Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Prognostic implication of the neoadjuvant rectal score and other biomarkers of clinical outcome in Hong Kong Chinese patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, for which pathological complete response is typically used as a surrogate survival endpoint. Neoadjuvant rectal score is a new biomarker that has been shown to correlate with survival. The main objectives of this study were to investigate factors contributing to pathological complete response, to validate the prognostic significance of neoadjuvant rectal score, and to investigate factors associated with a lower neoadjuvant rectal score in a cohort of Hong Kong Chinese. METHODS: Data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy from August 2006 to October 2018 were retrieved from hospital records and retrospectively analysed. RESULTS: Of 193 patients who had optimal response to neoadjuvant chemoradiotherapy and surgery, tumour down-staging was the only independent prognostic factor that predicted pathological complete response (P<0.0001). Neoadjuvant rectal score was associated with overall survival (hazard ratio [HR]=1.042, 95% confidence interval [CI]=1.021-1.064; P<0.0001), disease-free survival (HR=1.042, 95% CI=1.022-1.062; P<0.0001), locoregional recurrence-free survival (HR=1.070, 95% CI=1.039-1.102; P<0.0001) and distant recurrence-free survival (HR=1.034, 95% CI=1.012-1.056; P=0.002). Patients who had pathological complete response were associated with a lower neoadjuvant rectal score (P<0.0001), but pathological complete response was not associated with survival. For patients with intermediate neoadjuvant rectal scores, late recurrences beyond 72 months from diagnosis were observed. CONCLUSION: Neoadjuvant rectal score is an independent prognostic marker of survival and disease recurrence in a cohort of Hong Kong Chinese patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

A review of reported cases of HIV pre-exposure prophylaxis failure with resultant breakthrough HIV infections.

OBJECTIVES: Early randomized controlled trials (RCTs) have confirmed high efficacy of pre-exposure prophylaxis (PrEP) for preventing HIV infection in men who have sex with men (MSM) with high HIV exposure risk. Nevertheless, some PrEP failure cases have been reported despite adequate drug adherence. This review aims to summarize the common features of PrEP failure cases and discuss the implications of upscaling PrEP programmes. METHODS: A search based on articles and clinical trials was conducted through Medline and OVID, with keywords for accessing publications reporting 'true' PrEP failure in the presence of documented adherence to daily regimen of co-formulated tenofovir disoproxil fumarate/emtricitabone. RESULTS: Ten cases of 'true' PrEP failure were identified, all of which were preceded by continued practice of condomless anal sex, despite documented adherence. Dried blood spot and/or hair analyses provided supporting evidence of adherence in eight cases. There was strong association of PrEP failure with recurrent or multiple sexually transmitted diseases and infection with resistant HIV viruses. Seroconversion was usually atypical or delayed because of significantly suppressed viral load, making diagnosis a clinical challenge. DISCUSSION: Although it is uncommon, 'true' PrEP failure can occur in a real-world situation, contrary to the outcome of early RCTs. Failure to identify HIV infection while on PrEP can potentially lead to the emergence of drug-resistant virus. To achieve effective HIV prevention, PrEP programmes should emphasize safer sexual practice in addition to drug adherence. Early identification of PrEP failure is crucial, which requires the development of highly sensitive assays and their clinical application.

Association of serum 25(OH)Vit-D levels with risk of pediatric fractures: a systematic review and meta-analysis.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Oncogenes expand during evolution to withstand somatic amplification.

Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Results: Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb; P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb; P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0; P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Conclusions: Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic amplification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene amplification and elucidated how cancers have shaped our genome to its present configuration.

Isolation of phage-display library-derived scFv antibody specific to Listeria monocytogenes by a novel immobilized method.

AIMS: To select Listeria monocytogenes-specific single-chain fragment variable (scFv) antibodies from a phage-display library by a novel simple and cost-effective immobilization method. METHODS AND RESULTS: Light expanded clay aggregate (LECA) was used as biomass support matrix for biopanning of a phage-display library to select L. monocytogenes-specific scFv antibody. Four rounds of positive selection against LECA-immobilized L. monocytogenes and an additional subtractive panning against Listeria innocua were performed. The phage clones selected using this panning scheme and LECA-based immobilization method exhibited the ability to bind L. monocytogenes without cross-reactivity toward 10 other non-L. monocytogenes bacteria. One of the selected phage clones was able to specifically recognize three major pathogenic serotypes (1/2a, 1/2b and 4b) of L. monocytogenes and 11 tested L. monocytogenes strains isolated from foods. CONCLUSIONS: The LECA-based immobilization method is applicable for isolating species-specific anti-L. monocytogenes scFv antibodies by phage display. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolated scFv antibody has potential use in development of immunoassay-based methods for rapid detection of L. monocytogenes in food and environmental samples. In addition, the LECA immobilization method described here could feasibly be employed to isolate specific monoclonal antibodies against any given species of pathogenic bacteria from phage-display libraries.

The level and pattern of physical activity among fifth-grade students in Ho Chi Minh City, Vietnam.

OBJECTIVES: Despite the benefits of physical activity (PA), a significant proportion of children do not meet physical activity guidelines (PAGs). However, most studies were among secondary-school-aged youth and relied on PA self-report. In addition, information regarding children's PA behaviors during specific segments of day/week is not usually collected. This study, therefore, investigated the level and pattern of PA among fifth-grade students in Ho Chi Minh City (HCMC), Vietnam. STUDY DESIGN: A complex cross-sectional survey was conducted on a representative sample of 619 fifth-grade students in eight public schools in urban areas of HCMC in 2016. METHODS: Demographic/anthropometric characteristics were measured using standard protocols. PA was measured using pedometers. After-school activities were measured using the Previous Day Physical Activity Recall questionnaire. Survey procedures with sampling weights were used for analyses. RESULTS: Approximately 18% of children met the PAG; 52.7% were overweight (OW)/obese (OB). On average, students recorded about 8800 steps/day. Boys were more active than girls at school and on weekdays. Students were more active at school on physical education (PE) days vs non-PE days and weekdays vs weekends. OW/OB students were more active at school on PE days. After-school PAs differed between boys and girls, whereas sedentary activities were popular among both the genders. CONCLUSIONS: Most fifth-grade students had insufficient PA levels. Patterns of PA are different at various times during the day and week. The finding emphasized an urgent need for interventions to improve children's PA and obesity in this area.

Increased perinatal remodelling of the pancreas in somatostatin-deficient mice: potential role of transforming growth factor-beta signalling in regulating beta cell growth in early life.

Early postnatal life is a critical period for development of the endocrine pancreas, involving remodelling of islet cells and maturation of secretory responses. Factors that regulate these processes are undefined. Somatostatin-secreting delta-cells are abundant in the developing pancreas and, because somatostatin inhibits growth, the hormone may regulate islet expansion in early life. The aim of this study was to investigate effects of somatostatin-deficiency on proliferation, apoptosis and pancreas expansion in the first 3 weeks of life in mice. Pancreases from control or somatostatin-knockout mice were analysed for beta cell, alpha cell and pancreatic volumes by morphometry, proliferation by BrdU incorporation and apoptosis by TUNEL labelling. Signalling pathways associated with proliferation and apoptosis were studied by immunohistochemistry and Western blotting. Knockout mice grew normally in the first 3 weeks of life, but had high circulating insulin that normalised by day 21. Beta cell, alpha cell and pancreatic volumes were decreased in knockout mice, accompanied by reduced proliferation and increased apoptosis in the pancreas. Decreased growth was not due to impaired Akt signalling, as Akt phosphorylation and nuclear cyclin-D2 increased in the knockout pancreas. Levels of TGF-ß1, a factor implicated in tissue remodelling, together with SMAD phosphorylation through which TGF-ß mediates its effects, were increased in the knockout pancreas. Beta cell expansion was impaired in knockout mice, potentially compensating for increased insulin secretion from islets lacking inhibitory effects of somatostatin, and was associated with increased TGF-ß1 levels. TGF-ß1 may represent an important regulator of beta cell mass in early life.

Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii.

Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period.

The role of primary transoral laser microsurgery in laryngeal cancer: a retrospective study.

OBJECTIVE: To investigate the oncologic and survival outcomes of primary transoral laser microsurgery in laryngeal cancer. DESIGN: Retrospective analysis of a database of all patients undergoing primary transoral laser microsurgery with or without adjunctive therapy from June 2000 to October 2013. The median follow-up time was 33 months. SETTING: A teaching hospital. PARTICIPANTS: Two hundred and three patients underwent primary transoral laser microsurgery. Of these, 166 had glottic and 37 had supraglottic squamous cell carcinoma. MAIN OUTCOME MEASURES: Overall survival, disease-specific survival, local control and rate of salvage laryngectomy. RESULTS: Primary transoral laser microsurgery was performed exclusively in 149 (73%) patients, 16 (8%) had transoral laser microsurgery followed by postoperative (chemo)radiotherapy, 6 (3%) had transoral laser microsurgery with neck dissection, and 32 (16%) had transoral laser microsurgery in combination with neck dissection and postoperative (chemo)radiotherapy. In glottic cancer, the 5-year local control was 86%, 86% and 76% in carcinoma in situ (Tis), early-stage (T1, T2) and late-stage (T3, T4) disease, respectively. The 5-year disease-specific survival was 93% in Tis, 96% in early-stage and 65% at late-stage disease. In supraglottic cancer, the 5-year local control was 66% in early-stage and 88% in late-stage disease. The 5-year disease-specific survival was 80% and 75%, respectively. The rate of salvage laryngectomy was 9.9%. CONCLUSION: In carefully selected patients with laryngeal cancer, primary transoral laser microsurgery with or without adjunctive therapy can be organ preserving. It can provide a valid treatment option for patients.