IntroductionIn FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone reduced the risk of cardiovascular (CV) and kidney events versus placebo in patients with type 2 diabetes and chronic kidney disease, on optimized renin–angiotensin system blockade. This FIDELITY post hoc subanalysis explores the efficacy and safety of finerenone in Asian patients.MethodsFor this subanalysis, efficacy outcomes included a CV composite (time to CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decrease from baseline over ≥4 weeks or renal death) outcome. Change in urine albumin-to-creatinine ratio (UACR) from baseline to month 4 and eGFR slopes were also assessed. All outcomes were assessed by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and UACR (<300 and ≥300 mg/g) subgroups. Safety outcomes were reported as treatment-emergent adverse events, including laboratory evaluations for hyperkalemia.ResultsIn the Asian subpopulation, 1412/2858 (49.4%) received finerenone. Finerenone-treated Asian patients had a lower risk of the composite CV outcome (hazard ratio [HR]=0.90; 95% confidence interval [CI], 0.70–1.15), and nominally significant reductions in the risk of ≥57% and ≥40% eGFR composite kidney outcomes (HR=0.64; 95% CI, 0.50–0.82 and HR=0.67; 95% CI, 0.56–0.80, respectively) versus those receiving placebo, irrespective of baseline eGFR and UACR. Data on change of eGFR from baseline over the course of the trials indicated that chronic kidney disease progression in Asian patients was slower with finerenone versus placebo. Overall safety outcomes were balanced between both populations. Serum potassium values with finerenone were similar between the Asian and non-Asian subpopulations (>5.5 mmol/L: 15.6% versus 17.1%; >6.0 mmol/L: 4.6% versus 2.9%, respectively), while hyperkalemia leading to permanent treatment discontinuation with finerenone was low in both populations (Asian: 1.5%; non-Asian: 1.8%).ConclusionFinerenone reduced the risk of CV and kidney events and demonstrated a well-tolerated safety profile in the FIDELITY Asian subpopulation.

Introduction: Although immune checkpoint inhibitor-associated myocarditis is relatively rare, it has the highest mortality rate among all immune-related adverse events, at 30–50%. Case Presentation: We encountered a case of advanced renal cancer in which immune checkpoint inhibitor-associated myocarditis was confirmed on autopsy. A 78-year-old man was diagnosed with a left renal tumor secondary to hematuria. A tumor biopsy was performed, and the tumor was diagnosed as cT4N0M1 clear cell renal carcinoma, which was classified as poor risk by the International mRCC Database Consortium. Combination therapy with pembrolizumab and axitinib was initiated. One month later, the patient developed anorexia, dizziness, and fatigue, which were judged to be adverse events due to systemic therapy, and the patient was admitted to the hospital urgently. After admission, the patient experienced a sudden drop in blood pressure and loss of consciousness and was referred to a cardiologist for treatment. Blood tests showed elevated brain‐type natriuretic peptide levels, but echocardiography showed good cardiac function. However, soon thereafter, the patient developed tachycardia, and echocardiography revealed a significant decline in systolic function, leading to the diagnosis of immune checkpoint inhibitor-associated myocarditis. Despite intensive care in the cardiac high-care unit and steroid administration, the patient died. An autopsy revealed necrotic changes in the myocardium, loss of myocardial cells, and severe lymphocyte infiltration, leading to a diagnosis of inhibitor-associated myocarditis. Conclusion: Delay in the initiation of treatment is considered a risk factor for poor prognosis, and the administration of high-dose steroids within 24 h of onset contributes to a better outcome. Herein, we discuss the pathology, diagnosis, and treatment of immune checkpoint inhibitor-associated myocarditis.

IntroductionIn FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone reduced the risk of cardiovascular (CV) and kidney events versus placebo in patients with type 2 diabetes and chronic kidney disease, on optimized renin–angiotensin system blockade. This FIDELITY post hoc subanalysis explores the efficacy and safety of finerenone in Asian patients.MethodsFor this subanalysis, efficacy outcomes included a CV composite (time to CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decrease from baseline over ≥4 weeks or renal death) outcome. Change in urine albumin-to-creatinine ratio (UACR) from baseline to month 4 and eGFR slopes were also assessed. All outcomes were assessed by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and UACR (<300 and ≥300 mg/g) subgroups. Safety outcomes were reported as treatment-emergent adverse events, including laboratory evaluations for hyperkalemia.ResultsIn the Asian subpopulation, 1412/2858 (49.4%) received finerenone. Finerenone-treated Asian patients had a lower risk of the composite CV outcome (hazard ratio [HR]=0.90; 95% confidence interval [CI], 0.70–1.15), and nominally significant reductions in the risk of ≥57% and ≥40% eGFR composite kidney outcomes (HR=0.64; 95% CI, 0.50–0.82 and HR=0.67; 95% CI, 0.56–0.80, respectively) versus those receiving placebo, irrespective of baseline eGFR and UACR. Data on change of eGFR from baseline over the course of the trials indicated that chronic kidney disease progression in Asian patients was slower with finerenone versus placebo. Overall safety outcomes were balanced between both populations. Serum potassium values with finerenone were similar between the Asian and non-Asian subpopulations (>5.5 mmol/L: 15.6% versus 17.1%; >6.0 mmol/L: 4.6% versus 2.9%, respectively), while hyperkalemia leading to permanent treatment discontinuation with finerenone was low in both populations (Asian: 1.5%; non-Asian: 1.8%).ConclusionFinerenone reduced the risk of CV and kidney events and demonstrated a well-tolerated safety profile in the FIDELITY Asian subpopulation.

IntroductionGastroesophageal reflux disease (GERD) is diagnosed based on bothersome symptoms, such as heartburn, and the presence of mucosal breaks endoscopically. Treatments that suppress gastric acid, such as proton pump inhibitor (PPI) and vonoprazan, are frequently administered. Several studies reported regarding the safety and side effects of long-term PPI administration, including an association with gastric polyps. We report a case of maintained symptom resolution and significantly shrank gastric polyps by performing step-down therapy, which is minimal acid-suppressing treatment.Case PresentationA female patient in her 60s taking proton pump inhibitor (PPI) for reflux esophagitis for >10 years. An upper gastrointestinal endoscopy revealed two gastric polyps measuring 20 mm and 10 mm. She was referred to our hospital for resection, but narrow-band imaging revealed a non-neoplastic lesion. PPI was discontinued and step-down therapy using vonoprazan was performed. During the treatment, a lifestyle guidance app (Muneyake PRO) was used to record daily heartburn symptoms, oral medication status, and daily life status. She was worried that her symptoms would worsen due to discontinuation, but she gained her understanding when the use of the app to monitor her symptoms was explained. The app was useful for understanding the progress of symptoms and the status of oral medication. Step-down therapy was performed only twice after PPI discontinuation, and symptoms have not worsened and follow-up endoscopy revealed significant gastric polyp shrinkage.ConclusionWe experienced a case in which minimal acid-suppression treatment; step-down therapy using vonoprazan resulted in GERD symptom control and significant gastric polyp shrinkage.

IntroductionGastroesophageal reflux disease (GERD) is diagnosed based on bothersome symptoms, such as heartburn, and the presence of mucosal breaks endoscopically. Treatments that suppress gastric acid, such as proton pump inhibitor (PPI) and vonoprazan, are frequently administered. Several studies reported regarding the safety and side effects of long-term PPI administration, including an association with gastric polyps. We report a case of maintained symptom resolution and significantly shrank gastric polyps by performing step-down therapy, which is minimal acid-suppressing treatment.Case PresentationA female patient in her 60s taking proton pump inhibitor (PPI) for reflux esophagitis for >10 years. An upper gastrointestinal endoscopy revealed two gastric polyps measuring 20 mm and 10 mm. She was referred to our hospital for resection, but narrow-band imaging revealed a non-neoplastic lesion. PPI was discontinued and step-down therapy using vonoprazan was performed. During the treatment, a lifestyle guidance app (Muneyake PRO) was used to record daily heartburn symptoms, oral medication status, and daily life status. She was worried that her symptoms would worsen due to discontinuation, but she gained her understanding when the use of the app to monitor her symptoms was explained. The app was useful for understanding the progress of symptoms and the status of oral medication. Step-down therapy was performed only twice after PPI discontinuation, and symptoms have not worsened and follow-up endoscopy revealed significant gastric polyp shrinkage.ConclusionWe experienced a case in which minimal acid-suppression treatment; step-down therapy using vonoprazan resulted in GERD symptom control and significant gastric polyp shrinkage.

Enfortumab vedotin (EV) has been approved for the treatment of many types of cancer, and its use is still expanding. It is an essential drug used as a standard treatment for advanced and metastatic urothelial carcinoma, but is known to cause various adverse events. We report a patient with metastatic urothelial carcinoma who experienced multiple adverse events associated with diabetic ketoacidosis (DKA) during EV treatment. The onset of DKA during EV treatment has been reported to be associated with poor prognosis. Although strict management was required in the intensive care unit, we were able to save his life. We report on the pathogenesis and management of drug-induced diabetic ketoacidosis caused by EV based on our case and a literature review.

Enfortumab vedotin (EV) has been approved for the treatment of many types of cancer, and its use is still expanding. It is an essential drug used as a standard treatment for advanced and metastatic urothelial carcinoma, but is known to cause various adverse events. We report a patient with metastatic urothelial carcinoma who experienced multiple adverse events associated with diabetic ketoacidosis (DKA) during EV treatment. The onset of DKA during EV treatment has been reported to be associated with poor prognosis. Although strict management was required in the intensive care unit, we were able to save his life. We report on the pathogenesis and management of drug-induced diabetic ketoacidosis caused by EV based on our case and a literature review.

Introduction: Although immune checkpoint inhibitor-associated myocarditis is relatively rare, it has the highest mortality rate among all immune-related adverse events, at 30–50%. Case Presentation: We encountered a case of advanced renal cancer in which immune checkpoint inhibitor-associated myocarditis was confirmed on autopsy. A 78-year-old man was diagnosed with a left renal tumor secondary to hematuria. A tumor biopsy was performed, and the tumor was diagnosed as cT4N0M1 clear cell renal carcinoma, which was classified as poor risk by the International mRCC Database Consortium. Combination therapy with pembrolizumab and axitinib was initiated. One month later, the patient developed anorexia, dizziness, and fatigue, which were judged to be adverse events due to systemic therapy, and the patient was admitted to the hospital urgently. After admission, the patient experienced a sudden drop in blood pressure and loss of consciousness and was referred to a cardiologist for treatment. Blood tests showed elevated brain‐type natriuretic peptide levels, but echocardiography showed good cardiac function. However, soon thereafter, the patient developed tachycardia, and echocardiography revealed a significant decline in systolic function, leading to the diagnosis of immune checkpoint inhibitor-associated myocarditis. Despite intensive care in the cardiac high-care unit and steroid administration, the patient died. An autopsy revealed necrotic changes in the myocardium, loss of myocardial cells, and severe lymphocyte infiltration, leading to a diagnosis of inhibitor-associated myocarditis. Conclusion: Delay in the initiation of treatment is considered a risk factor for poor prognosis, and the administration of high-dose steroids within 24 h of onset contributes to a better outcome. Herein, we discuss the pathology, diagnosis, and treatment of immune checkpoint inhibitor-associated myocarditis.

Although the response to combination therapy has been reported in patients with brain metastases from advanced renal cancer, treatment-related cerebral hemorrhage has not been adequately studied. The CheckMate 9ER clinical trial of nivolumab and cabozantinib excluded patients with brain metastases. Therefore, the associated treatment outcomes in these patients with brain metastases are unclear. Herein, we report a case of bleeding from brain metastases in a patient with advanced renal cancer after gamma knife combination therapy with nivolumab and cabozantinib. Fortunately, the cerebral hemorrhage of the patient was alleviated by conservative treatment. Despite treatment interruption, the metastatic lesions reduced in size, and treatment was gradually resumed. In this case study, we report the risk of cerebral hemorrhage in combination therapy for brain metastasis cases, how to manage hemorrhage cases, and their prognosis.

Although the response to combination therapy has been reported in patients with brain metastases from advanced renal cancer, treatment-related cerebral hemorrhage has not been adequately studied. The CheckMate 9ER clinical trial of nivolumab and cabozantinib excluded patients with brain metastases. Therefore, the associated treatment outcomes in these patients with brain metastases are unclear. Herein, we report a case of bleeding from brain metastases in a patient with advanced renal cancer after gamma knife combination therapy with nivolumab and cabozantinib. Fortunately, the cerebral hemorrhage of the patient was alleviated by conservative treatment. Despite treatment interruption, the metastatic lesions reduced in size, and treatment was gradually resumed. In this case study, we report the risk of cerebral hemorrhage in combination therapy for brain metastasis cases, how to manage hemorrhage cases, and their prognosis.