Combination of Fat-Free Muscle Index and Total Spontaneous Portosystemic Shunt Area Identifies High-Risk Cirrhosis Patients.

Background: Sarcopenia and spontaneous portosystemic shunts (SPSSs) are common complications of liver cirrhosis, and both are associated with higher rates of hepatic encephalopathy (HE) development in these patients. This study aimed to evaluate the simultaneous impact of skeletal muscle mass and spontaneous portosystemic shunting, measured from routine diagnostic CT on outcomes in patients with liver cirrhosis. Methods: Retrospective analysis of patients with cirrhosis. Skeletal muscle mass [including fat-free muscle index (FFMI) as a surrogate for sarcopenia] and total cross-sectional spontaneous portosystemic shunt area (TSA) were quantified from CT scans. The primary endpoint was the development of HE, while the secondary endpoint was 1-year mortality. Results: One hundred fifty-six patients with liver cirrhosis were included. Patients with low (L-) FFMI and large (L-)TSA showed higher rates of HE development. In multivariable analysis, L-FFMI and L-TSA were independent predictors of HE development (L-FFMI HR = 2.69, CI 1.22-5.93; L-TSA, HR = 2.50, CI = 1.24-4.72) and 1-year mortality (L-FFMI, HR = 7.68, CI 1.75-33.74; L-TSA, HR = 3.05, CI 1.32-7.04). The simultaneous presence of L-FFMI and L-TSA exponentially increased the risk of HE development (HR 12.79, CI 2.93-55.86) and 1-year mortality (HR 13.66, CI 1.75-106.50). An easy sequential algorithm including FFMI and TSA identified patients with good, intermediate, and poor prognoses. Conclusion: This study indicates synergy between low skeletal muscle mass and large TSA to predict exponentially increased risk of HE development and mortality in liver cirrhosis. Simultaneous screening for sarcopenia and TSA from routine diagnostic CT may help to improve the identification of high-risk patients using an easy-to-apply algorithm. Clinical Trial registration: [ClinicalTrials.gov], identifier [NCT03584204].

Supramolecular Hydrogels: Design Strategies and Contemporary Biomedical Applications.

Self-assembly of supramolecular hydrogels is driven by dynamic, non-covalent interactions between molecules. Considerable research effort has been exerted to fabricate and optimise supramolecular hydrogels that display shear-thinning, self-healing, and reversibility, in order to develop materials for biomedical applications. This review provides a detailed overview of the chemistry behind the dynamic physicochemical interactions that sustain hydrogel formation (hydrogen bonding, hydrophobic interactions, ionic interactions, metal-ligand coordination, and host-guest interactions). Novel design strategies and methodologies to create supramolecular hydrogels are highlighted, which offer promise for a wide range of applications, specifically drug delivery, wound healing, tissue engineering and 3D bioprinting. To conclude, future prospects are briefly discussed, and consideration given to the steps required to ultimately bring these biomaterials into clinical settings.

Selectively Cross-Linked Tetra-PEG Hydrogels Provide Control over Mechanical Strength with Minimal Impact on Diffusivity.

Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These in vivo-like 3D environments provide a basis for tissue engineering and cell therapies but also for research into fundamental biological questions and disease modeling. The physical properties of PEG hydrogels can be modulated to provide mechanical cues to encapsulated cells; however, the impact of changing hydrogel stiffness on the diffusivity of solutes to and from encapsulated cells has received only limited attention. This is particularly true in selectively cross-linked "tetra-PEG" hydrogels, whose design limits network inhomogeneities. Here, we used a combination of theoretical calculations, predictive modeling, and experimental measurements of hydrogel swelling, rheological behavior, and diffusion kinetics to characterize tetra-PEG hydrogels' permissiveness to the diffusion of molecules of biologically relevant size as we changed polymer concentration, and thus hydrogel mechanical strength. Our models predict that hydrogel mesh size has little effect on the diffusivity of model molecules and instead predicts that diffusion rates are more highly dependent on solute size. Indeed, our model predicts that changes in hydrogel mesh size only begin to have a non-negligible impact on the concentration of a solute that diffuses out of hydrogels for the smallest mesh sizes and largest diffusing solutes. Experimental measurements characterizing the diffusion of fluorescein isothiocyanate (FITC)-labeled dextran molecules of known size aligned well with modeling predictions and suggest that doubling the polymer concentration from 2.5% (w/v) to 5% produces stiffer gels with faster gelling kinetics without affecting the diffusivity of solutes of biologically relevant size but that 10% hydrogels can slow their diffusion. Our findings provide confidence that the stiffness of tetra-PEG hydrogels can be modulated over a physiological range without significantly impacting the transport rates of solutes to and from encapsulated cells.

Controlled underdilation using novel VIATORR® controlled expansion stents improves survival after transjugular intrahepatic portosystemic shunt implantation.

BACKGROUND & AIMS: Smaller 8-mm diameter transjugular intrahepatic portosystemic shunts (TIPS) appear to be more beneficial than larger 10-mm TIPS stent-grafts, but lack the ability for secondary dilation in cases of clinical ineffectiveness. Underdilated VIATORR® TIPS stent grafts (VTS) expand passively, whereas novel VIATORR Controlled Expansion (VCX) stent grafts do not. This study evaluated the impact on survival of underdilated VCX compared with VTS in patients with decompensated cirrhosis. METHODS: This was a prospective case-control study including patients with cirrhosis receiving TIPS using 10-mm VCX underdilated to 8 mm. Patients with cirrhosis receiving 10-mm VTS underdilated to 8 mm were matched for age, sex, indication for TIPS, and liver function. RESULTS: A total of 114 patients (47 VCX, 47 VTS, and 20 fully dilated VCX/VTS) were included. After TIPS implantation, underdilated VCX diameter was 8.0 (7.8-9.2) mm at a median time of 359 (87-450) days, compared with VTS at 9.9 (9.7-10.0) mm (p <0.001). The portosystemic pressure gradient immediately after TIPS procedure and after 7 days did not change significantly in VCX [mean 9.4 (± 0.8) vs. 10.4 (± 0.7) mmHg, p = 0.115). Hospital readmission rates for hepatic encephalopathy were 23% (n = 11) vs 51% (n = 24) for VCX and VTS (p <0.001), respectively. Patients with VCX had significantly lower rates of large-volume paracentesis (n = 5 [11%] vs. n = 10 [21%], p = 0.017) and heart failure (n = 1 [2%] vs. n = 7 [15%], p = 0.015). One-year mortality for underdilated VCX and VTS was 15% (n = 7) and 30% (n = 14) and, for fully dilated VCX/VTS, was 45% (n = 9) (log-rank p = 0.008), respectively. CONCLUSIONS: This study demonstrated that VCX stent grafts underdilated to 8 mm do not passively expand to nominal diameter and suggests reduced hospital readmissions because of hepatic encephalopathy, uncontrolled ascites, and heart failure, and improved 1-year survival compared with underdilated VTS. LAY SUMMARY: Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in selected patients with liver cirrhosis and acute variceal bleeding or refractory ascites. Smaller 8-mm diameter TIPS stent grafts appear to improve patient outcome compared with larger 10-mm diameter stent grafts. Novel VIATORR® Controlled Expansion (VCX) stent grafts facilitate safe and stable underdilation to 8 mm of large 10-mm diameter stent grafts with improved patient outcome (survival, hepatic encephalopathy, ascites and heart failure) compared with legacy VIATORR TIPS stent graft (VTS). Thus, the use of underdilated VCX could preserve heart function. CLINICAL TRIALS REGISTRATION: The study is registered at Clinicaltrials.govNCT03628807.

Alteration of contrast enhanced ultrasound (CEUS) of hepatocellular carcinoma in patients with cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS).

Transjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions [23 TIPS (11 HCC), 26 no TIPS (15 HCC)]. 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.

Interactions of bile salts with a dietary fibre, methylcellulose, and impact on lipolysis.

Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis. BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements. In vitro lipolysis studies were performed to evaluate the effect of BS on MC-stabilised emulsion droplets microstructure, with confocal microscopy, and free fatty acids release, with the pH-stat method. Our results demonstrate that BS structure dictates their interactions with MC, which, in turn, impact lipolysis. Compared to NaTC, NaTDC alters MC viscoelasticity more significantly, which may correlate with its weaker ability to promote lipolysis, and desorbs from the interface at lower concentrations, which may explain its higher propensity to destabilise emulsions.