Background: Mechanical thrombectomy with stenttriever devices is associated with significantly better outcomes than thrombolysis alone in the treatment of acute ischaemic stroke. Thrombus aspiration achieves high patency rates, but clinical outcomes are variable. The aim of this study was to examine the effect of different suction conditions on perfusate flow during aspiration thrombectomy. Results:The mathematical model predicted that in a patent vessel perfusate is drawn from upstream of the catheter tip, while in an occluded system perfusate is drawn from the vessel proximal to the device tip, with no traction on the occlusion distal of the tip. The in-vitro experiments confirmed the predictions of this model. In the occluded vessel aspiration had no effect on the thrombus unless the tip of the catheter was in direct contact with the thrombus. Conclusion:These experiments suggest that aspiration is only effective if the catheter tip is in direct contact with the thrombus. If the catheter tip is not in contact with the thrombus aspirate is drawn from the vessels proximal of the occlusion. This could affect collateral flow in vivo.

Background The COVID-19 pandemic has created a hiatus in in-person clinical assessments due to safety and logistical concerns. We aimed to evaluate student perception and utility of an online Integrated Structured Clinical Examinations (ISCEs) during the pandemic. Methods Final-year medical students from a single institution were offered an online mock ISCE through a student-to-student (“near-peer”) teaching-programme. A questionnaire-based cross-sectional study was conducted pre- and post-online mock ISCE. Results Sixty-four students completed the study. Pre- and post-data showed an increase in confidence (p<0.0001), less worry regarding the online format (p<0.0001) and less anxiety about excelling in ISCEs (p<0.001). Students felt that having done the mock, an online format would more positively affect their overall performance (p=0.007). Conclusion This study demonstrates a positive change in student perception and confidence in online ISCEs. Online ISCEs are thus feasible, though sole reliance on this format may provide an incomplete assessment of student’s overall clinical competency.

BackgroundGraves' orbitopathy has a profound negative impact on quality of life. Surgery is undertaken to preserve vision, correct diplopia and improve aesthetics. We sought to quantify the effect of different surgical approaches on quality of life. MethodsElectronic databases Ovid-MEDLINE, EMBASE were used from inception until 22 nd March, 2021 to identify studies assessing quality of life pre-and post-surgical intervention for Graves' orbitopathy. Two reviewers independently extracted data and performed quality assessments.Random-effects and Bayesian models for meta-analyses were utilised. Results10 articles comprising 632 patients with a mean age of 48.4 years (range 16-85 years) were included. All used the Graves' Ophthalmopathy Quality of Life questionnaire (GO-QOL). For GO-QOL appearance, the pooled standardised mean improvement for patients after surgery was +0.72 (95% CI 0.50-0.94) I 2 69% (95% CI 52-80%). For GO-QOL visual functioning, the pooled SMD for patients after surgery was +0.41 (95% CI 0.25-0.58) I 2 60% (95% CI 36-74%).For visual appearance, orbital decompression yielded the greatest improvement (SMD +0.84, 95% CI 0.54-1.13) followed by eyelid surgery (SMD +0.38, 95% CI 0.05-0.70), while strabismus correction had no significant effect (SMD +0.94, 95% CI -0.10-1.99). Conversely strabismus correction was associated with the greatest improvement (SMD +1.25, 95% CI 0.29-2.

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Background: HTLV-1/2 mother-to-child transmission (MTCT) is an important route for the maintenance of HTLV-1/2 within populations and disproportionally contributes to the burden of HTLV-1-associated diseases. Avoidance of breastfeeding is the safest recommendation to prevent MTCT. Due to the benefits of breastfeeding, alternative methods that would allow seropositive mothers to breastfeed their babies are needed. There is limited knowledge about HTLV-1/2 infection and breastmilk. Methods: Paired blood and milk samples collected from HTLV-1/2 seropositive mothers were tested for HTLV-1 proviral load (PVL) quantification and for the detection of anti-HTLV-1/2 IgG. Results: All breastmilk samples had detectable anti-HTLV-1/2 IgG. HTLV-1/2 proviral DNA was detected in all samples except for one. HTLV-1 PVL and IgG binding ratio (BR) was similar in milk and plasma. However, antibody titer was significantly higher in blood (Median (95%CI): Milk:128 (32–512); Plasma:131,584 (16,000–131,584), p < 0.05). There was a strong correlation between HTLV-1 PVL, anti-HTLV-1/2 IgG BR, and titer when comparing milk and blood. PVL did not correlate with antibody BR nor titer in blood or milk. Conclusions: Anti-HTLV-1/2 IgG are present in milk in the same proportion as blood but in lower quantity. PVL in milk correlates with blood.

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation.

Human T-lymphotropic viruses type 1 and 2 (HTLV-1/2) are prevalent in endemic clusters globally, and HTLV-1 infects at least 5 to 10 million individuals. Infection can lead to inflammation in the spinal cord, resulting in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or adult T cell leukemia/lymphoma (ATL). Obtaining venous blood for serological screening, typically performed using enzyme immunoassays (EIAs), is invasive, sometimes socially unacceptable, and has restricted large-scale seroprevalence studies. Collecting oral fluid (OF) is a noninvasive alternative to venesection. In this study, an IgG antibody capture EIA was developed and validated to detect anti-HTLV-1/2 IgG in OF. OF and plasma specimens were obtained from seropositive HTLV-1/2-infected patients attending the National Centre for Human Retrovirology (n = 131) and from HTLV-1/2-uninfected individuals (n = 64). The assay showed good reproducibility and high diagnostic sensitivity (100%) and specificity (100%) using both OF and plasma. The Murex HTLV I+II commercial assay was evaluated and did not detect anti-HTLV-1/2 IgG in 14% (5/36) of OF specimens from seropositive donors. The reactivities of OF and plasma in the IgG capture correlated strongly (r = 0.9290) and were not significantly affected by delayed extraction when held between 3°C and 45°C for up to 7 days to simulate field testing. The use of OF serological screening for HTLV-1/2 infection could facilitate large-scale seroprevalence studies, enabling active surveillance of infection on a population level.

BackgroundRecent reports show that about 10% of UK-graduate doctors leave the country to pursue specialty training elsewhere. Our article aims to evaluate the motivating factors for UK graduates to leave the National Health Service (NHS), especially during the COVID-19 pandemic and Brexit.Study designCross-sectional study.MethodA novel 22-item questionnaire was disseminated at a webinar series regarding the application process to pursue residency training in six different countries/regions from 2 August 2020 to 13 September 2020. The data was analysed using Kruskal-Wallis rank-sum with post-hoc Wilcoxon test to compare the difference in significance among the motivating factors.Results1118 responses from the UK medical students and doctors were collected; of which, 1001 (89.5%) were medical students, and 88 (7.9%) were junior doctors. There was a higher propensity for leaving after the Foundation Programme compared with other periods (p<0.0001 for all comparisons). There was no difference between desire for leaving after core surgical/medical training and specialty training (p=0.549). However, both were significantly higher than leaving the NHS after medical school (p<0.0001). Quality of life and financial prospects (both p<0.0001) were the most agreed reasons to leave the NHS, followed by clinical and academic opportunities and, subsequently, family reasons.ConclusionFuture work on the quality of life for doctors in the UK should be explored, especially among those considering leaving the NHS. Policymakers should focus on assessing the difference in working hours, on-call hours and wages that may differ among healthcare systems.