ABSTRACT
Leptomeningeal melanoma metastases (LMM) are associated with poor survival. Diagnosis is based on clinical presentation, brain MRI and cerebrospinal fluid (CSF) analysis. Inconclusive findings at initial presentation can delay treatment. In this single-center case series, detection of BRAFV600- and NRASQ61-mutant cell-free tumor DNA (cfDNA) in CSF was evaluated as a complementary diagnostic biomarker. In 12 patients with clinical suspicion of LMM, a retrospective analysis of MRI, CSF cytology and cfDNA analysis on 1 mL of CSF using the Idylla® platform was carried out. Nine patients displayed MRI abnormalities suggesting LMM. CSF analysis identified malignant cells in three patients (including one without MRI abnormalities). BRAFV600- or NRASQ61-mutant cfDNA was detected in CSF of nine patients (eight with and one without MRI abnormalities; all patients with positive CSF cytology). Subsequent follow-up confirmed LMM in all patients with positive and in one patient with a negative CSF cfDNA analysis (sensitivity 81.8%; specificity 100%). Our findings suggest that analyzing BRAFV600- and NRASQ61-mutant cfDNA in CSF using the Idylla® platform holds promise as a sensitive and specific complementary diagnostic biomarker for LMM, particularly in case of inconsistency between imaging and CSF cytology. The 110-min analysis can facilitate urgent treatment decisions.
ABSTRACT
BACKGROUND: Infective endocarditis (IE) is a life-threatening disease. Despite advancements in diagnostic methods, the initial clinical presentation of IE remains a valuable asset. Therefore, the impact of clinical presentation on outcomes and its association with microorganisms and IE localization were assessed herein. METHODS: This retrospective study included 183 patients (age 68.9 ± 14.2 years old, 68.9% men) with definite IE at two tertiary care hospitals in Belgium. Demographic data, medical history, clinical presentation, blood cultures, imaging data and outcomes were recorded. RESULTS: In-hospital mortality rate was 22.4%. Sixty (32.8%) patients developed embolism, 42 (23%) shock, and 103 (56.3%) underwent surgery during hospitalization. Shock at admission predicted embolism during hospitalization (odds ratio [OR] 2.631, 95% confidence interval [CI] 1.119-6.184, p = 0.027). A new cardiac murmur at admission predicted cardiac surgery (OR 1.949, 95% CI 1.007- -3.774, p = 0.048). Methicillin resistant Staphylococcus aureus predicted in-hospital mortality and shock (p = 0.005, OR 6.945, 95% CI 1.774-27.192 and p = 0.015, OR 4.691, 95% CI 1.348-16.322, respectively). Mitral valve and aortic valve IE predicted in-hospital death (p = 0.039, OR 2.258, 95% CI 1.043-4.888) and embolism (p = 0.017, OR 2.328, 95% CI 1.163-4.659), respectively. CONCLUSIONS: In this retrospective study, shock at admission independently predicted embolism during hospitalization in IE patients. Moreover, a new cardiac murmur at admission predicted the need for cardiac surgery. This emphasizes the importance of a comprehensive initial clinical evaluation in combination with imaging and microbiological data, in order to identify high-risk IE patients early.
