Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study.

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

Renal arteriolar hyalinosis, not intimal thickening in large arteries, is associated with cardiovascular events in people with biopsy-proven diabetic nephropathy.

AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Clonal Deletion Established via Invariant NKT Cell Activation and Costimulatory Blockade Requires In Vivo Expansion of Regulatory T Cells.

Recently, the immune-regulating potential of invariant natural killer T (iNKT) cells has attracted considerable attention. We previously reported that a combination treatment with a liposomal ligand for iNKT cells and an anti-CD154 antibody in a sublethally irradiated murine bone marrow transplant (BMT) model resulted in the establishment of mixed hematopoietic chimerism through in vivo expansion of regulatory T cells (Tregs). Herein, we show the lack of alloreactivity of CD8(+) T cells in chimeras and an early expansion of donor-derived dendritic cells (DCs) in the recipient thymi accompanied by a sequential reduction in the donor-reactive Vß-T cell receptor repertoire, suggesting a contribution of clonal deletion in this model. Since thymic expansion of donor DCs and the reduction in the donor-reactive T cell repertoire were precluded with Treg depletion, we presumed that Tregs should preform before the establishment of clonal deletion. In contrast, the mice thymectomized before BMT failed to increase the number of Tregs and to establish CD8(+) T cell tolerance, suggesting the presence of mutual dependence between the thymic donor-DCs and Tregs. These results provide new insights into the regulatory mechanisms that actively promote clonal deletion.

ABO-Incompatible Living Kidney Transplants: Evolution of Outcomes and Immunosuppressive Management.

ABO-incompatible living kidney transplantation (ABO-ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO-ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO-ILKT compared with those from ABO-compatible living kidney transplantation (ABO-CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032-including 247 ABO-ILKT and 785 ABO-CLKT cases-were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO-compatibility. In the past decade, ABO-ILKT and ABO-CLKT recipients yielded almost equivalent outcomes with respect to the 9-year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59-3.22, p = 0.455). The graft survival rate for ABO-ILKT conducted between 2005 and 2013 was better than that for ABO-ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13-0.72, p = 0.007). ABO-ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO-incompatibility. Currently, ABO-ILKT is an acceptable treatment for patients with end-stage renal disease.

Snell's Law for Spin Waves.

We report the experimental observation of Snell's law for magnetostatic spin waves in thin ferromagnetic Permalloy films by imaging incident, refracted, and reflected waves. We use a thickness step as the interface between two media with different dispersion relations. Since the dispersion relation for magnetostatic waves in thin ferromagnetic films is anisotropic, deviations from the isotropic Snell's law known in optics are observed for incidence angles larger than 25° with respect to the interface normal between the two magnetic media. Furthermore, we can show that the thickness step modifies the wavelength and the amplitude of the incident waves. Our findings open up a new way of spin wave steering for magnonic applications.

Pre-harvest foliar application of ethephon strengthens gibberellins-induced fruit expansion in Pyrus pyrifolia.

To identify the roles of ethylene in fruit development in Japanese pear Pyrus pyrifolia 'Niitaka', one of the non-climacteric genotypes, source-sink strength and fruit development during fruit expansion were investigated when ethephon was applied after a conventional gibberellic acid (GA) lanolin paste treatment on the pedicel. The results demonstrate that the conventional GA treatment during the early stage of fruit expansion resulted in larger fruit size and advanced fruit maturation, but pre-harvest foliar application of ethephon only advanced fruit maturation. However, pre-harvest foliar application of ethephon with a preceding conventional GA treatment during the early stage of fruit expansion dramatically improved fruit size and advanced fruit maturation over GA or ethephon alone. Moreover, the early foliar application of ethephon showed a better efficacy in increasing fruit size than the late spraying. A further study revealed that when ethephon was applied after the conventional GA treatment, it improved source-sink strength associated with leaf photosynthesis and the specific rate of [13C] accumulation in fruit, and also strengthened cell expansion more than did GA or ethephon alone.

Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05).

BACKGROUND: In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC. PATIENTS AND METHODS: Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS). RESULTS: From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group. CONCLUSION: The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

A novel approach inducing transplant tolerance by activated invariant natural killer T cells with costimulatory blockade.

Invariant natural killer T (iNKT) cells are one of the innate lymphocytes that regulate immunity, although it is still elusive how iNKT cells should be manipulated for transplant tolerance. Here, we describe the potential of a novel approach using a ligand for iNKT cells and suboptimal dosage of antibody for CD40-CD40 ligand (L) blockade as a powerful method for mixed chimerism establishment after allogenic bone marrow transplantation in sublethally irradiated fully allo recipients. Mixed-chimera mice accepted subsequent cardiac allografts in a donor-specific manner. High amounts of type 2 helper T cytokines were detected right after iNKT cell activation, while subsequent interferon-gamma production by NK cells was effectively inhibited by CD40/CD40L blockade. Tolerogenic components, such as CD11c(low) mPDCA1(+) plasmacytoid dendritic cells and activated regulatory T cells (Tregs) expressing CD103, KLRG-1 and PD-1, were subsequently augmented. Those activating Tregs seem to be required for the establishment of chimerism because depletion of the Tregs 1 day before allogenic cell transfer resulted in a chimerism brake. These results collectively suggest that our new protocol makes it possible to induce donor-specific tolerance by enhancement of the innate ability for immune tolerance in place of the conventional immunosuppression.

Comparison of melanoma guidelines in the U.S.A., Canada, Europe, Australia and New Zealand: a critical appraisal and comprehensive review.

There are several well-established guidelines for the staging of melanoma and the size of excisional margins, along with recommendations for sentinel lymph node biopsy. Guidelines have been proposed in the U.S.A. (National Comprehensive Cancer Network), Canada (Cancer Care Ontario and Canadian Medical Association), Europe (European Society for Medical Oncology) and Australia and New Zealand (Australian Cancer Network). The guidelines set by these groups are largely based on current evidence, or expert panel consensus where evidence is lacking. The recommendations are more controversial and varying where there is a lack of level-one evidence in the literature (e.g. screening, adjuvant therapy, follow-up intensity). We review the evidence and available literature for the management of melanoma worldwide.

Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.

We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine kinase Akt. However, the molecular mechanisms downstream of Akt in this process have not been elucidated. Cadmium has a potential to accumulate misfolded proteins, and proteotoxicity is involved in cadmium toxicity. To clear the roles of Akt in cadmium exposure-induced RTCs death, we investigated the possibility that Akt could regulate proteotoxicity through autophagy in cadmium chloride (CdCl2)-exposed HK-2 human renal proximal tubular cells. CdCl2 exposure promoted the accumulation of misfolded or damaged proteins, the formation of aggresomes (pericentriolar cytoplasmic inclusions), and aggrephagy (selective autophagy to degrade aggresome). Pharmacological inhibition of Akt using MK2206 or Akti-1/2 enhanced aggrephagy by promoting dephosphorylation and nuclear translocation of transcription factor EB (TFEB)/transcription factor E3 (TFE3), lysosomal transcription factors. TFEB or TFE3 knockdown by siRNAs attenuated the protective effects of MK2206 against cadmium toxicity. These results suggested that aberrant activation of Akt attenuates aggrephagy via TFEB or TFE3 to facilitate CdCl2-induced cell death. Furthermore, these roles of Akt/TFEB/TFE3 were conserved in CdCl2-exposed primary human RTCs. The present study shows the molecular mechanisms underlying Akt activation that promotes cadmium-induced RTCs death.

Transient lymphopenia breaks costimulatory blockade-based peripheral tolerance and initiates cardiac allograft rejection.

Lymphopenia is induced by lymphoablative therapies and chronic viral infections. We assessed the impact of lymphopenia on cardiac allograft survival in recipients conditioned with peritransplant costimulatory blockade (CB) to promote long-term graft acceptance. After vascularized MHC-mismatched heterotopic heart grafts were stably accepted through CB, lymphopenia was induced on day 60 posttransplant by 6.5 Gy irradiation or by administration of anti-CD4 plus anti-CD8 mAb. Long-term surviving allografts were gradually rejected after lymphodepletion (MST = 74 ± 5 days postirradiation). Histological analyses indicated signs of severe rejection in allografts following lymphodepletion, including mononuclear cell infiltration and obliterative vasculopathy. Lymphodepletion of CB conditioned recipients induced increases in CD44(high) effector/memory T cells in lymphatic organs and strong recovery of donor-reactive T cell responses, indicating lymphopenia-induced proliferation (LIP) and donor alloimmune responses occurring in the host. T regulatory (CD4(+) Foxp(3+)) cell and B cell numbers as well as donor-specific antibody titers also increased during allograft rejection in CB conditioned recipients given lymphodepletion. These observations suggest that allograft rejection following partial lymphocyte depletion is mediated by LIP of donor-reactive memory T cells. As lymphopenia may cause unexpected rejection of stable allografts, adequate strategies must be developed to control T cell proliferation and differentiation during lymphopenia.

Enhancement of intestinal immune function in mice by ß-D-glucan from aureobasidium pullulans ADK-34.

ß-Glucans, glucose polymers that are the main constituents of the outer cell walls of micro-organisms such as fungi and yeast, are known to play an immunostimulatory role. We prepared ß-glucan (ß-(1-3),(1-6)-D-glucan) from an edible cultured fungus through fermentation techniques using a strain of Aureobasidium pullulans ADK-34. The purity of this ß-glucan preparation (AP-FBG) was demonstrated to be high through various instrumental analyses. We then examined the effects of AP-FBG on intestinal immune systems. We prepared Peyer's patch (PP) cells and measured interleukin (IL)-5, IL-6, and IgA production in culture media with AP-FBG. We found that both cytokines and IgA increased; furthermore, IL-6 secreted by PP dendritic cells (PPDCs) cultured in the presence of AP-FBG significantly increased. We tested IgA production after oral administration of AP-FBG for 2 weeks and found that AP-FBG tended to promote the production of IgA in the small intestine. Interestingly, we observed a significant increase in IgA production in the small intestines of mice treated with cyclophosphamide (CY; an immunosuppressant) after oral administration of AP-FBG diet compared with CY-treated and control diet mice. Production of IL-6 and IgA by PP cells and IL-6 production by PPDCs in AP-FBG-fed and CY-treated mice also increased. These results demonstrate that AP-FBG has the ability to activate PPDC and induce IL-6 production and IgA secretion in PP cells. These abilities were more clearly expressed when AP-FBG was orally administered in a CY-induced immunosuppressed condition. Therefore, AP-FBG may be a useful ingredient for preparing functional foods with immunomodulatory activities.

Comparison of prognosis of separated and non-separated tooth autotransplantation.

The aim of this study was to compare the prognosis of separated and non-separated tooth autotransplantation of the upper first and second molars with complete root formation undertaken at dental clinics. The participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. This study analysed 35 separated teeth and 22 non-separated teeth of 47 participants ranging from 27 to 76 years of age (mean age: 55·0 years) after data screening and elimination. The cumulative post-transplantation survival rate at 10 years was 77·1% for separated teeth and 63·6% for non-separated teeth as calculated with the Kaplan-Meier method. There were no significant differences between separated teeth and non-separated teeth in a log rank test (P = 0·687). Separated-tooth autotransplantation can help fill narrow recipient sites and increase occlusal supporting zones, but the clinical success rate was only 48·6%. Although transplantation of teeth with complete root formation has limited prognosis, transplantation of upper first and second molars, whether separated or non-separated, is a viable option to replace missing teeth.

Gender difference in tooth autotransplantation with complete root formation: a retrospective survey.

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance.

Influence of age on tooth autotransplantation with complete root formation.

The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient.

Current status of organ transplantation in Japan.

To overcome severe donor shortage, Japanese doctors over the years have developed innovative strategies to maximize organs transplanted per brain death donor and expanded the donor pool using living donors. They also used living and marginal organs and drastically improved living donor lung, liver, pancreas and kidney transplantations. Moreover, they initiated ABO blood type incompatible liver transplantation advancements and succeeded in overcoming the blood type barrier in kidney and liver transplantations. Similar efforts are underway for pancreas transplantation. Furthermore, Japanese doctors have developed a nonaggressive step to achieve immunosuppression following organ transplantation by carefully monitoring donor-specific hyporesponsiveness and infectious immunostatus. However, the institution of amendments to allocation systems and the intensification of efforts to decrease living donor morbidity and to increase the number of brain death donors have remained important issues needing attention. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations.

Chronic antibody-mediated rejection is reduced by targeting B-cell immunity during an introductory period.

Transplantation across blood group antigen and human leukocyte antigen (HLA) barriers are immunologically high risk. Both splenectomy and rituximab injection were developed to overcome those immunological barriers. The idea behind these treatments is to control B-cell immunity before and after renal transplantation and antibody production. Between January 2001 and December 2004, recipients underwent pretransplant double-filtration plasmapheresis (DFPP) and splenectomy at the time of transplantation in the ABO-incompatible group (ABO-I-SPX; n= 45). From January 2005 to June 2009, a low dose of rituximab was given as an alternative to splenectomy (ABO-I-RIT; n = 57). As a control group, we selected 83 cases of ABO-C living-donor kidney transplantation between January 2001 and December 2007 (ABO-C). We compared the graft survival rate and chronic antibody-mediated rejection (C-AMR) rate between ABO-C and ABO-I kidney transplantation with induction treatment. C-AMR rates 2 years after the operation were 8.8, 3.5 and 28.9%, and de novo donor-specific anti-HLA antibody (DSHA) positive rates were 2.2, 1.7 and 18.1% in the ABO-I-SPX, ABO-I-RIT and ABO-C groups, respectively. The ABO-C group showed the highest rate of C-AMR and de novo DSHA. B-cell depletion protocols, such as splenectomy or rituximab administration, reduced C-AMR after kidney transplantation.

A retrospective survey of autotransplantation of teeth in dental clinics.

The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor (P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics.