Cost and clinical outcome of islet transplantation in Norway 2010-2015.

Islet transplantation is a minimally invasive ß-cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here, we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from January 2010 to June 2015. Patients were retrospectively divided into three groups. Thirteen patients received either one or two islet transplantation alone (ITA), while five patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan-Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation. An estimated 70% maintain at least partial graft function, defined as fasting C-peptide >0.1 nmol L-1 , and 47% maintain a HbA1c below 6.5% or 2 percent points lower than before ITA. For all groups combined, we estimate that 44% of the patients have a 50% reduction in insulin requirement 4 years after the initial islet transplantation. The average cost for an islet transplantation procedure was 347 297±60 588 NOK, or 35 424±6182 EUR, of which isolation expenses represent 34%. We hereby add to the common pool of growing experience with islet transplantation and also describe the cost of the treatment at our center.

Intracellular sirolimus concentration is reduced by tacrolimus in human pancreatic islets in vitro.

MAIN PROBLEM: Islet transplantation has become a promising treatment for type 1 diabetes. However, immunosuppressive drugs used today cause islet deterioration and modification strategies are necessary. But little is known about pharmacokinetics interactions and intracellular concentrations of immunosuppressive drugs in human islets. METHODS: We determined the pharmacokinetics of tacrolimus and sirolimus in islets by measuring intracellular concentration after exposure alone or in combination at two different doses up to 48 h. A quantification technique established in our laboratory using a Micromass Quattro micro API MS/MS-instrument with electrospray ionization was used. Islets function was measured by oxygen consumption rates. Presence of drug transporters OATP1B1 and ABCB1 and metabolizing enzyme CYP3A4 in islets were quantified using real-time quantitative PCR. RESULTS: Islets incubated with tacrolimus and sirolimus had a significant decrease in intracellular concentration of sirolimus compared to sirolimus alone. Reduced intracellular sirolimus concentration was followed by increased p70S6k phosphorylation suggesting preservation of the mTOR-signaling pathway. Drug transporters OATP1B1 and ABCB1 and enzyme CYP3A4 were expressed in human islets, but were not involved in the reduced sirolimus concentration by tacrolimus. CONCLUSION: These findings provide new knowledge of the drug interaction between tacrolimus and sirolimus, suggesting that tacrolimus has an inhibitory effect on the intracellular concentration of sirolimus in human islets.

Graft function 1 year after pregnancy in an islet-transplanted patient.

Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), but pregnancy has generally not been advised for women after receiving an islet allograft. We hereby describe what is to our knowledge the first successful pregnancy and persistent graft function in a woman 4 years after her initial islet transplantation. A 37-year-old woman with brittle type 1 diabetes was transplanted with two separate islet graft infusions, eventually becoming insulin independent. Ten months after her second transplantation, her immunosuppression was switched from tacrolimus and sirolimus to tacrolimus, azathioprine, and prednisolone, due to her wish to become pregnant. She became pregnant one year later, and after 38 weeks of uncomplicated pregnancy, she gave birth to a healthy child by C-section. The current report suggests that pregnancy and childbirth can be accomplished after islet transplantation without loss of islet graft function.

Brassiere Cup Size Agreement between Patients and Plastic Surgeons: Do Surgeons and Patients Speak the Same Size Language?

Patients undergoing plastic surgery of the breasts often communicate their size expectations as a brassiere cup size. However, multiple factors may cause a miscommunication between the surgeon and patient when brassiere cup size is used as a measure of results. The aim of this study was to determine the degree of agreement between disclosed and estimated brassiere cup size and also interrater agreement. Methods: Three-dimensional (3D) scans of 32 subjects were evaluated by 10 plastic surgeons estimating cup size using the American brassiere system. The surgeons were blinded to all parameters, including the 3D surface software-derived volume measures of the Vectra scan. The 3D scans of the anterior torsos were viewed. The plastic surgeons' estimations were compared with the cup sizes stated by the subjects (disclosed cup size), using simple and weighted Kappa statistics. Results: Agreement between the estimated and disclosed brassiere sizes was only slight (0.1479 ± 0.0605) using a simple Kappa analysis. Even when a Fleiss-Cohen-weighted comparison was used, only moderate agreement (0.6231 ± 0.0589) was found. The interrater agreement intraclass correlation coefficient was 0.705. Rater accuracy varied. The percentage of time spent in cosmetic practice and gender were not significantly correlated with accuracy. Conclusions: Agreement between cup size disclosed by subjects and estimates by plastic surgeons was low. A miscommunication between the surgeon and patient may occur when using brassiere sizes to communicate wishes and estimates in procedures that involve changes in breast volume.

Beyond the 21-cm Notch-to-nipple Myth: Golden Proportions in Breast Aesthetics.

BACKGROUND: The 21-cm notch-to-nipple distance has been accepted without academic scrutiny as a key measure in breast aesthetics. The Fibonacci sequence and phi ratio occur frequently in nature. They have previously been used to assess aesthetics of the face, but not the breast. This study aims to assess if the static 21-cm measure or the proportional phi ratio is associated with ideal breast aesthetics. METHOD: Subclavicular-breast height and breast width were used to calculate the aesthetic ratio. Subjects were subsequently aesthetically rated. A one-sample t-test was used to determine if the ratio for each breast differed from phi. Breast scores with one, both, or no breasts were compared with an optimal phi ratio. Analysis of variance was performed. Tukey-Kramer adjustment for multiple comparisons was used when pairwise comparisons were conducted. RESULTS: Five subjects (14%) had bilateral optimal phi ratio breasts. Four subjects (11%) had one breast with an optimal phi ratio. Subjects with bilateral optimal phi ratios had significantly higher overall breast scores than those with only one optimal breast (Δ = 0.86, P = 0.025) or no optimal breast (Δ = 0.73, P = 0.008). Distance from optimal Fibonacci nipple position was moderately to strongly correlated with aesthetic score (-0.630, P = 0.016). No correlation was found between 21-cm notch-to-nipple distance and aesthetic score. CONCLUSION: The bilateral optimal phi ratio is correlated with high overall aesthetic scores, as is the optimal Fibonacci nipple position. No correlation was found between 21-cm notch-to-nipple distance and overall aesthetic score.

An Aesthetic Factor Priority List of the Female Breast in Scandinavian Subjects.

Background: There is little consensus about the relative determinative value of each individual factor in female breast aesthetics. When performing breast surgery with an aesthetic goal, certain factors will be more important than others. The purpose of this study was to make an aesthetic factor rank list to determine the relative contributions to overall breast aesthetics. Method: Volunteers were scanned using the 3-dimensional Vectra system. Ten Scandinavian plastic surgeons rated 37 subjects, using a validated scoring system with 49 scoring items. The correlation between specific aesthetic factors and overall breast aesthetic scores of the subjects were calculated using Pearson's r, Spearman's ρ, and Kendall's τ. Results: A very strong correlation was found between overall breast aesthetic score and lower pole shape (0.876, P < 0.0001). This was also true for upper pole shape (0.826, P < 0.0001) and breast height (0.821, P < 0.0001). A strong correlation was found between overall breast aesthetic score and nipple position (0.733, P < 0.0001), breast size (0.644, P < 0.0001), and breast width (0.632, P < 0.0001). Factors that were only moderately correlated with aesthetic score were intermammary distance (0.496, P = 0.002), nipple size and projection (0.588, P < 0.0001), areolar diameter (0.484, P < 0.0001), and areolar shape (0.403, P < 0.0001). Perceived symmetry was a weak factor (0.363, P = 0.027). Conclusions: Aesthetic factors of the female breast can be ranked in a priority list. Shape of the lower pole and upper pole and breast height are primary factors of female breast aesthetics. These should be prioritized in any aesthetic breast surgery. Vertical dimensional factors seem to be more determinative than horizontal factors.

Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids.

Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 µg/L), sirolimus (30 µg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 µg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.

Anakinra and tocilizumab enhance survival and function of human islets during culture: implications for clinical islet transplantation.

Pretreatment culture before islet transplantation represents a window of opportunity to ameliorate the proinflammatory profile expressed by human ß-cells in duress. Anakinra (IL-1 receptor antagonist) and tocilizumab (monoclonal IL-6 receptor antibody) are two known anti-inflammatory agents successfully used in the treatment of inflammatory states like rheumatoid arthritis. Both compounds have also been shown to reduce blood glucose and glycosylated hemoglobin in diabetic patients. We therefore sought to evaluate the impact of anakinra and tocilizumab on human ß-cells. The islets were precultured with or without anakinra or tocilizumab and then transplanted in a marginal mass model using human islets in immunodeficient mice. Islet viability was evaluated in an in vitro model. The pretreatment culture led to a significantly improved engraftment in treated islets compared to the vehicle. Anakinra and tocilizumab are not toxic to human islets and significantly reduce markers of inflammation and cell death. These results strongly support a pretreatment culture with anakinra and tocilizumab prior to human islet transplantation.