Improved Efficiency of the Clinical Diagnostic Criteria for Familial Hypercholesterolemia in Children: A Comparison of the Japan Atherosclerosis Society Guidelines of 2017 and 2022.

AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. METHODS: From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. RESULTS: Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. CONCLUSION: The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.

Myocarditis as an immune-related adverse event following treatment with ipilimumab and nivolumab combination therapy for metastatic renal cell carcinoma: a case report.

BACKGROUND: Immune checkpoint inhibitors are new immunotherapy drugs globally used for many malignancies, including renal cell carcinoma. Myocarditis as an immune-related adverse event is rare but highly fatal, suggesting that its frequency may be higher than reported. This paper describes a case of myocarditis that developed asymptomatically following ipilimumab and nivolumab combination therapy for renal cell carcinoma. CASE PRESENTATION: A 71-year-old Asian man who presented to hospital with fever, fatigue, and weight loss of approximately 10 kg within 2 months was diagnosed with Xp.11.2 translocation renal cell carcinoma. Computed tomography revealed multiple lung masses, mediastinal lymph node enlargement, and a level II tumor thrombus reaching the inferior vena cava (cT3bN0M1; International Metastatic Renal Cell Carcinoma Database Consortium, poor risk). Ipilimumab/nivolumab combination therapy was started as induction therapy. The patient experienced acute interstitial nephritis as an immune-related adverse event after treatment initiation; however, a good response to steroid therapy was observed. The antitumor effect of the immunotherapy was notable. Although he experienced pulmonary embolism, it seemed asymptomatic and harmless; thus, a second infusion was introduced. From the eighth day, he demonstrated rapidly worsening cardiogenic shock with asymptomatic electrocardiographic changes and drastic drop in cardiac biomarkers, and a diagnosis of myocarditis as an immune-related adverse event was made. Although immediate methylprednisolone mini-pulse therapy followed by tapered prednisolone prevented mortality, extensive myocardial fibrosis with marked ejection fraction decline persisted as a sequela. Consequently, follow-up without treatment was instituted; however, much of the tumor response initially observed was maintained over several months. CONCLUSION: Physicians treating patients with immune checkpoint inhibitors should be aware of their potentially life-threatening cardiotoxic effects. This study emphasized the importance of a high index of suspicion, prompt diagnosis, and early intervention in patients who present with cardiac abnormalities and possible myocarditis after receiving immunotherapy.

False-Positive 18F-FDG and 18F-Fluorothymidine Uptake in a Patient With Round Atelectasis.

A 64-year-old man with no significant medical history demonstrated a right lower lobe opacity on routine chest radiography. Transaxial CT showed a round, well-circumscribed, pleural mass with comet-tail sign in the right lower lobe and pleural thickening with pleural effusion. F-FDG PET/CT showed hypermetabolic activity in the mass (SUVmax 9.61). F-fluorothymidine PET/CT also showed mild increased uptake in the mass (SUVmax 3.26). Lung biopsy and follow-up CT scan revealed round atelectasis.