Avacopan's potential to decrease MPO-ANCA titres concurrent with ameliorated activity in ANCA-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies.

Prognostic Factors for Resolution Delay of Lower Urinary Tract Symptoms in Patients with Prostate Cancer after Low-Dose-Rate Brachytherapy.

Urinary storage symptoms after low-dose-rate brachytherapy (LDR-BT) with iodine-125 have been noted to be less likely to improve to baseline compared to voiding symptoms. This study aimed to evaluate the chronological changes in the overactive bladder symptom score (OABSS) and the time-to-resolution of OABSS in patients undergoing LDR-BT. Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were enrolled. The OABSS was evaluated before and after LDR-BT. Patients were divided into the OABSS resolution and resolution delay groups, and the association between OABSS resolution delay and clinicopathological covariates was evaluated. In total, 237 patients were enrolled in this study, with a median follow-up of 88.3 months. The OABSS in both groups worsened at 3 months following operation and gradually recovered at 9 months; however, the OABSS in the resolution delay group tended to worsen again after that. In the multivariate analysis, preoperative OABSS and the change from baseline to maximal OABSS were associated with OABSS resolution. To our knowledge, this is the first study to evaluate the delayed resolution of OABSS after LDR-BT in patients with prostate cancer. A low baseline OABSS and significant changes in the OABSS from baseline were independent predictors of delayed OABSS resolution.

In-Hospital Cancer Mortality Prediction by Multimodal Learning of Non-English Clinical Texts.

Predicting important outcomes in patients with complex medical conditions using multimodal electronic medical records remains challenge. We trained a machine learning model to predict the inpatient prognosis of cancer patients using EMR data with Japanese clinical text records, which has been considered difficult due to its high context. We confirmed high accuracy of the mortality prediction model using clinical text in addition to other clinical data, suggesting applicability of this method to cancer.

Renal tamponade in a patient with hydronephrosis-related Page kidney.

A 48-year-old woman presented with hyperreninemic hypertension and renal dysfunction and was diagnosed with hydronephrosis-related Page kidney. The pathophysiology was "renal tamponade", in which the kidney was compressed by the renal pelvis and Gerota's fascia, resulting in intrarenal microvascular ischemia. Ureteral stent placement promptly improved the hyperreninemic hypertension and renal dysfunction, and additional perirenal fluid drainage gradually improved these conditions. These observations indicated the following three points. First, renal compression-induced renin-angiotensin-aldosterone system upregulation plays an important role in the pathogenesis of Page kidney. Second, physicians should consider perirenal fluid drainage as a therapeutic option in addition to ureteral stenting in patients with hydronephrosis-related Page kidney. Third, bilateral perirenal subcapsular hematomas in this case could be caused by hydronephrosis. Hydronephrosis-induced intrarenal pressure elevation possibly caused chronic perirenal subcapsular hemorrhage at the vulnerable sites of the renal cortex and peeling of the renal capsule from the cortex, resulting in the bilateral massive subcapsular hematomas and Page kidney.

The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

Chronological changes of lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer using SpaceOAR® system.

Background: The aim of this study is to investigate chronological changes of lower urinary tract symptoms (LUTS) in patients with prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) followed by the insertion of SpaceOAR® system (SpaceOAR). Methods: In this retrospective study, 483 patients with localized prostate cancer underwent LDR-BT at the Gifu University Hospital between August 2004 and December 2020. SpaceOAR was inserted in 30 patients after LDR-BT (SpaceOAR group), and 453 patients received LDR-BT alone (non-SpaceOAR group). The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), quality of life due to urinary symptoms (IPSS-QOL), and uroflowmetry (UFM), including maximum flow rate (Qmax), voided volume, and post-voided residual urine (PVR), were evaluated before LDR-BT, and at 1, 3, 6, 9, and 12 months after LDR-BT. The outcomes were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values and those of covariates in relation to UFM. Results: The IPSS, OABSS, IPSS-QOL, Qmax, and voided volume were not significantly associated with either group. According to the PVR interaction effect, the insertion of SpaceOAR was significantly affected by chronological changes in PVR (P = 0.001). Three months after LDR-BT, PVR in the SpaceOAR group was significantly higher than that in the non-SpaceOAR group (49.8 mL vs. 30.5 mL; P = 0.002). Conclusion: SpaceOAR use may temporally increase PVR; however, IPSS, OABSS, IPSS-QOL, Qmax, and voided volume were not significantly associated with LUTS before and after LDR-BT. The combination of LDR-BT and SpaceOAR may be acceptable for treating patients with prostate cancer regarding the chronological changes in LUTS after brachytherapy.

Efficacy and Safety of Cabozantinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

Seroma as a Rare Complication of Autologous Arteriovenous Fistula Creation in the Forearm of a Hemodialysis Patient: A Case Report.

Aim of the study: Seromas are rarely reported as complications of autologous arteriovenous fistula creation. Case description: An 89-year-old woman was hospitalized for hemodialysis and underwent an autologous arteriovenous fistula creation in the forearm. During cephalic vein expansion using a heparinized saline solution, leakage occurred. A suture was placed to control the leakage, and a Penrose drain was inserted. Serosanguineous drainage ceased on postoperative day two; however, a seroma occurred approximately two weeks after the surgery. Follow-up ultrasonography revealed no growth tendency; therefore, excision and aspiration were unnecessary. Conclusion: This seroma was associated with postoperative dead space, surgical technique, and patient clinical status. Sufficient preoperative ultrasonographic vascular mapping is required to avoid inappropriate handling of veins and prevent seroma formation. Postoperative ultrasonographic follow-up is recommended due to the future risk of fistula dysfunction and infection associated with seroma enlargement, which may necessitate surgical seroma excision.

Diabetes Mellitus as a Predictive Factor for Urinary Tract Infection for Patients Treated with Kidney Transplantation.

Background and Objectives: We aimed to investigate the rate of incidence and risk factors of post-transplant urinary tract infection (UTI) in patients receiving kidney transplantation (KT) at our institution. Materials and Methods: A retrospective cohort study was carried out on patients who underwent KT for end-stage kidney disease (ESKD) from January 2008 to December 2021 at Gifu University Hospital. UTI was defined as the existence of bacterial and/or fungal infection in urine with ≥105 colony-forming units/mL, with or without urinary and/or systemic symptoms of UTI. Patients were divided into two groups: those with UTI after KT (UTI group) and those without UTI (non-UTI group). The primary endpoint of this study was the relationship between covariates and UTI after KT. Results: Two hundred and forty patients with ESKD received KT at Gifu University Hospital. Thirty-four participants developed UTI after surgery, and the most common pathogen was Escherichia coli. At the end of the follow-up, graft loss was observed in six patients (2.5%), independent of UTI episodes. In the multivariate analysis, diabetes mellitus (DM) was statistically associated with post-transplant UTI in kidney transplant recipients. Conclusions: Preoperative serum glucose control in patients with DM may have a crucial role in preventing UTI and preserving renal function after KT.

Effectiveness and Safety of Molecular-Targeted Therapy after Nivolumab Plus Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.

Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma after Discontinuing Pembrolizumab as a Second-Line Treatment: A Retrospective Multicenter Real-World Cohort Study.

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.