Nanotechnology-Based Approaches for Cosmeceutical and Skin Care: A Systematic Review.

Cosmeceuticals have gained great importance and are among the top-selling products used for skin care. Because of changing lifestyles, climate, and increasing pollution, cosmeceuticals are utilized by every individual, thereby making cosmeceuticals a fruitful field for research and the economy. Cosmeceuticals provide incredibly pleasing aesthetic results by fusing the qualities of both cosmetics and medicinal substances. Cosmeceuticals are primarily utilized to improve the appearance of skin by making it smoother, moisturized, and wrinkle-free, in addition to treating dermatological conditions, including photoaging, burns, dandruff, acne, eczema, and erythema. Nanocosmeceuticals are cosmetic products that combine therapeutic effects utilizing nanotechnology, allowing for more precise and effective target-specific delivery of active ingredients, and improving bioavailability.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

RNA-Small-Molecule Interaction: Challenging the "Undruggable" Tag.

RNA targeting, specifically with small molecules, is a relatively new and rapidly emerging avenue with the promise to expand the target space in the drug discovery field. From being "disregarded" as an "undruggable" messenger molecule to FDA approval of an RNA-targeting small-molecule drug Risdiplam, a radical change in perspective toward RNA has been observed in the past decade. RNAs serve important regulatory functions beyond canonical protein synthesis, and their dysregulation has been reported in many diseases. A deeper understanding of RNA biology reveals that RNA molecules can adopt a variety of structures, carrying defined binding pockets that can accommodate small-molecule drugs. Due to its functional diversity and structural complexity, RNA can be perceived as a prospective target for therapeutic intervention. This perspective highlights the proof of concept of RNA-small-molecule interactions, exemplified by targeting of various transcripts with functional modulators. The advent of RNA-oriented knowledge would help expedite drug discovery.

Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy.

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10-6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model. CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

Autoimmune Lupus Enteritis with Pan Gastrointestinal Involvement in an Adult Patient with Systemic Lupus Erythematosus: Complete Response to Belimumab.

Autoimmune lupus enteritis in systemic lupus erythematosus (SLE) is a rare manifestation that comprises of gastrointestinal tract inflammation with supportive images and/or biopsy findings. We report a unique case of widespread lupus enteritis occurring late in the disease process and in isolation without additional features of active SLE but in the presence of SLE serological activity. There was no clear evidence of active mesenteric vasculitis, intestinal pseudo-obstruction, protein-losing enteropathy, or coagulopathy by imaging or histopathology. This is the first reported case of an SLE patient with pan-gastrointestinal involvement of lupus enteritis responding to Belimumab, with complete resolution of the gastrointestinal syndrome and no further recurrence of gastrointestinal events. Rapid diagnosis and prompt immunomodulatory treatment of lupus-related enteritis are critical to avoid potentially life-threatening complications.

Screening of potential inhibitors against structural proteins from Monkeypox and related viruses of Poxviridae family via docking and molecular dynamics simulation.

Monkeypox virus (MPXV) is an orthopoxvirus which causes zoonotic infection in humans. Even though sporadic cases of this infection are limited to the African continent, but if the infection continues to increase unabated, it can be a cause of serious concern for the human populace. Smallpox vaccination has been in use against monkeypox infection but it only provides mild protection. In the current study, we have screened novel small molecules (estrone fused heterocycles (EH1-EH7)) exhibiting good binding with monkeypox virus protein and related proteins from Poxviridae family of viruses via computational approaches. EH1-7 series of small molecules selected for the work have been synthesized via cycloaddition methodology. Docking and Molecular Dynamics (MD) results highlight EH4 compound to have strong binding affinity towards monkeypox and other related viral proteins selected for the study. Thus, computational outcomes suggest EH4 as a good candidate against monkeypox. Currently, no antiviral medication has been approved against monkeypox and the treatment is only via therapeutics available for smallpox and related conditions that may be helpful against monkeypox. Our study is thus an attempt to screen novel compounds against monkeypox infection, which would, in turn, facilitate development of novel therapeutics against Poxviridae family. HIGHLIGHTSMonkeypox infection is a public health emergency and necessitates immediate drug discovery.Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses.Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus.Estrone-fused heterocycles compounds are promising anti-viral agents as per our in silico analysis.Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions.Communicated by Ramaswamy H. Sarma.

Monkeypox: This orthopoxvirus leads to mpox (monkeypox) disease which shows symptoms similar to that smallpox, however to less severe extent.Poxviridae family: This is commonly a family of double-stranded DNA viruses. The natural hosts for these viruses are arthropods and Vertebrates.Molecular Dynamic simulation: MD simulation is crucial for determining the ligand's stability and revealing the duration of its interaction with the respective macromolecular structure.Molecular Docking: Molecular docking aids in determining specific sites where the ligand binds with the macromolecule as well as its binding affinity. Bioinformatics tools such as docking have been widely employed for aiding drug discovery efforts.Protein binding energy: On docking protein with the ligand, the binding energy shows the free energy change during binding process between protein-ligand.

Bacterial cell permeability study by metal oxide and mixed metal oxide nanoparticles: analysis of the factors contributing to the antibacterial activity of nanoparticles.

In this work, we investigate the nanoparticle-cell wall interaction by NiO and mixed metal oxide CuO-NiO nanoparticles. We have synthesized and characterized the nanoparticles using XRD, FESEM, EDS, UV vis. spectroscopy, FTIR, Zeta, and TEM analysis in our previous work. Furthermore, a preliminary antibacterial study showed that both the nanoparticles performed very well as antibacterial agents. In this extended work, we investigate the mechanism of interaction of NiO and CuO-NiO nanoparticles with S. aureus and E. coli cells as there are number of studies for antibacterial mechanism of CuO nanoparticles. The uptake of crystal violet dye in the outer bacterial membrane, the release of ß-galactosidase enzyme, and relative electric conductivity assay were used to investigate changes in the permeability and integrity of the cell membrane. Superoxide ions, which are produced intracellularly as ROS by nanoparticles, severely damage bacterial membranes. Zeta potential measurement, which resulted in surface charge neutralization, proved membrane instability. FTIR analysis was used to identify changes in the proteins, carbohydrates, and fatty acids that make up the chemical composition of cell surfaces. AFM imaging demonstrated extensive alteration of the nanomechanical and surface characteristics. Confocal microscopy examination supported the DNA fragmentation and nanoparticle-cell adhesion. Due to their enhanced antibacterial activity when compared to monometallic oxide nanoparticles, this study demonstrated that mixed metal oxides can be employed in the health and biomedical sectors.

Extensive retroperitoneal multiloculated abscesses after open cholecystectomy associated with bile leak: a case report.

Retroperitoneal abscesses are rare and life-threatening. The incidence of abscesses after open cholecystectomies is <1% disregarding location. 11 cases reporting post-cholecystectomy retroperitoneal abscesses were archived on PubMed, 7 associated with gallstone retaining or spillage. Hereby, we present a case of extensive retroperitoneal multiloculated abscesses after open cholecystectomy complicated with bile leak, while no gallstone was noted. Early evaluation for retroperitoneal abscesses is critical if the patient does not clinically improve after cholecystectomy. Early treatment with drainage of the abscesses, antibiotics, and endoscopic retrograde cholangiopancreatography intervention to achieve source control can greatly improve the clinical outcome.

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma.

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC.

Tuberculosis: An Overview of the Immunogenic Response, Disease Progression, and Medicinal Chemistry Efforts in the Last Decade toward the Development of Potential Drugs for Extensively Drug-Resistant Tuberculosis Strains.

Tuberculosis (TB) is a slow growing, potentially debilitating disease that has plagued humanity for centuries and has claimed numerous lives across the globe. Concerted efforts by researchers have culminated in the development of various strategies to combat this malady. This review aims to raise awareness of the rapidly increasing incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, highlighting the significant modifications that were introduced in the TB treatment regimen over the past decade. A description of the role of pathogen-host immune mechanisms together with strategies for prevention of the disease is discussed. The struggle to develop novel drug therapies has continued in an effort to reduce the treatment duration, improve patient compliance and outcomes, and circumvent TB resistance mechanisms. Herein, we give an overview of the extensive medicinal chemistry efforts made during the past decade toward the discovery of new chemotypes, which are potentially active against TB-resistant strains.

Self-organization of random copolymers to nanopatterns by localized e-beam dosing.

Strategic electron beam (e-beam) irradiation on the surface of an ultrathin (<100 nm) film of polystyrene-poly(methyl methacrylate) (PS-PMMA) random copolymer followed by solvent annealing stimulates a special variety of dewetting, leading to large-area hierarchical nanoscale patterns. For this purpose, initially, a negative (positive) tone of resist PS (PMMA) under weak e-beam exposure is exploited to produce an array of sites composed of cross-linked PS (chain-scissioned PMMA). Subsequently, annealing with the help of a developer solvent engenders dewetted patterns in the exposed zones where PMMA blocks are confined by the blocks of cross-linked PS. The e-beam dosage was systematically varied from 180µC cm-2to 10 000µC cm-2to explore the tone reversal behavior of PMMA on the dewetted patterns. Remarkably, at relatively higher e-beam dosing, both PMMA and PS blocks act as negative tones in the exposed zone. In contrast, the chain scission of PMMA in the periphery of the exposed regions due to scattered secondary electrons caused confined dewetting upon solvent annealing. Such occurrences eventually lead to pattern miniaturization an order of magnitude greater than with conventional thermal or solvent vapor annealed dewetting. Selective removal of PMMA blocks of RCP using a suitable solvent provided an additional 50% reduction in the size of the dewetted features.

Integrating baseline MR imaging biomarkers into BCLC and CLIP improves overall survival prediction of patients with hepatocellular carcinoma (HCC).

OBJECTIVES: We aimed to evaluate the independent predictive role of baseline imaging biomarkers for overall survival (OS) and transplant-free survival (TFS) in patients with HCC and assess the incremental value of these biomarkers to current staging systems. METHODS: In this retrospective IRB approved study, the clinical, laboratory, and imaging parameters of 304 HCC patients were collected. Cox regression model was utilized to identify the potential predictors of survival. Recursive partitioning test was utilized to identify the optimal ADC cutoff for stratifying patients' OS. Patients were stratified based on Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Binary ADC value (above vs. below the cutoff) and tumor margin (well- vs. ill-defined) were integrated into BCLC and CLIP. OS and TFS was compared for patients based on standard criteria with and without imaging biomarkers. RESULTS: At baseline, patients with low tumor ADC and well-defined tumor margin (favorable imaging biomarkers) had longer survival, as compared to those with high ADC and ill-defined tumor margin (unfavorable imaging biomarkers) (median OS of 43 months vs. 7 months, respectively) (p < 0.001). Tumor ADC and tumor margin remained strong independent predictors of survival after adjustment for demographics, BCLC and CLIP staging, and tumor burden. Incorporating ADC and tumor margin improved performance of OS prediction by 9% in BCLC group and 6% in CLIP group. CONCLUSION: Incorporating ADC and tumor margin to current staging systems for HCC significantly improve prediction of OS and TFS of these criteria. KEY POINTS: • ADC and tumor margin are predictors of overall survival in HCC patients, independent of clinical, laboratory, and other imaging variables. • Adding ADC and tumor margin improved the prognostic value of BCLC and CLIP criteria by 9% and 6%, respectively. • High ADC and ill-defined tumor margin at baseline predicted poor survival, regardless of patient's liver function and general health status.

Post-TACE changes in ADC histogram predict overall and transplant-free survival in patients with well-defined HCC: a retrospective cohort with up to 10 years follow-up.

OBJECTIVES: To evaluate the role of change in apparent diffusion coefficient (ADC) histogram after the first transarterial chemoembolization (TACE) in predicting overall and transplant-free survival in well-circumscribed hepatocellular carcinoma (HCC). METHODS: Institution database was searched for HCC patients who got conventional TACE during 2005-2016. One hundred four patients with well-circumscribed HCC and complete pre- and post-TACE liver MRI were included. Volumetric MRI metrics including tumor volume, mean ADC, skewness, and kurtosis of ADC histograms were measured. Univariate and multivariable Cox models were used to test the independent role of change in imaging parameters to predict survival. P values < 0.05 were considered significant. RESULTS: In total, 367 person-years follow-up data were analyzed. After adjusting for baseline liver function, tumor volume, and treatment modality, incremental percent change in ADC (ΔADC) was an independent predictor of longer overall and transplant-free survival (p = 0.009). Overall, a decrease in ADC-kurtosis (ΔkADC) showed a strong role in predicting longer survival (p = 0.021). Patients in the responder group (ΔADC ≥ 35%) had the best survival profile, compared with non-responders (ΔADC < 35%) (p < 0.001). ΔkADC, as an indicator of change in tissue homogeneity, could distinguish between poor and fair survival in non-responders (p < 0.001). It was not a measure of difference among responders (p = 0.244). Non-responders with ΔkADC ≥ 1 (homogeneous post-TACE tumor) had the worst survival outcome (HR = 5.70, p < 0.001), and non-responders with ΔkADC < 1 had a fair survival outcome (HR = 2.51, p = 0.029), compared with responders. CONCLUSIONS: Changes in mean ADC and ADC kurtosis, as a measure of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in well-circumscribed HCC, in order to monitor early response to TACE and identify patients with treatment failure and poor survival outcome. KEY POINTS: • Changes in the mean and kurtosis of ADC histograms, as the measures of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in patients with well-defined HCC. • A ≥ 35% increase in volumetric ADC after TACE is an independent predictor of good survival, regardless of the change in ADC histogram kurtosis. • In patients with < 35% ADC change, a decrease in ADC histogram kurtosis indicates partial response and fair survival, while ∆kurtosis ≥ 1 correlates with the worst survival outcome.

Nanometer-Thick Superhydrophobic Coating Renders Cloth Mask Potentially Effective against Aerosol-Driven Infections.

The advent of COVID-19 pandemic has made it necessary to wear masks across populations. While the N95 mask offers great performance against airborne infections, its multilayered sealed design makes it difficult to breathe for a longer duration of use. The option of using highly breathable cloth or silk masks especially for a large populace is fraught with the danger of infection. As a normal cloth or silk mask absorbs airborne liquid, it can be a source of plausible infection. We demonstrate the chemical modification of one such mask, Eri silk, to make it hydrophobic (contact angle of water is 143.7°), which reduces the liquid absorption capacity without reducing the breathability of the mask significantly. The breathability reduces only 22% for hydrophobic Eri silk compared to the pristine Eri silk, whereas N95 shows a 59% reduction of breathability. The modified hydrophobic silk can repel the incoming aqueous liquid droplets without wetting the surface. The results indicate that a multilayered modified silk mask to make it hydrophobic can be an affordable and breathable alternative to the N95 mask.

Non-equilibrium thermal annealing of a polymer blend in bilayer settings for complex micro/nano-patterning.

Micro phase separation in a thin film of a polymer blend leads to interesting patterns on different substrates. A plethora of studies in this field discussed the effect of the surface energy of the underlying tethered polymer brush or substrate on the final morphology of the polymer blend. The conventional process toward the final morphology is rather slow. Here, aiming fast lithography, we induce the kinetically driven morphological evolution by rapid thermal annealing (RTA) of the polymer blend of polystyrene (PS) and polymethylmethacrylate (PMMA) in bilayer settings at a very high temperature. The underlying film consists of untethered constituent homopolymers or their blend or random-co-polymer (RCP). Apart from the phase inversion of the blend on the PS homopolymer, a rich morphology of the blend on the RCP underlayer is uncovered with systematic investigation of the film using sequential washing with selective solvents. The dissolution characteristics and the thermal stability of the constituent polymers corroborated the observation. Based on the understanding of the morphological evolution, fabrication of a complex shaped micro/nano-pattern with multiple length scales is demonstrated using this blend/RCP system. This study shows a novel methodology for easy fabrication of hierarchical small length scale complex structures.

Role of volumetric multiparametric MRI in distinguishing between intraductal papillary mucinous neoplasms and serous cystadenoma.

PURPOSE: To evaluate the use of volumetric multiparametric MRI in differentiating pancreatic intraductal papillary mucinous neoplasms (IPMNs) from serous cystadenomas (SCAs) METHODS: Included patients (123 patients with pancreatic cystic neoplasms (PCNs) measuring ≥ 10 mm) were stratified into two groups based on cyst type. Axial cyst size, region of interest (ROI)-based apparent diffusion coefficient (ADC) and volumetric data, including cyst volume, volumetric apparent diffusion coefficient (vADC), and volumetric venous enhancement (vVE) were extracted and compared between the two groups. Univariate and multiple logistic regression was used to develop models for distinguishing between IPMNs and SCAs. RESULTS: Volume and size of the cysts, vVE and vADC and ROI-ADC were significantly different between the two groups. Cyst volume was significantly larger in SCAs (median = 14.1cm3, IQR 3.5-42.5) than in IPMNs (median = 2.5 cm3, IQR 1.1-6) (p < 0.001). IPMNs had a higher volumetric ADC value in comparison to SCAs (2925 ± 294 × 10-6 mm2/s vs 2521 ± 202 × 10-6 mm2/s, p < 0.001). However, IPMNs had lower vVE values compared to SCAs (37 signal intensity (SI) vs 86 SI, p < 0.001). Area under the ROC Curve (AUC) of the model that included vADC and cyst volume had 95% accuracy in distinguishing between the two groups. In comparison, the AUC of the model that included ROI-ADC and axial cyst size had 84% accuracy in distinguishing between the two groups. A threshold of 2615 × 10-6 mm2/s for volumetric ADC resulted in the identification of IPMNs from SCAs with sensitivity and specificity of 90.8% and 73.5%, respectively. CONCLUSION: IPMNs had smaller cyst volume, higher volumetric ADC and lower volumetric VE values compared to SCAs. Volumetric multiparametric MRI could be useful in differentiating between the IPMN and SCA groups.

Role of tumor margin and ADC change in defining the need for additional treatments after the first TACE in patients with unresectable HCC.

PURPOSE: To define the number of TACE sessions needed to improve patients' overall survival (OS) in different subgroups of unresectable HCC. METHODS: This retrospective cohort included 180 patients who got TACE between 2005-2016 as the initial treatment for unresectable HCC. Tumor margin (well- vs. ill-defined) was determined by two radiologists at baseline. Well-defined group was divided into two groups (ADC-responders vs. ADC-nonresponders) based on %ADC change (ΔADC-cutoff = 25 %). Accordingly, patients were categorized into three groups, ill-defined, well-defined ADC-responders, or well-defined ADC-nonresponders. Cox-analysis was used to compare the survival benefit of multiple TACE in different groups. RESULTS: Ill-defined HCC (n = 108) was associated with worse survival (HR = 1.95,p < 0.001). Multiple TACE were associated with increased OS (HR = 0.88,p = 0.033) in these patients, with significant survival improvement after ≥4TACE. ΔADC was not related to OS in ill-defined group. In well-defined group (n = 72), multiple TACE were not associated with improved OS (HR = 0.181,p = 0.090). These patients were categorized into two groups based on ΔADC-cutoff. ADC-responders (ΔADC≥25 %) had the longest survival than other groups(p = 0.015). Multiple TACE sessions were not associated with better OS in this group (HR = 1.004,p = 0.982). By contrast, incremental number of TACE were associated with significantly longer OS in ADC-nonresponders (ΔADC<25 %) (HR = 0.79,p = 0.034). These patients' OS significantly improved after ≥3TACE. CONCLUSION: The survival benefit of sequential TACE sessions varies for different HCC subgroups. There was no significant survival benefit associated with multiple TACE in well-defined lesions responding to the first TACE. The most survival benefit was for ADC-nonresponder well-defined group and it was least for ill-defined HCC group, regardless of ADC-response.

Cross-sectional imaging in patients with primary sclerosing cholangitis: Single time-point liver or spleen volume is associated with survival.

AIM: To evaluate the association between single time-point quantitative liver and spleen volumes in patients with PSC and transplant-free survival, independent of Mayo risk score. MATERIALS AND METHODS: This HIPAA-compliant retrospective study included 165 PSC patients in a hospital. Total (T), and lobar (right [R], left [L], and caudate [C]) liver volumes and spleen volume (S) were measured. Adverse outcome was identified as being on liver transplantation list, transplantation or death (outcome 1), and transplantation or death (outcome 2). Cox-regression was performed to assess the predictive value of volumetric parameters to predict transplant-free survival with and without Mayo risk score. Stratified analysis by Mayo risk score categories was performed to assess the discriminative value of volumes in the model. Prediction models were developed dependent of Mayo score, based on patients demographics, lab values and volumetric measures for both defined outcomes. Kaplan-Meier curves were depicted for different liver and spleen volumes. P value <0.05 was considered statistically significant. RESULTS: In this cohort (age 43 ±â€¯17 years; 59 % men) 51 % of patients had adverse outcome. Cox-regression analysis demonstrated statistically significant association between values of T, L, R, C, S, L/T, and C/T and outcome 1; and also statistically significant association between values C, S, and C/T and outcome 2. Prediction models included age, INR, total bilirubin, AST, variceal bleeding, S, and C for outcome 1 and age, INR, total bilirubin, AST, variceal bleeding, and S for outcome 2. CONCLUSIONS: Based on our observational study, quantitative liver and spleen volumes may be associated with transplant-free survival in patients with PSC and may have the potential for predicting the outcome but this should be validated by randomized clinical trial studies.

Does the change in volumetric functional MR metrics post-TACE predict histopathologic grading of hepatocellular carcinoma?

OBJECTIVES: To evaluate whether the change in volumetric ADC (vADC) and volumetric venous enhancement (vVE) after transarterial chemoembolization (TACE) can predict the histologic grading of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPPA-compliant retrospective study was approved by our institutional review board. The study population included 106 HCC patients (147 index lesions) who had MR imaging within 3 months before and after TACE and pathologic report of the HCC either by biopsy or liver transplantation/resection between 2001 and 2017. Volumetric measurements of venous enhancement (VE) and apparent diffusion coefficient (ADC) were performed on baseline and post-TACE MRI. The tumors were histologically classified into two low-grade and high-grade groups. The parameters between two groups were compared using bivariate and multivariate analyses. RESULTS: Median change in vADC, vVE, and absolute vADC skewness after TACE was higher in low-grade HCCs as compared with high-grade HCCs (p < 0.001, p = 0.005, p = 0.04, respectively). Combining ΔvADC, ΔvVE, and the etiology for background liver disease in multivariate analysis had the highest accuracy in distinguishing high-grade tumors (AUC = 91%). CONCLUSION: ΔvADC and ΔvVE after TACE are potential predictors of HCC histopathological grading. Combining functional MRI biomarkers with the etiology of liver disease can enhance the accuracy in assessing degree of differentiation. KEY POINTS: • Change in volumetric functional MRI biomarkers after TACE can be a non-invasive method to evaluate tumor histopathology in HCC. • The etiology of background liver disease might be a predictor of tumor degree of differentiation.

Role of baseline volumetric functional MRI in predicting histopathologic grade and patients' survival in hepatocellular carcinoma.

OBJECTIVES: We aimed to evaluate the role of volumetric ADC (vADC) and volumetric venous enhancement (vVE) in predicting the grade of tumor differentiation in hepatocellular carcinoma (HCC). METHODS: The study population included 136 HCC patients (188 lesions) who had baseline MR imaging and histopathological report. Measurements of vVE and vADC were performed on baseline MRI. Tumors were histologically classified into low-grade and high-grade groups. The parameters between the two groups were compared using Mann-Whitney U and chi-square tests for continuous and categorical parameters, respectively. Area under receiver operating characteristic (AUROC) was calculated to investigate the accuracy of vADC and vVE. Logistic regression and multivariable Cox regression were used to unveil the potential parameters associated with high-grade HCC and patient's survival, respectively. RESULTS: Lesions with higher vADC values and a higher absolute vADC skewness were more likely to be high grade on histopathology assessment (p = 0.001 and p = 0.0291, respectively). Also, vVE showed a trend to be higher in low-grade lesions (p = 0.079). Adjusted multivariable model including vADC, vVE, and vADC skewness could strongly predict HCC degree of differentiation (AUROC = 83%). Additionally, a higher Child-Pugh score (HR = 2.39 [p = 0.02] for score 2 and HR = 3.47 [p = 0.001] for score 3), vADC skewness (HR = 1.52, p = 0.02; per increments in skewness), and tumor volume (HR = 1.1, p = 0.001; per 100 cm3 increments) showed the highest association with patients' survival. CONCLUSIONS: vADC and vVE have the potential to accurately predict HCC differentiation. Additionally, some imaging features in combination with patients' clinical characteristics can predict patient survival. KEY POINTS: • Volumetric functional MRI metrics can be considered as non-invasive measures for determining tumor histopathology in HCC. • Estimating patient survival based on clinical and imaging parameters can be used for modifying management approach and preventing unnecessary adverse events.