Lethal Immune Myocarditis and Myasthenia Gravis Due to Anti-PD-1 Treatment for a Bladder Cancer Patient: A Case Report and Possible Treatment Inspiration.

Immune checkpoint inhibitors (ICI) have become a new hope for many patients with advanced cancer by blocking tumor immune escape. Bladder cancer is a common malignant tumor of the urinary tract epithelium that often relapses and metastasizes after surgery, chemotherapy, and radiotherapy. Immunotherapy has dramatically improved patient survival rates and clinical benefits as a new, potentially effective therapy. However, avoidance of various immune-related adverse events (irAEs) remains an implausible idea. ICI-induced myocarditis is different from viral myocarditis, and mortality is still high with the current treatment. We report the case of an 82-year-old female patient with ICI-induced fulminant myocarditis and myasthenia gravis. Although she actively accepted the current mainstream treatment for immune-related myocarditis and myasthenia, she died of heart and respiratory failure. Analyzing and reporting the patient's disease development process and the changes in related indicators may help peers gain a deeper understanding of immune-related adverse events and reduce the mortality of immune-related myocarditis.

Integrated bioinformatics analysis identifies a Ferroptosis-related gene signature as prognosis model and potential therapeutic target of bladder cancer.

Background: Bladder cancer (BLCA) is one of the most prevalent cancers worldwide. Ferroptosis is a newly discovered form of non-apoptotic cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRGs) in BLCA has not yet been well studied. Method and materials: In this study, we performed consensus clustering based on FRGS and categorized BLCA patients into 2 clusters (C1 and C2). Immune cell infiltration score and immune score for each sample were computed using the CIBERSORT and ESTIMATE methods. Functional annotation of differentially expressed genes were performed by Gene Ontology (GO) and KEGG pathway enrichment analysis. Protein expression validation were confirmed in Human Protein Atlas. Gene expression validation were performed by qPCR in human bladder cancer cell lines lysis samples. Result: C2 had a significant survival advantage and higher immune infiltration levels than C1. Additionally, C2 showed substantially higher expression levels of immune checkpoint markers than C1. According to the Cox and LASSO regression analyses, a novel ferroptosis-related prognostic signature was developed to predict the prognosis of BLCA effectively. High-risk and low-risk groups were divided according to risk scores. Kaplan-Meier survival analyses showed that the high-risk group had a shorter overall survival than the low-risk group throughout the cohort. Furthermore, a nomogram combining risk score and clinical features was developed. Finally, SLC39A7 was identified as a potential target in bladder cancer. Discussion: In conclusion, we identified two ferroptosis-clusters with different prognoses using consensus clustering in BLCA. We also developed a ferroptosis-related prognostic signature and nomogram, which could indicate the outcome.

Malakoplakia of urinary bladde: 3 cases reports and review.

OBJECTIVE: This study aims to explore the clinical diagnosis and treatment methods of bladder malakoplakia (MUB) to enhance the understanding of the disease. METHODS: A retrospective analysis of the diagnosis and treatment processes of three cases of MUB treated in our department was conducted. Relevant literature from both domestic and international sources was reviewed to provide a comprehensive analysis. RESULTS: All three patients underwent transurethral resection of bladder lesions combined with antibiotic therapy, and two of them received transurethral instillation of gemcitabine. There were two cases with two recurrences each, and one case with four recurrences, with the latter also concurrently presenting with unilateral ureteral malakoplakia. Postoperative pathology confirmed MUB in all three cases. Close follow-up revealed no significant recurrence in the patients. CONCLUSION: The effective diagnosis rate is increased by conducting multiple deep, repetitive, and randomly selected live tissue examinations. The definitive diagnosis of MUB relies on pathological histological examination. Treatment involving a combination of antibiotics and transurethral resection of bladder lesions proves to be effective. Exploring the use of bladder instillation of gemcitabine widens the spectrum of MUB treatment methods.

Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1.

Tumor-derived exosomes are highly correlated with tumor progression and angiogenesis. This study was designed to probe the role of tumor-derived exosomal miR-1247-3p in mediating the angiogenesis in bladder cancer. Exosomes isolation from the culture medium of normal or bladder cancer cell lines was performed using a differential centrifugation method. miR-1247-3p expression in exosomes and cells was detected by quantitative real-time PCR (qRT-PCR). The effect of exosomes on the angiogenesis of human umbilical vein endothelial cells (HUVECs) was assessed using cell counting kit-8 (CCK-8), transwell and tube formation assays. The interaction between miR-1247-3p and forkhead box protein O1 (FOXO1) was studied using luciferase reporter and RNA pull down assays. Exosomes were successfully isolated from T24, UM-UC-3, and SV-HUC-1 cells, as confirmed by corresponding identifications. Functional experiments revealed that exosomes derived from T24 and UM-UC-3 cells significantly enhanced the abilities of proliferation, migration, angiogenesis, and vascular endothelial-derived growth factor (VEGF) secretion in HUVECs. miR-1247-3p was highly expressed in exosomes derived from T24 and UM-UC-3 cells, and exosomes derived from miR-1247-3p inhibitor-transfected cells reduced HUVEC viability, migration, tube formation, and VEGF level. FOXO1 was confirmed as a direct target of miR-1247-3p. Rescue assays suggested that the effect of miR-1247-3p inhibition on the viability, migration, and angiogenesis of HUVECs was partly abrogated by the knockdown of FOXO1. Our data suggest that miR-1247-3p is up-regulated in tumor-derived exosomes, thereby inhibiting FOXO1 expression and facilitating angiogenesis in bladder cancer.

Assessment of the Contrast-Enhanced Ultrasound in Percutaneous Nephrolithotomy for the Treatment of Patients with Nondilated Collecting System.

Purpose: To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in percutaneous nephrolithotomy (PCNL) for kidney stone patients without hydronephrosis. Methods: Patients with nondilated collecting system kidney stones who underwent PCNL between October 2018 and December 2019 at our hospital were enrolled in this study. Patients who met the inclusion criteria were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided PCNL group. The operation results of the two groups were compared, including the number of attempts for effective puncture, duration to effective puncture, stone clearance rate, blood loss, postoperative complications, and hospital stay. Results: Fifty-six patients with a nondilated collecting system who underwent PCNL for 60 kidneys were included in this study, including 4 patients who underwent bilateral PCNL due to bilateral renal stones. There were 30 kidneys in each group. All patients successfully underwent PCNL. The CEUS-guided PCNL group had more accurate punctures, with a higher effective rate of one puncture and shorter puncture time. There was no statistically significant difference in stone clearance rate between the two groups. Four cases of double channels were established in the conventional US-guided PCNL group, while there was only one case in the CEUS-guided PCNL group. In the CEUS-guided PCNL group, most cases (96.7%, 29/30) had no or only mild complications, which were significantly better than the conventional US-guided PCNL group (76.7%, 23/30). The mean postoperative hemoglobin loss in the CEUS-guided PCNL group was 9.5 (range 1-25) g/L, which was significantly lower than 15.5 (range 5-52) g/L in the conventional US-guided PCNL group. Conclusion: The CEUS technique can improve visibility of the nondilated renal collecting system, facilitate selection of suitable calix, and identify renal calix fornix. It also benefits needle placement in patients with a nondilated collecting system.

Ceftazidime-related urinary calculi in a young boy: a case report.

Certain drugs can cause kidney stones but as far as we are aware, ceftazidime-related urinary calculi have not been previously reported. We report here a case of an 8-year-old boy who developed hydronephrosis secondary to urinary calculi after receiving ceftazidime 2.0 g by intravenous infusion daily for two weeks. Previously, his left kidney showed no signs of disease. A retrograde double J ureteral stent was inserted, ceftazidime terminated, fluids increased and urine alkalised. On day 25, the patient showed no signs of kidney stones or hydronephrosis. Clinicians should be aware of the possibility of ceftazidime-related urinary calculi particularly if patients are receiving long-term treatment.