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The persistent organ shortage has led to the consideration of “marginal” donors, including those of advanced age, but the outcomes of using living kidney donors aged 70 years or older remain debated. This multicenter retrospective cohort study aimed to evaluate the propriety of kidney donation from older adult donors by analyzing the association between transplant outcomes and recipient age. Using data from 633 adult living-donor kidney transplants, we compared an elderly donor group (age ≥ 70 years, n  = 75) with a non-elderly donor group (age < 70 years, n  = 558). After 1:1 propensity score matching, the elderly donor group showed significantly lower death-censored graft survival. However, this disadvantage disappeared entirely in recipients aged 50 years or older, who exhibited comparable death-censored graft survival to those with non-elderly donors ( p  = 0.743). In contrast, recipients younger than 50 years who received grafts from elderly donors had markedly inferior death-censored graft survival ( p  = 0.008). In conclusion, using living kidney donors aged ≥ 70 years is a viable strategy to expand the donor pool, but its success is influenced by recipient age. These results support an age-sensitive approach in counseling and decision-making for kidney transplantation.

PurposeThis study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM).MethodsOutcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS).ResultsAfter PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27–0.56 vs. HR 0.50; 95% CI 0.30–0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50–1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30–0.98 vs. HR 0.49; 95% CI 0.29–0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34–2.06).ConclusionThe comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

Background Cardiovascular diseases are still highly prevalent after kidney transplantation. However, little is known about the impact of the timing of rejection episodes on cardiovascular disease. The study aimed to analyze the influence of the timing of rejection episodes on cardiovascular events in recipients of living donor kidney transplantation. Methods We studied 572 living donor kidney transplant recipients from the Michinoku Renal Transplant Network (MRTN), which includes 6 centers in the Tohoku region of Japan. Fine-Gray proportional hazards regression analysis with time-dependent variables was used to assess the effect of rejection episode on cardiovascular events. Recipients were divided into three groups: those without rejection (non-rejection, 370 patients), rejection within 6 months after transplantation (early rejection, 99 patients), and rejection after 6 months (late rejection, 103 patients). The effect of timing on cardiovascular events was evaluated using Fine-Gray proportional hazards regression analysis. Results During a median follow-up of 77 months, 70 patients experienced cardiovascular events. Rejection episodes were significantly associated with cardiovascular events (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.26–3.43, P  = 0.004), along with age and dialysis vintage. The 5-year cumulative incidence of cardiovascular events was significantly higher in the late rejection group than in the early rejection group (15% vs. 3.3%, P  = 0.021). However, no significant difference in 5-year cumulative cardiovascular event incidence was observed between the early rejection and non-rejection groups. Late rejection was significantly associated with cardiovascular events (HR: 2.40, 95% CI: 1.38–4.18, P  = 0.002), whereas early rejection was not significantly correlated with cardiovascular event risk (HR: 1.18, P  = 0.670). Conclusions Rejections occurring more than 6 months after transplantation is significantly associated with risk of cardiovascular events. Trial registration number 2019-099-1, date of registration; 3 Dec. 2019, retrospectively registered. Graphical Abstract

Objectives The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. Methods We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. Results Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. Conclusion Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.

Background Rituximab (RIT) induction therapy is widely used for desensitization against ABO-incompatible living-donor kidney transplants (KT). However, the efficacy of valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) disease and infection in KT recipients (KTRs) following RIT induction remains unclear. Methods The current multicenter retrospective study included 213 KTRs who received low-dose RIT induction between 1998 and 2021, across 6 facilities included in the Michinoku Renal Transplant Network (MRTN). VGCV dosage varied from 450 mg/day (twice weekly) to 900 mg/day (daily), with treatment durations of 3–12 months. The primary and secondary endpoints were the incidence of CMV disease and infection, respectively. Results The incidence of CMV disease was significantly higher in the VGCV group (23.5%; 16 patients) than in the non-VGCV group (5.5%; 8 patients) ( p  < 0.01). The incidence of CMV infection was 54.5% (79 patients) in the non-VGCV group and 48.5% (33 patients) in the VGCV group, with no significant difference ( p  = 0.42). In the subgroup of CMV-seronegative KTRs receiving allografts from CMV-seropositive donors (CMV IgG (D + /R-)), 18 out of 24 KTRs received VGCV prophylaxis, of whom 10 (55.6%) developed CMV disease. Within this subgroup, only 4 KTRs received VGCV with the standard protocol (900 mg daily for 6 months), and none developed CMV disease. Conclusion Insufficient VGCV prophylaxis does not reduce the incidence of CMV disease in KTRs following low-dose RIT induction. Despite concerns about leukopenia due to RIT and VGCV, in KTRs with CMV IgG (D + /R−) serostatus, VGCV prophylaxis with a standard protocol may be advisable.

Background This study aimed to compare the outcomes of living donor kidney transplantation with blood- and non-blood-related donors across multiple facilities. Previous reports comparing these outcomes have been single-center studies. As the donors were the recipients’ spouses in all cases with non-blood-related donors, we independently compared the outcomes of wife-to-husband (WTH) and husband-to-wife (HTW) transplantations. No previous multicenter studies have compared transplant outcomes between spouses in this manner. Methods This retrospective study used a shared database including 643 cases from 6 facilities that primarily used tacrolimus as a calcineurin inhibitor. We used propensity score matching to compare the outcomes of transplantations with blood- and non-blood-related donors and those of WTH and HTW transplantations. Results Of the 643 cases examined, 381 and 262 had blood- and non-blood-related donors, respectively. All non-blood-related donor cases had spouses as donors. After propensity score matching, 84 cases each were selected from the blood- and non-blood-related donor groups for comparison, with no significant intergroup difference in the time to graft loss. Among the 262 interspousal transplantations, 91 were HTW transplantations and 171 were WTH transplantations. Following propensity score matching, 58 cases each were selected from the WTH and HTW groups for comparison, with no significant intergroup difference in the time to graft loss. Conclusions In this large multicenter retrospective study, no significant differences were observed in the outcomes of transplantations with blood- and non-blood-related donors. Furthermore, no significant differences were observed in the outcomes of WTH and HTW cases. Many centers that use tacrolimus-based four-drug immunosuppressive therapy may have similar trends as those observed in this study, making our findings significant for planning transplantation involving kidneys donated from patients’ spouses.

PurposeWe assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies.MethodsThe medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted.ResultsA total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34–0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33–1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42–2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups.ConclusionsUpfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Background: Obesity is increasingly prevalent among kidney transplant candidates; however, its impact on graft outcomes in Asian populations is not well characterized. We evaluated the association between preoperative obesity and living-donor kidney transplantation outcomes in Japan. Methods: We analyzed 623 living-donor kidney transplants performed from 1998 to 2021 at six centers in northern Japan. Recipients were categorized by body mass index (BMI) at transplant, and multivariable Cox regression was employed for assessing graft outcomes. Results: Obesity (BMI, ≥30 kg/m2; n = 27 [4.3%]) was the strongest graft failure predictor (hazard ratio, 4.62) compared with normal-weight recipients. Moreover, overweight status (BMI, 25–29.9 kg/m2), acute rejection, and older donor age were independent risk factors. Despite similar rejection rates across the BMI groups, recipients with obesity exhibited persistently impaired kidney function from 1-week posttransplant to the 5-year follow-up. Patient survival was comparable across BMI groups; however, underweight status (BMI < 18.5 kg/m2) was associated with higher mortality. Conclusions: Preoperative obesity and overweight status were significant risk factors for graft failure in Japanese living-donor kidney transplant recipients. Meanwhile, the mortality rate was significantly higher in the patients with underweight status at transplant. Pre-transplant weight optimization and shared decision-making with candidates warrant consideration.

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m2). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

Objectives Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC. Methods Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60 mg/m 2 on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560 mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed. Results Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8 months, and the median total time of chemotherapy holiday was 7.7 months (range 1.7–35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS ( p  = 0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC + CT genotype ( p  = 0.036). Conclusion Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC.