Immunosuppression for islet transplantation.

The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen is a significant breakthrough that allows the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year ; however, the rate is reduced to 50% at 3 years, attributed to prolonged tacrolimus exposure. Recently, immunosuppression agents such as cyclosporine, mycophenolate mofetil, and the novel agent FTY 720 have been used instead of tacrolimus. Lymphocytedepleting antibodies such as anti-thymocyte globulin, alemtuzumab, and hOKT3gamma 1 (ala, ala) have been launched, and a costimulatory blockade of anti-CD40 monoclonal antibodies and CTLA4-Ig will be attempted in the near future. Moreover, the potential of a novel immunosuppressing peptide could now be realized using new technology called the protein transduction system. In this review, we show some of the most recent contributions to the advancement of knowledge in this field

High-performance Ge/Si electro-absorption optical modulator up to 85°C and its highly efficient photodetector operation

We studied a high-speed Ge/Si electro-absorption optical modulator (EAM) evanescently coupled with a Si waveguide of a lateral p–n junction for a high-bandwidth optical interconnect over a wide range of temperatures from 25 °C to 85 °C. We demonstrated 56 Gbps high-speed operation at temperatures up to 85 °C. From the photoluminescence spectra, we confirmed that the bandgap energy dependence on temperature is relatively small, which is consistent with the shift in the operation wavelengths with increasing temperature for a Ge/Si EAM. We also demonstrated that the same device operates as a high-speed and high-efficiency Ge photodetector with the Franz-Keldysh (F-K) and avalanche-multiplication effects. These results demonstrate that the Ge/Si stacked structure is promising for both high-performance optical modulators and photodetectors integrated on Si platforms

The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab

Objectives: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. Methods: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. Results: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. Conclusions: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.Kaneshiro S., Ebina K., Hirao M., et al. The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab. Modern Rheumatology 27, 42 (2017); https://doi.org/10.1080/14397595.2016.1181315

The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis

The aim of this 12-month, observational study was to compare the effects of switching daily teriparatide (TPTD) to oral bisphosphonates (BP) therapy or denosumab (DMAb) therapy in patients with primary osteoporosis. Patients [n = 78; 71 postmenopausal women and seven men; mean age 76.3 (64–94) years; mean duration of prior daily TPTD therapy 20.1 (6–24) months] were allocated to either the (1) “switch-to-BP” group [n = 36; weekly alendronate 35 mg (n = 19), weekly risedronate 17.5 mg (n = 12), monthly minodronate 50 mg (n = 5)]; or (2) “switch-to-DMAb” group (n = 42; 60 mg sc every 6 months) based on each physicians’ decision. Changes in bone mineral density (BMD) and serum bone turnover markers were monitored every 6 months. No significant difference was observed in baseline clinical characteristics between the groups. After 12 months, the increase in BMD was significantly greater in the switch-to-DMAb group compared to the switch-to-BP group: lumbar spine (6.2 vs. 2.6 %; P < 0.01), total hip (4.2 vs. 1.1 %; P < 0.05), and femoral neck (3.5 vs. 1.4 %; P < 0.05). In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (−55.8 vs. −32.8 %; P < 0.01) and ucOC (−85.5 vs. −65.0 %; P < 0.001), while no significant difference was observed in PINP (−67.5 vs. −62.1 %). Switching daily TPTD to DMAb significantly increased BMD and decreased bone resorption marker compared to switching to oral BP at 12 months, and thus may provide an effective sequential treatment option after daily TPTD treatment.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00774-015-0731-xEbina K., Hashimoto J., Kashii M., et al. The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis. Journal of Bone and Mineral Metabolism 35, 91 (2017); https://doi.org/10.1007/s00774-015-0731-x

Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteotomy for hallux valgus. Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40–93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13–50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon’s discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatarsophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade). Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p <.001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4–34.2, interposition: 18.4–37.1; p =.02), function (without interposition: 20.8–33.6, interposition: 18.3–36.6; p =.005), total score (without interposition: 41.5–81.8, interposition: 38.5–88.5; p <.001), and the MTP joint space (without interposition: 1.4–1.5 mm, interposition: 1.6–2.6 mm; p <.001) with significant correlation between the total JSSF score (r =.40; p =.001). Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes.Ebina K., Hirao M., Tsuboi H., et al. Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus. Modern Rheumatology 30, 204 (2020); https://doi.org/10.1080/14397595.2019.1572261