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BACKGROUNDThe objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine diagnostic use within HCA Healthcare UK.METHODSWe used serum samples from a pre-Covid era patient cohort (n=50, pre-December 2019), designated SARS-CoV-2 negative, and serum samples from a SARS-CoV-2 RT-PCR-positive cohort (n=90) taken > 14 days post symptom onset (April-May 2020). We evaluated 6 ELISA assays including one confirmation assay to investigate antibody specificity. We also evaluated one point-of-care lateral flow device and one high throughput electrochemiluminescence immunoassay.RESULTSThe ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%. The LFIA showed 100% specificity and 80% sensitivity using smaller sample numbers. The Roche CLIA immunoassay showed 100% specificity and 90.7% sensitivity. When used in conjunction, the Euroimmun nucleocapsid (NC) and spike-1 (S1) IgG ELISA assays had a sensitivity of 95.6%. The confirmation IgG assay showed 92.6% of samples tested contained both NC and S1 antibodies, 32.7% had NC, S1 and S2 and 0% had either S1 or S2 only.CONCLUSIONSThese first generation assays were not calibrated against reference material and the results are reported qualitatively. The Roche assay and the Euroimmun NC and S1 assays had the best sensitivity overall in our hands. Combining the assays detecting NC and S1/S2 antibody increased diagnostic yield. A portfolio of next generation SARS-CoV-2 immunoassays will be necessary in any future studies of herd and vaccine induced immunity.

Background Assessing the risk of post-surgical mortality is a key component of pre-surgical planning. The Surgical Outcome Risk Tool (SORT) uses pre-operative variables to predict 30-day mortality. The aim of this study was to externally validate SORT in patients undergoing major abdominal surgery. Methods Data were collected from patients treated in five independent hospitals in the UK. Individualised SORT scores were calculated, and area under the receiver operating characteristic (AUROC) and precision-recall curves (PRC) plus 95% confidence intervals (CI) were drawn to test the ability of SORT to identify in-hospital death. Outcomes of patients with a SORT predicted risk of mortality of ≥ 5% (high risk) were compared to those with a predicted risk of < 5% (standard risk). Results The study population comprised 3305 patients, mean age 51 years, 2783 (84.2%) underwent elective surgery most frequently involving the colon (24.6%), or liver, pancreas or gallbladder (18.2%). Overall, 1551 (46.9%) patients were admitted to ICU and 29 (0.88%) died. The AUROC of SORT for discriminating patients at risk of death in hospital was 0.899 (95% CI 0.849 to 0.949) and the PRC 0.247. In total, 72 (2.18%) patients were stratified as high risk. There were more unplanned ICU admissions and deaths in this group compared to the standard risk group (25.0% and 3.3%, versus 3.1% and 0.5%, respectively). Conclusion We externally validated SORT in a large population of abdominal surgery patients. SORT performed well in patients with lower risk profiles, but underpredicted adverse outcomes in the higher risk group.

The study aim was to evaluate patient individualized Cyberknife® treatment for heterogeneous skull-base tumors. Patients treated between 2009 and 2013 at The Harley Street Clinic were studied. In total, 66 patients received 15–30 Gy in 1–5 fractions to a median planning target volume (PTV) of 6.4 cc, including patients with secondary, multiple, residual and recurrent tumors, and those with tumors of uncertain pathological type. Outcome analysis was pragmatically restricted to 35 patients who had single, primary tumors treated with curative intent, and sufficient diagnostic and outcome information. Sixteen vestibular schwannoma patients with median PTV 3.8 cc (range 0.81–19.6) received 18–25 Gy in 3–5 fractions: 81% showed no acute toxicity, 50% reported no late toxicity, 71% of symptoms were stable/improved and local control was 100% at 11.4 months median follow-up. Twelve meningioma patients with median PTV of 5.5 cc (range 0.68–22.3) received 17–30 Gy in 1–5 fractions: 83% experienced no acute toxicity, 33% reported no late toxicity, 88% of symptoms were stable/improved and local control was 100% at 22.1 months median follow-up. Seven patients with other tumor types with median PTV of 24.3 cc (range 7.6–100.5) received 15–28.5 Gy in 1–5 fractions: 57% experienced no acute toxicity, 57% reported no late toxicities, 66% of symptoms were stable and local control was 43% at 14.9 months median follow-up. When tumor types were considered together, smaller tumors (PTV < 6.4 cc) showed reduced acute toxicity (p = 0.01). Overall, smaller benign tumors showed low acute toxicity, excellent local control, and good symptom management: a focus on enhanced neurological preservation may refine outcomes. For other tumor types outcome was encouraging: a focus on optimal dose and fractionation scheduling may reduce toxicity and improve local control. Individual patient experiences are detailed where valuable lessons were gained for optimizing local control and minimizing toxicity.

Pancreatic carcinoma is an aggressive disease and radiotherapy treatment delivery to the primary tumor is constrained by the anatomical close location of the duodenum, stomach, and small bowel. Duodenal dose tolerance for radiosurgery in 2-5 fractions has been largely unknown. The literature was surveyed for quantitative models of risk in 1-5 fractions and we analyzed our own patient population of 44 patients with unresectable pancreatic tumors who received 3 or 5 fractions of stereotactic body radiotherapy (SBRT) between March 2009 and March 2013. A logistic model was constructed in the dose-volume histogram (DVH) Evaluator software for the duodenal D50%, D30cc, D5cc, D1cc, and maximum point dose D0.035cc. Dose tolerance limits from the literature were overlaid onto the clinical duodenal data in the form of a DVH Risk Map, with risk levels of the published limits estimated from the model of clinical data. In 3 fractions, Kopek 2010 found a statistically significant difference in D1cc of patients with no common terminology criteria for adverse events (CTCAE) v3 grade 2 or higher duodenal complications (mean D1cc = 25.3Gy) as compared with patients with grade 2 or higher toxicity (mean D1cc = 37.4Gy). From the logistic model of our duodenal data in 3 fractions, D1cc = 25.3Gy had 4.7% risk of grade 3-4 hemorrhage or stricture and D1cc = 37.4Gy had 20% risk. The 10% risk level was D1cc = 31.4Gy and we were able to keep duodenum dose for all our patients later this level.