrasound has emerged as a pivotal tool in the rehabilitation sector, particularly in assessing lateral ankle ligament injuries. This article will highlight its benefits over traditional diagnostic methods and the emerging role of MSK diagnostic ultrasound as a superior tool for accurate, cost-effective, and comprehensive assessment of these injuries. We discuss the technology's ability to provide objective, real-time imagery, facilitating accurate diagnosis, treatment planning, and injury monitoring emphasizing the need for a standardized approach to ultrasound evaluation to improve diagnostic accuracy and patient outcomes.

MSK Diagnostic Ultrasound for the Assessment of the Acromioclavicular Joint.

The acromioclavicular joint (ACJ), a key element in shoulder movement and stability, is prone to various injuries such as sprains, dislocations, and osteoarthritis, typically resulting from physical trauma or wear and tear. Accurate and timely diagnosis is paramount for effective treatment and rehabilitation. Musculoskeletal (MSK) ultrasound has emerged as a pivotal diagnostic tool due to its ability to visualize soft tissues and provide real-time imaging. This non-invasive tool is also invaluable for monitoring healing progress and the evolution of osteoarthritic changes. This article reviews the application of MSK ultrasound in the evaluation of ACJ injuries, highlighting its advantages, specific applications, and recent technological advancements that enhance its diagnostic capabilities.

Metabolic imaging of human embryos is predictive of ploidy status but is not associated with clinical pregnancy outcomes: a pilot trial.

STUDY QUESTION: Does fluorescence lifetime imaging microscopy (FLIM)-based metabolic imaging assessment of human blastocysts prior to frozen transfer correlate with pregnancy outcomes? SUMMARY ANSWER: FLIM failed to distinguish consistent patterns in mitochondrial metabolism between blastocysts leading to pregnancy compared to those that did not. WHAT IS KNOWN ALREADY: FLIM measurements provide quantitative information on NAD(P)H and flavin adenine dinucleotide (FAD+) concentrations. The metabolism of embryos has long been linked to their viability, suggesting the potential utility of metabolic measurements to aid in selection. STUDY DESIGN, SIZE, DURATION: This was a pilot trial enrolling 121 IVF couples who consented to have their frozen blastocyst measured using non-invasive metabolic imaging. After being warmed, 105 couples' good-quality blastocysts underwent a 6-min scan in a controlled temperature and gas environment. FLIM-assessed blastocysts were then transferred without any intervention in management. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight metabolic parameters were obtained from each blastocyst (4 for NAD(P)H and 4 for FAD): short and long fluorescence lifetime, fluorescence intensity, and fraction of the molecule engaged with enzyme. The redox ratio (intensity of NAD(P)H)/(intensity of FAD) was also calculated. FLIM data were combined with known metadata and analyzed to quantify the ability of metabolic imaging to differentiate embryos that resulted in pregnancy from embryos that did not. De-identified discarded aneuploid human embryos (n = 158) were also measured to quantify correlations with ploidy status and other factors. Statistical comparisons were performed using logistic regression and receiver operating characteristic (ROC) curves with 5-fold cross-validation averaged over 100 repeats with random sampling. AUC values were used to quantify the ability to distinguish between classes. MAIN RESULTS AND THE ROLE OF CHANCE: No metabolic imaging parameters showed significant differences between good-quality blastocysts resulting in pregnancy versus those that did not. A logistic regression using metabolic data and metadata produced an ROC AUC of 0.58. In contrast, robust AUCs were obtained when classifying other factors such as comparison of Day 5 (n = 64) versus Day 6 (n = 41) blastocysts (AUC = 0.78), inner cell mass versus trophectoderm (n = 105: AUC = 0.88) and aneuploid (n = 158) versus euploid and positive pregnancy embryos (n = 108) (AUC = 0.82). LIMITATIONS, REASONS FOR CAUTION: The study protocol did not select which embryo to transfer and the cohort of 105 included blastocysts were all high quality. The study was also limited in number of participants and study sites. Increased power and performing the trial in more sites may have provided a stronger conclusion regarding the merits of the use of FLIM clinically. WIDER IMPLICATIONS OF THE FINDINGS: FLIM failed to distinguish consistent patterns in mitochondrial metabolism between good-quality blastocysts leading to pregnancy compared to those that did not. Blastocyst ploidy status was, however, highly distinguishable. In addition, embryo regions and embryo day were consistently revealed by FLIM. While metabolic imaging detects mitochondrial metabolic features in human blastocysts, this pilot trial indicates it does not have the potential to serve as an effective embryo viability detection tool. This may be because mitochondrial metabolism plays an alternative role post-implantation. STUDY FUNDING/COMPETING INTEREST(S): This study was sponsored by Optiva Fertility, Inc. Boston IVF contributed to the clinical site and services. Becker Hickl, GmbH, provided the FLIM system on loan. T.S. was the founder and held stock in Optiva Fertility, Inc., and D.S. and E.S. had options with Optiva Fertility, Inc., during this study. TRIAL REGISTRATION NUMBER: The study was approved by WCG Connexus IRB (Study Number 1298156).

Transient Elastography Is the Best-Performing Non-Invasive Test of Liver Fibrosis in Obese Asian Patients with Non-Alcoholic Fatty Liver Disease: A Pilot, Cross-Sectional Study.

Background and Objectives: The prevalence of NAFLD (non-alcoholic fatty liver disease) is increasing, and up to 64% of Asian patients with NAFLD are obese. Non-invasive tests (NITs) for the assessment of liver fibrosis are increasingly being used, but data on their performance in obese Asian patients are lacking. In this pilot cross-sectional study, we aim to compare the distribution of serum and radiological markers of fibrosis between obese Asian biopsy-proven NAFLD patients with and without fibrosis and estimate the diagnostic accuracies of these indices. Materials and Methods: Obese Asian patients with NAFLD and who had undergone a liver biopsy showing histological evidence of NAFLD were invited to participate. Liver fibrosis was assessed using laboratory (APRI, AAR, BARD, FIB4, NFS, and Asia-Pacific NAFLD advanced fibrosis score) and imaging modalities (TE: transient elastography, MRE: magnetic resonance elastography, and SWU: shear wave ultrasonography). Results: A total of 16 patients were included in the final analysis. On liver biopsy, nine patients (56.3%) had significant fibrosis (F2 or higher), and six of these patients had advanced fibrosis (F3 or higher). F4 fibrosis was present in one patient (6.3%). For the laboratory markers, we found that the BARD score correctly identified five out of six patients with advanced fibrosis (83.4%, p value 0.045). Among all the NITs studied, liver stiffness measured by TE had the highest accuracy of 87.5% in its established threshold of 8.5 kPa for the detection of advanced fibrosis. MRE also performed well (81.2% in 3.64 kPa). Conclusions: In conclusion, TE has performed well in the detection of advanced fibrosis in obese Asian patients with biopsy-proven NAFLD in our pilot study. Further large-scale definitive studies are needed to validate the results of our findings.

Speech changes in old age: Methodological considerations for speech-based discrimination of healthy ageing and Alzheimer's disease.

BACKGROUND: Recent evidence suggests that speech substantially changes in ageing. As a complex neurophysiological process, it can accurately reflect changes in the motor and cognitive systems underpinning human speech. Since healthy ageing is not always easily discriminable from early stages of dementia based on cognitive and behavioural hallmarks, speech is explored as a preclinical biomarker of pathological itineraries in old age. A greater and more specific impairment of neuromuscular activation, as well as  a specific cognitive and linguistic impairment in dementia, unchain discriminating changes in speech. Yet, there is no consensus on such discriminatory speech parameters, neither on how they should be elicited and assessed. AIMS: To provide a state-of-the-art on speech parameters that allow for early discrimination between healthy and pathological ageing; the aetiology of these parameters; the effect of the type of experimental stimuli on speech elicitation and the predictive power of different speech parameters; and the most promising methods for speech analysis and their clinical implications. METHODS & PROCEDURES: A scoping review methodology is used in accordance with the PRISMA model. Following a systematic search of PubMed, PsycINFO and CINAHL, 24 studies are included and analysed in the review. MAIN CONTRIBUTION: The results of this review yield three key questions for the clinical assessment of speech in ageing. First, acoustic and temporal parameters are more sensitive to changes in pathological ageing and, of these two, temporal variables are more affected by cognitive impairment. Second, different types of stimuli can trigger speech parameters with different degree of accuracy for the discrimination of clinical groups. Tasks with higher cognitive load are more precise in eliciting higher levels of accuracy. Finally, automatic speech analysis for the discrimination of healthy and pathological ageing should be improved for both research and clinical practice. CONCLUSIONS & IMPLICATIONS: Speech analysis is a promising non-invasive tool for the preclinical screening of healthy and pathological ageing. The main current challenges of speech analysis in ageing are the automatization of its clinical assessment and the consideration of the speaker's cognitive background during evaluation. WHAT THIS PAPER ADDS: What is already known on the subject Societal aging  goes hand in hand with the rising incidence of ageing-related neurodegenerations, mainly Alzheimer's disease (AD). This is particularly noteworthy in countries with longer life expectancies. Healthy ageing and early stages of AD share a set of cognitive and behavioural characteristics. Since there is no cure for dementias, developing methods for accurate discrimination of healthy ageing and early AD is currently a priority. Speech has been described as one of the most significantly impaired features in AD. Neuropathological alterations in motor and cognitive systems would underlie specific speech impairment in dementia. Since speech can be evaluated quickly, non-invasively and inexpensively, its value for the clinical assessment of ageing itineraries may be particularly high. What this paper adds to existing knowledge Theoretical and experimental advances in the assessment of speech as a marker of AD have developed rapidly over the last decade. Yet, they are not always known to clinicians. Furthermore, there is a need to provide an updated state-of-the-art on which speech features are discriminatory to AD, how they can be assessed, what kind of results they can yield, and how such results should be interpreted. This article provides an updated overview of speech profiling, methods of speech measurement and analysis, and the clinical power of speech assessment for early discrimination of AD as the most common cause of dementia. What are the potential or actual clinical implications of this work? This article provides an overview of the predictive potential of different speech parameters in relation to AD cognitive impairment. In addition, it discusses the effect that the cognitive state, the type of elicitation task and the type of assessment method may have on the results of the speech-based analysis in ageing.

The Prevalence of Liver Fibrosis Stages on More than 23,000 Liver Stiffness Measurements by Vibration-Controlled Transient Elastography: A Single Center Study.

Vibration-controlled transient elastography (VCTE) was the first non-invasive method used for assessing liver fibrosis in patients with chronic liver disease. Over the years, many studies have evaluated its performance. It is now used globally, and, in some countries, it represents the primary step in evaluating liver fibrosis. The aim of this study is to assess the feasibility of VCTE and highlight the prevalence of liver fibrosis stages assessed by VCTE in a large cohort of patients at a single study center. We also aimed to observe the trends in liver stiffness (LS) values over the years according to each type of hepatopathy. A retrospective study was conducted over a period of 13 years (2007-2019) and included patients who presented to our clinic for LS measurements (LSMs), either with known liver diseases or with suspected liver pathology who were undergoing fibrosis screening. The database contained a total of 23,420 measurements. Valid LSMs were obtained in 90.91% (21,291/23,420) of the cases, while 2129 (9.09%) of the measurements were either failed or unreliable. In untreated patients with chronic viral hepatitis, LS values tended to increase during the years, while in patients undergoing antiviral therapy LS values significantly decreased. Our comprehensive study, one of the largest of its kind spanning 13 years, emphasizes the reliability and significance of VCTE in real-world clinical settings.

Ultra-High-Resolution Time-of-Flight MR-Angiography for the Noninvasive Assessment of Intracranial Aneurysms, Alternative to Preinterventional DSA?

PURPOSE: The 3D time-of-flight (TOF) magnetic resonance angiography (MRA) at 3T shows high sensitivity for intracranial aneurysms but is inferior to three-dimensional digital subtraction angiography (3D-DSA) regarding aneurysm characteristics. We applied an ultra-high-resolution (UHR) TOF-MRA using compressed sensing reconstruction to investigate the diagnostic performance in preinterventional evaluation of intracranial aneurysms compared to conventional TOF-MRA and 3D-DSA. METHODS: In this study 17 patients with unruptured intracranial aneurysms were included. Aneurysm dimensions, configuration, image quality and sizing of endovascular devices were compared between conventional TOF-MRA at 3T and UHR-TOF with 3D-DSA as gold standard. Quantitatively, contrast-to-noise ratios (CNR) were compared between TOF-MRAs. RESULTS: On 3D-DSA, 25 aneurysms in 17 patients were detected. On conventional TOF, 23 aneurysms were detected (sensitivity: 92.6%). On UHR-TOF, 25 aneurysms were detected (sensitivity: 100%). Image quality was not significantly different between TOF and UHR-TOF (p = 0.17). Aneurysm dimension measurements were significantly different between conventional TOF (3.89 mm) and 3D-DSA (4.2 mm, p = 0.08) but not between UHR-TOF (4.12 mm) and 3D-DSA (p = 0.19). Irregularities and small vessels at the aneurysm neck were more frequently correctly depicted on UHR-TOF compared to conventional TOF. Comparison of the planned framing coil diameter and flow-diverter (FD) diameter revealed neither a statistically significant difference between TOF and 3D-DSA (coil p = 0.19, FD p = 0.45) nor between UHR-TOF and 3D-DSA (coil: p = 0.53, FD 0.33). The CNR was significantly higher in conventional TOF (p = 0.009). CONCLUSION: In this pilot study, ultra-high-resolution TOF-MRA visualized all aneurysms and accurately depicted aneurysm irregularities and vessels at the base of the aneurysm comparably to DSA, outperforming conventional TOF. UHR-TOF with compressed sensing reconstruction seems to represent a non-invasive alternative to pre-interventional DSA for intracranial aneurysms.

Non-invasive central aortic pressure measurement: what limits its application in clinical practice?

The following article highlights the need for methodological transparency and consensus for an accurate and non-invasive assessment of central aortic blood pressure (aoBP), which would contribute to increasing its validity and value in both clinical and physiological research settings. The recording method and site, the mathematical model used to quantify aoBP, and mainly the method applied to calibrate pulse waveforms are essential when estimating aoBP and should be considered when analyzing and/or comparing data from different works, populations and/or obtained with different approaches. Up to now, many questions remain concerning the incremental predictive ability of aoBP over peripheral blood pressure and the possible role of aoBP-guided therapy in everyday practice. In this article, we focus on "putting it on the table" and discussing the main aspects analyzed in the literature as potential determinants of the lack of consensus on the non-invasive measurement of aoBP.

DAPS score - a novel score for prediction of significant fibrosis in incidentally detected asymptomatic hepatitis B subjects.

Aim of the study: Significant fibrosis is an indication for treatment in hepatitis B patients with normal transaminase levels. The present study was aimed at analyzing the factors associated with significant fibrosis in incidentally detected asymptomatic hepatitis B subjects (IDAHS) and developing a model for fibrosis prediction for use in low-resource settings. Material and methods: This is a single-center retrospective analysis of data on IDAHS who had undergone FibroScan. The variables associated with significant fibrosis in the derivation cohort were subjected to multivariate analysis by logistic regression. The model was applied to the validation cohort for fibrosis prediction. Results: A total of 299 patients (mean age: 42.6 years, males: 63.2%) were included in the model derivation. Significant fibrosis was found in 27.4% (82/299) of the patients and 16.8% (30/178) of those with normal transaminase. On multivariate analysis, age, lower platelet count, and presence of diabetes were associated with fibrosis. Serum glutamic pyruvic transaminase (SGPT) was included in the model as it was nearing towards in multivariate analysis. The DAPS (diabetes, age, platelet count, SGPT) score was proposed with equal weightage to each variable. Based on the cumulative score, patients were categorized as having low risk (DAPS score 0-2) or high risk (DAPS score 3-4). The specificity of the model in derivation and validation cohorts was 98.2% and 97.6%, respectively, while the accuracy was 83.6% and 80%, respectively. Conclusions: Approximately 17% of IDAHS with normal transaminase have significant fibrosis. The DAPS score can be used easily as a bedside tool for assessment of significant fibrosis in IDAHS with excellent specificity.

Quantitative T2 mapping monitoring the maturation of engineered elastic cartilage in a rabbit model.

BACKGROUND: Cartilage tissue engineering provides a promising approach to reconstruct craniofacial defects, and a noninvasive method is needed to assess its effectiveness. Although magnetic resonance imaging (MRI) has been used to evaluate articular cartilage in vivo, few studies focused on its feasibility in monitoring engineered elastic cartilage (EC). METHODS: Auricular cartilage, silk fibroin (SF) scaffold, and EC consisting of rabbit auricular chondrocytes and SF scaffold were transplanted subcutaneously into the rabbit back. In eight weeks after transplantation, grafts were imaged by MRI using PROSET, PDW VISTA SPAIR, 3D T2 VISTA, 2D MIXED T2 Multislice, and SAG TE multiecho sequences, followed by histological examination and biochemical analysis. Statistical analyses were performed to identify the association between T2 values and biochemical indicator values of EC. RESULTS: In vivo imaging shows that 2D MIXED T2 Multislice sequence (T2 mapping) clearly distinguished the native cartilage, engineered cartilage and fibrous tissue. T2 values showed high correlations with cartilage-specific biochemical parameters at different time points, especially the elastic cartilage specific protein elastin (ELN, r= -0.939, P < 0.001). CONCLUSION: Quantitative T2 mapping can effectively detect the in vivo maturity of engineered elastic cartilage after subcutaneously transplantation. This study would promote the clinical application of MRI T2 mapping in monitoring engineered elastic cartilage in the repair of craniofacial defects.

Accuracy of FIB-4 and APRI scores compared to transient elastography for liver fibrosis in patients with HIV and HBV co-infection.

BACKGROUND: Due to economic shortages and concern about occupational exposure to HIV, liver biopsy and transient elastography (TE) are rarely available in patients with HIV/HBV co-infection in China, where HIV/HBV co-infection is prevalent. METHODS: The accuracy of FIB-4 and APRI for predicting liver fibrosis was compared with TE results in a series of 460 HIV/HBV co-infected patients. RESULTS: FIB-4 and APRI scores were strongly correlated to liver stiffness measurement scores by TE, and the correlation index was 81.4-96.3. An FIB-4 index >1.5 had a positive predictive value of 95.2% to consider fibrosis with a sensitivity of 85.7%. An APRI index >0.5 had a positive predictive value of 98.2% to consider fibrosis with a sensitivity of 76.0%. A FIB-4 value <1.5 or APRI <0.5 were concordant with TE results to exclude fibrosis in 94.4% and 96.8%, respectively. A FIB-4 value >1.5 or APRI >0.5 were concordant with fibrosis diagnosed by TE in 77.6-89.4% and 70.7-80.9%, respectively. CONCLUSIONS: In areas with limited resources, FIB-4 and APRI indexes were accurate, simple and inexpensive methods for assessing liver fibrosis in patients with HIV/HBV co-infection.

The Association Between Non-Clinically Apparent Liver Fibrosis and Pulmonary Arterial Hypertension in Hispanic Patients.

Background: Pulmonary arterial hypertension (PAH) is a deadly cardiopulmonary disease with multi-organ involvement including impaired liver function. Liver dysfunction in PAH is poorly understood but significantly associated with morbidity and mortality. Hispanics have a significantly higher prevalence of non-alcoholic fatty liver disease (NAFLD) and evidence of more advanced disease in comparison to other ethnic groups. The clinical impact of NAFLD in Hispanic PAH patients is unknown. We aimed to investigate the impact of a validated scoring system, non-alcoholic fatty liver disease fibrosis score (NFS), to predict the degree of liver fibrosis in a Hispanic PAH population and its relationship to hemodynamics, functional class, and outcomes. Methods: A retrospective review of all treatment-naive Hispanic patients with group I World Health Organization (WHO) pulmonary hypertension (PH) at a single academic center between February 2016 and March 2021 was performed. Patients with history of substance or alcohol abuse, non-group I WHO PH, pre-existent liver disease, chronic kidney disease, atrial fibrillation, thyroid disease, and warfarin use were excluded from the study. The diagnosis of group I WHO PH was determined by cardiac catheterization after the exclusion of other etiologies. NFS was calculated for each patient and correlated with functional capacity, hemodynamics, N-terminal-pro-B-type natriuretic peptide (NT-proBNP), and survival. Results: A total of 96 Hispanic patients were included in our study. The median age of patients in our cohort was 49 years (interquartile range: 15) and 69% of our cohort were females. Higher NFSs indicating advanced hepatic fibrosis (F3-F4) were found to correlate with elevated right-sided cardiac filling pressures (r = 0.27, P = 0.03), elevated levels of NT-proBNP (r = 0.32, P = 0.01), lower 6-minute walk distance (6MWD) (r = -0.49, P = 0.001), lower functional capacity (World Health Organization functional class, WHO-FC, r = -0.35, P = 0.051), a higher prevalence of diabetes (21.1% versus 51.9%, P = 0.001), a higher prevalence of risk factors for metabolic syndrome (81.5% versus 65.0%, P = 0.035), and worse 5-year survival rates. Conclusion: In Hispanic patients with PAH, NFSs correlate with the degree of right-sided pressure overload. In addition, advanced NFSs were independently associated with lower 5-year survival rates and added prognostic information to other established risk parameters in PAH. This study suggests that screening for liver disease in this vulnerable patient population can aid in earlier detection leading to discussion of lifestyle modifications and possible escalation of PAH-targeted therapies, thus leading to potential improvement in survival rates.

The autonomic nervous system in atrial fibrillation-pathophysiology and non-invasive assessment.

The autonomic nervous system plays a crucial role in atrial fibrillation pathophysiology. Parasympathetic hyperactivity result in a shortening of the action potential duration, a reduction of the conduction wavelength, and as such facilitates reentry in the presence of triggers. Further, autonomic remodeling of atrial myocytes in AF includes progressive sympathetic hyperinnervation by increased atrial sympathetic nerve density and sympathetic atrial nerve sprouting. Knowledge on the pathophysiological process in AF, including the contribution of the autonomic nervous system, may in the near future guide personalized AF management. This review focuses on the role of the autonomic nervous system in atrial fibrillation pathophysiology and non-invasive assessment of the autonomic nervous system.

Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma.

BACKGROUND: Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC). METHODS: Patients with newly diagnosed HCC were prospectively recruited. Pre-treatment MR elastography and PDFF were performed on tumor and non-tumor regions. HCC treatment was categorized as potentially curative (resection/ablation) or non-curative (locoregional/systemic therapy). HCC recurrence, liver-related complications (ascites/ variceal bleeding/ hepatic encephalopathy) and mortality were monitored. RESULTS: Of the 158 recruited patients (mean age 62.9 years, 84.2% male, 82.9% viral hepatitis), 58.2% (n = 92) and 41.8% (n = 66) received potentially curative and non-curative therapy, respectively. Pre-treatment non-tumor liver stiffness independently predicted liver-related complications, regardless of treatment type (HR 1.384, 95% CI 1.067-1.796, p = 0.014). In the potentially curative therapy group, non-tumor stiffness and non-tumor PDFF were independently associated with HCC recurrence (HR 1.308, 95% CI 1.022-1.673 & HR 1.080, 95% CI 1.009-1.156 respectively, both p < 0.05); and non-tumor PDFF predicted mortality (HR 1.160, 95% CI 1.038-1.296, p = 0.009). In the non-curative group, tumor stiffness independently predicted liver-related complications (HR 1.299, 95% CI 1.023-1.651, p = 0.032), and a combination of tumor stiffness ≥ 5.7 kPa plus non-tumor stiffness ≥ 3.7 kPa was associated with a two-fold risk of liver-related complications (86.7% vs 40.0%, p < 0.001). CONCLUSION: Pre-treatment MR elastography and PDFF over tumor and non-tumor regions demonstrated prognosticating roles in HCC. Simultaneous measurements of both metrics during conventional MR liver should be considered in the diagnostic workup of HCC.

Non-invasive oocyte quality assessment.

Oocyte quality is perhaps the most important limiting factor in female fertility; however, the current methods of determining oocyte competence are only marginally capable of predicting a successful pregnancy. We aim to review the predictive value of non-invasive techniques for the assessment of human oocytes and their related cells and biofluids that pertain to their developmental competence. Investigation of the proteome, transcriptome, and hormonal makeup of follicular fluid, as well as cumulus-oocyte complexes are currently underway; however, prospective randomized non-selection-controlled trials of the future are needed before determining their prognostic value. The biological significance of polar body morphology and genetics are still unknown and the subject of debate. The predictive utility of zygotic viscoelasticity for embryo development has been demonstrated, but similar studies performed on oocytes have yet to be conducted. Metabolic profiling of culture media using human oocytes are also limited and may require integration of automated, high-throughput targeted metabolomic assessments in real time with microfluidic platforms. Light exposure to oocytes can be detrimental to subsequent development and utilization of time-lapse imaging and morphometrics of oocytes is wanting. Polarized light, Raman microspectroscopy, and coherent anti-Stokes Raman scattering are a few novel imaging tools that may play a more important role in future oocyte assessment. Ultimately, the integration of chemistry, genomics, microfluidics, microscopy, physics, and other biomedical engineering technologies into the basic studies of oocyte biology, and in testing and perfecting practical solutions of oocyte evaluation, are the future for non-invasive assessment of oocytes.

Non-invasive assessment of liver abnormalities in pediatric Fontan patients.

Liver abnormalities are well known among long-term survivors of Fontan palliation, which remains the definite surgery for complex congenital heart disease and single ventricle physiology. Pediatric data however are scarce. We assessed the prevalence and degree of liver abnormalities in pediatric Fontan patients through non-invasive investigations suitable for longitudinal follow-up. Thirty-five patients with a median age of 11.8 years (5.2-16.6) and median time since Fontan of 6 years (1.17-13.83) were studied. Each child underwent a blood test, liver Doppler ultrasound (US), and transient elastography (TE). Healthy children were used as controls for TE measurement. AST, ALT, γGT, and direct bilirubin were abnormal in respectively 12 (34%), 5 (14%), 24 (69%), and 7 (20%) patients, while platelet count was decreased in 7 (20%). Splenomegaly was present in 7 (20%) patients. Portal vein mean flow velocity was < 15 cm/s in 19 (54%) patients indicative of portal hypertension. Twenty-two patients (63%) showed inferior vena cava collapsibility index values below 17%, indicating venous congestion. Hepatic artery and superior mesenteric artery resistance index were inversely correlated with time post Fontan (p < 0.05). TE values in Fontan patients were significantly higher than controls, with a median of 12.6 versus 4.6 kPa (p < 0.001) and were already increased shortly after Fontan completion. Conclusion: Liver abnormalities are frequently observed in pediatric Fontan patients. The non-invasive investigations used were not able to confirm liver fibrosis or differentiate hepatic congestion from fibrosis. Based on our findings, we propose a prospective screening protocol with serial measurements of laboratory, (Doppler) US, and TE parameters. What is Known: • Hepatic dysfunction is a well-known consequence of the Fontan circulation. • The natural history of Fontan-associated liver disease in the pediatric age group remains unclear. What is New: • Liver abnormalities are frequently observed in pediatric Fontan patients; however, differentiating liver fibrosis and hepatic congestion with non-invasive investigations remains challenging. Sonographic Doppler measurements may improve our insight in both Fontan-associated liver disease development and the functioning of the Fontan circulation. • A prospective screening protocol is proposed to improve our ability to detect Fontan-associated liver disease early on and understand its natural history.

Non-invasive Metabolomic Profiling of Embryo Culture Medium Using Raman Spectroscopy With Deep Learning Model Predicts the Blastocyst Development Potential of Embryos.

Purpose: This study aimed to establish a non-invasive predicting model via Raman spectroscopy for evaluating the blastocyst development potential of day 3 high-quality cleavage stage embryos. Methods: Raman spectroscopy was used to detect the metabolic spectrum of spent day 3 (D3) embryo culture medium, and a classification model based on deep learning was established to differentiate between embryos that could develop into blastocysts (blastula) and that could not (non-blastula). The full-spectrum data for 80 blastula and 48 non-blastula samples with known blastocyst development potential from 34 patients were collected for this study. Results: The accuracy of the predicting method was 73.53% and the main different Raman shifts between blastula and non-blastula groups were 863.5, 959.5, 1,008, 1,104, 1,200, 1,360, 1,408, and 1,632 cm-1 from 80 blastula and 48 non-blastula samples by the linear discriminant method. Conclusion: This study demonstrated that the developing potential of D3 cleavage stage embryos to the blastocyst stage could be predicted with spent D3 embryo culture medium using Raman spectroscopy with deep learning classification models, and the overall accuracy reached at 73.53%. In the Raman spectroscopy, ribose vibration specific to RNA were found, indicating that the difference between the blastula and non-blastula samples could be due to materials that have similar structure with RNA. This result could be used as a guide for biomarker development of embryo quality assessment in the future.

Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection.

BACKGROUND: Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. METHODS: This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. RESULTS: Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009-0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2-5 years and 5-10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). CONCLUSION: cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection.