Mitochondrial Fraction of Circulating Cell-Free DNA as an Indicator of Human Pathology.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management.

Factors affecting the timing of recovery from whiplash neck injuries: study of a cohort of 134 patients pursuing litigation.

INTRODUCTION: A cohort of 134 patients presenting in medico-legal practice with whiplash neck injury following a motor vehicle accident was studied prospectively by personal interviewing. MATERIALS AND METHODS: Injury- and patient-related factors with possible influence to the timing of recovery were analysed with univariate and multivariate statistical methods. RESULTS: Logistic regression showed significant association between high physical demand patient occupation and recovery within 6 months from injury (P = 0.036, coefficient 1.5, odds ratio 4.47) while initiation of physiotherapy treatment was associated with prolongation of symptoms for more than 6 months following injury (P < 0.001, coefficient -2.6, odds ratio 0.08). An association between development of arm pain (P = 0.01), upper limb numbness or paraesthesia (P = 0.03) and bilateral trapezius pain (P = 0.04) and persistence of whiplash-related symptoms was also observed. These findings must be taken into account in evaluation and treatment of patients with acute whiplash injuries pursuing litigation.