IgG assay in COVID-19 patients. Methods: Residual sera from 177 symptomatic SARS-CoV-2-positive patients and 163 non-COVID-19 patients were tested for antibody with the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, Chicago, USA). Clinical records for COVID-19 patients were reviewed to determine the time from onset of clinical illness to testing. Results: Specificity of the assay was 100.0% (95%CI: 97.1e100.0%). The clinical sensitivity of the assay varied depending on time from onset of symptoms, increasing with longer periods from the onset of clinical illness. The clinical sensitivity at 6 days was 8.6% (7/81; 95%CI: 3.8e17.5%), at 7e13 days 43.6% (17/39; 95%CI: 28.2e60.2%), at 14e20 days 84.0% (21/25; 95%CI: 63.1e94.7%), and at 21 days 84.4% (27/ 32; 95%CI: 66.5e94.1%). Clinical sensitivity was higher in the 14-day group compared to <14 days. There were no differences between the 14e20-day and 21-days groups; the combined clinical sensitivity for these groups (14 days) was 84.2% (49/57; 71.6e92.1%). Conclusion:The Abbott SARS-CoV-2 IgG test has high specificity. Clinical sensitivity was limited in the early stages of disease but improved from 14 days after the onset of clinical symptoms.

The ability to acquire surgical skills requires consistent practice, and evidence suggests that many of these technical skills can be learnt away from the operating theatre. The aim of this review article is to discuss the importance of surgical simulation today and its various types, exploring the effectiveness of simulation in the clinical setting and its challenges for the future. Surgical simulation offers the opportunity for trainees to practise their surgical skills prior to entering the operating theatre, allowing detailed feedback and objective assessment of their performance. This enables better patient safety and standards of care. Surgical simulators can be divided into organic or inorganic simulators. Organic simulators, consisting of live animal and fresh human cadaver models, are considered to be of high-fidelity. Inorganic simulators comprise virtual reality simulators and synthetic bench models. Current evidence suggests that skills acquired through training with simulators, positively transfers to the clinical setting and improves operative outcome. The major challenge for the future revolves around understanding the value of this new technology and developing an educational curriculum that can incorporate surgical simulators.

The coronavirus disease 2019 (COVID-19) is a zoonotic viral infection originating from Wuhan, China in December 2019. The World Health Organization has classified this pandemic as a global health emergency due to its virulent nature of transmission, which may lead to acute respiratory distress syndrome. Singapore’s health ministry has responded with enhanced surveillance of COVID-19 for all suspected pneumonia cases, further increasing the volume of testing via real-time reverse transcription PCR, as well as samples necessitating stringent infectious control. Collectively, this has implications on the total testing process, laboratory operations and its personnel due to biosafety concerns. Turnaround time for routine testing may also be affected. The aim of this article is to present our tertiary institution’s early experience with managing this emerging crisis and offer practical considerations for the preanalytical, analytical and postanalytical phases of laboratory testing in this cohort of patients.

In this study, we evaluated and compared six SARS-CoV-2 serology kits including the Abbott SARS-CoV-2 IgG assay, Beckman Access SARS-CoV-2 IgG assay, OCD Vitros OCD Anti-SARS-CoV-2 Total antibody assay, Roche Elecsys Anti SARS-CoV-2 assay, Siemens SARS-CoV-2 Total assay, and cPass surrogate viral neutralising antibody assay. A total of 336 non-duplicated residual serum samples that were obtained from COVID-19 confirmed patients (n=173) on PCR and negative controls (n=163) obtained pre-December 2019 before the COVID-19 pandemic were used for the study. These were concurrently analysed on the different immunoassay platforms and correlated with clinical characteristics. Our results showed all assays had specificity ranging from 99.3% to 100.0%. Overall sensitivity across all days of symptoms, in descending order were OCD (49.1%, 95% CI 41.8-56.5%), cPass (44.8%, 95% CI 37.5-52.3%), Roche (41.6%, 95% CI 34.5-49.0%), Siemens (39.9%, 95% CI 32.9-47.3%), Abbott (39.8%, 95% CI 32.9-47.3%) and Beckman (39.6%, 95% CI 32.5-47.3%). Testing after at least 14 days from symptom onset is required to achieve AUCs greater than 0.80. OCD and cPass performed the best in terms of sensitivity for >21 days symptoms with 93.3% (95% CI, 73.5-99.2%) and 96.7% (95% CI, 82.8-99.9%), respectively. Both also shared the greatest concordance, kappa 0.963 (95% CI 0.885-1.0), p<0.001, and had the lowest false negative rates. Serology results should be interpreted with caution in certain cases. False negatives were observed in a small number of individuals with COVID-19 on immunosuppressive therapy, paucisymptomatic or who received antiretroviral therapy. In conclusion, all assays exhibited excellent specificity and total antibody assays with spike protein configurations generally outperformed nucleocapsid configurations and IgG assays in terms of diagnostic sensitivity.

GRP78/BiP is a key member of the molecular chaperone heat shock protein (Hsp) 70 family. It has a critical role in prostate cancer (PC) including Pten loss-driven carcinogenesis, but the molecular basis of this remains unclear. We investigated the effect of GRP78 and its putative client proteins, including androgen receptor (AR) in clinical PC. Expression of GRP78 and key Hsp70-hsp90 client proteins (HER2, HER3, AR and AKT) were studied in an incidence tissue microarray (TMA) of prostate cancer. The relationship of GRP78 and AR was further tested in in vitro cell models (LNCaP and its derived LNCaP-CR subclone) and a matched TMA of hormone-naïve (HNPC) and castrate-resistant prostate cancer (CRPC). In vitro and in vivo expression of GRP78 and client proteins were assessed by western blotting and immunohistochemistry, respectively, using the weighted histoscore method. Significant co-expression of GRP78, pAKT, HER2, HER3 and AR was observed in PC. Abnormal AR, GRP78 and pAKT expression have significant impact on patient survival. GRP78 expression in AR(+) tumours was significantly higher than in AR(-) tumours. In keeping with our clinical data, activation of AR by dihydrotestosterone (DHT) potently activated GRP78 expression in both LNCaP and LNCaP-CR cells. For the first time, using a matched HNPC and CRPC TMA, enhanced cytoplasmic and membranous GRP78 expression was observed in CRPC. Future prospective studies are therefore warranted to validate GRP78 as prognostic marker and therapeutic target, in the context of the AR and pAKT status. In summary, GRP78 is co-expressed with Hsp70-hsp90 client proteins. Up-regulated expression of AR and GRP78 expression in untreated prostate cancer predicts a less favourable outcome. This points to the importance of understanding in the molecular interaction among AR, GRP78 and AKT.

Context: The use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests detect antibodies in the host, contributing to the identification of individuals who have been exposed to Coronavirus Disease 2019 (COVID-19). Objective: To critically evaluate two commercially available SARS-CoV-2 serology tests. Design: A total of 333 unique, non-duplicated serum samples obtained from COVID-19 patients (n=170) and negative controls (n=163) obtained pre-December 2019 were used in the study. Samples were tested on the Roche E411 and Abbott Architect i4000SR platforms and results were correlated to reverse transcription polymerase chain reaction (PCR) results and clinical symptoms. Results: There was a strong level of agreement in the qualitative results between both assays with a Cohen's kappa value of 0.840, P&lt;.001. The specificity for both Roche and Abbott were excellent at 100%. Roche exhibited marginally better performance in the ≥21 days group with a sensitivity of 90.6% (95% CI 75.8–96.8%) versus Abbott's sensitivity 84.4% (95% CI 68.3 – 93.1%) as well as the 14–20 days group with a sensitivity of 85.7% (95% CI 65.4 – 95.0%) versus Abbott sensitivity 81.0% (95% CI 60.0 – 92.3%). Less than 14 days of symptoms groups exhibited poor sensitivity at &lt;50% for both assays. The area under curve (AUC ± standard error) for Roche (0.894 ± 0.025, P&lt; .001) and Abbott (0.884 ± 0.026, P &lt;.001) were very similar. Potential confounders for negative serological results include antiretroviral medication use and pauci-symptomatic patients. Conclusions: Specificities for high throughput Roche and Abbott immunoassays are excellent but users need to be cautious to interpret serological test results after 14 days of symptoms to avoid false negatives

IMPORTANCEAcute ischemic stroke (AIS) is a known neurological complication in patients with respiratory symptoms of COVID-19 infection. However, AIS has not been described as a late sequelae in patients without respiratory symptoms of COVID-19. OBJECTIVE To assess AIS experienced by adults 50 years or younger in the convalescent phase of asymptomatic COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS This case series prospectively identified consecutive male patients who received care for AIS from public health hospitals in Singapore between May 21, 2020, and October 14, 2020. All of these patients had laboratory-confirmed asymptomatic COVID-19 infection based on a positive SARS-CoV-2 serological (antibodies) test result. These patients were individuals from South Asian countries (India and Bangladesh) who were working in Singapore and living in dormitories. The total number of COVID-19 cases (54 485) in the worker dormitory population was the population at risk. Patients with ongoing respiratory symptoms or positive SARS-CoV-2 serological test results confirmed through reverse transcriptase-polymerase chain reaction nasopharyngeal swabs were excluded. MAIN OUTCOMES AND MEASURES Clinical course, imaging, and laboratory findings were retrieved from the electronic medical records of each participating hospital. The incidence rate of AIS in the case series was compared with that of a historical age-, sex-, and ethnicity-matched national cohort. RESULTS A total of 18 male patients, with a median (range) age of 41 (35-50) years and South Asian ethnicity, were included. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The median (range) National Institutes of Health Stroke Scale score was 5 (1-25).Ten patients (56%) presented with a large vessel occlusion, of whom 6 patients underwent intravenous thrombolysis and/or endovascular therapy. Only 3 patients (17%) had a possible cardiac source of embolus. The estimated annual incidence rate of AIS was 82.6 cases per 100 000 people in this study compared with 38.2 cases per 100 000 people in the historical age-, sex-, and ethnicitymatched cohort (rate ratio, 2.16; 95% CI, 1.36-3.48; P < .001). CONCLUSIONS AND RELEVANCEThis case series suggests that the risk for AIS is higher in adults 50 years or younger during the convalescent period of a COVID-19 infection without respiratory symptoms. Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.

No abstract