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Objective: In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Methods: Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. Results: There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Conclusions: Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to describe the evolution of the seroprevalence of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-positive patients included in two cohorts in Taiwan. Methods: We retrospectively collected the information on demographic and clinical characteristics of 4,025 and 3,856 HIV-positive Taiwanese, who were aged 18 years or older at designated hospitals around Taiwan in 2004–2007, when an outbreak of HIV infection was occurring, and 2012–2016, when the outbreak was controlled with the implementation of harm reduction program, respectively. Comparisons of HCV seropositivity were made among different age and risk groups for HIV transmission between these two cohorts. Results: The overall HCV seroprevalence of the 2004–2007 cohort and 2012–2016 cohort was 43.4% (1,288/2,974) and 18.6% (707/3,793), respectively (P<0.001). The HCV seroprevalence among injecting drug users (IDUs), though decreasing, was constantly high across the two cohorts, 96.4% and 94.0% (P = 0.02), respectively, and all age groups. In contrast, the corresponding figures among men who have sex with men (MSM) and heterosexuals in the two cohorts were 5.9% vs. 3.5% (P = 0.002) and 9.4% vs. 10.9% (P = 0.59), respectively. Among sexually transmitted HIV-positive patients, HCV seropositivity was significantly correlated with age (adjusted odds ratio [aOR], per 1-year increase, 1.03; 95% confidence interval [CI], 1.02–1.05) and a rapid plasma reagin (RPR) titer ≥1:8 (aOR, 1.58; 95% CI, 1.03–2.43) in a multivariate analysis including age, gender, route for HIV transmission, baseline CD4 count and plasma HIV RNA load, the presence of hepatitis B surface antigen, and an RPR titer ≥1:8. Compared with heterosexuals, the aOR for HCV seropositivity among MSM was 0.47 (95% CI, 0.31–0.72). Conclusions: HCV seroprevalence among HIV-positive patients in Taiwan decreased with time, probably related to the inclusion of younger adults and more non-IDUs, and remained high among IDUs. HCV seropositivity was associated with age and an RPR titer ≥1:8 among patients who acquired HIV through sexual contact. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to describe the seroprevalence of hepatitis A virus (HAV) in HIV-positive adult patients in Taiwan between 2012 and 2016 and to examine the evolution of HAV seroprevalence between 2004–2007 and 2012–2016. Methods: Clinical information and data of anti-HAV antibody results were collected from 2,860 antiretroviral-naïve HIV-positive Taiwanese aged 18 years or older who initiated combination antiretroviral therapy at 11 hospitals around Taiwan between 2012 and 2016 (2012–2016 cohort). A multivariate logistic regression model was applied to identify independent variables associated with HAV seropositivity. Comparisons of HAV seroprevalences and associated clinical characteristics were made between this 2012–2016 cohort and a previous cohort of 1580 HIV-positive patients in 2004–2007 (2004–2007 cohort). Results: Of the 2,860 HIV-positive patients between 2012 and 2016, the overall HAV seropositivity rate was 21.2% (605/2860), which was independently associated with an older age (adjusted odds ratio [AOR], per 1-year increase, 1.13; 95% confidence interval [95% CI], 1.11–1.15) and co-infection with hepatitis B virus (AOR 1.44; 95% CI, 1.08–1.93). Residence in southern Taiwan (AOR 0.49; 95% CI, 0.34–0.72) was inversely associated with HAV seropositivity. The overall HAV seroprevalence in the 2012–2016 cohort was significantly lower than that in the 2004–2007 cohort (21.2% vs 60.9%, p<0.01). The decreases of HAV seropositivity rate were observed in nearly every age-matched group, which suggested the cohort effect on HAV seroepidemiology. However, among individuals aged 25 years or younger, the HAV seropositivity rate increased from 3.8% (2/52) in the 2004–2007 cohort to 8.5% (50/587) in the 2012–2016 cohort, with 95.4% (560/587) being MSM in this age group of the latter cohort. Conclusions: HAV seroprevalence has decreased with time among HIV-positive adults in Taiwan. The cohort effect has increased the number of young HIV-positive patients that are susceptible to HAV infection in a country without nationwide childhood vaccination program against HAV. [ABSTRACT FROM AUTHOR]

Objectives: The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan. Methods: Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART. Results: We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04–1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04–1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33–2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04–2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14–13.65) and older age (AHR, 1.06; 95% CI, 1.03–1.10). Conclusions: While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC). Methodology/Principal Findings: This study was divided into four phases: (I) Ten candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 10 HCC patients with chronic hepatitis B virus (HBV) infection and 10 age- and sex-matched healthy subjects. (II) Marker validation by real-time RT-PCR on HBV patients with (n = 48) or without HCC (n = 48), and healthy subjects (n = 24). (III) Marker detection by real-time RT-PCR in sera from another 14 HCC patients before and 1 month after surgical resection. (IV) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients. Although miR-222, miR-223 or miR-21 were significantly up- or down-regulated between HCC patients and healthy controls, no significant difference was observed in the levels of these miRNAs between HBV patients without and with HCC. MiR-122 in serum was significantly higher in HCC patients than healthy controls (p<0.001). More importantly, it was found that the levels of miR-122 were significantly reduced in the post-operative serum samples when compared to the pre-operative samples. Although serum miR-122 was also elevated in HBV patients with HCC comparing with those without HCC, the difference was at the border line (p = 0.043). Conclusions/Significance: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients. [ABSTRACT FROM AUTHOR]

By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC. [ABSTRACT FROM AUTHOR]

Sciatic nerve entrapment can occur as post-operative complication of perineal hernia repair when sacrotuberous ligament is incorporated during hernia deficit closure. This results in sciatic sensory loss and paralysis of the hind leg. This study investigated the spatial relationship of sciatic nerve and sacrotuberous ligament and their surface topographic projection of 68 cadavers (29 Beagles and 39 Taiwanese mongrels) with various heights (25-56 cm). By gross dissection, the sacrotuberous ligament and sciatic nerve were exposed and their distance in between was measured along four parts (A, B, C, D) of sacrotuberous ligament. The present study revealed that the C was the section of sacrotuberous ligament where the sciatic nerve and the sacrotuberous ligament are closest to each other. Furthermore, a positive correlation was observed between C and height of the dogs. From the present study, we found that the C in smaller dogs has the shortest distance between the sciatic nerve and the sacrotuberous ligament, and thus the most vulnerable to sciatic nerve entrapment, and needs to be avoided or approached cautiously during perineal hernia repair.