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Abstract Background Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients (>65 years). Methods Between 1989–2016, 139 patients >65 years-old were listed for liver transplantation, and 76 (55%) were transplanted. Patient outcome and characteristics were evaluated separately for the time period before (1989–2004) and after (2005–2016) MELD-implementation. Post-transplant outcome was compared between the elderly cohort and LT-recipients aged 18–65 years (n = 1395). Results Overall survival of patients >65 years was better in the MELD-era compared to the earlier period (1- and 5-year-survival: 73%, 60% vs. 69%, 37%, respectively; p = 0.055). The main differences between the two groups included higher recipient age (p = 0.001) and BMI (p = 0.001), higher donor age (p < 0.001), less need of intraoperative red blood cells (p = 0.008) and a lower number of postoperative rejections (p = 0.03) after 2004. Comparing the overall survival of patients transplanted in the MELD-era aged 18–65 years vs. >65 years displayed comparable 1- and 5 year-survival rates (81%, 68% vs. 73% and 60%, respectively, p = 0.558). Conclusion In the modern era, outcome of patients receiving LT with >65 years is comparable to <65 year-old patients. After careful evaluation, patients >65 years old should be considered for LT. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ta was used as a model material to study the effect of rolling on the fracture toughness of ultrafine-grained materials. • Cold Rolling induces a pronounced grain elongation and leads to a significant increase of the fracture toughness. • The origin of the fracture toughness enhancement is mainly based on the activation of a delamination fracture mechanism. The fracture characteristics of severely plastically deformed (SPD) materials exhibit large variations in the quasi-static fracture resistance depending on factors such as the investigated material, testing temperature and grain aspect ratio. Especially the latter one is considered to control the frequently observed orientation dependent fracture toughness. A question that arises thereby is how the fracture properties for certain testing directions could be actively tuned by tailoring the grain aspect ratio. In this contribution this issue has been investigated by changing the aspect ratio of ultrafine-grained tantalum processed by high pressure torsion through post-rolling operations which induced a substantial increase of the grain length while keeping the strength on a comparable level. Samples in interesting testing directions were manufactured and tested. The increase of the aspect ratio results in the technically significant testing directions to an enhancement of the fracture toughness. Delamination toughening, which is promoted by the change of the aspect-ratio, has been indentified to be the main cause for the toughness enhancement and represents therefore a feasible pathway for optimizing the damage tolerance of SPD-processed materials. [ABSTRACT FROM AUTHOR]

Abstract Background This study investigated the impact of Model of end-stage liver disease (MELD)-score introduction (MELDi) on waitlist mortality and post-liver transplant (LT) survival in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Methods LT candidates with PSC or PBC listed between January 1983 and March 2016 were included and followed until December 2016. After MELDi in 2004, PBC patients were listed according to labMELD, PSC patients according to the highest MELD during active cholangitis (chMELD). Results In total, 100 PBC and 76 PSC patients were included. Waitlist mortality in PBC was significantly higher than in PSC (16% vs. 5.3%, p = 0.031), whereas PSC patients were significantly more often withdrawn from the waitlist due to improved condition (3.0% vs. 13.2%, p = 0.017). Competing risks analysis identified MELDi (HR = 4.12) and PBC (HR = 2.95) as significant predictors of waitlist mortality. Yet, overall 10 y-patient survival increased after MELDi by 18.8% leading to a 1 y-, 5 y-, and 10 y-patient survival of 98.2%, 70.6% and 70.6% in PBC, and 83.3%, 83.3%, and 80.6% in PSC, respectively. Conclusions PSC patients showed significantly lower waitlist mortality irrespective of MELDi, whereas in PBC waitlist mortality further increased after MELDi. Utility of MELD and chMELD did not impair post LT outcome. [ABSTRACT FROM AUTHOR]

A high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery. The cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression. In the SIMMUN cohort, the inflammatory marker neopterin (β = 0.47 [95% CI: 0.34–0.61]), SARS-CoV-2-positivity (0.42 [0.16–0.68]), mental stress (0.18 [0.055–0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (−0.38 [−0.68 to −0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: −0.22 [−0.38 to −0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: −0.15 [−0.26 to −0.036]). Serotonin (0.76 [0.34–1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28–0.99]) were higher during recovery than in acute SARS-CoV-2 infection. SARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19. • Mental health impairment is common following COVID-19. • Kynurenine and catecholamine pathway activity might be the pathophysiological link. • Data from two cohorts were analyzed using multi-parameter linear modeling. • Inflammation, SARS-CoV-2 infection, mental stress, age influence kynurenine/tryptophan. • Inflammation was associated with lower systemic serotonin and dopamine availability. [ABSTRACT FROM AUTHOR]

Abstract: In the Obernberg valley, the Eastern Alps, landforms recently interpreted as moraines are re-interpreted as rock avalanche deposits. The catastrophic slope failure involved an initial rock volume of about 45million m³, with a runout of 7.2km over a total vertical distance of 1330m (fahrböschung 10°). 36Cl surface-exposure dating of boulders of the avalanche mass indicates an event age of 8.6±0.6ka. A 14C age of 7785±190calyr BP of a palaeosoil within an alluvial fan downlapping the rock avalanche is consistent with the event age. The distal 2km of the rock-avalanche deposit is characterized by a highly regular array of transverse ridges that were previously interpreted as terminal moraines of Late-Glacial. ‘Jigsaw-puzzle structure’ of gravel to boulder-size clasts in the ridges and a matrix of cataclastic gouge indicate a rock avalanche origin. For a wide altitude range the avalanche deposit is preserved, and the event age of mass-wasting precludes both runout over glacial ice and subsequent glacial overprint. The regularly arrayed transverse ridges thus were formed during freezing of the rock avalanche deposits. [Copyright &y& Elsevier]

Abstract: During the 2009/10 pandemic of influenza A (H1N1), the American Society of Transplantation and other health organizations recommended that immunocompromised patients should be vaccinated as the key preventive measure. Since there are no data available for the immunogenicity of the unadjuvanted pandemic influenza vaccine in immunocompromised patients – as opposed to the adjuvanted preparation – the objective of this study was to evaluate the immunogenicity of an adjuvant-free H1N1 vaccine in recipients of solid organ transplants. Patients were recruited at the Vienna General Hospital, Austria. The vaccination schedule consisted of 2 doses of a whole-virion, vero cell derived, inactivated, non-adjuvanted influenza A/California/07/2009 (H1N1) vaccine given with an interval of 3 weeks. A hemagglutination inhibition (HI) assay on blood samples obtained prior to the first and after each vaccination was used for serologic analysis. The primary immunologic endpoint was the seroconversion rate, defined as the proportion of subjects with an individual 4-fold increase in HI titer of at least 1:40. In addition, virus-specific IgG antibodies to the pandemic H1N1 strain were measured using a commercially available ELISA. Twenty-five organ transplant patients (16 males, 9 females) aged 25–79 years were vaccinated and provided blood samples for serologic analysis. The time elapsed since transplantation was 10 months to 25 years (mean: 9 years; 95% CI 6–13 years). The vaccine was well tolerated and no local adverse events were noticed. After two vaccinations 37% of the patients demonstrated seroconversion in the HI assay as defined above and 70% had virus-specific IgG antibodies. Among the HI vaccine responders were 6 of 14 heart transplant recipients and 1 of 4 liver transplant recipients. The number and type of immunosuppressive agents did not significantly differ in their effect on the immune response. Our results show that the novel vero cell derived and adjuvant-free pandemic A/California/07/2009 (H1N1) influenza vaccine induced limited but measurable immune responses in adult recipients of solid organ transplants. [Copyright &y& Elsevier]

Background & Aims: Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT. Methods: Osteopontin expression was investigated immunohistochemically in a unique population of 125 HCC-patients undergoing OLT between 1982 and 2002, including 81 patients (65%) outside the Milan criteria. Multivariate analysis of factors associated with median overall survival (OS) and time to recurrence (TTR) was performed. Results: Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5years was 77%, 62%, 52%, and 43% (median survival 37months). Overall survival was significantly longer without expression of OPN (p<0.05; (median OS: 56 vs. 23months). The same was true for median TTR (p =0.008). Outside Milan criteria, patients without OPN-expression had better prognosis (median OS: 37.8 vs. 19.2months, p =0.003). Tumor recurrence in patients transplanted outside Milan criteria occurred in 43% (23 of 54) of patients without and 70% (19 of 27, p =0.018) of patients with OPN-expression after a median TTR of 83.5 vs. 13.9months. On multivariate analysis, vascular invasion and OPN-expression were independently associated with OS and TTR in HCC-patients after OLT. Conclusions: Immunohistochemically detectable Osteopontin in HCC is an independent predictor of tumor recurrence and survival in patients beyond Milan criteria undergoing OLT. [ABSTRACT FROM AUTHOR]

: ObjectivesThe right renal vein (RRV) may be difficult to anastomose in right cadaveric kidney transplantation, especially in obese recipients in whom iliac vessels are deep. In this study, gain of length and feasibility in the presence of vascular variations obtained with three common techniques of renal vein augmentation—clamshell (CS), transverse closure of the inferior vena cava (TC), and cava conduit (CC)— were analyzed and compared to the Carrel-patch technique.: MethodsThe renal vasculature and the inferior vena cava of 119 cadavers were accurately dissected and measured, and the vascular variations documented. The CS technique augmented the RRV at most by one fourth, the TC by one half the diameter of the inferior vena cava, and the CC by the length of the infrarenal inferior vena cava. An experienced transplant surgeon evaluated the situs for the feasibility of the techniques.: ResultsThe variations found were multiple veins (right, 23%; left, 6.7%), a retroaortal left vein (2.5%), a renal collar (6%); and multiple arteries (right, 20.2%; left, 19%). The RRV length varied from 21 to 71 mm, and the right renal artery (RRA) length varied between 44 and 111 mm. The RRA/RRV ratios ranged between 3.4 and 1.2. The achieved gains of length were 129% with the CS (possible in 81.5%), 190% with the TC (possible in 62.4%), and 388.4% with the CC (possible in 80.7%).: ConclusionsThe median RRV is one half the RRA in length so that length augmentation could be an advantage. Anatomic variations limit the choice of technique. Overall, augmentation was possible in 80%; the CS technique seldom resulted in a length equal to that of the RRA, the TC was the most susceptible to variations, and the CC always surpassed the RRA in length. Harvesting the RRV en bloc with the inferior vena cava enables the surgeon to best adapt donor vessels to the recipient''s anatomy. [Copyright &y& Elsevier]

Effect ofMTHFR 677C>T on plasma total homocysteine levels in renal graft recipients. Background. Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. Methods. We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. Results. The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the... [ABSTRACT FROM AUTHOR]