The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma.

Melanoma currently lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Circulating tumor DNA (ctDNA), originating from tumor cells and detectable in plasma, has emerged as a possible biomarker in patients with metastatic melanoma. In this retrospective, single-center study, we collected 129 plasma samples from 79 patients with stage IIIB-IV melanoma as determined by the American Joint Committee on Cancer (AJCC, 8th edition). For the determination of ctDNA levels, we used eight different assays of droplet digital polymerase chain reaction (ddPCR) to detect the most common hotspot mutations in the BRAF and NRAS genes. The aim of the study was to investigate the association of the detectability of ctDNA at a non-prespecified time point in a patient's treatment with tumor progression, and to correlate ctDNA with commonly used biomarkers (protein S100, LDH, and CRP). Patients with detectable ctDNA progressed more frequently in PET-CT within 12 months than those without detectable ctDNA. Detectability of ctDNA was associated with shorter OS in univariate and multivariate analyses. ctDNA was detectable in a statistically significantly larger proportion of patients with distant metastases (79%) than in patients with no distant metastases or only intracranial metastases (32%). Elevated protein S100 and CRP correlated better with detectable ctDNA than LDH. This study supports the potential of ctDNA as a prognostic biomarker in patients with metastatic melanoma. However, additional prospective longitudinal studies with quantitative assessments of ctDNA are necessary to investigate the limitations and strengths of ctDNA as a biomarker.

Low Plasma Sphingomyelin Levels Show a Weak Association with Poor Neurological Outcome in Cardiac Arrest Patients: Results from the Prospective, Observational COMMUNICATE Trial.

There is interest in novel blood markers to improve risk stratification in patients presenting with cardiac arrest. We assessed associations of different plasma sphingomyelin concentrations and neurological outcome in patients with cardiac arrest. In this prospective observational study, adult patients with cardiac arrest were included upon admission to the intensive care unit (ICU). We studied associations of admission plasma levels of 15 different sphingomyelin species with neurological outcome at hospital discharge (primary endpoint) defined by the modified Rankin Scale by the calculation of univariable and multivariable logistic regression models adjusted for age, gender, and clinical shock markers. We included 290 patients (72% males, median age 65 years) with 162 (56%) having poor neurological outcome at hospital discharge. The three sphingomyelin species SM C24:0, SM(OH) C22:1, and SM(OH) C24:1 were significantly lower in patients with poor neurological outcome compared to patients with favorable outcome with areas under the curve (AUC) of 0.58, 0.59, and 0.59. SM(OH) C24:1 was independently associated with poor neurological outcome in a fully-adjusted regression model (adjusted odds ratio per log-transformed unit increase in SM(OH) C24:1 blood level 0.18, 95% CI 0.04 to 0.87, p=0.033). Results were similar for 1-year mortality. Low admission sphingomyelin levels showed a weak association with poor neurological outcome in patients after cardiac arrest. If validated in future studies, a better understanding of biological sphingomyelin function during cardiac arrest may help to further advance the therapeutic approach and risk stratification in this vulnerable patient group.

Depression and anxiety in relatives of out-of-hospital cardiac arrest patients: Results of a prospective observational study.

PURPOSE: Relatives of patients admitted to the intensive care unit (ICU) with out-of-hospital cardiac arrest (OHCA) may suffer from adverse psychological outcomes. We assessed prevalence and risk factors for depression and anxiety in such relatives 90 days after ICU admission. MATERIALS AND METHODS: This study included consecutive relatives of OHCA patients admitted to the ICU of University Hospital in Basel, Switzerland. Relatives were interviewed upon admission regarding psychosocial risk factors and satisfaction with communication. Symptoms of depression and anxiety were assessed by Hospital Anxiety and Depression Scale (HADS) 90 days after inclusion. RESULTS: Of 101 included relatives, 17% and 13% of relatives reported symptoms of depression and anxiety, respectively. Witnessing cardiopulmonary resuscitation was associated with depression (gender- and age-adjusted odds ratio [OR] 6.71; 95%CI 1.27 to 35.34; p = .025). Satisfaction with information and decision-making was associated with lower risk of depression (adjusted OR 0.95; 95%CI 0.91 to 0.99; p = .013). Unemployment (adjusted OR 10.42; 95%CI 1.18 to 92.35; p = .035) and lower perceived health status were associated with anxiety (adjusted OR 0.93; 95%CI 0.87 to 0.99; p = .025). CONCLUSIONS: Many relatives of OHCA patients report symptoms of depression and anxiety after 90 days. Improving initial care and communication may help to reduce these risks.