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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.

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An auditory-visual speech benefit, the benefit that visual speech cues bring to auditory speech perception, is experienced from early on in infancy and continues to be experienced to an increasing degree with age. While there is both behavioural and neurophysiological evidence for children and adults, only behavioural evidence exists for infants - as no neurophysiological study has provided a comprehensive examination of the auditory-visual speech benefit in infants. It is also surprising that most studies on auditory-visual speech benefit do not concurrently report looking behaviour especially since the auditory-visual speech benefit rests on the assumption that listeners attend to a speaker's talking face and that there are meaningful individual differences in looking behaviour. To address these gaps, we simultaneously recorded electroencephalographic (EEG) and eye-tracking data of 5-month-olds, 4-year-olds and adults as they were presented with a speaker in auditory-only (AO), visual-only (VO), and auditory-visual (AV) modes. Cortical tracking analyses that involved forward encoding models of the speech envelope revealed that there was an auditory-visual speech benefit [i.e., AV > (A + V)], evident in 5-month-olds and adults but not 4-year-olds. Examination of cortical tracking accuracy in relation to looking behaviour, showed that infants' relative attention to the speaker's mouth (vs. eyes) was positively correlated with cortical tracking accuracy of VO speech, whereas adults' attention to the display overall was negatively correlated with cortical tracking accuracy of VO speech. This study provides the first neurophysiological evidence of auditory-visual speech benefit in infants and our results suggest ways in which current models of speech processing can be fine-tuned.

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The coronavirus disease 2019 (COVID-19) pandemic has accelerated the need for rapid implementation of diagnostic assays for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in respiratory specimens. While multiple molecular methods utilize nasopharyngeal specimens, supply chain constraints and need for easier and safer specimen collection warrant alternative specimen types, particularly saliva. Although saliva has been found to be a comparable clinical matrix for detection of SARS-CoV-2, evaluations of diagnostic and analytic performance across platforms for this specimen type are limited. Here, we compared two methods for SARS-CoV-2 detection in saliva: the Roche cobas(R) 6800/8800 SARS-CoV-2 real-time RT-PCR Test and the Agena Biosciences MassARRAY(R) SARS-CoV-2 Panel/MassARRAY(R) System. Overall, both systems had high agreement with one another, and both demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of each platform and determined the limit of detection of the Roche assay was four times lower than that of Agena for saliva specimens (390.6 v. 1,562.5 copies/mL). Furthermore, across individual target components of each assay, T2 and N2 targets had the lowest limits of detection for each platform, respectively. Together, we demonstrate that saliva represents an appropriate specimen for SARS-CoV-2 detection in two technologies that have high agreement and differ in analytical sensitivities overall and across individual component targets. The addition of saliva as an acceptable specimen and understanding the sensitivity for testing on these platforms can further inform public health measures for screening and detection to combat the COVID-19 pandemic.

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New York City (NYC) emerged as a coronavirus disease 2019 (COVID-19) epicenter in March 2020, but there is limited information regarding potentially unrecognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first reported case. We utilized a sample pooling strategy to screen for SARS-CoV-2 RNA in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across our NYC health system who were evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We obtained complete SARS-CoV-2 genome sequences from samples collected between late February and early March. Additionally, we detected SARS-CoV-2 RNA in pooled specimens collected in the week ending 25 January 2020, indicating that SARS-CoV-2 caused sporadic infections in NYC a full month before the first officially documented case.

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INTRODUCTION@#Large-volume paracentesis (LVP) is the first-line treatment for decompensated cirrhosis with refractory ascites. While ascitic drain removal (ADR) within 72 hours of the procedure was once considered safe, it was uncertain whether ADR within 24 hours could further reduce the risk of ascitic drain-related bacterial peritonitis (AdBP). This study aimed to investigate the association between the timing of ADR and the presence of AdBP.@*METHODS@#All patients with cirrhosis with refractory ascites who underwent LVP in our institution from 2014 to 2017 were studied. AdBP was diagnosed based on an ascitic fluid neutrophil count ≥ 250 cells/mm@*RESULTS@#A total of 131 patients who underwent LVP were followed up for 1,806 patient-months. Their mean age was 68.3 ± 11.6 years, and 65.6% were male. Their mean Model for End-Stage Liver Disease score was 15.2. The overall incidence of AdBP was 5.3%. ADR beyond 24 hours was significantly associated with a longer median length of stay (five days vs. three days, p < 0.001), higher risk of AdBP (0% vs. 8.9%, p = 0.042) and acute kidney injury (AKI) following LVP (odds ratio 20.0, 95% confidence interval 2.4-164.2, p = 0.021). The overall survival was similar in patients who underwent ADR within and beyond 24 hours of LVP.@*CONCLUSION@#ADR within 24 hours of LVP is associated with a reduced risk of AdBP and AKI. As AdBP is associated with resistant organisms and AKI, we recommend prompt ADR within 24 hours, especially in patients who have Child-Pugh class C alcoholic cirrhosis.

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Background/Aims@#Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. @*Methods@#In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013–2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. @*Results@#A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). @*Conclusion@#In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

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Background/Aims@#Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. @*Methods@#In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013–2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. @*Results@#A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). @*Conclusion@#In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

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By conducting a retrospective, cross-sectional analysis of SARS-CoV-2 seroprevalence in a sentinel group (enriched for SARS-CoV-2 infections) and a screening group (representative of the general population) using >5,000 plasma samples from patients at Mount Sinai Hospital in New York City (NYC), we identified seropositive samples as early as in the week ending February 23, 2020. A stark increase in seropositivity in the sentinel group started the week ending March 22 and in the screening group in the week ending March 29. By the week ending April 19, the seroprevalence in the screening group reached 19.3%, which is well below the estimated 67% needed to achieve community immunity to SARS-CoV-2. These data potentially suggest an earlier than previously documented introduction of SARS-CoV-2 into the NYC metropolitan area. One Sentence SummarySeroprevalence of SARS-CoV-2 in cross-sectional samples from New York City rose from 0% to 19.3% from early February to mid-April.

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INTRODUCTION@#Spontaneous bacterial peritonitis (SBP) is the commonest complication of liver cirrhosis. Timely and appropriate treatment of SBP is crucial, particularly with the rising worldwide prevalence of multidrug-resistant organisms (MDROs). We aimed to investigate the clinical outcomes of SBP in Singapore.@*METHODS@#All cirrhotic patients with SBP diagnosed between January 2014 and December 2017 were included. Nosocomial SBP (N-SBP) was defined as SBP diagnosed more than 48 hours after hospitalisation. Clinical outcomes were analysed as categorical outcomes using univariate and multivariate analysis.@*RESULTS@#There were 33 patients with 39 episodes of SBP. Their mean age was 64.5 years and 69.7% were male. The commonest aetiology of cirrhosis was hepatitis B (27.3%). The Median Model for End-stage Liver Disease (MELD) score was 17; 33.3% had acute-on-chronic liver failure and 60.6% had septic shock at presentation. N-SBP occurred in 25.6% of SBP cases. N-SBP was more commonly associated with MDROs, previous antibiotic use in the past three months (p = 0.014) and longer length of stay (p = 0.011). The 30-day and 90-day mortality among SBP patients was 30.8% and 51.3%, respectively. MELD score > 20 was a predictor for 30-day mortality. N-SBP and MELD score > 20 were predictors for 90-day mortality.@*CONCLUSION@#N-SBP was significantly associated with recent antibiotic use, longer hospitalisation, more resistant organisms and poorer survival among patients with SBP. N-SBP and MELD score predict higher mortality in SBP. Judicious use of antibiotics may reduce N-SBP and improve survival among cirrhotic patients.

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Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular chaperones for cellular proteins essential for cell viability and growth as well as having numerous cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which some of the most extensively studied are the HSP90 and HSP70 families. Important members of these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis, inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.