Prostate Cancer: Early Detection and Assessing Clinical Risk Using Deep Machine Learning of High Dimensional Peripheral Blood Flow Cytometric Phenotyping Data

Detecting the presence of prostate cancer (PCa) and distinguishing low- or intermediate-risk disease from high-risk disease early, and without the need for potentially unnecessary invasive biopsies remains a significant clinical challenge. The aim of this study is to determine whether the T and B cell phenotypic features which we have previously identified as being able to distinguish between benign prostate disease and PCa in asymptomatic men having Prostate-Specific Antigen (PSA) levels < 20 ng/ml can also be used to detect the presence and clinical risk of PCa in a larger cohort of patients whose PSA levels ranged between 3 and 2617 ng/ml. The peripheral blood of 130 asymptomatic men having elevated Prostate-Specific Antigen (PSA) levels was immune profiled using multiparametric whole blood flow cytometry. Of these men, 42 were subsequently diagnosed as having benign prostate disease and 88 as having PCa on biopsy-based evidence. We built a bidirectional Long Short-Term Memory Deep Neural Network (biLSTM) model for detecting the presence of PCa in men which combined the previously-identified phenotypic features (CD8+CD45RA-CD27-CD28- (CD8+ Effector Memory cells), CD4+CD45RA-CD27-CD28- (CD4+ Effector Memory cells), CD4+CD45RA+CD27-CD28- (CD4+ Terminally Differentiated Effector Memory Cells re-expressing CD45RA), CD3-CD19+ (B cells), CD3+CD56+CD8+CD4+ (NKT cells) with Age. The performance of the PCa presence ‘detection’ model was: Acc: 86.79 ( ± 0.10), Sensitivity: 82.78% (± 0.15); Specificity: 95.83% (± 0.11) on the test set (test set that was not used during training and validation); AUC: 89.31% (± 0.07), ORP-FPR: 7.50% (± 0.20), ORP-TPR: 84.44% (± 0.14). A second biLSTM ‘risk’ model combined the immunophenotypic features with PSA to predict whether a patient with PCa has high-risk disease (defined by the D’Amico Risk Classification) achieved the following: Acc: 94.90% (± 6.29), Sensitivity: 92% (± 21.39); Specificity: 96.11 (± 0.00); AUC: 94.06% (± 10.69), ORP-FPR: 3.89% (± 0.00), ORP-TPR: 92% (± 21.39). The ORP-FPR for predicting the presence of PCa when combining FC+PSA was lower than that of PSA alone. This study demonstrates that AI approaches based on peripheral blood phenotyping profiles can distinguish between benign prostate disease and PCa and predict clinical risk in asymptomatic men having elevated PSA levels.

Effects of Intended Scapular Posterior Tilt Motion on Trapezius Muscle Electromyography Activity

The intended scapular motion is a strategy to strengthen the lower trapezius (LT). However, few studies have explored the effects of the intended scapular posterior tilt motion on selective LT activation. Thus, the present study investigated the effect of the intended scapular posterior tilt on the electromyography (EMG) activity of trapezius muscles during prone shoulder horizontal abduction (PSHA). Eighteen asymptomatic men performed three types of PSHA: (1) preferred PSHA, (2) PSHA with the intended scapular posterior tilt, and (3) PSHA with the intended scapular posterior tilt and trunk extension. EMG activity of the upper trapezius (UT), middle trapezius (MT), and LT were measured during PSHAs. Scapular posterior tilt angle, with and without the intended scapular posterior tilt, were measured using inclinometer. The results indicated that LT muscle activity increased when scapular posterior tilt was applied with and without trunk extension (14–16%), compared to the preferred condition, during PSHA (p < 0.05). However, the addition of trunk extension to PSHA with the intended scapular posterior tilt increased the UT muscle activity (28%) and the UT/LT (29%) and UT/MT (31%) ratios (p < 0.05). The scapular posterior tilt angle was higher (15%) when applying the intended scapular posterior tilt (p = 0.020). These findings suggest that the intended scapular posterior tilt may be a useful strategy for selective LT muscle activation.

Trichomonas vaginalis detection in urogenital specimens from symptomatic and asymptomatic men and women using the cobas TV/MG test

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas® T. vaginalis /Myocoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of commercially available NAATs and culture using urogenital specimens. A total of 2,064 subjects (984 men and 1,080 women, 940 [45.5%] symptomatic, 1124 [54.5%] asymptomatic) were evaluable. In women, sensitivity ranged from 99.4% (95% confidence interval [CI] 96.8–99.9%) using vaginal samples to 94.7 (95% CI 90.2–97.2%) in PreservCyt samples. Specificity ranged from 98.9–96.8% (95% CI 95.4–97.8%). In men, the cobas TV/MG assay was 100% sensitive for the detection of T. vaginalis in both male urine samples and meatal swabs, with specificity of 98.4% in urine samples and 92.5% in meatal swabs. The cobas TV/MG is a suitable diagnostic test for the detection of T.vaginalis, which could support public health efforts towards infection control and complement existing STI programs.

Non-classical pathogens as causative agents of proctitis in men who have sex with men

Background This study aimed to identify enteric and sexually acquired rectal pathogens, other than chlamydia and gonorrhoea, associated with symptomatic proctitis in MSM. Methods Anorectal swab samples were obtained from MSM presenting with rectal symptoms and a clinical diagnosis of proctitis at the Melbourne Sexual Health Centre between January-2017 and March-2019. Samples that tested positive for Neisseria gonorrhoeae and Chlamydia trachomatis were excluded. As a comparison group, anorectal samples were also obtained from MSM not reporting symptoms of proctitis between November-2018 and February-2019. Samples from both groups were tested for 15 viral, bacterial and protozoal enteric pathogens using PCR. Results Anorectal samples from 499 men with symptomatic proctitis and 506 asymptomatic men were analysed. Age, HIV status and PrEP use did not differ between men with proctitis and asymptomatic men. Treponema pallidum was more common in men with proctitis (risk difference [RD]=3.6%; 95% CI:2.0-5.2%). Most men with anorectal T. pallidum presented with painful anal primary infections. Shigella spp. was more common among men with proctitis compared to asymptomatic men (RD=1.8%; 95%CI:0.1-3.5%). Most men with Shigella did not report diarrhoea. Mycoplasma genitalium was more common in men with proctitis (RD=4.3%; 95%CI:1.1-7.5%). HSV-1 (RD=10.1%; 95%CI:6.8-13.3%) and HSV-2 (RD=7.2%; 95%CI:4.5-10.0%) were more common with proctitis. Conclusions Testing for T. pallidum, Shigella and HSV should be considered in MSM presenting with symptomatic proctitis. These data provide support for M. genitalium as a significant cause of proctitis. A comprehensive diagnostic evaluation is required for MSM with proctitis.

Culture obtained from urethral swab of asymptomatic men who screen positive for Neisseria gonorrhoeae by urine nucleic acid amplification testing

BackgroundIn a previous study of men attending Melbourne Sexual Health Centre who had Neisseria gonorrhoeae detected by urine Aptima Combo 2 (AC2) testing, 11% were asymptomatic. This study aimed to determine whether N. gonorrhoeae can be cultured from asymptomatic men screening positive for N. gonorrhoeae by nucleic acid amplification testing (NAAT) of urine.MethodsBetween 1 July 2017 and 31 March 2019, all men attending Melbourne Sexual Health Centre were tested for N. gonorrhoeae by AC2 testing of urine whether urethral symptoms were reported or not. NAAT-positive men were recalled and a urethral swab performed for gonococcal culture using modified Thayer-Martin media with determination of minimum inhibitory concentrations (MICs) by agar dilution.ResultsThere were 1001 cases (860 individuals) positive for N. gonorrhoeae by urine AC2: 892 (89%) reported urethral symptoms; 109 (11%) did not. Twenty-five asymptomatic cases were excluded because of antibiotic use at or following screening. Of the remaining 84 asymptomatic men, 41 (49%) had a urethral swab performed a median of 5 days after screening. Twenty-one men had urethral discharge at the return visit, 11 of whom reported the discharge at the return visit. Of the 41 men who were swabbed, 31 (76%; 95% CI 60% to 88%) were culture positive for N. gonorrhoeae. Among the 21 men who subsequently developed discharge, 19 (90%; 95% CI 70% to 99%) were culture positive. Among the 20 men who remained asymptomatic, 12 (60%; 95% CI 36% to 81%) were culture positive. MIC profiles were obtained from all isolates.ConclusionsGonorrhoea was isolated in most but not all asymptomatic men screening positive for N. gonorrhoeae by urine NAAT. Clinicians should consider performing urethral culture in such men to ensure optimal surveillance for antimicrobial resistance. Isolation of N. gonorrhoeae by culture in men without discharge indicates these are true infections with viable organisms.