Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

Non-Destructive Evaluation of the Cutting Surface of Hardwood Finger Joints

In this study, the surface parameters wettability, roughness, and adhesive penetration, which are important for wood bonding, were investigated and evaluated utilizing non-destructive methods after different mechanical processing. For this purpose, beech and birch finger joints were prepared with different cutting combinations (three cutters with different sharpness levels and two feed rates) in an industrial process. Effects and interactions on the surface parameters resulting from the different cutting combinations were evaluated using three Full Factorial Designs. The various cutting parameters had a predominantly significant influence on the surface parameters. The effects and identified interactions highlight the complexity of the cutting surface and the importance of wood bonding. In this respect, a new finding is that with sharper cutters, higher contact angles of the adhesives occur. The methods (contact angle measurement, laser scanning microscopy, and brightfield microscopy) used were well suited to make effects visible and quantifiable, which can be of interest for the quality control of the wood processing industry. The results can help to better understand and evaluate the design of wood surfaces via machining and the bonding of hardwoods. Possibly the results can contribute to further standardizing the production of load-bearing hardwood finger joints and making them more efficient

Determination of the Bonding Strength of Finger Joints Using a New Test Specimen Geometry

In this study, a specimen geometry for testing finger joints was developed using finite element simulation and proofed by experimental testing. Six different wood species and three adhesives were used for finger-jointing specimens. With the test specimen geometry, the bonding strength of the finger joints was determined without the usual self-locking of the joint. Under load, the test specimen geometry introduces maximum stress at the beginning of the bond line (adhesive zone). However, the test specimen geometry does not generate a symmetric stress state. The main difficulty here is the flank angle of the finger joint geometry. The wood species and adhesives significantly influenced the performance of the finger joints

Determination of the Bonding Strength of Finger Joints Using a New Test Specimen Geometry

In this study, a specimen geometry for testing finger joints was developed using finite element simulation and proofed by experimental testing. Six different wood species and three adhesives were used for finger-jointing specimens. With the test specimen geometry, the bonding strength of the finger joints was determined without the usual self-locking of the joint. Under load, the test specimen geometry introduces maximum stress at the beginning of the bond line (adhesive zone). However, the test specimen geometry does not generate a symmetric stress state. The main difficulty here is the flank angle of the finger joint geometry. The wood species and adhesives significantly influenced the performance of the finger joints

Monitoring of Beech Glued Laminated Timber and Delamination Resistance of Beech Finger-Joints in Varying Ambient Climates

In this study, varying ambient climates were simulated in a test building by changing temperature and relative humidity. Beech glued laminated timber (glulam, Fagus sylvatica, L.) was freshly installed in the test building and monitoring of the change in wood moisture content of the glulam resulting from the variations in climate was carried out. Subsequently, finger-jointed beech specimens were exposed to the variations in relative humidity measured in the course of the monitoring experiment on a laboratory scale, and thus an alternating climate regime was derived from the conditions in the test building. Its influence on the delamination of the finger-joints was evaluated. In addition, it was examined whether beech finger-joints using commercial adhesive systems fulfil the normative requirements for delamination resistance according to EN 301 (2018) and whether different bonding-wood moisture levels have an effect on the delamination of the finger-joints. In the context of the monitoring experiment, there was a clear moisture gradient in the beech glulam between the inner and near-surface wood. The applied adhesive systems showed almost the same delamination resistance after variation of relative humidity. The normative requirements were met by all PRF-bonded and by most PUR-bonded beech finger-joints with higher bonding wood moisture content

Monitoring of Beech Glued Laminated Timber and Delamination Resistance of Beech Finger-Joints in Varying Ambient Climates

In this study, varying ambient climates were simulated in a test building by changing temperature and relative humidity. Beech glued laminated timber (glulam, Fagus sylvatica, L.) was freshly installed in the test building and monitoring of the change in wood moisture content of the glulam resulting from the variations in climate was carried out. Subsequently, finger-jointed beech specimens were exposed to the variations in relative humidity measured in the course of the monitoring experiment on a laboratory scale, and thus an alternating climate regime was derived from the conditions in the test building. Its influence on the delamination of the finger-joints was evaluated. In addition, it was examined whether beech finger-joints using commercial adhesive systems fulfil the normative requirements for delamination resistance according to EN 301 (2018) and whether different bonding-wood moisture levels have an effect on the delamination of the finger-joints. In the context of the monitoring experiment, there was a clear moisture gradient in the beech glulam between the inner and near-surface wood. The applied adhesive systems showed almost the same delamination resistance after variation of relative humidity. The normative requirements were met by all PRF-bonded and by most PUR-bonded beech finger-joints with higher bonding wood moisture content

Non-Destructive Evaluation of the Cutting Surface of Hardwood Finger Joints

In this study, the surface parameters wettability, roughness, and adhesive penetration, which are important for wood bonding, were investigated and evaluated utilizing non-destructive methods after different mechanical processing. For this purpose, beech and birch finger joints were prepared with different cutting combinations (three cutters with different sharpness levels and two feed rates) in an industrial process. Effects and interactions on the surface parameters resulting from the different cutting combinations were evaluated using three Full Factorial Designs. The various cutting parameters had a predominantly significant influence on the surface parameters. The effects and identified interactions highlight the complexity of the cutting surface and the importance of wood bonding. In this respect, a new finding is that with sharper cutters, higher contact angles of the adhesives occur. The methods (contact angle measurement, laser scanning microscopy, and brightfield microscopy) used were well suited to make effects visible and quantifiable, which can be of interest for the quality control of the wood processing industry. The results can help to better understand and evaluate the design of wood surfaces via machining and the bonding of hardwoods. Possibly the results can contribute to further standardizing the production of load-bearing hardwood finger joints and making them more efficient

Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis

Background: We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). Patients and Methods: We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18\ua0years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72\ua0months (range 8\u2013182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Results: Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy