Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorobutane sulfonic acid (PFBS), 6:2 fluorotelomer sulfonic acid (6:2 FTS), and GenX are tested for diffusion and sorption ...through thermoplastic polyurethane (TPU) and three ethylene interpolymer alloy (PVC-EIA) liners (EIA1, EIA2, and EIA3) with decreasing ketone ethylene ester (KEE) contents. The tests were conducted at room temperature (23 °C), 35 °C, and 50 °C. The tests show significant diffusion through the TPU as manifested by a decrease in the source concentration and an increase in the receptor concentrations of PFOA and PFOS over time, especially at higher temperatures. On the other hand, the PVC-EIA liners show excellent diffusive resistance to the PFAS compounds especially at 23 °C. At higher temperatures, the diffusion resistance of the PVC-EIA liner with the lowest KEE content, EIA3, was best at 50 °C followed by EIA1 (highest KEE content) and finally EIA2. Sorption tests showed no measurable partitioning of any of the compounds to the liners examined. Based on 535 days of diffusion testing, permeation coefficients are provided for all the compounds considered for the four liners at three temperatures. In addition, the Pg values for PFOA and PFOS are provided for a linear low density polyethylene (LLDPE) and a coextruded LLDPE - ethylene vinyl alcohol (EVOH) geomembrane based on 1246 to 1331 days of testing and are compared to those estimated for EIA1, EIA2, and EIA3.
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•Provides estimates for the permeation and diffusion coefficients of PFOS, PFOA, PFBS, 6:2FTS and GenX through TPU and PVC-EIA liners based on diffusion tests at temperatures of 23 oC, 35 oC and 50 oC.•Compares the relative diffusive resistance of TPU and PVC-EIA liners to PFOS, PFOA, PFBS, 6:2FTS and GenX with LLDPE liners.•Significant diffusion of PFAS through the TPU geomembranes is observed relative to the PVC-EIA and LLDPE geomembranes tested.•PVC-EIA and LLDPE geomembranes show very little PFAS diffusion through them making them excellent diffusion barriers.•PVC-EIA3 and the two LLDPE geomembranes allowed no measurable PFAS diffusing through them in 500 days under all temperature conditions making them better than PVC-EIA 1 and PVC-EIA 2 at PFAS resistance.
Summary
Background: Prognosis in cirrhotic patients has had a resurgence of interest because of liver transplantation and new therapies for complications of end‐stage cirrhosis. The model for ...end‐stage liver disease score is now used for allocation in liver transplantation waiting lists, replacing Child‐Turcotte‐Pugh score. However, there is debate as whether it is better in other settings of cirrhosis.
Aim: To review studies comparing the accuracy of model for end‐stage liver disease score vs. Child‐Turcotte‐Pugh score in non‐transplant settings.
Results: Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only one of five, showed model for end‐stage liver disease to be superior to Child‐Turcotte‐Pugh to predict 3‐month mortality, but not for 12‐month mortality. Prognosis of cirrhosis studies (with 2569 patients) none of four showed significant differences between the two scores for either short‐ or long‐term prognosis whereas no differences for variceal bleeding studies (with 411 cirrhotics). Modified Child‐Turcotte‐Pugh score, by adding creatinine, performed similarly to model for end‐stage liver disease score. Hepatic encephalopathy and hyponatraemia (as an index of ascites), both components of Child‐Turcotte‐Pugh score, add to the prognostic performance of model for end‐stage liver disease score.
Conclusions: Based on current literature, model for end‐stage liver disease score does not perform better than Child‐Turcotte‐Pugh score in non‐transplant settings. Modified Child‐Turcotte‐Pugh and model for end‐stage liver disease scores need further evaluation.
Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC).
We conducted a randomised phase II/III trial in ...patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322.
The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively.
Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.
•First diffusion study of per- and polyfluoroalkyl substances through geomembranes.•Provides parameters for calculating the impact of PFAS in MSW leachate to the environment.•Reports low flux of PFOA ...through LLDPE and LLDPE coextruded with EVOH geomembranes.•Reports low flux of PFOS through LLDPE and LLDPE coextruded with EVOH geomembranes.
Diffusion of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) through 0.1 mm and 0.75 mm LLDPE and 0.1 mm and 0.75 mm LLDPE coextruded with ethyl vinyl alcohol (denoted as CoEx) at room temperature (23 °C), 35 °C, and 50 °C is examined. These tests had negligible source depletion throughout the monitoring period, indicating limited contaminant partitioning and diffusion through the LLDPE. At 483 days, 23 °C receptor PFOA and PFOS concentrations, cr, were <8 μg/L (cr/co < 3.2 × 10−4) for all tests, and at 399 days elevated temperature receptor concentrations were < 0.4 μg/L (cr/co < 1.6 × 10−5) at 35 °C and <0.5 μg/L (cr/co < 2.0 × 10−5) at 50 °C for both PFOA and PFOS. LLDPE partitioning coefficient, Sgf was 0.9–1.4 (PFOA) and 2.8–5.3 (PFOS) based on sorption tests at 23 °C. Based on the best estimates of permeation coefficient, PgCoEx, for CoEx was consistently lower than PgLLDPE. For PFOA, CoEx had PgCoEx < 0.26 × 10−16 m2/s at 23 °C, <11 × 10−16 m2/s (35 °C), and < 10 × 10−16 m2/s (50 °C) while LLDPE had PgLLDPE < 3.1 × 10−16 m2/s (23 °C), <13 × 10−16 m2/s (35 °C), and <19 × 10−16 m2/s (50 °C). For PFOS, CoEx and LLDPE had PgCoEx < 0.55 × 10−16 m2/s and PgLLDPE < 3.2 × 10−16 m2/s (23 °C), PgCoEx < 8.3 × 10−16 m2/s and PgLLDPE < 40 × 10−16 m2/s (35 °C), and PgCoEx < 8.2 × 10−16 m2/s and PgLLDPE < 52 × 10−16 m2/s (50 °C). These values are preliminary and may change (e.g., decrease) as more data comes available over time. The Pg values deduced for PFOA and PFOS are remarkably lower than those reported for other contaminants of concern, excepting BPA, which exhibits similar behaviour.
Tumour biopsy is usually considered mandatory for patient management by oncologists. Currently percutaneous ablation is used therapeutically for cirrhotic patients with small hepatocellular carcinoma ...(HCC), not suitable for resection or waiting for liver transplantation. However malignant seeding is a recognized complication of both diagnostic and therapeutic procedures in patients with HCC. Although percutaneous therapy whether with or without biopsy of a suspected HCC nodule may minimize the risk of seeding, this has not been confirmed.
To evaluate the risk of seeding, defined as new neoplastic disease occurring outside the liver capsule, either in the subcutaneous tissue or peritoneal cavity following needle biopsy and/or local ablation therapy (LAT).
A literature search resulted in 179 events in 99 articles between January 1983 and February 2007: 66 seedings followed liver biopsy, 26 percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33 PEI; 26 RFA).
In 41 papers specifying the total number of patients biopsied and/or treated, the median risk of seeding was 2.29% (range 0-11%) for biopsy group; 1.4% (1.15-1.85%) for PEI when used with biopsy and 0.61% (0-5.56%) for RFA without biopsy, 0.95% (0-12.5%) for RFA with biopsy and 0.72% (0-10%) for liver nodules (including non-HCC nodules) biopsied and ablated.
Risk of seeding with HCC is substantial and appears greater with using diagnostic biopsy alone compared to therapeutic percutaneous procedures. This risk is particularly relevant for patients being considered for liver transplantation.
Summary
Background Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients.
Aims To evaluate 6‐week mortality in cirrhotic ...patients admitted to an ICU, and to compare general and liver‐specific prognostic scores.
Methods A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child–Pugh, Model for End‐stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves.
Results Major indication for admission was respiratory failure (35.6%). Median (range) Child–Pugh, APACHE II, MELD and SOFA scores were 11 (5–15), 18 (0–44), 24 (6–40) and 11 (0–21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, ≥3 = 90%), higher FiO2, lactate, urea and bilirubin; resulting in good discrimination area under receiver operating characteristic curve (AUC) = 0.83, similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child–Pugh (AUC = 0.78 and 0.72, respectively).
Conclusions Cirrhotics admitted to ICU with ≥3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child–Pugh scores.
Summary
Background Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of ...serum creatinine in the model for end‐stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA.
Aim To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis.
Method We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis.
Results Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the ‘gold standard’, but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft‐Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine.
Conclusions Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.
SUMMARY
Background and Aim The potential prognostic value for survival of nutritional status in cirrhotics after adjusting Child–Pugh classification and Model for End‐Stage Liver Disease has not ...been evaluated.
Methods We used Kaplan–Meier and Cox proportional hazards regression models to identify factors associated with mortality in a cohort of 222 cirrhotics M/F:145/77 median age 52 (18–68) years with prospectively collected nutritional parameters as well as modified subjective global nutritional assessment, Royal Free Hospital‐Subjective Global Assessment index. Follow‐up was censored at the time of transplantation. Other variables were ones in Child–Pugh and Model for End‐Stage Liver Disease scores, age, aetiology of cirrhosis and renal function,
Results Pretransplant mortality (Kaplan–Meier) was 21% by 2 years (135 patients were transplanted). Among the nutritional parameters, only Royal Free Hospital‐Subjective Global Assessment remained significantly associated with mortality in multivariable models (P = 0.0006). The final model included the following variables: urea (P = 0.0001), Royal Free Hospital‐Subjective Global Assessment (P = 0.003), age (P = 0.0001), Child–Pugh grade (P = 0.009) and prothrombin time (P = 0.003). The results were similar when the Child–Pugh grade was replaced by the Model for End‐Stage Liver Disease score in the model, and whether a competing risks model was used.
Conclusions Nutritional indices add significantly to both Child–Pugh grade and Model for End‐Stage Liver Disease scores when assessing the patient prognosis.
A particularly important role is played by the reduced RES activity, due to the presence of extrahepatic and intrahepatic shunts through sinusoids without Kupffer cells, reduced number of Kupffer ...cells, and impaired Kupffer cell function. ...cirrhotics with impaired RES phagocytic activity (as assessed by elimination of 99 m technetium-sulphur colloid) develop acute bacterial infections more frequently than cirrhotics with normal RES phagocytic activity. 2 Both community and hospital acquired bacterial infections are frequently diagnosed in cirrhotics, most frequently spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, and skin infections. 3 Their incidence rises with worsening liver function. 3 Importantly, half of these episodes are asymptomatic. 1 Recently, bacterial infections and/or endotoxaemia have been associated with failure to control variceal bleeding, 4 more early variceal rebleeding, 5 abnormalities in coagulation, 6, 7 vasodilatation of the systemic vasculature, 8 and worsening liver function. 9 There has also been increased recognition that bacterial infections are involved in several pathophysiological abnormalities in cirrhosis.
This paper documents the design and construction of MUSE, the world's first permanent magnet (PM) stellarator and the first quasi-axisymmetric experiment. The purpose of MUSE is to develop and assess ...a new way of building optimised stellarators that uses simple planar coils PMs. Our PM optimisation algorithm consists of initialising a geometry to pack dipoles densely, running the FAMUS code to minimise surface field error subject to PM constraints and applying discrete jumps to reach a physically realisable solution. FAMUS treats the PM system as a set of ideal point dipoles. From there we construct finite-volume magnet towers to be housed in 3D-printed PM holders. We describe the design of the PM holders, which were validated by laser metrology. We analyse the effects of finite permeability, sensitivity to perturbations and magnetostatic forces. An exact analytic formula for the magnetic field from a finite-volume PM tower is presented to compute PM–PM forces and stress on the PM holder. Stellarator construction is complete and experiments are underway.
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