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Objectives: The current study explored whether social support received from either mediated or in-person contact varied among international students depending on the level of social ties (stronger/weaker) with existing support groups. This study also examined whether in-person or computer mediated social support (CMSS) is a better predictor of acculturative stress which might influence mental health of international students. Methods: An online survey was conducted among 179 international students across three U.S. universities. Results: Results showed that international students perceive stronger online social ties compared to in-person social ties, t (125)=- 3.57, p  < .001. Stronger ties with CMSS significantly negatively influence acculturative stress compared to in-person social support for international students, ( b  = -0.24, 95% CI [-0.45, -0.03]). This indicates that as CMSS increases, acculturative stress decreases among international students. Conclusions: This study concludes that online social support groups can positively influence mental health of college student populations, particularly those who feel stressed out.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant ( K i ) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated K i of 3.93 μ M. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low. SIGNIFICANCE STATEMENT: The authors used the endogenous biomarker coproporphyrin I (CP-I) and identified abiraterone as a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B3 in vitro. Subsequent physiologically based pharmacokinetic (PBPK) simulations and clinical observations suggested an absence of OATP1B-mediated interaction between abiraterone and CP-I among prostate cancer patients. This multipronged study concluded that the interaction risk between abiraterone acetate and substrates of OATP1Bs is low, demonstrating the application of PBPK-CP-I modeling in predicting OATP1B-mediated interaction implicating abiraterone., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Glutathione-S-transferases (GST) enzymes detoxify xenobiotics and are implicated in response to anticancer therapy. This study evaluated the association of GST theta 1 (GSTT1), GSTT2, and GSTT2B with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) response in non-muscle-invasive bladder cancer treatment. In vitro assessments of GSTT2 knockout (KO) effects were performed using cell lines and dendritic cells (DCs) from GSTT2KO mice. Deletion of GSTT2B, GSTT1, and single-nucleotide polymorphisms in the promoter region of GSTT2 was analysed in patients ( n = 205) and healthy controls ( n = 150). Silencing GSTT2 expression in MGH cells (GSTT2B FL/FL ) resulted in increased BCG survival ( p < 0.05) and decreased cellular reactive oxygen species. In our population, there are 24.2% with GSTT2B Del/Del and 24.5% with GSTT2B FL/FL . With ≤ 8 instillations of BCG therapy ( n = 51), 12.5% of GSTT2B Del/Del and 53.8% of GSTT2B FL/FL patients had a recurrence ( p = 0.041). With ≥9 instillations ( n = 153), the disease recurred in 45.5% of GSTT2B Del/Del and 50% of GSTT2B FL/FL . GSTT2 FL/FL patients had an increased likelihood of recurrence post-BCG therapy (HR 5.5 [1.87-16.69] p < 0.002). DCs from GSTT2KO mice produced three-fold more IL6 than wild-type DCs, indicating a robust inflammatory response. To summarise, GSTT2B Del/Del patients respond better to less BCG therapy and could be candidates for a reduced surveillance regimen.

Patients with preexisting kidney disease or acute kidney injury had poorer outcomes in coronavirus disease 2019 (COVID-19) illness. Lymphopenia was associated with more severe illness. Risk stratification with simple laboratory tests may help appropriate site patients in a cost-effective manner and ease the burden on healthcare systems. We examined a ratio of serum creatinine level to absolute lymphocyte count at presentation (creatinine-lymphocyte ratio, CLR) in predicting outcomes in hospitalized patients with COVID-19. We analyzed 553 consecutive polymerase chain reaction-positive SARS-COV-2 hospitalized patients. Patients with end-stage kidney disease were excluded. Serum creatinine and full blood count (FBC) examination were obtained within the first day of admission. We examined the utility of CLR in predicting adverse clinical outcomes (requiring intensive care, mechanical ventilation, acute kidney injury requiring renal replacement therapy or death). An optimized cutoff of CLR > 77 was derived for predicting adverse outcomes (72.2% sensitivity, and 83.9% specificity). Ninety-seven patients (17.5%) fell within this cut off. These patients were older and more likely to have chronic medical conditions. A higher proportion of these patients had adverse outcomes (13.4% vs 1.1%, P < .001). On receiver operating curve analyses, CLR predicted patients who had adverse outcomes well (area under curve [AUC] = 0.82, 95%CI 0.72-0.92), which was comparable to other laboratory tests like serum ferritin, C-reactive protein and lactate dehydrogenase. Elevated CLR on admission, which may be determined by relatively simple laboratory tests, was able to reasonably discriminate patients who had experienced adverse outcomes during their hospital stay. This may be a simple and cost-effective means of risk stratification and triage., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Major bleeding and receiving blood products in cancer surgery are associated with increased postoperative complications and worse outcomes. Tranexamic acid (TXA) reduces blood loss and improves outcomes in various surgical specialities. We performed a systematic review and meta-analysis to investigate TXA use on blood loss in elective abdominal and pelvic cancer surgery., Methods: A literature search was performed for studies comparing intravenous TXA versus placebo/no TXA in patients undergoing major elective abdominal or pelvic cancer surgery., Results: Twelve articles met the inclusion criteria, consisting of 723 patients who received TXA and 659 controls. Patients receiving TXA were less likely to receive a red blood cell (RBC) transfusion (p < 0.001, OR 0.4 95% CI [0.25, 0.63]) and experienced less blood loss (p < 0.001, MD -197.8 ml, 95% CI [-275.69, -119.84]). The TXA group experienced a smaller reduction in haemoglobin (p = 0.001, MD -0.45 mmol/L, 95% CI [-0.73, -0.18]). There was no difference in venous thromboembolism (VTE) rates (p = 0.95, OR 0.98, 95% CI [0.46, 2.08])., Conclusions: TXA use reduced blood loss and RBC transfusion requirements perioperatively, with no significant increased risk of VTE. However, further studies are required to assess its benefit for cancer surgery in some sub-specialities., (© 2022 Wiley Periodicals LLC.)

Coronavirus Disease 2019 (COVID-19) serology has an evolving role in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, its use in hospitalized patients with acute respiratory symptoms remains unclear. Hospitalized patients with acute respiratory illness admitted to an isolation ward were recruited. All patients had negative nasopharyngeal swab polymerase chain reaction (PCR) for SARS-CoV-2. Serological studies using four separate assays (cPass: surrogate neutralizing enzyme-linked immunosorbent assay [ELISA]; Elecsys: N-antigen based chemiluminescent assay; SFB: S protein flow-based; epitope peptide-based ELISA) were performed on stored plasma collected from patients during the initial hospital stay, and a convalescent visit 4-12 weeks later. Of the 51 patients studied (aged 54, interquartile range 21-84; 62.7% male), no patients tested positive on the Elecsys or cPass assays. Out of 51 patients, 5 had antibodies detected on B-cell Epitope Assay and 3/51 had antibodies detected on SFB assay. These 8 patients with positive serological test to COVID-19 were more likely to have a high-risk occupation (p = 0.039), bacterial infection (p = 0.028), and neutrophilia (p = 0.013) during their initial hospital admission. Discrepant COVID-19 serological findings were observed among those with recent hospital admissions and bacterial infections. The positive serological findings within our cohort raise important questions about the interpretation of sero-epidemiology during the current pandemic., (© 2022 Wiley Periodicals LLC.)

Objectives: Predictive scores are important tools for the triage of patients with coronavirus disease 2019. The PRIORITY score is advantageous because it does not require laboratory and radiologic information. However, the original development and validation cohorts studied only unvaccinated patients in early 2020. We aimed to externally validate the PRIORITY score in a cohort of patients with the novel delta and omicron variants of coronavirus disease 2019 and mixed vaccination status., Methods: A total of 410 patients were included in a cross-sectional sampling of all patients admitted to the National Centre of Infectious Diseases on October 27, 2021. A further 102 and 136 patients with vaccine-breakthrough Delta and Omicron variant infection from April to August and December 2021, respectively, were also included. Variables at the time of admission were collected retrospectively from medical records and used to calculate the probability of deterioration using the PRIORITY model., Results: Of the total 648 included patients, 447 (69.0%) were vaccinated. The mean age was 61.6 years (standard deviation ± 19.0 years), and 268 patients (41.4%) were female. A total of 112 patients (17.3%) met the primary outcome of developing critical illness or mortality. The performance of the score in this cohort was comparable with the original cohorts, with an area under the receiver operating characteristic curve for all patients of 0.794 (95% CI, 0.752-0.835; p < 0.001), regression coefficient of 1.069, and intercept of 0.04. Subgroup analysis of unvaccinated and vaccinated patients showed that performance was superior in vaccinated individuals, with an area under the receiver operating characteristic curve of 0.684 (95% CI, 0.608-0.760; p < 0.0001) and 0.831 (95% CI, 0.772-0.891; p < 0.0001), respectively., Discussion: Our data support the continued use of the PRIORITY score in this era of novel variants and increased vaccination uptake., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Reliable methods to detect the presence of SARS-CoV-2 at venues where people gather are essential for epidemiological surveillance to guide public policy. Communal screening of air in a highly crowded space has the potential to provide early warning on the presence and potential transmission of SARS-CoV-2 as suggested by studies early in the epidemic. As hospitals and public facilities apply varying degrees of restrictions and regulations, it is important to provide multiple methodological options to enable environmental SARS-CoV-2 surveillance under different conditions. This study assessed the feasibility of using high-flowrate air samplers combined with RNA extraction kit designed for environmental sample to perform airborne SARS-CoV-2 surveillance in hospital setting, tested by RT-qPCR. The success rate of the air samples in detecting SARS-CoV-2 was then compared with surface swab samples collected in the same proximity. Additionally, positive RT-qPCR samples underwent viral culture to assess the viability of the sampled SARS-CoV-2. The study was performed in inpatient ward environments of a quaternary care university teaching hospital in Singapore housing active COVID-19 patients within the period of February to May 2020. Two types of wards were tested, naturally ventilated open-cohort ward and mechanically ventilated isolation ward. Distances between the site of air sampling and the patient cluster in the investigated wards were also recorded. No successful detection of airborne SARS-CoV-2 was recorded when 50 L/min air samplers were used. Upon increasing the sampling flowrate to 150 L/min, our results showed a high success rate in detecting the presence of SARS-CoV-2 from the air samples (72%) compared to the surface swab samples (9.6%). The positive detection rate of the air samples along with the corresponding viral load could be associated with the distance between sampling site and patient. The furthest distance from patient with PCR-positive air samples was 5.5 m. The airborne SARS-CoV-2 detection was comparable between the two types of wards with 60%-87.5% success rate. High prevalence of the virus was found in toilet areas, both on surfaces and in air. Finally, no successful culture attempt was recorded from the environmental air or surface samples., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/introduction: There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms., Aim: We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort., Design and Methods: Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever-Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement., Results: There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P<0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P<0.001). The presence of fever (OR 4.096, 95% CI 1.737-9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point., Discussion/conclusion: In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Haematological markers such as absolute lymphopenia have been associated with severe COVID-19 infection. However, in the literature to date, the cohorts described have typically included patients who were moderate to severely unwell with pneumonia and who required intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 admitted to a single centre in Singapore., Methods: We examined 554 consecutive PCR positive SARS-COV-2 patients admitted to a single tertiary healthcare institution from Feb 2020 to April 2020. In all patients a full blood count was obtained within 24 h of presentation., Results: Patients with pneumonia had higher neutrophil percentages (66.5 ± 11.6 vs 55.2 ± 12.6%, p  < 0.001), lower absolute lymphocyte count (1.5 ± 1.1 vs 1.9 ± 2.1 x109/L, p  < 0.011) and absolute eosinophil count (0.2 ± 0.9 vs 0.7 ± 1.8 × 109/L, p  = 0.002). Platelet counts (210 ± 56 vs 230 ± 61, p  = 0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories., Conclusion: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.

This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 10 7 colony forming units (cfu)) and low dose (1 × 10 6 cfu) BCG Tokyo with and without cytokine genes ( GMCSF + IFNα ) were evaluated in C57BL/6J mice ( n = 12-16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice ( n = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with GMCSF + IFNα gene therapy, can induce effective systemic immunity.