Objective:To determine if neurofilament light (NfL), glial fibrillary acidic protein (GFAp), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.Methods:Patients with TBI (n=162) and controls (n=68) were prospectively enrolled between 2009–2018. Of the 162 patients, 102 underwent repeated serum, functional outcome, brain MRI volumetry, and DTI assessments at 30, 90, and 180 days, and 1, 2, 3, 4, and 5 years after TBI.Results:At enrolment, patients with TBI had increased serum NfL compared to controls (p<0.0001). Serum NfL decreased over the course of five years, but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with Area Under the Receiver-Operating Characteristic Curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrolment, serum GFAp was elevated in TBI patients compared to controls (p<0.001). GFAp showed a biphasic release in serum, with levels decreasing during the first six months of injury, whereafter increased over the subsequent study visits. The highest AUROC for GFAp was measured at 30 days distinguishing moderate and severe TBI patients from controls (both 0.89). Serum tau and UCH-L1 showed weak associations to TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.Conclusions:Serum NfL shows greater diagnostic and prognostic utility than GFAp, tau, and UCH-L1 for subacute and chronic TBI.Classification of Evidence:This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.

Objective:To determine if serum neurofilament light (NfL) correlates with cerebrospinal fluid (CSF) NfL, TBI diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI).Methods:Participants were prospectively enrolled in Sweden and the United States between 2011-2019. The Swedish cohort included 45 hockey players with acute concussion (AC) sampled at six days, 31 repetitive concussion (RC) with persistent post-concussive symptoms (PCS) assessed with paired CSF and serum (median, 1.3 years after concussion), 28 preseason controls, and 14 non-athletic controls. Our second cohort included 230 clinic-based participants (162 with TBI and 68 controls. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n=30), 90 (n=48), and 180 (n=59) days, and 1 (n=84), 2 (n=57), 3 (n=46), 4 (n=38), and 5 (n=29) years after injury.Results:In athletes with paired specimens, CSF and serum NfL were correlated (r=0.71, p<0.0001). CSF and serum NfL distinguished players with PCS >1-year from PCS ≤1-year (Area Under the Receiver-Operating Characteristic Curve [AUROC], 0.81 and 0.80). The AUROC for PCS >1-year vs preseason controls were 0.97. In the clinic-based cohort, NfL at enrolment distinguished patients with mild vs moderate vs severe TBI (p<0.001 and p=0.048). Serum NfL decreased over the course of five years (ß=–0.09 log pg/mL, p<0.0001), but remained significantly elevated compared to controls. Serum NfL correlated with measures of functional outcome, MRI brain atrophy, and DTI estimates of TAI.Conclusions:Serum NfL shows promise as a biomarker for acute and repetitive sports-related concussion and patients with subacute and chronic TBI.Classification of Evidence:This study provides Class III evidence that increased concentrations of NfL distinguish TBI from controls.

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Purpose Catheter-associated bacteriuria (CAB) with transurethral catheters is almost inevitable. Suprapubic catheters (SPCs) are widely considered to decrease the risk of CAB. However, SPCs are implants similarly prone to microbial biofilm formation. The spectrum of colonising pathogens has not been investigated. The aim of this prospective study was: (1) to assess the diversity of microbial suprapubic catheter colonisation (MSPCC), (2) to identify risk factors and (3) to investigate its association with CAB and catheter-associated urinary tract infection (CA-UTI). Methods A total of 218 SPCs from 112 patients were studied. Urine specimens were obtained after device replacement or removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex, age, indwelling time, and underlying disease were recorded. Results Sonicate-fluid culture (SFC) detected MSPCC in 95 %. Increasing indwelling time correlated with MSPCC (p \ 0.05). Negative SFC was more frequent when antibiotic prophylaxis was applied at time of catheter placement (15 vs. 2 %, p \ 0.05). Most commonly isolated were Enterobacteriaceae (45.8 %), followed by Enterococcus spp. (25.7 %) and Pseudomonas aeruginosa (10.3 %). CAB and CA-UTI were observed in 95 and 11 %, respectively. Conclusions This study provides the first analysis of MSPCC. Indwelling time increases, whereas antibiotic prophylaxis decreases the risk of MSPCC. The spectrum of pathogens is comparable to the one obtained from urethral catheter biofilms. Urine specimens could not demonstrate the microbial diversity of MSPCC. SPCs are not preferable to urethral catheters to reduce CAB. Whether the risk of CA-UTI could be minimised by SPCs remains to be clarified.

Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (p = 2.45 × 10−5), rs6983267 (8q24) (p = 4.48 × 10−7), and rs10993994 (10q11) (p = 1.40 × 10−3) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10−9) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility.

Using a contingent of 62 patients of which 46 were BPH and 16 were PCa, we report definitive concentrations of uPA and PAI-1 in tumour tissue extracts and show that the uPA/PAI-1 ratio emerges as a candidate marker to distinguish between BPH and PCa.

Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale–Extended (GOS-E) score (p’s < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.