Background: The DLTR was created in 1999. It holds data on recipients of explanted metabolically ... more Background: The DLTR was created in 1999. It holds data on recipients of explanted metabolically disturbed livers. Results: By Dec 2012, 1085 domino liver transplantations (DLT) in 1065 patients were reported from 62 hospitals in 21 countries. Male/female ratio is 74% and 26%, respectively, with a mean recipient age at time of transplantation of 55.5±9.2 yrs (range 1.9-73.9 yrs, median 56.7 yrs). Overall, the frequency of retransplantation in DLT recipients was 7%. The vast majority of livers used for DLT come from familial transthyretin amyloidotic (FAP) affl icted donors (99%), but there is also the use of livers with metabolic disorders such as Hyperoxalosis, Maple Syrup Urine Disease and Hypercholesterolemia. Altogether, main diagnoses in DLT recipients were HCC (39%), alcoholic cirrhosis (20%) and HCV (16%), but in the last 5-year period HCV decreased to 12% while alcoholic cirrhosis increased to 26%. The percentage of HCC remains the same. Survival was similar in FAP liver donors and non-donor FAP patients. In the whole material, DLT recipients with malignancy had inferior survival compared to non-malignant recipients, a difference that disappeared when analyzing the last 5 years. Tumor recurrence and septicemia caused the majority of deaths (39%). Surprisingly, signifi cantly better graft survival was seen in recipients of non-Val30Met mutated livers compared to Val30Met mutated livers (5-yr survival 73% and 66%, respectively, p<0.05). The DLTR contains eight patients retransplanted 7-11 years after DLT because of FAP symptoms. Conclusion: By careful recipient selection and done by experienced teams DLT is of value and can signifi cantly contribute in relieving organ shortage. Short-term outcome in DLT recipients is excellent. Long-term survival must also be deemed good bearing in mind the dismal prognosis in these patients without transplantation. The comparable survival in DLT recipients with and without malignancies in recent years may be due to better DLT recipient selection criteria. The risk of transmitting de novo amyloidosis with the grafted liver is real and cannot be neglected. This report is presented on behalf of all reporting members of the DLTR.
This research is aimed to find out the influence of the financial performance and the firm size t... more This research is aimed to find out the influence of the financial performance and the firm size to the stock return. The dependent variable is the stock return. Meanwhile the independent variables are firm size and financial performance which is measured by Current Ratio (CR), Return on Assets (ROA), and Price Earning Ratio (PER). The population is all property and real estate companies which are listed in Indonesian Stock Exchange (IDX) in 2011-2015 periods. The sample collection technique has been carried out by using purposive sampling method so 26 property and realestate companies which are listed in the Indonesian Stock Exchange (IDX) have been selected as samples. The data analysist technique has been done by using multiple linear regression analysis and the SPSS 23. The classic assumption test (the test of normalitas, heteroskedastisitas, autokorelasi, and multikolenieritas) is carried out before the multiple regression analysis. Based on the results of hypothesis test shows that return on assets (ROA) give positive influence on stock return whereas the current ratio (CR), price earnings ratio (PER) and firm size give no influence to the stock return.
Introduction: This study aimed to investigate the acute rejection rate and graft function after l... more Introduction: This study aimed to investigate the acute rejection rate and graft function after liver transplantation according to pre-transplantation donor specifi c antibody (DSA) status and changing pattern of DSA after liver transplantation. Patients and methods: This study was prospectively designed observational study from March 2011 to October 2013. Forty patients were enrolled in this study. Singe
We apply Schmidt's Subspace Theorem to establish Arithmetic General Theorems for projective varie... more We apply Schmidt's Subspace Theorem to establish Arithmetic General Theorems for projective varieties over number and function fields. Our first result extends an analogous result of M. Ru and P. Vojta. One aspect to its proof makes use of a filtration construction which appears in work of Autissier. Further, we consider work of M. Ru and J. T.-Y. Wang, which pertains to an extension of K. F. Roth's theorem for projective varieties in the sense of D. McKinnon and M. Roth. Motivated by these works, we establish our second Arithmetic General Theorem, namely a form of Roth's theorem for exceptional divisors. Finally, we observe that our results give, within the context of Fano varieties, a sufficient condition for validity of the main inequalities predicted by Vojta.
To transplant or not to transplant - Lessons learned from 20 years global collaboration in liver ... more To transplant or not to transplant - Lessons learned from 20 years global collaboration in liver transplantation for hereditary transthyretin amyloidosis
Flow cytometry at Week 10 and 12 found equivalent number of Foxp3+ Treg cells in spleens of all 3... more Flow cytometry at Week 10 and 12 found equivalent number of Foxp3+ Treg cells in spleens of all 3 groups but increased Foxp3+ Treg cells in draining lymph nodes in IL6R/HN group (13.2% ±2.0) in comparison to IgG/HN group (10% ± 1.0) and CFA alone (8.5% ± 1.1). Immunohistochemistry showed reduced glomerular IgG deposition in IL6R/HN group at Week10. Conclusions: IL6-R blockade limits Heymann Nephritis and may potentially infl uence the Treg/Th17 axis.
Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimu... more Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n ¼ 67; bid, n ¼ 62). PK data were available for 77 patients (tacrolimus qd, n ¼ 45; bid, n ¼ 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC 0-24) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ngÁh/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ngÁh/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC 0-24 and concentration at 24 hours for tacrolimus qd and bid (r ¼ 0.92 and r ¼ 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with Abbreviations: AE, adverse event; AUC 0-24 , area under the curve from 0 to 24 hours; AZA, azathioprine; bid, twice daily; BPAR, biopsy-proven acute rejection; C 24 , concentration at 24 hours; C max , maximum concentration; C min , minimum blood concentration; MMF, mycophenolate mofetil; NEC, not elsewhere classified; PK, pharmacokinetics; qd, once daily; SD, standard deviation; T max , time to maximum concentration. This study and statistical analyses, and the editorial and project management services of Acumed involved in the preparation of this manuscript, were supported by Astellas Pharma Europe, Ltd.
Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in th... more Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characteriz... more Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits.The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation.The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.
The efficacy and safety of tacrolimus-and cyclosporine-based immunosuppressive regimens were comp... more The efficacy and safety of tacrolimus-and cyclosporine-based immunosuppressive regimens were compared in a prospectively defined subgroup of kidney transplant recipients from the European, open, multicentre, 2 : 1 randomised, parallel group study. Patients were stratified as high risk for immunological events if they had a panel-reactive antibodies grade greater than 80 7' 0 and/or a previous transplant functional for less than 1 year. The primary efficacy variables evaluated were the incidence of acute rejection, steroid usage and patient and graft survival. Safety was assessed based on adverse events and laboratory evaluations. At 1 year, the tacrolimus group (n = 22) had a lower incidence of biopsy-proven acute rejection (31.8 %) and a higher graft survival (86.0 %) than the 1 1 patients in the cyclosporine group (54.5 % and 72.0 %, respectively). The frequencies of adverse events were similar between the two groups. The tacrolimus regimen appears more beneficial for high risk patients than cyclosporine.
Background: The DLTR was created in 1999. It holds data on recipients of explanted metabolically ... more Background: The DLTR was created in 1999. It holds data on recipients of explanted metabolically disturbed livers. Results: By Dec 2012, 1085 domino liver transplantations (DLT) in 1065 patients were reported from 62 hospitals in 21 countries. Male/female ratio is 74% and 26%, respectively, with a mean recipient age at time of transplantation of 55.5±9.2 yrs (range 1.9-73.9 yrs, median 56.7 yrs). Overall, the frequency of retransplantation in DLT recipients was 7%. The vast majority of livers used for DLT come from familial transthyretin amyloidotic (FAP) affl icted donors (99%), but there is also the use of livers with metabolic disorders such as Hyperoxalosis, Maple Syrup Urine Disease and Hypercholesterolemia. Altogether, main diagnoses in DLT recipients were HCC (39%), alcoholic cirrhosis (20%) and HCV (16%), but in the last 5-year period HCV decreased to 12% while alcoholic cirrhosis increased to 26%. The percentage of HCC remains the same. Survival was similar in FAP liver donors and non-donor FAP patients. In the whole material, DLT recipients with malignancy had inferior survival compared to non-malignant recipients, a difference that disappeared when analyzing the last 5 years. Tumor recurrence and septicemia caused the majority of deaths (39%). Surprisingly, signifi cantly better graft survival was seen in recipients of non-Val30Met mutated livers compared to Val30Met mutated livers (5-yr survival 73% and 66%, respectively, p<0.05). The DLTR contains eight patients retransplanted 7-11 years after DLT because of FAP symptoms. Conclusion: By careful recipient selection and done by experienced teams DLT is of value and can signifi cantly contribute in relieving organ shortage. Short-term outcome in DLT recipients is excellent. Long-term survival must also be deemed good bearing in mind the dismal prognosis in these patients without transplantation. The comparable survival in DLT recipients with and without malignancies in recent years may be due to better DLT recipient selection criteria. The risk of transmitting de novo amyloidosis with the grafted liver is real and cannot be neglected. This report is presented on behalf of all reporting members of the DLTR.
This research is aimed to find out the influence of the financial performance and the firm size t... more This research is aimed to find out the influence of the financial performance and the firm size to the stock return. The dependent variable is the stock return. Meanwhile the independent variables are firm size and financial performance which is measured by Current Ratio (CR), Return on Assets (ROA), and Price Earning Ratio (PER). The population is all property and real estate companies which are listed in Indonesian Stock Exchange (IDX) in 2011-2015 periods. The sample collection technique has been carried out by using purposive sampling method so 26 property and realestate companies which are listed in the Indonesian Stock Exchange (IDX) have been selected as samples. The data analysist technique has been done by using multiple linear regression analysis and the SPSS 23. The classic assumption test (the test of normalitas, heteroskedastisitas, autokorelasi, and multikolenieritas) is carried out before the multiple regression analysis. Based on the results of hypothesis test shows that return on assets (ROA) give positive influence on stock return whereas the current ratio (CR), price earnings ratio (PER) and firm size give no influence to the stock return.
Introduction: This study aimed to investigate the acute rejection rate and graft function after l... more Introduction: This study aimed to investigate the acute rejection rate and graft function after liver transplantation according to pre-transplantation donor specifi c antibody (DSA) status and changing pattern of DSA after liver transplantation. Patients and methods: This study was prospectively designed observational study from March 2011 to October 2013. Forty patients were enrolled in this study. Singe
We apply Schmidt's Subspace Theorem to establish Arithmetic General Theorems for projective varie... more We apply Schmidt's Subspace Theorem to establish Arithmetic General Theorems for projective varieties over number and function fields. Our first result extends an analogous result of M. Ru and P. Vojta. One aspect to its proof makes use of a filtration construction which appears in work of Autissier. Further, we consider work of M. Ru and J. T.-Y. Wang, which pertains to an extension of K. F. Roth's theorem for projective varieties in the sense of D. McKinnon and M. Roth. Motivated by these works, we establish our second Arithmetic General Theorem, namely a form of Roth's theorem for exceptional divisors. Finally, we observe that our results give, within the context of Fano varieties, a sufficient condition for validity of the main inequalities predicted by Vojta.
To transplant or not to transplant - Lessons learned from 20 years global collaboration in liver ... more To transplant or not to transplant - Lessons learned from 20 years global collaboration in liver transplantation for hereditary transthyretin amyloidosis
Flow cytometry at Week 10 and 12 found equivalent number of Foxp3+ Treg cells in spleens of all 3... more Flow cytometry at Week 10 and 12 found equivalent number of Foxp3+ Treg cells in spleens of all 3 groups but increased Foxp3+ Treg cells in draining lymph nodes in IL6R/HN group (13.2% ±2.0) in comparison to IgG/HN group (10% ± 1.0) and CFA alone (8.5% ± 1.1). Immunohistochemistry showed reduced glomerular IgG deposition in IL6R/HN group at Week10. Conclusions: IL6-R blockade limits Heymann Nephritis and may potentially infl uence the Treg/Th17 axis.
Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimu... more Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n ¼ 67; bid, n ¼ 62). PK data were available for 77 patients (tacrolimus qd, n ¼ 45; bid, n ¼ 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC 0-24) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ngÁh/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ngÁh/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC 0-24 and concentration at 24 hours for tacrolimus qd and bid (r ¼ 0.92 and r ¼ 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with Abbreviations: AE, adverse event; AUC 0-24 , area under the curve from 0 to 24 hours; AZA, azathioprine; bid, twice daily; BPAR, biopsy-proven acute rejection; C 24 , concentration at 24 hours; C max , maximum concentration; C min , minimum blood concentration; MMF, mycophenolate mofetil; NEC, not elsewhere classified; PK, pharmacokinetics; qd, once daily; SD, standard deviation; T max , time to maximum concentration. This study and statistical analyses, and the editorial and project management services of Acumed involved in the preparation of this manuscript, were supported by Astellas Pharma Europe, Ltd.
Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in th... more Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characteriz... more Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits.The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation.The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.
The efficacy and safety of tacrolimus-and cyclosporine-based immunosuppressive regimens were comp... more The efficacy and safety of tacrolimus-and cyclosporine-based immunosuppressive regimens were compared in a prospectively defined subgroup of kidney transplant recipients from the European, open, multicentre, 2 : 1 randomised, parallel group study. Patients were stratified as high risk for immunological events if they had a panel-reactive antibodies grade greater than 80 7' 0 and/or a previous transplant functional for less than 1 year. The primary efficacy variables evaluated were the incidence of acute rejection, steroid usage and patient and graft survival. Safety was assessed based on adverse events and laboratory evaluations. At 1 year, the tacrolimus group (n = 22) had a lower incidence of biopsy-proven acute rejection (31.8 %) and a higher graft survival (86.0 %) than the 1 1 patients in the cyclosporine group (54.5 % and 72.0 %, respectively). The frequencies of adverse events were similar between the two groups. The tacrolimus regimen appears more beneficial for high risk patients than cyclosporine.
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