Comparison of Oncological Outcomes between Transperitoneal and Retroperitoneal Approaches in Laparoscopic Nephroureterectomies for Upper Tract Urothelial Carcinoma.

Background and Objectives: Our aim was to clarify the oncological outcomes of the two different approaches to laparoscopic nephroureterectomies (LNUs) in Japan, and to examine whether there were any significant differences between the transperitoneal approach and the retroperitoneal approach. Materials and Methods: We retrospectively evaluated patients who underwent an LNU for upper tract urothelial carcinoma (UTUC) from January 2013 to December 2022. We identified 52 patients who underwent a transperitoneal LNU (tLNU) and 93 who underwent a retroperitoneal LNU (rLNU). We adopted age, smoking, and pT-stage matching, and 43 patients were classified in each group. We investigated the time from surgery to recurrence (RFS: recurrence-free survival), the time to death (OS: overall survival), and the time to non-urothelial-tract recurrence-free survival (NUTRFS). A Cox regression analysis was performed to evaluate the risk factors that influenced recurrence. Results: There were no significant differences in the RFS, OS, and NUTRFS between the two matched groups. In the multivariate Cox regression analysis, the pT stage (pT3≥ vs. pT2≤) had an HR = 2.09 and a p = 0.01, and was an independent prognostic risk factor regarding cancer recurrence. Conclusions: There were no significant differences in the oncological outcomes between the tLNU and rLNU groups. It is suggested that the transperitoneal approach should be selected for LNUs.

Experience with Tandem Pre-Dilution Online Hemodiafiltration and Centrifugal Plasma Exchange in Pretransplant Desensitization for Abo-Incompatible Kidney Transplantation: A Case Report.

BACKGROUND: In the use of therapeutic plasma exchange (TPE) as antibody removal therapy for ABO-incompatible (ABOi) kidney transplantation, it is technically possible to perform online hemodiafiltration (OHDF) and TPE simultaneously for patients who are receiving OHDF. In this study, we report tandem therapy of pre-dilution OHDF and centrifugal plasma exchange (cTPE), instead of membrane plasma exchange, which is the mainstay of TPE in Japan. METHODS: A total of 14 sessions of tandem cTPE and pre-dilution OHDF were performed as preoperative antibody removal therapy for 6 ABOi kidney transplant recipients. cTPE intra-circuit pressure, decreased antibody titer, and adverse events were evaluated. The study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not prisoners or individuals who were coerced or paid. RESULTS: The tandem therapy was completed safely in 12 of the 14 sessions, with no problems such as pressure upper and lower limit alarms or circuit coagulation. In 2 sessions, the tandem therapy had to be interrupted due to coagulation on the dialysis circuit side. Antibody titers were reduced by a median of 3-fold for both IgG and IgM. There was no acute antibody-associated rejection. CONCLUSIONS: In preoperative apheresis therapy for ABOi kidney transplantation, tandem therapy of pre-dilution OHDF and cTPE may be a useful treatment option that can be performed safely and results in sufficient reduction of antibody levels.

Daprodustat for Post-Transplant Anemia in Renal Transplant Recipients.

BACKGROUND: Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has been reported to be effective in treating conservative renal failure and renal anemia in patients undergoing dialysis. However, its effects on post-transplant anemia have not yet been reported. This study aimed to determine whether daprodustat may be a useful treatment for post-transplant anemia. MATERIALS: Excluding 5 cases in which the drug was discontinued due to side effects, 21 post-transplant patients treated with daprodustat for ≥12 months and available for follow-up were analyzed. Changes in hemoglobin levels, iron metabolism, estimated glomerular filtration rate, and low-density lipoprotein levels were evaluated over 1 year. RESULTS: The average hemoglobin level was 10.1 g/dL before treatment, and after 1, 2, 3, 6, 9, and 12 months, these had increased significantly to 10.9, 11.2, 11.9, 12.3, 12.3, and 12.6, respectively. Ferritin levels were significantly lower throughout the 12-month study period. Transferrin saturation was significantly lower than before treatment during the first 6 months, with no significant differences after that. The participants' estimated glomerular filtration rate and low-density lipoprotein cholesterol levels did not change significantly throughout the treatment. CONCLUSION: Daprodustat significantly increased hemoglobin levels was easily dose-adjusted and was relatively safe for continuous use over 1 year. It was also effective in patients who had responded inadequately to erythropoiesis-stimulating agents. Therefore, we conclude that daprodustat may be a useful treatment for post-transplant anemia.

Arteriovenous Fistula Closure Using a Simple Ligation Technique After Kidney Transplantation.

BACKGROUNDS: There are advantages and disadvantages with closure of an arteriovenous fistula (AVF) after kidney transplantation, but some cases require closure. The general procedure for closure is angioplasty with exposure of the anastomotic site, but this is often time-consuming and complicated. We have developed a simpler, less invasive, and shorter procedure for AVF closure, in which the anastomotic site itself is not peeled off and the outflow vein close to this site is ligated using 1-0 silk. In this study, we examined the utility of this procedure. METHODS: A retrospective case series study was conducted by review of electronic medical records of patients and surgeries. All patients (n = 52) who underwent AVF closure after kidney transplantation at our hospital between January 2008 and April 2021 were reviewed. Perioperative and long-term postoperative results were examined. This study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not from prisoners, or from those individuals who are coerced of paid. RESULTS: Simple ligation was performed for 46 patients (88.5%). The median time after renal transplantation was 40 (24.5-66.5) months. Median operative time and blood loss were 20 (12.2-30) minutes and 10 (5-15) mL, respectively. Two patients (4.3%) developed the aneurysm after the AVF closure using the simple ligation. CONCLUSION: The simple ligation technique had a relatively shorter operative time and only 2 cases had aneurysm formation. These results suggest that this technique is an option for closure of an AVF after kidney transplantation.

New-onset Kidney Biopsy-proven Membranous Nephropathy Induced End-stage Kidney Disease in a Living Donor: A Case Report.

Thirteen years after kidney donation, a 70-year-old man was referred to a nephrologist because of proteinuria. The serum creatinine, albumin, and urinary protein levels were 2.39 mg/dL, 3.0 g/dL, and 6.72 g/gCr, respectively. A kidney biopsy revealed thickening of the glomerular basement membrane with sub-epithelial deposits, suggesting membranous nephropathy. Considering the apparent interstitial fibrosis and diffuse glomerulosclerosis, supportive treatment was chosen. However, 11 months after the kidney biopsy, hemodialysis was required. The present case constitutes an important teaching point, as glomerular disease can occur in living donors and require careful and long-term medical checkup examinations.

Investigation of eligibility for adjuvant therapy from real-world data of patients with urothelial carcinoma undergoing radical cystectomy and radical nephroureterectomy.

OBJECTIVE: Adjuvant nivolumab prolonged disease-free survival compared with placebo in patients at high risk of recurrence following radical cystectomy or radical nephroureterectomy in the CheckMate 274 trial. However, the ideal eligibility criteria for adjuvant therapy in real-world clinical practice remain controversial. METHODS: We retrospectively analyzed clinical data of 409 patients who underwent radical cystectomy (n = 252) or radical nephroureterectomy (n = 157) and validated the risk of recurrence based on the classification used in the CheckMate 274 trial. We also investigated the impact of perioperative chemotherapy, lymph node dissection and pathological factors on prognosis. RESULTS: The median follow-up time was 37.5 and 32.1 months in bladder cancer and upper tract urothelial carcinoma, respectively. Among the high-risk patients based on CheckMate 274 trial, disease-free survival was considerably shorter for bladder cancer and upper tract urothelial carcinoma patients than for low-risk patients (hazard ratios: 4.132 and 7.101, respectively). The prevalence of adjuvant chemotherapy in high-risk patients was low (24 and 38% for bladder cancer and upper tract urothelial carcinoma, respectively). The extent of lymph node dissection in bladder cancer and presence of lymph node dissection in upper tract urothelial carcinoma did not affect prognosis. Cox proportional multivariate analysis revealed CheckMate 274-high-risk as a poor prognostic factor in bladder cancer and upper tract urothelial carcinoma. CONCLUSIONS: This study validated the risk classification for recurrence following radical cystectomy and radical nephroureterectomy using the CheckMate 274 criteria in real-world practice. Further research would help assess the degree of benefit obtained from adjuvant nivolumab.

Trend in overall survival from the start of first-line chemotherapy in patients with metastatic urothelial carcinoma.

New approaches involving immune checkpoint inhibitors and antibody-drug conjugates prolong overall survival in patients with metastatic urothelial carcinoma. However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve overall survival in patients with metastatic urothelial carcinoma over time remains unclear. Hence, we investigated the overall survival trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. We retrospectively evaluated 195 patients from a single center. They were treated with chemotherapy, pembrolizumab, or avelumab or enfortumab vedotin. The treatment was categorized into chemotherapy, pembrolizumab or avelumab/enfortumab vedotin period. The new agents prolonged overall survival from the start of first-line therapy. Furthermore, sequential treatment with these agents in real-world clinical practice has been reported to prolong overall survival. These study results will have major implications when a new first-line therapy is approved in the future.

DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis.

Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma (UC) induced by dimethylarsinic acid (DMAV), a major organic metabolite of arsenic. We performed genome-wide DNA methylation and microarray gene expression analyses of DMAV-induced rat UCs and the urothelium of rats treated for 4 weeks with DMAV. We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV. We also found that CPXM1 is aberrantly methylated and downregulated in human bladder cancers and human bladder cancer cells. Genes with aberrant DNA methylation and downregulated expression in DMAV-exposed bladder urothelium and in DMAV-induced UCs in rats, suggest that these alterations occurred in the early stages of arsenic-induced bladder carcinogenesis. Further study to evaluate the functions of these genes will advance our understanding of the role of aberrant DNA methylation in arsenic bladder carcinogenesis, and will also facilitate the identification of new therapeutic targets for arsenic-related bladder cancers.

Male Renal Transplant Recipients' Experiences From Their Wives' Pregnancy and Childbirth.

This study aimed to analyze male renal transplant recipients' experience with their partners' pregnancy and childbirth and to investigate their methods of nursing their condition. We performed semistructured interviews and collected data from 6 Japanese males who underwent a kidney transplant after their partner had given birth. The data were analyzed using the Qualitative Synthesis Method (KJ Method). The mean age of the participants at data collection was 40.3 ± 4.7 years, whereas it was 34.7 ± 5.8 years when the transplant was performed. The Qualitative Synthesis Method revealed 7 symbols related to the pregnancy and childbirth experience of the partners of male kidney transplant recipients. Males who received a kidney transplant struggled with severe renal disease before the transplant. They also experienced indecisiveness about whether they should go through with the transplant. However, their lives changed because of the transplant and having children. This situation resulted in a sense of responsibility and a reason to live robustly for the male kidney transplant recipients. Nevertheless, they faced distress as kidney transplant patients. Their wives supported them through this experience. They communicated to their children what they learned from the experience while effectively dealing with their condition. The improvement in their sexual function resulting from the transplant influenced their determination to get married. It is necessary to offer information about the recovery of fertility and the possibility of having a child when choosing renal replacement therapy, give explanations based on evidence, and construct a counseling system.

Analysis of Risk Factors for Infusion-Related Reactions Following Rituximab Administration in Patients with Desensitization before Renal Transplantation.

Infusion-related reactions (IRRs) are the major side effects of rituximab administration. Although several studies have reported predictive markers for IRRs in patients with malignancies, there are no such reports for patients without malignancies. Accordingly, we aimed to clarify the predictive markers for rituximab-induced IRRs in renal transplant recipients. This retrospective study included 116 inpatients aged ≥18 years who received an initial dose of 150 mg/m2 of rituximab for desensitization before renal transplantation with loxoprofen and diphenhydramine before rituximab infusion between June 2007 and February 2022. Overall, 45 patients were evaluated and 71 patients were excluded in this study. IRRs were observed in 12 (26.7%) patients. The proportion of men in the IRRs group was significantly higher than that in the non-IRRs group (p = 0.023). Additionally, body weight, body surface area (BSA), and body mass index (BMI) were significantly higher in the IRRs group than in the non-IRRs group (body weight, p = 0.0058; BSA, p = 0.0051; BMI, p = 0.017). Their cutoff values for predicting rituximab-induced IRRs, based on the receiver-operating characteristic curve, were 74.850 kg, 1.910 m2 and 24.164 kg/m2, respectively. In conclusion, the male sex, high actual body weight, BSA, and BMI may be new predictive markers for rituximab-induced IRRs in renal transplant recipients. Therefore, clinicians should carefully monitor patients who receive rituximab before renal transplantation and present with the predictive markers.

Recent advances in immune checkpoint inhibitors in the treatment of urothelial carcinoma: A review.

Treatment options for urothelial carcinoma were limited until the emergence of immune checkpoint inhibitors, and even now, the prognosis of metastatic disease is poor compared with the other two major genitourinary cancers, renal cell carcinoma and prostate cancer. Despite the increasing use of immune checkpoint inhibitors in the sequential treatment of urothelial carcinoma, conflicting results from similar randomized clinical trials call into question the efficacy of this treatment. In addition, physicians must be aware of the clinical characteristics of immune checkpoint inhibitors, including immune-related adverse events, pseudo- and hyperprogression. This review summarizes the conflicting results of recent clinical trials and provides insights into the role of immune checkpoint inhibitors in the treatment of urothelial carcinoma.

A Case of Bariatric Surgery for a Japanese Kidney Transplant Recipient With Diabetes Mellitus: A Case Report.

The patient, a 54-year-old woman, underwent a living donor kidney transplant at Osaka City University Hospital 7 years before the bariatric surgery. Her comorbidities were diabetes, sleep apnea, and severe obesity (weight 103 kg, body mass index [BMI] 36 kg/m2), and her diabetes was poorly controlled with an HbA1c of 8.5%. On admission, she weighed 99 kg, BMI was 34 kg/m2, Serum creatinine (S-Cre) was 1.54 mg/dL, and HbA1c was 7.1%. A laparoscopic sleeve gastrectomy was performed, and her weight decreased without complications during the perioperative period. She was discharged on postoperative day 28. Two months after surgery, her weight was 87 kg, BMI 30 kg/m2, S-Cre 1.34 mg/dL, HbA1c 6.7 %, renal function improved, urine protein decreased, and insulin dosage decreased dramatically. We report this valuable case because there are no reports of bariatric surgery in Japanese renal transplant recipients.

Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles (complete English translation of the Japanese version).

BACKGROUND: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients. METHODS: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. RESULTS: EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). CONCLUSIONS: KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.

Frailty and sarcopenia in older kidney transplant recipients: a cross-sectional study.

PURPOSE: The aging of the kidney transplant population is accelerating, and measures against geriatric syndromes including frailty and sarcopenia, which elevate the risk of needing long-term care and even death, are being considered important. Recently, both the frailty and sarcopenia criteria for Asians were revised based on various research reports and clinical experiences. The purpose of this study is twofold: firstly, to investigate the prevalence of frailty based on the revised Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Kihon Checklist (KCL) and that of sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) 2019 as well as the relationship between frailty and sarcopenia, and secondly, to determine the concurrent validity of the KCL with the revised J-CHScriteria in older kidney transplant recipients. METHODS: This study was a single-center cross-sectional investigation carried out on older kidney transplant recipients who visited our hospital from August 2017 to February 2019. The diagnosis of frailty was assessed using the revised J-CHS criteria and the KCL. The diagnosis of sarcopenia was made by low skeletal muscle mass and either low physical performance or low muscle strength based on the AWGS 2019. To examine the relationship between frailty and sarcopenia, categorical variables were compared using chi-squared test and continuous variables Mann-Whitney U test. Spearman's correlation analysis was used to investigate the correlation between the KCL score and the revised J-CHS score. The concurrent validity of the KCL for estimating frailty based on the revised J-CHS criteria was evaluated using the receiver operating characteristics (ROC) curve analysis. RESULTS: A total of 100 older kidney transplant recipients were enrolled in this study. The median age was 67, 63 (63%) were males, and the median time after transplant was 95 months. The prevalence of frailty based on the revised J-CHS criteria and the KCL, and sarcopenia based on the AWGS 2019 was 15%, and 19%, and 16% respectively. Sarcopenia was significantly associated with frailty based on the KCL (p = 0.016), while not with frailty based on the revised J-CHS criteria (p = 0.11). The KCL score significantly correlated with the revised J-CHS score (p < 0.001). The area under the ROC curve was 0.91. CONCLUSION: Frailty and sarcopenia are interrelated complex geriatric syndromes that are risk factors for adverse health outcomes. In older kidney transplant recipients, frailty and sarcopenia were highly prevalent and frequently co-existed. Furthermore, the KCL was verified as a useful tool for frailty screening in these patient. Easy identification of patients with frailty, which is reversible, can help clinicians institute appropriate corrective measures for kidney transplant recipients to improve transplant outcomes.

Kidney Transplantation After Renal Transcatheter Arterial Embolization for Cyst Infection in a Hemodialysis Patient With Autosomal Dominant Polycystic Kidney Disease: A Case Report.

A 31-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) required antibiotic therapy for repeated renal cyst infections. The patient was scheduled for a living donor renal transplant with her mother as the donor. Two months before surgery, the patient was admitted to the hospital due to a severe renal cyst infection that improved with antibiotic treatment and percutaneous drainage, but the scheduled surgery was postponed. Transcatheter arterial embolization (TAE) was performed to control repeated renal cyst infections. Seven months after TAE, the patient underwent living donor renal transplantation. The postoperative course was uneventful, and the patient was discharged from the hospital on immunosuppressive medication 26 days after surgery with no evidence of recurrent infection or deterioration of renal function. Thirty months after transplantation, there has been no recurrence of infection.

Irradiation plus myeloid-derived suppressor cell-targeted therapy for overcoming treatment resistance in immunologically cold urothelial carcinoma.

BACKGROUND: Radiotherapy (RT) has recently been highlighted as a partner of immune checkpoint inhibitors. The advantages of RT include activation of lymphocytes while it potentially recruits immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). This study aimed to investigate the mechanism of overcoming treatment resistance in immunologically cold tumours by combining RT and MDSC-targeted therapy. METHODS: The abscopal effects of irradiation were evaluated using MB49 and cisplatin-resistant MB49R mouse bladder cancer cells, with a focus on the frequency of immune cells and programmed cell death-ligand 1 (PD-L1) expression in a xenograft model. RESULTS: MB49R was immunologically cold compared to parental MB49 as indicated by the fewer CD8+ T cells and lower PD-L1 expression. Polymorphonuclear MDSCs increased in both MB49 and MB49R abscopal tumours, whereas the infiltration of CD8+ T cells increased only in MB49 but not in MB49R tumours. Interestingly, PD-L1 expression was not elevated in abscopal tumours. Finally, blocking MDSC in combination with RT remarkably reduced the growth of both MB49 and MB49R abscopal tumours regardless of the changes in the frequency of infiltrating CD8+ T cells. CONCLUSIONS: The combination of RT and MDSC-targeted therapy could overcome treatment resistance in immunologically cold tumours.

Reliability and Validity of the Japanese Version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale in Kidney Transplant Recipients.

A valid and reliable instrument that can measure adherence is needed to identify nonadherent patients and to improve adherence. However, there is no validated Japanese self-report instrument to evaluate adherence to immunosuppressive medications for transplant patients. The purpose of this study was to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS). Methods: We translated the BAASIS into Japanese and developed the Japanese version of the BAASIS (J-BAASIS) according to the International Society of Pharmacoeconomics and Outcomes Research task force guidelines. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias checklist. Results: A total of 106 kidney transplant recipients were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was found to be 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the medication event monitoring system, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the "medication compliance" subscale was 0.38 (P < 0.001). Conclusions: The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate adherence can help clinicians to identify medication nonadherence and institute appropriate corrective measures to improve transplant outcomes.

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

OBJECTIVES: Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy for advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to elucidate sequencing strategies of RAM and DOC following prior treatments, including immune checkpoint inhibitor (ICI), cytotoxic agent (CTx) alone, bevacizumab (BEV), and tyrosine kinase inhibitor (TKI). METHODS: We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx alone, BEV, and TKI, respectively. By tumor response to such treatments, the patients were further classified into "complete response (CR) + partial response (PR)," "stable disease," and "progressive disease" groups, respectively. We compared RAM and DOC efficacy among these groups. RESULTS: In total, 237 patients were registered. In the group with prior ICI, the objective response rate and disease control rate were significantly higher than those without prior ICI (p = 0.012 and 0.028, respectively), and the median progression-free survival (PFS) was also significantly longer (p = 0.027). There were no significant differences in PFS between the groups with and without CTx alone, BEV, and TKI. Multivariate analysis revealed that prior ICI was an independent factor associated with better PFS. Furthermore, the prior ICI group with CR + PR significantly prolonged PFS compared to the group without prior ICI (p = 0.013). CONCLUSION: RAM and DOC may be preferably administered after ICI, rather than after CTx alone, BEV, or TKI, and, furthermore, enhanced if the prior ICI has a favorable tumor response.

Outcomes of Chemoimmunotherapy Among Patients With Extensive-Stage Small Cell Lung Cancer According to Potential Clinical Trial Eligibility.

Importance: Chemoimmunotherapy is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). However, whether findings from pivotal trials can be extrapolated to the clinical practice setting remains unclear. Objective: To compare treatment outcome gaps following first-line chemoimmunotherapy for patients with ES-SCLC between those who met and did not meet the eligibility criteria used in previous clinical trials. Design, Setting, and Participants: A prospective cohort study was conducted from September 1, 2019, to September 30, 2020, at 32 hospitals in Japan, with at least 12 months of follow-up. Participants included consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as first-line therapy. Exposures: Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered trial-eligible. Main Outcomes and Measures: The primary outcome was 6-month progression-free survival. The secondary outcomes were differences in progression-free survival, overall survival, and safety according to whether key clinical trial eligibility criteria were met. Results: A total of 207 patients were analyzed (median age, 72 years; range, 46-87 years; 170 [82%] were male). Sixty-four patients (31%) were older adults (age ≥75 years), and most (184 [89%]) had an Eastern Cooperative Oncology Group performance status of 0 or 1. There were 132 (64%) trial-eligible patients. The 6-month progression-free survival rate for all patients was 38.8% (95% CI, 32.4%-45.7%). The median progression-free survival was 5.1 months in trial-eligible patients and 4.7 months in trial-ineligible patients (hazard ratio, 0.72; 95% CI, 0.53-0.97; P = .03). The proportion of patients who achieved disease control was 93% (118 of 127) in trial-eligible patients and 77% (55 of 71) in trial-ineligible patients (P = .002). The median overall survival was 15.8 months in trial-eligible patients and 13.1 months in trial-ineligible patients (hazard ratio, 0.73; 95% CI, 0.51-1.07; P = .10). The rate of severe adverse events was numerically higher among trial-ineligible patients than among trial-eligible patients (39% vs 27%; P = .07). Conclusions and Relevance: In this cohort study, the overall treatment outcome was comparable to that reported in pivotal clinical trials. However, treatment outcomes after chemoimmunotherapy might differ between trial-eligible and trial-ineligible patients. These findings suggest that trial-eligibility criteria may be useful in clinical practice, and further studies using data from clinical practice settings are required to inform regulatory approval and clinical decision-making.

Kidney transplantation for a transgender male.

The proportion of transgender people has increased over time, but few cases of transgender people undergoing kidney transplantation have been described. A 41-year-old transgender man (female-to-male) had chronic kidney disease caused by IgA nephropathy. He had received testosterone therapy and sex reassignment surgeries (chest masculinization surgery, metoidioplasty, scrotoplasty, and hysterectomy-ovariectomy) since he was 19 years due to gender incongruence. He underwent a preemptive living-donor kidney transplantation from his wife. His skeletal muscle mass was closer to that of a female than that of a male and suggested that eGFR should be calculated with the equation based on the gender assigned at birth (female) rather than the gender identity (male). Moreover, the recovery of kidney function due to successful kidney transplantation decreased serum gonadotropin levels, but normalization of his sex hormone profile was not achieved. Further accumulation of experience with kidney transplantation for transgender people is needed.