Jeremy Yuen-Chun Teoh

Outcomes of traumatic brain injury in Hong Kong: Validation with the TRISS, CRASH, and IMPACT models

We aimed to test prognostic models (the Trauma Injury Severity Score, International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury, and Corticosteroid Randomisation After Significant Head Injury models) for 14-day mortality, 6-month mortality, and 6-month unfavorable outcome in a cohort of trauma patients with traumatic brain injury (TBI) in Hong Kong. We analyzed 661 patients with significant TBI treated in a regional trauma centre in Hong Kong over a 3-year period. The discriminatory power of the models was assessed as the area under the receiver operating characteristic curve. One-sample t-tests were used to compare actual outcomes in the cohort against predicted outcomes. All three prognostic models were shown to have good discriminatory power and no significant systemic over-estimation or under-estimation. In conclusion, all three predictive models are applicable to eligible TBI patients in Hong Kong. These predictive models can be utilized to audit TBI management outcomes for trauma service development in the future.

Genomewide bisulfite sequencing reveals the origin and time-dependent fragmentation of urinary cfDNA

Urinary cell-free (cf) DNA holds great potential as a completely noninvasive form of liquid biopsy. Knowledge of the composition of cfDNA by tissue of origin is useful for guiding its clinical uses. We conducted a global survey of urinary cfDNA composition using genomewide bisulfite sequencing. While previous studies focused on detecting cfDNA from a single source at a time, genomewide tissue specific methylation signatures allow us to simultaneously deduce the proportional contribution from each contributing tissue. The proportional contributions derived from methylation deconvolution are highly correlated with those calculated using allograft-derived donor-specific genetic markers in the urine of hematopoetic stem cell and renal transplant recipients. We found a large variation of proportional contributions from different tissues. We then assessed if cfDNA undergoes time-dependent fragmentation in urine by conducting in vitro incubation experiments. In vitro incubation at 37°C showed that urinary cfDNA concentration decreased under first order kinetics with a half-life of 2.6 to 5.1h. This is reflected in parallel by a decrease in the proportion of long fragments and increase in amplitude of 10bp periodicity seen in the cfDNA size profile. This global survey of urinary cfDNA has deepened our understanding of the composition, degradation and variation of cfDNA in the urinary tract and has laid a foundation for the use of genomewide urinary cfDNA sequencing as a molecular diagnostics tool.

Intracranial aneurysm size responsible for spontaneous subarachnoid haemorrhage

Abstract Introduction. It has been theorised that the relationship between smaller body size and smaller ruptured intracranial aneurysms in Asians indirectly supports the treatment of small, unruptured intracranial aneurysms. There has also been uncertainty regarding whether the progress that has been made in neuroimaging allows for better detection of smaller ruptured intracranial saccular aneurysms. Therefore, we conducted this systemic review of ruptured intracranial saccular aneurysm sizes according to region and time. Material and Methods. Computerised MEDLINE and PubMed searches of the literature for population-based studies of ruptured intracranial saccular aneurysms were carried out from 1 January 1980 to 1 March 2011. Statistical analyses were generated using SPSS for Windows, Version 15.0 (SPSS Inc., Chicago, IL) and Comprehensive MetaAnalysis 2.0 for Windows (Biostat, Englewood, NJ). The results of the meta-analyses are presented with 95% confidence intervals (CIs). Results. Six eligible population- or hospital-based studies were analysed. The percentage of ruptured intracranial aneurysms measuring less than 5 mm was 28.4% (95% CI: 18.1% to 41.6%, I2 = 98%). The percentage of ruptured intracranial aneurysms measuring less than 10 mm was 76.7% (95% CI: 69.2% to 82.9%, I2 = 89%). A higher proportion of patients with ruptured intracranial aneurysms of less than 5 mm was found in Asia compared to other regions. Similarly, a higher proportion of patients with ruptured intracranial aneurysms of less than 10 mm was found in Asia compared to other regions. Conclusions. The present findings suggest that ruptured intracranial aneurysms are smaller in Asians and should be confirmed in future prospective international multi-centre registries to assess ethnicity. Whether these findings support treating smaller unruptured intracranial aneurysms in Asians should be investigated.

Androgen deprivation therapy, diabetes and poor physical performance status increase fracture risk in Chinese men treated for prostate cancer

Abstract We investigated the fracture risk after androgen deprivation therapy (ADT) for prostate cancer in the Chinese population. All Chinese prostate cancer patients who were treated primarily by radical prostatectomy or radiotherapy, with or without further ADT, from year 2000 to 2009 were reviewed. We compared the fracture risk in patients who were given ADT (ADT group) with those who were not given any ADT (non-ADT group). Potential risk factors including age, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease and performance status were reviewed. The fracture risk was analyzed with Kaplan–Meier and multivariate Cox regression analyses. Our cohort consisted of 200 patients in the non-ADT group and 252 patients in the ADT group. The ADT group was shown to have higher fracture risk (p = 0.036) upon Kaplan–Meier analysis. Upon multivariate Cox regression analyses, diabetes mellitus (HR 4.39, 95% CI 1.08–17.83, p = 0.039), poor performance status (HR 3.14, 95% CI 1.24–8.00, p = 0.016) and the use of ADT (HR 4.89, 95% CI 1.03–23.17, p = 0.045) were associated with increased fracture risk. In conclusion, the fracture risk should be considered while deciding on ADT in Chinese men, especially in diabetic patients with poor performance status.

Risk of new-onset diabetes after androgen deprivation therapy for prostate cancer in the Asian population

The associations of androgen deprivation therapy (ADT) with its adverse events in the Asian population remained largely unknown. We investigated the risk of new‐onset diabetes mellitus (DM) after ADT for prostate cancer in the Asian population.

Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong

OBJECTIVE Previous reports on the risk of stroke after androgen deprivation therapy for prostate cancer were largely based on Caucasians. We investigated the risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. METHODS All Chinese prostate cancer patients who were treated primarily with radical prostatectomy or radiotherapy, with (androgen deprivation therapy group) or without (non-androgen deprivation therapy group) further androgen deprivation therapy, at our hospital from year 2000-09 were reviewed. Potential risk factors of ischemic stroke including age, baseline prostate-specific antigen, Gleason score, clinical T stage, hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, history of stroke, use of androgen deprivation therapy and duration of androgen deprivation therapy were reviewed. The risk of ischemic stroke after androgen deprivation therapy was analyzed with Kaplan-Meier and multivariate Cox regression analyses. RESULTS A total of 452 patients were included, consisting of 200 patients in the non-androgen deprivation therapy group and 252 patients in the androgen deprivation therapy group. The androgen deprivation therapy group appeared to have increased risk of ischemic stroke when compared with the non-androgen deprivation therapy group (P = 0.063) upon Kaplan-Meier analysis. Upon multivariate Cox regression analyses, older age (hazard ratio 1.13, 95% confidence interval 1.04-1.22, P = 0.003), hyperlipidemia (hazard ratio 4.61, 95% confidence interval 2.01-10.54, P < 0.001) and the use of androgen deprivation therapy (hazard ratio 3.32, 95% confidence interval 1.14-9.67, P = 0.028) were associated with increased risk of ischemic stroke. CONCLUSIONS There was increased risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. The risk of ischemic stroke should be considered while deciding on androgen deprivation therapy, especially in older patients with known history of hyperlipidemia.

Nuclear receptor profiling in prostatospheroids and castration-resistant prostate cancer

Nuclear receptors (NRs), which belong to a superfamily of transcription factors and consist of a total of 48 members in humans, govern the expression of genes involved in a board range of developmental, reproductive, metabolic and immunological programs. Given the significant importance of androgen receptor and a few known NRs in the progression of prostate cancer, we surveyed the expression profiles of the entire NR superfamily in three-dimensional cultured prostatospheroids derived from different prostate cancer cell lines and a tumor xenograft model of castration-resistant prostate cancer VCaP-CRPC by quantitative real-time RT-PCR. Our results revealed that prostatospheroids and castration-relapse VCaP-CRPC xenografts, both contained enriched populations of prostate cancer stem/progenitor-like cells (PCSCs), displayed distinct expression patterns of NRs. Intriguingly, most of these differentially expressed NRs were orphan NRs and showed upregulation. Pairwise analysis identified five orphan NRs (including RORβ, TLX, COUP-TFII, NURR1 and LRH-1) that showed common upregulation in both mRNA and protein levels in the prostatospheroids and castration-relapse VCaP-CRPC xenografts, and overexpression of these orphan NRs could increase cancer stem cell marker expressions and enhance spheroid formation capacity in prostate cancer cells, suggesting that these orphan NRs might perform positive roles in the growth regulation of PCSCs and castration-resistant prostate cancer. Together, our NR expression dataset not only revealed the distinct physiologic status and regulatory roles governed by the networks of specific NRs but also some of these identified orphan NRs could be the potential therapeutic targets for PCSCs or castration-resistant prostate cancer.

“Aging males” symptoms and general health of adult males: a cross-sectional study

Abstract A cross-sectional study was conducted to explore the prevalence and severity of health-related complaints perceived by adult males of Hong Kong by using the Hong Kong Traditional Chinese versions of the Aging males’ symptoms (AMS) scale and the 5-dimensional and 3-level European Quality of life (EQ-5D-3L) questionnaire. A total of 825 adult males aged 40 years or above were surveyed, and observed that 80% of the population was living with little-to-mild levels of aging symptoms with mean total scores ranged between 26.02 ± 7.91 and 32.99 ± 7.91 in different age groups. Such symptoms were correlated with age, especially for the somato-vegetative and sexual symptoms. The most severe AMS symptoms were observed in the oldest age group at 70 years or above, with 76%, 34% and 70% living with moderate-to-severe levels of somato-vegetative, psychological and sexual symptoms, respectively. The result was highly correlated with the EQ-5D-3L questionnaire. Secondly, the Hong Kong Aging males’ symptoms (AMS) scale was shown to have good reliability with test–retest coefficient at 0.79 (ranged 0.66–0.87) and Cronbach’s alpha coefficient at 0.88 (ranged 0.70–0.84). In summary, the population of Hong Kong male adults was commonly living with little-to-mild levels of aging symptoms, whereas their severity was correlated with age.

The effect of renal cortical thickness on the treatment outcomes of kidney stones treated with shockwave lithotripsy.

Purpose Because the shock wave passes through various body tissues before reaching the stone, stone composition may affect the treatment efficacy of shock wave lithotripsy (SWL). We investigated the effect of various tissue components along the shock wave path on the success of SWL. Materials and Methods From October 2008 to August 2010, a total of 206 patients with kidney stones sized 5 to 20 mm were prospectively recruited for a study of the factors that affect the outcome of treatment with a Sonolith Vision lithotripter. Successful SWL was defined as either stone-free status or residual fragments <4 mm at 12 weeks. Logistic regression analysis was performed to assess the factors that predicted treatment outcomes. Potential predictors included the patients age, shock wave delivery rate, stone volume (SV), mean stone density (MSD), skin-to-stone distance (SSD), and the mean thickness of the three main components along the shock wave path: renal cortical thickness (KT), muscle thickness (MT), and soft-tissue thickness (ST). Results The mean age of the patients was 53.8 years (range, 25-82 years). The overall treatment success rate after one session of SWL was 43.2%. The mean KT, MT, and ST were 26.9, 16.6, and 40.8 mm, respectively. The logistic regression results showed that a slower shock wave delivery rate, smaller SV, a lower MSD, and a thicker KT were found to be significant predictors for successful SWL. SSD, MT, and ST were not predictors of successful treatment. Conclusions Among the main tissue components along the shock wave path, a thicker KT was a favorable factor for successful SWL after adjustment for SV, MSD, and the shock wave delivery rate.

Secondary hemorrhage after bipolar transurethral resection and vaporization of prostate

Introduction: We evaluated the factors associated with secondary hemorrhage after bipolar transurethral resection of prostate (TURP) and vaporization of prostate. Materials and Methods: The perioperative data of patients undergoing endoscopic surgery for benign prostatic hyperplasia (BPH) were prospectively collected. Procedures involved included bipolar TURP, bipolar vaporization of prostate, and hybrid bipolar TURP/vaporization of prostate. Secondary hemorrhage was defined as bleeding between 48 h and 30 days postsurgery requiring hospital attendance with or without admission. Risk factors for secondary hemorrhage were analyzed. Results: From 2010 to 2013, 316 patients underwent bipolar surgery for BPH. Bipolar TURP accounted for 48.1% of the procedures, bipolar vaporization accounted for 20.3% of the procedures, and the rest were hybrid TURP/vaporization of prostate. Among this cohort of patients, fifty patients had secondary hemorrhage with hospital attendance. Consumption of platelet aggregation inhibitors (PAIs) was found to be associated with secondary hemorrhage (P < 0.0005). Age, prostate volume, operation type, the use of 5-alpha reductase inhibitors, and being with a urethral catheter before operation were not found to be statistically significant risk factors for secondary hemorrhage. Conclusions: Secondary hemorrhage after bipolar surgery for BPH is a common event. Consumption of PAI is a risk factor for such complication.