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Introduction: Significant ventilator-associated pneumonia and mortality were found in COVID-19 patients who required mechanical ventilation which calls for non-invasive means in managing respiratory failure. Methods: We retrospectively reviewed patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital in Hong Kong with severe acute respiratory syndrome coronavirus 2 infection from 28 November to 15 December 2020. Patients' laboratory, respiratory parameters and outcome data were recorded and analysed. Results: Eleven received prone ventilation. The median age was 67 (inter-quartile range: 59-72) years, and median COVID-19 GRAM score was 151 (inter-quartile range: 133-181), representing a high-risk group. There were significant improvements 1 h after awake proning in SpO2 (95% vs 92%, p = 0.008), FiO2 (0.4 vs 0.5, p = 0.003), SpO2/FiO2 (240 vs 184, p = 0.005), respiratory rate (19 vs 26, p = 0.006) and respiratory rate - oxygenation index (13.22 vs 7.67, p = 0.003; Table 1). Although not reaching statistical significance, the median PaO2, PaCO2 and PaO2/FiO2 improved after proning. The overall intubation rate was 22% and intensive care unit mortality was 22%, which is in contrast to 65.5% and 27.6%, respectively, in the first three waves. Although did not reach statistical significance, those received prone ventilation tend to have a lower ICU mortality (9.1% vs 42.9%, p = 0.245) and hospital mortality (18.2% vs 42.9%, p = 0.326). Conclusion: Awake proning potentially minimizes complications from invasive ventilation and provides a low-cost low-risk treatment option in COVID-19 patients with respiratory failure. This is particularly important when healthcare resources are strained at times of a pandemic.

Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. Patients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis. Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.

The risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA. Consecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients). Overall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96-4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07-3.75; = 0.031) was independently associated with the composite outcome in older patients. In older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events.

Background and purposeSymptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics (CFD) models were associated with the risk of stroke recurrence. We aimed to develop and compare stroke risk prediction nomograms in sICAS, based on vascular risk factors and these metrics.MethodsPatients with 50%–99% sICAS confirmed in CT angiography (CTA) were enrolled. Conventional vascular risk factors were collected. Severity of luminal stenosis in sICAS was dichotomised as moderate (50%–69%) and severe (70%–99%). Translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified via CTA-based CFD modelling; the haemodynamic status of sICAS was classified as normal (normal PR&WSSR), intermediate (otherwise) and abnormal (abnormal PR&WSSR). All patients received guideline-recommended medical treatment. We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression, in predicting the primary outcome, recurrent ischaemic stroke in the same territory (SIT) within 1 year.ResultsAmong 245 sICAS patients, 20 (8.2%) had SIT. The D2H2A nomogram, incorporating diabetes, dyslipidaemia, haemodynamic status of sICAS, hypertension and age ≥50 years, showed good calibration (P for Hosmer-Lemeshow test=0.560) and discrimination (C-statistic 0.73, 95% CI 0.60 to 0.85). It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis, compared with nomograms composed of conventional vascular risk factors only, and plus the severity of luminal stenosis in sICAS. Sensitivity analysis in patients with anterior-circulation sICAS showed similar results.ConclusionsThe D2H2A nomogram, incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models, could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment.

BackgroundIntracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse.MethodsWe prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%–99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI.ResultsAmong 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load.ConclusionsUlcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Background and purposeCerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs.MethodsIn this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs.ResultsA total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH.ConclusionsIn Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

Introduction: Cerebral small vessel disease (CSVD) commonly exists in patients with symptomatic intracranial atherosclerotic disease (sICAD). We aimed to investigate the associations of hemodynamic features of sICAD lesions with imaging markers and overall burden of CSVD. Patients and methods: Patients with anterior-circulation sICAD (50%–99% stenosis) were analyzed in this cross-sectional study. Hemodynamic features of a sICAD lesion were quantified by translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) via CT angiography-based computational fluid dynamics modeling. PR ⩽median was defined as low (“abnormal”) PR, and WSSR ⩾ fourth quartile as high (“abnormal”) WSSR. For primary analyses, white matter hyperintensities (WMHs), lacunes, and cortical microinfarcts (CMIs) were assessed in MRI and summed up as overall CSVD burden, respectively in ipsilateral and contralateral hemispheres to sICAD. Enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) were assessed for secondary analyses. Results: Among 112 sICAD patients, there were more severe WMHs, more lacunes and CMIs, and more severe overall CSVD burden ipsilaterally than contralaterally (all p < 0.05). Abnormal PR and WSSR (vs normal PR and WSSR) was significantly associated with moderate-to-severe WMHs (adjusted odds ratio = 10.12, p = 0.018), CMI presence (5.25, p = 0.003), and moderate-to-severe CSVD burden (12.55; p = 0.033), ipsilaterally, respectively independent of contralateral WMHs, CMI(s), and CSVD burden. EPVSs and CMBs were comparable between the two hemispheres, with no association found with the hemodynamic metrics. Discussion and conclusion: There are more severe WMHs and CMI(s) in the hemisphere ipsilateral than contralateral to sICAD. The hemodynamic significance of sICAD lesions was independently associated with severities of WMHs and CMI(s) ipsilaterally. Graphical abstract

Background The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders. Methods Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3. Results Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship ( P -values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models ( P -values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed. Conclusion Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.

We evaluated the reliability of early life nasopharyngeal carcinoma (NPC) aetiology factors in the questionnaire of an NPC case-control study in Hong Kong during 2014–2017. 140 subjects aged 18+ completed the same computer-assisted questionnaire twice, separated by at least 2 weeks. The questionnaire included most known NPC aetiology factors and the present analysis focused on early life exposure. Test-retest reliability of all the 285 questionnaire items was assessed in all subjects and in 5 subgroups defined by cases/controls, sex, time between 1 st and 2 nd questionnaire (2–29/≥30 weeks), education (secondary or less/postsecondary), and age (25–44/45–59/60+ years) at the first questionnaire. The reliability of items on dietary habits, body figure, skin tone and sun exposure in early life periods (age 6–12 and 13–18) was moderate-to-almost perfect, and most other items had fair-to-substantial reliability in all life periods (age 6–12, 13–18 and 19–30, and 10 years ago). Differences in reliability by strata of the 5 subgroups were only observed in a few items. This study is the first to report the reliability of an NPC questionnaire, and make the questionnaire available online. Overall, our questionnaire had acceptable reliability, suggesting that previous NPC study results on the same risk factors would have similar reliability.

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.