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INTRODUCTION: Both short and long PFNA are employed to treat intertrochanteric fractures. Controversy exists in the choice between the two nails as each implant has specific characteristics and theoretical advantages. This retrospective study seeks to examine the operative complication rates and clinical outcomes of short versus long (Proximal Femoral Nail Antirotation) PFNA in the treatment of intertrochanteric fractures. MATERIALS AND METHODS: Between July 2011 and February 2015, 155 patients underwent PFNA insertion. The decision on whether to use a short or long PFNA nail, locked or unlocked, was determined by the attending operating surgeon. Visual Analogue Pain Score (VAS) Harris Hip Scores (HHS), Short-form 36 Health Questionnaire (SF-36) and Parker Mobility Scores (PMS) were collected at six weeks, six months and one year post-operatively. RESULTS: A total of 137 (88.4%) patients were successfully followed-up. Forty-two (30.7%) patients received a short PFNA. The patients were similar in baseline characteristics of age, gender, and comorbidities. Operative time was significantly longer in the short PFNA group (62 ±17 mins) versus the long PFNA group (56±17). While the patients in both groups achieved improvement in all outcome measures, there was no significant difference between the groups in terms of HHS (61.0 ±16.0 vs 63.0 ±16.8, p=0.443), PMS (2.3±1.5 vs 2.7±2.1, p=0.545) and VAS (1.7±2.9 vs 1.8 ±2.2 p=0.454). There were 3 (7.1%) and 7 (7.4%) complications in the short versus long PFNA group, respectively. CONCLUSIOM: Both short and long PFNA had similar clinical outcomes and complication rates in the treatment of intertrochanteric fractures in an Asian population.

Introduction: The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer., Methods: All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale., Results: Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D'amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively., Conclusion: SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

Background: Problematic Instagram use (PIGU), a specific type of internet addiction, is prevalent among adolescents and young adults. In certain instances, Instagram acts as a platform for exhibiting photos of risk-taking behavior that the subjects with PIGU upload to gain likes as a surrogate for gaining peer acceptance and popularity., Aims: The primary objective was to evaluate whether addiction-specific cues compared with neutral cues, i.e., negative emotional valence cues vs. positive emotional valence cues, would elicit activation of the dopaminergic reward network (i.e., precuneus, nucleus accumbens, and amygdala) and consecutive deactivation of the executive control network [i.e., medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC)], in the PIGU subjects., Method: An fMRI cue-induced reactivity study was performed using negative emotional valence, positive emotional valence, and truly neutral cues, using Instagram themes. Thirty subjects were divided into PIGU and healthy control (HC) groups, based on a set of diagnostic criteria using behavioral tests, including the Modified Instagram Addiction Test (IGAT), to assess the severity of PIGU. In-scanner recordings of the subjects' responses to the images and regional activity of the neural addiction pathways were recorded., Results: Negative emotional valence > positive emotional valence cues elicited increased activations in the precuneus in the PIGU group. A negative and moderate correlation was observed between PSC at the right mPFC with the IGAT scores of the PIGU subjects when corrected for multiple comparisons [ r = -0.777, ( p < 0.004, two-tailed)]., Conclusion: Addiction-specific Instagram-themed cues identify the neurobiological underpinnings of Instagram addiction. Activations of the dopaminergic reward system and deactivation of the executive control network indicate converging neuropathological pathways between Instagram addiction and other types of addictions., (Copyright © 2020 Nasser, Sharifat, Rashid, Hamid, Rahim, Loh, Ching, Hoo, Ismail, Tyagi, Mohammad and Suppiah.)

Objective: Problematic smartphone use (PSU) is the development of pathological dependence at the expense of performing activities of daily living, thus having negative health and psychological impact on the users. Previous PSU studies focused on medical students and little is known regarding its effect on students undergoing other courses. The objective of this study is to identify the pattern of smartphone usage and determine the psychological factors affecting PSU among undergraduate students in Malaysia and compare the pattern among students from different fields of study., Method: A prospective cross-sectional study was conducted using the validated Smartphone Addiction Scale-Malay version (SAS-M) questionnaire. One-way ANOVA was used to determine the correlation between the PSU among the students categorised by their ethnicity, hand dominance and by their field of study. MLR analysis was applied to predict PSU based on socio-demographic data, usage patterns, psychological factors and fields of study., Results: A total of 1060 students completed the questionnaire. Most students had some degree of problematic usage of the smartphone. Students used smartphones predominantly to access SNAs, namely Instagram. Longer duration on the smartphone per day, younger age at first using a smartphone and underlying depression carried higher risk of developing PSU, whereas the field of study (science vs. humanities based) did not contribute to an increased risk of developing PSU., Conclusion: Findings from this study can help better inform university administrators about at- risk groups of undergraduate students who may benefit from targeted intervention designed to reduce their addictive behaviour patterns.

Objective: To identify regions of the brain affected during cognitive working memory during tasks to assess attention, planning and decision making among military aviation personnel who have chronic intermittent exposure to high altitude environment., Method: A case-control study was conducted in the Universiti Putra Malaysia among eight military personnel, four of whom had chronic intermittent exposure to high altitude training. They were divided into two groups, chronic intermittent exposure group (CE) (n=4) and a control group (n=4). They underwent a task-based functional magnetic resonance imaging (fMRI) that utilised spatial working memory task to objectively evaluate the neural activation in response to the Tower of London paradigm. Each correct answer was given a score of one and the maximum achievable score was 100%., Results: A consecutive dichotomised group of CE (4/8) and control (4/8) of age-matched military aviation personnel with a mean age of 37.23±5.52 years; showed significant activation in the right middle frontal gyrus (MFG). This in turn was positively correlated with response accuracy. A significant difference in the response accuracy was noted among both the groups at p<0.05., Conclusion: At the minimum results of power analysis of this preliminary fMRI study, our group of aviation personnel who had chronic intermittent exposure to hypobaric hypoxic environment, did not have any significant decrease in cognitive function namely attention, decision-making and problem solving compared to controls during a working memory task.

Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1 / PD-L2 expression, or epigenetic mutations ( IDH1/2, BAP1 ) and FGFR / PRKA -related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer. Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116-35. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047 ., (©2017 American Association for Cancer Research.)

AT rich interactive domain 1A (ARID1A) is one of the most commonly mutated genes in a broad variety of tumors. The mechanisms that involve ARID1A in ampullary cancer progression remains elusive. Here, we evaluated the frequency of ARID1A and KRAS mutations in ampullary adenomas and adenocarcinomas and in duodenal adenocarcinomas from two cohorts of patients from Singapore and Romania, correlated with clinical and pathological tumor features, and assessed the functional role of ARID1A . In the ampullary adenocarcinomas, the frequency of KRAS and ARID1A mutations was 34.7% and 8.2% respectively, with a loss or reduction of ARID1A protein in 17.2% of the cases. ARID1A mutational status was significantly correlated with ARID1A protein expression level (P=0.023). There was a significant difference in frequency of ARID1A mutation between Romania and Singapore (2.7% versus 25%, P=0.04), suggestive of different etiologies. One somatic mutation was detected in the ampullary adenoma group. In vitro studies indicated the tumor suppressive role of ARID1A . Our results warrant further investigation of this chromatin remodeller as a potential early biomarker of the disease, as well as identification of therapeutic targets in ARID1A mutated ampullary cancers.

Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, KDM6A (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of KDM6A mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in KDM6A -mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in KDM6A -null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that KDM6A -null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in KDM6A -null cell lines. EZH2 inhibition delayed tumor onset in KDM6A -null cells and caused regression of KDM6A -null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of KDM6A , which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2., (Copyright © 2017, American Association for the Advancement of Science.)

Background: GI stromal tumours (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients., Objectives: We sought to identify genetic alterations associated with high-risk GIST, explore their molecular consequences, and test their utility as prognostic markers., Designs: Exome sequencing of 18 GISTs was performed (9 patients with high-risk/metastatic and 5 patients with low/intermediate-risk), corresponding to 11 primary and 7 metastatic tumours. Candidate alterations were validated by prevalence screening in an independent patient cohort (n=120). Functional consequences of SETD2 mutations were investigated in primary tissues and cell lines. Transcriptomic profiles for 8 GISTs (4 SETD2 mutated, 4 SETD2 wild type) and DNA methylation profiles for 22 GISTs (10 SETD2 mutated, 12 SETD2 wild type) were analysed. Statistical associations between molecular, clinicopathological factors, and relapse-free survival were determined., Results: High-risk GISTs harboured increased numbers of somatic mutations compared with low-risk GISTs (25.2 mutations/high-risk cases vs 6.8 mutations/low-risk cases; two sample t test p=3.1×10 -5 ). Somatic alterations in the SETD2 histone modifier gene occurred in 3 out of 9 high-risk/metastatic cases but no low/intermediate-risk cases. Prevalence screening identified additional SETD2 mutations in 7 out of 80 high-risk/metastatic cases but no low/intermediate-risk cases (n=29). Combined, the frequency of SETD2 mutations was 11.2% (10/89) and 0% (0/34) in high-risk and low-risk GISTs respectively. SETD2 mutant GISTs exhibited decreased H3K36me3 expression while SETD2 silencing promoted DNA damage in GIST-T1 cells. In gastric GISTs, SETD2 mutations were associated with overexpression of HOXC cluster genes and a DNA methylation signature of hypomethylated heterochromatin. Gastric GISTs with SETD2 mutations, or GISTs with hypomethylated heterochromatin, showed significantly shorter relapse-free survival on univariate analysis (log rank p=4.1×10 -5 )., Conclusions: Our data suggest that SETD2 is a novel GIST tumour suppressor gene associated with disease progression. Assessing SETD2 genetic status and SETD2-associated epigenomic phenotypes may guide risk stratification and provide insights into mechanisms of GIST clinical aggressiveness., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The Personal Data Protection Act (PDPA) of Singapore was first passed in 2012, with subsequent enforcement regulations effective in 2014. Although medical education via digital platforms is not often used in medical schools in Singapore as of yet, many current means of communication at all levels in the medical community from medical schools to clinics to hospitals are unsecure and noncompliant with the PDPA., Objective: This pilot study will assess the effectiveness of MyDoc, a secure, mobile telehealth application and messaging platform, as an educational tool, secure communications tool, and a tool to raise awareness of the PDPA., Methods: By replacing current methods of communication with MyDoc and using weekly clinical case discussions in the form of unidentifiable clinical photos and questions and answers, we raised awareness the PDPA among medical students and gained feedback and determined user satisfaction with this innovative system via questionnaires handed to 240 medical students who experienced using MyDoc over a 6-week period., Results: All 240 questionnaires were answered with very positive and promising results, including all 100 students who were not familiar with the PDPA prior to the study attributing their awareness of it to MyDoc., Conclusions: Potential uses of MyDoc in a medical school setting include PDPA-compliant student-to-student and student-to-doctor communication and clinical group case discussions with the sharing of patient-sensitive data, including clinical images and/or videos of hospital patients that students may benefit from viewing from an educational perspective. With our pilot study having excellent results in terms of acceptance and satisfaction from medical students and raising awareness of the PDPA, the integration of a secure, mobile digital health application and messaging platform is something all medical schools should consider, because our students of today are our doctors of tomorrow., Competing Interests: Conflicts of Interest: None declared.

Objective: To better define the concordance of visual loss in patients with nonarteritic anterior ischemic optic neuropathy (NAION)., Methods: The medical records of 86 patients with bilateral sequential NAION were reviewed retrospectively, and visual function was assessed using visual acuity, Goldmann visual fields, color vision, and relative afferent papillary defect. A quantitative total visual field score and score per quadrant were analyzed for each eye using the numerical Goldmann visual field scoring method., Results: Outcome measures were visual acuity, visual field, color vision, and relative afferent papillary defect. A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P=.01), global visual field (P<.001), superior visual field (P<.001), and inferior visual field (P<.001). The mean deviation of total (P<.001) and pattern (P<.001) deviation analyses was significantly less between fellow eyes than between first and second eyes of different patients., Conclusions: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION.