A randomized cross-over study of cryopreserved platelets in prophylactic transfusions of thrombocytopenic patients.

BACKGROUND: The short shelf-life of liquid-stored platelets (LP) at 20-24°C poses shortage and wastage challenges. Cryopreserved platelets have significantly extended shelf-life, and were safe and efficacious for therapeutic transfusions of bleeding patients in the Afghanistan conflict and phase 2 randomized studies. Although hematology patients account for half of platelets demand, there is no randomized study on prophylactic cryopreserved platelet transfusions in them. METHODS: We performed a phase 1b/2a randomized cross-over study comparing the safety and efficacy of cryopreserved buffy coat-derived pooled platelets (CP) to LP in the prophylactic transfusions of thrombocytopenic hematology patients. RESULTS: A total of 18 adults were randomly assigned 1:1 to CP and LP for their first thrombocytopenic period (TP) of up to 28-days. A total of 14 crossed over to the other platelet-arm for the second TP. Overall, 17 subjects received 51 CP and 15 received 52 LP. CP-arm had more treatment emergent adverse event (29.4% vs. 13.3% of subjects, 9.8% vs. 3.8% of transfusions) than LP-arm but all were mild. No thromboembolism was observed. Both arms had similar bleeding rates (23.5% vs. 26.7% of subjects) which were all mild. Subjects in CP-arm had lower average corrected count increments than LP-arm (mean [SD] 5.6 [4.20] vs. 22.6 [9.68] ×109 /L at 1-4 h, p < .001; 5.3 [4.84] vs. 18.2 [9.52] ×109 /L at 18-30 h, p < .001). All TEG parameters at 1-4 h and maximum amplitude (MA) at 18-30 h improved from baseline post-CP transfusion (p < .05) though improvements in K-time and MA were lower than LP (p < .05). DISCUSSION: During shortages, CP may supplement LP in prophylactic transfusions of thrombocytopenic patients.

Evaluation of eight commercial Zika virus IgM and IgG serology assays for diagnostics and research.

Several commercial Zika virus (ZIKV) serology assays have been developed since the recognition of ZIKV outbreaks as a Public Health Emergency of International Concern in 2016. However, test interpretation for ZIKV serology can be challenging due to antibody cross-reactivity with other flaviviruses like dengue virus (DENV). Therefore, we sought to evaluate the performance of eight commercially available ZIKV IgM and IgG assays across three testing platforms, namely, immunochromatographic tests (ICT), ELISAs and immunofluorescence tests (IIFT). The test panel comprised of 278 samples, including acute and convalescent sera or plasma from ZIKV-confirmed, DENV-confirmed, non-ZIKV and non-DENV patients, and residual sera from healthy blood donors. The ZIKV IgM and IgG serology assays yielded higher test sensitivities of 23.5% - 97.1% among ZIKV convalescent samples as compared to 5.6% - 27.8% among ZIKV acute samples; the test specificities were 63.3% - 100% among acute and convalescent DENV, non-DENV samples. Among the ELISAs and IIFTs, the Diapro ZIKV IgM ELISA demonstrated high test sensitivity (96%) and specificity (80%) when tested on early convalescent samples, while the Euroimmun ZIKV IgG ELISA yielded the highest test specificity of 97% - 100% on samples from non-ZIKV patients and healthy blood donors. For rapid ICTs, the LumiQuick IgM rapid ICT yielded low test sensitivity, suggesting its limited utility. We showed that commercial ZIKV IgM and IgG serology assays have differing test performances, with some having moderate to high test sensitivities and specificities when used in a dengue endemic setting, although there were limitations in IgG serology.

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.

Force of Infection and True Infection Rate of Dengue in Singapore: Implications for Dengue Control and Management.

National data on dengue notifications do not capture all dengue infections and do not reflect the true intensity of disease transmission. To assess the true dengue infection rate and disease control efforts in Singapore, we conducted age-stratified serosurveys among residents after a 2013 outbreak that was the largest dengue outbreak on record. The age-weighted prevalence of dengue immunoglobulin G among residents was 49.8% (95% confidence interval: 48.4, 51.1) in 2013 and 48.6% (95% confidence interval: 47.0, 50.0) in 2017; prevalence increased with age. Combining these data with those from previous serosurveys, the year-on-year estimates of the dengue force of infection from 1930 to 2017 revealed a significant decrease from the late 1960s to the mid-1990s, after which the force of infection remained stable at approximately 10 per 1,000 persons per year. The reproduction number (R0) had also declined since the 1960s. The reduction in dengue transmission may be attributed to the sustained national vector program and partly to a change in the age structure of the population. The improved estimated ratio of notified cases to true infections, from 1:14 in 2005-2009 to 1:6 in 2014-2017, signifies that the national notification system, which relies on diagnosed cases, has improved over time. The data also suggest that the magnitudes of dengue epidemics cannot be fairly compared across calendar years and that the current disease control program remains applicable.

Ex vivo haemostatic capacity of plasma upon thawing and beyond: a comparison between fresh frozen plasma (FFP) and frozen plasma prepared from whole blood stored at room temperature up to 24 hours postcollection (RTFP24).

BACKGROUND/OBJECTIVES: We compared the ex vivo haemostatic capacity of RTFP24 with FFP upon thawing and >24 h post-thaw. We included thrombin generation (TG) as few studies had compared global haemostatic function, and most did not directly compare RTFP24 with FFP >24 h post-thaw. MATERIALS/METHODS: Twenty units each of RTFP24 and FFP were measured for coagulation factors and thrombin generation upon thawing (D0) and 4 days post-thaw (D4). Labile factors were also measured from D1 to D3. 10 single cryoprecipitate units were each prepared from FFP and RTFP24, and measured for FXIII, FVIII and fibrinogen at D0. RESULTS: At D0, RTFP24 was comparable to FFP except for lower FV, protein S, endogenous thrombin potential (ETP) and higher FXIII. These differences were likely clinically insignificant since 95% and 80% of RTFP24 met our laboratory's reference ranges for FV/protein S and ETP, respectively. There were no differences between RTFP24- and FFP-derived cryoprecipitate. At D4, RTFP24 was comparable to FFP except for lower FV, ETP, and higher FXI and FXIII. More RTFP24 than FFP had ETP lower than our laboratory's reference range (45% vs 15%). Multiple coagulation factors and all TG parameters declined from their respective baselines. The percentage declines were comparable or less in RTFP24, except for protein C, fibrinogen and time to peak. CONCLUSION: RTFP24 and FFP, and their derived cryoprecipitate have comparable haemostatic capacity upon thawing. RTFP24 has poorer TG potential than FFP >24 h post-thaw, not supporting universal extension of RTFP24's shelf life except to facilitate urgent transfusions for massive haemorrhage.

Prevalence of hepatitis C virus infection and the IL28B genotype polymorphism among blood donors and high-risk populations.

INTRODUCTION: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive. METHODS: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented. RESULTS: Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%. CONCLUSION: Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.

Identification of circulating microRNA signatures for breast cancer detection.

PURPOSE: There is a quest for novel noninvasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples. EXPERIMENTAL DESIGN: miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCR panels. Serum samples from healthy individuals (n = 22) were also used as normal controls. Significant serum miRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n = 132) and healthy controls (n = 101). RESULTS: The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91. CONCLUSION: The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers.