We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on ...pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5‐year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1‐ and 5‐year recurrence‐free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1‐ and 5‐year recurrence‐free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under‐staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1‐ and 5‐year recurrence‐free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under‐staging when compared to the Milan criteria.
The UCSF criteria for hepatocellular carcinoma applied as selection criteria for liver transplantation based on pre‐operative imaging are associated with excellent post‐transplant survival, without a higher risk of tumor recurrence or under‐staging than the Milan criteria.
Fundamental to the efficacy of cognitive training (CT) is its dose. Here we used the power and breadth afforded by a large dataset to measure precisely dose-response (D-R) functions for CT and to ...examine the generality of their magnitude and form. The present observational study involved 107,000 users of Lumosity, a commercial program comprising computer games designed to provide CT over the internet. In addition to training with Lumosity games, these users took an online battery of cognitive assessments (NeuroCognitive Performance Test, NCPT) on two or more occasions separated by at least 10 weeks. Changes in performance on the NCPT between the first and second assessments were examined as a function of the amount of intervening gameplay. The resulting D-R functions were obtained both for overall performance on the NCPT and performance on its eight subtests. Also examined were differences between D-R functions from demographic groups defined by age, gender, and education. Monotonically increasing D-R functions, well fit by an exponential approach to an asymptote, were found consistently for overall performance on the NCPT, performance on seven of the eight subtests, and at each level of age, education, and gender. By examining how individual parameters of the D-R functions varied across subtests and groups, it was possible to measure separately changes in the effects on NCPT performance of 1) transfer from CT and 2) direct practice due to repeated testing. The impact of both transfer and direct practice varied across subtests. In contrast, while the effects of direct practice diminished with age, those of transfer remained constant. Besides its implications for CT by older adults, this latter finding suggests that direct practice and transfer do not involve identical learning processes, with transfer being limited to learning processes that remain constant across the adult lifespan.
The applicability of islet transplantation as treatment for type 1 diabetes is limited by renal and islet toxicities of currently available immunosuppressants. We describe a novel immunosuppressive ...regimen using the antileukocyte functional antigen‐1 antibody efalizumab which permits long‐term islet allograft survival while reducing the need for corticosteroids and calcineurin inhibitors (CNI). Eight patients with type 1 diabetes and hypoglycemic unawareness received intraportal allogeneic islet transplants. Immunosuppression consisted of antithymocyte globulin induction followed by maintenance with efalizumab and sirolimus or mycophenolate. When efalizumab was withdrawn from the market in mid 2009, all patients were transitioned to regimens consisting of mycophenolate and sirolimus or mycophenolate and tacrolimus. All patients achieved insulin independence and four out of eight patients became independent after single‐islet transplants. Insulin independent patients had no further hypoglycemic events, hemoglobin A1c levels decreased and renal function remained stable. Efalizumab was well tolerated and no serious adverse events were encountered. Although long‐term follow‐up is limited by discontinuation of efalizumab and transition to conventional imunnosuppression (including CNI in four cases), these results demonstrate that insulin independence after islet transplantation can be achieved with a CNI and steroid‐free regimen. Such an approach may minimize renal and islet toxicity and thus further improve long‐term islet allograft survival.
An immunosuppressive regimen based on the anti‐LFA‐1 antibody efalizumab showed some promising results in eight islet transplant recipients. See Editorial by Oberholzer et al 1725.
Among the non-pharmacological methods under development for maintaining cognitive function across the lifespan is computerized cognitive training (CCT). There has been considerable interest in using ...CCT to slow or remediate age-related cognitive decline, both normal and pathological. Toward these ends, it would be useful to know how the effects of CCT on cognitive function vary over the course of normal cognitive aging. Are there changes in either 1) the overall efficacy of CCT or 2) which cognitive faculties are affected? To address these two questions, we reanalyzed results from a large online study by Hardy et al. (1) of 4,715 adults between 18 and 80 that examined effects of CCT on both a neuropsychological test battery and self-reported ratings of cognition and affect in daily living. Combined across all participants, Hardy et al. found greater improvement on both types of assessment following 10 weeks of CCT with the commercial program Lumosity, as compared to practice with a control activity involving computerized crossword puzzles. The present study compared the size of these effects on the older (50-80) and younger (18-49) participants. To address the question of overall efficacy, we examined CCT effects (treatment minus control) on overall performance of the test battery and mean rating. No significant difference on either measure was found between the two age cohorts. To address the question of whether the same magnitude of overall effects on both age cohorts was due to equivalent effects on the same set of underlying cognitive functions, we examined the patterns of CCT effects across individual subtests and rated items. These patterns did not differ significantly between the two age cohorts. Our findings suggest that benefits from CCT can occur to a similar degree and in a similar way across an extended part of the adult lifespan. Moreover, the overall effects of CCT delivered over the internet were of the same small to medium size as those typically found in the lab or clinic. Besides improving access and reducing the cost of CCT for older adults, delivery over the internet makes long-term training more practicable, which could potentially yield larger benefits.
Our purpose here is to describe our experience with important hemobilia following PTBD and to determine whether left-sided percutaneous transhepatic biliary drainage (PTBD) is associated with an ...increased incidence of important hemobilia compared to right-sided drainages. We reviewed 346 transhepatic biliary drainages over a four-year period and identified eight patients (2.3%) with important hemobilia requiring transcatheter embolization. The charts and radiographic files of these patients were reviewed. The side of the PTBD (left versus right), and the order of the biliary ductal branch entered (first, second, or third) were recorded. Of the 346 PTBDs, 269 were right-sided and 77 were left-sided. Of the eight cases of important hemobilia requiring transcatheter embolization, four followed right-sided and four followed left-sided PTBD, corresponding to a bleeding incidence of 1.5% (4/269) for right PTBD and 5.2% (4/77) for left PTBD. The higher incidence of hemobilia associated with left-sided PTBD approached, but did not reach the threshold of statistical significance (p = 0.077). In six of the eight patients requiring transcatheter embolization, first or second order biliary branches were accessed by catheter for PTBD. All patients with left-sided bleeding had first or proximal second order branches accessed by biliary drainage catheters. In conclusion, a higher incidence of hemobilia followed left-versus right-sided PTBD in this study, but the increased incidence did not reach statistical significance.
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