Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

OBJECTIVE: To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). METHODS: This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 µg/mL and 510 µg/mL). RESULTS: Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 µg/mL and > 510 µg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 µg/mL and > 510 µg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 µg/mL and > 510 µg/mL. CONCLUSIONS: The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 µg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Epidemiology and outcomes of geriatric and non-geriatric patients with drug allergy labels in Hong Kong.

INTRODUCTION: Adverse drug reactions are more common in geriatric patients than in younger patients, but there have been insufficient studies concerning the epidemiology or burden of drug allergy labels in geriatric patients. We prospectively investigated the prevalence and outcomes of geriatric patients with drug allergy labels in a cohort of hospitalised patients. METHODS: Patients admitted to a regional hospital over a 6-month period were recruited for this study. All patients with drug allergy labels were prospectively followed until discharge; clinical data were anonymously extracted for analyses. Patients were categorised into either geriatric (aged ≥65 years) or non-geriatric (aged <65 years) groups. Demographic characteristics, clinical outcomes, and prevalences of drug allergy labels were compared between groups. RESULTS: There were 4361 admissions involving 3641 patients during the 6-month study period. Overall, 492 patients (13.5%) had drug allergy labels, consisting of 151 non-geriatric patients (30.7%) and 341 geriatric patients (69.3%). The prevalence of drug allergy labels did not significantly differ between geriatric and non-geriatric patients (13.5% vs 13.5%, P=0.976). Significantly more patients in the geriatric group had drug allergy labels to cardiovascular system drugs (15.5% vs 4.6%, P=0.001). Geriatric patients had a significantly lower rate of direct discharge from the hospital (73.0% vs 88.1%, P<0.001) and required transfers to convalescent or rehabilitation care for further management. CONCLUSIONS: More than 13% of hospitalised geriatric patients had drug allergy labels. The leading causes of drug allergy labels were similar between geriatric and non-geriatric patients. Geriatric patients with drug allergy labels had significantly more labelled allergies to cardiovascular system drugs and adverse clinical outcomes.

Burnout and well-being in young doctors in Hong Kong: a territory-wide cross-sectional survey.

INTRODUCTION: This territory-wide study evaluated the level of burnout and health status among young doctors in Hong Kong. METHODS: All young doctors in Hong Kong, defined as residents-in-training or doctors within 10 years of their specialist registration, were invited to participate in an online cross-sectional survey. This survey used standardised questionnaires including the Copenhagen Burnout Inventory (CBI) for burnout, Patient Health Questionnaire-9 for depression, and general health questionnaires. RESULTS: In total, 514 doctors completed the survey; 284 were doctors within 10 years of their specialist registration, while 230 were residents-in-training. There were 277 women (54%); among all respondents, the mean age was 33.7 ± 6.1 years. Using a CBI subscale cut-off score of ≥50 (moderate and higher), 72.6% (n=373) of respondents reported personal burnout; 70.6% (n=363) of respondents reported work-related burnout; and 55.4% (n=285) of respondents reported client-related burnout. Furthermore, 24% (n=125) of respondents were "somewhat dissatisfied" with their present job position; 4% (n=19) of respondents were "very dissatisfied" with their present job position. The prevalence of depression among respondents was 21% (n=110). CONCLUSIONS: In this territory-wide cross-sectional survey of young doctors in Hong Kong, a high prevalence of burnout was identified among young doctors; respondents exhibited a considerable level of depression and substantial dissatisfaction with their current positions. Strategies to address these problems must be formulated to ensure the future well-being of the medical and dental workforce in Hong Kong.

Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus.

OBJECTIVE: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Evaluation of a multiplex flow immunoassay versus conventional assays in detecting autoantibodies in systemic lupus erythematosus.

INTRODUCTION: Conventional diagnostic assays are being replaced with automated multiplex assays, but their performance needs to be evaluated. We compared a multiplex flow immunoassay with conventional techniques in the detection of antinuclear antibodies (ANAs) and antibodies to specific extractable nuclear antigens (ENAs) in serum samples from patients with systemic lupus erythematosus. METHODS: A total of 140 consecutive Chinese patients with systemic lupus erythematosus and 41 healthy controls were included. The automated BioPlex 2200 ANA Screen assay (Bio-Rad Laboratories, Hercules [CA], US) was compared with indirect immunofluorescence. In addition, use of BioPlex 2200 to detect anti-ENA antibodies was compared with in-house assays of countercurrent immunoelectrophoresis (CIEP), enzyme-linked immunosorbent assay (ELISA), and line blot. RESULTS: The sensitivity and specificity of BioPlex in detecting ANAs (91.4% and 95.1%, respectively) were comparable to those of indirect immunofluorescence (90.7% and 85.4%, respectively). Overall, BioPlex achieved the best agreement with ELISA in detecting anti-ENA antibodies: agreement was >90% for most antibody types (κ=0.79-0.94). In contrast, agreement was poorest with CIEP, ranging from 85.6% (κ=0.33) for anti-Sm antibodies to 93.9% (κ=0.88) for anti-Ro antibodies. Overall, BioPlex and ELISA had the highest sensitivity, whereas CIEP had the highest specificity. In terms of disease association, anti-Sm detected by CIEP had the best positive predictive value and specificity for lupus nephritis. CONCLUSIONS: In a local lupus cohort, BioPlex showed comparable sensitivity to indirect immunofluorescence in detecting ANAs and comparable performance to ELISA in detecting anti-ENA antibodies. However, CIEP was the best method in terms of disease specificity.

Immunoglobulin G4-related disease in Hong Kong: clinical features, treatment practices, and its association with multisystem disease.

INTRODUCTION: Immunoglobulin G4-related disease remains an under-recognised and evolving disease. Local data are sparse and previous publications have been limited to individual case reports or case series only. We conducted this study to review the clinical features, treatment practices, and factors associated with multisystem involvement in Hong Kong. We described the clinical features and treatment modalities of the largest cohort of immunoglobulin G4-related disease in our locality thus far. METHODS: We retrospectively evaluated all patients with immunoglobulin G4-related disease between January 2003 and December 2015 in Queen Mary Hospital and combined this with patient data extracted from previous local publications. We analysed the clinical features, treatment practices, and factors associated with the number of organ systems involved. RESULTS: A total of 104 patients (55 from Queen Mary Hospital and 49 from literature review) were identified. Patients were predominantly older men (mean [standard deviation] age, 61.9 [12.7] years; male-to-female ratio=3:1) and 94.4% had elevated pre-treatment serum immunoglobulin G4 levels. Hepatobiliary and pancreatic system (40.4%), salivary gland (33.7%), lymph node (29.8%), and eye (19.2%) were the most common organ systems involved. Lymphadenopathy was associated with glucocorticoid use (odds ratio=2.65; 95% confidence interval, 1.08-6.54; P=0.034). Pre-treatment serum immunoglobulin G4 levels correlated with the number of organ systems involved (ß=0.347; P=0.004) and, specifically, more associated with patients having salivary gland involvement than those without (mean, 1109 mg/dL vs 599 mg/dL; P=0.012). CONCLUSION: We identified pre-treatment serum immunoglobulin G4 to be associated with multisystem disease, especially with salivary gland involvement, highlighting its potential for disease prognostication and monitoring. Increased physician awareness and multidisciplinary efforts are required for early diagnosis and optimal management of this masquerading disease.

Systemic lupus erythematosus patients with past neuropsychiatric involvement are associated with worse cognitive impairment: a longitudinal study.

Longitudinal studies on cognitive impairment in patients with past history of neuropsychiatric lupus (NPSLE) are scant. In this study, NPSLE patients and matched disease and healthy controls were examined with a full battery of neuropsychological tests that covered eight cognitive domains at two time-points 12 months apart. Confounders, including depressive and anxiety symptoms, were measured by the Hospital Anxiety and Depression Scale. Eighteen NPSLE, 18 patients with systemic lupus erythematosus (SLE) who had no previous cerebral involvement (non-NPSLE) and 16 healthy subjects were recruited. NPSLE patients consistently reported more cognitive and anxiety symptoms than non-NPSLE patients over both time-points. NPSLE patients had significantly worse memory, simple and complex attention compared to non-NPSLE patients, among which memory remained significantly impaired after adjustment for confounders. NPSLE patients demonstrated a trend of higher raw scores of some neurocognitive tests upon re-evaluation over 12 months, but NPSLE patients did not demonstrate any practice effect. In conclusion, NPSLE patients had significantly worse and persistently impaired memory and learning deficits compared to non-NPSLE patients over the 12-month re-assessment period.

How we flipped the medical classroom.

Flipping the classroom centres on the delivery of print, audio or video based material prior to a lecture or class session. The class session is then dedicated to more active learning processes with application of knowledge through problem solving or case based scenarios. The rationale behind this approach is that teachers can spend their face-to-face time supporting students in deeper learning processes. In this paper we provide a background literature review on the flipped classroom along with a three step approach to flipping the classroom comprising implementing, enacting and evaluating this form of pedagogy. Our three step approach is based on actual experience of delivering a flipped classroom at the University of Hong Kong. This initiative was evaluated with positive results. We hope our experience will be transferable to other medical institutions.

Allergy in Hong Kong: an unmet need in service provision and training.

Many children in Hong Kong have allergic diseases and epidemiological data support a rising trend. Only a minority of children will grow out of their allergic diseases, so the heavy clinical burden will persist into adulthood. In an otherwise high-quality health care landscape in Hong Kong, allergy services and training are a seriously unmet need. There is one allergy specialist for 1.5 million people, which is low not only compared with international figures, but also compared with most other specialties in Hong Kong. The ratio of paediatric and adult allergists per person is around 1:460 000 and 1:2.8 million, respectively, so there is a severe lack of adult allergists, while the paediatric allergists only spend a fraction of their time working with allergy. There are no allergists and no dedicated allergy services in adult medicine in public hospitals. Laboratory support for allergy and immunology is not comprehensive and there is only one laboratory in the public sector supervised by accredited immunologists. These findings clearly have profound implications for the profession and the community of Hong Kong and should be remedied without delay. Key recommendations are proposed that could help bridge the gaps, including the creation of two new pilot allergy centres in a hub-and-spoke model in the public sector. This could require recruitment of specialists from overseas to develop the process if there are no accredited allergy specialists in Hong Kong who could fulfil this role.

Nanoscale control of graphene electrodes.

Single layer graphene nano-gaps are fabricated by applying the method of feedback-controlled electroburning to notched ribbon devices, which are plasma etched from CVD grown graphene that is wet-transferred onto pre-patterned metal electrodes. Electrical and structural characterizations show that nanometer size gaps form at the center of the notch. We have processed a total number of 1079 devices using this method with a fabrication yield of 71%. Our results demonstrate precise control over the size and position of the nano-gaps, and open up the possibility of graphene electrodes for large-scale integrated molecular devices.

The CD11b-integrin (ITGAM) and systemic lupus erythematosus.

Variations at the ITGAM gene, which encodes for the CD11b chain of the Mac-1 (alphaMbeta2; CD11b/CD18; complement receptor-3) integrin, is one of the strongest genetic risk factors for systemic lupus erythematosus (SLE). More specifically, a genetic variant (rs1143679) which results in an arginine to histidine substitution at position 77 in the extracellular portion of the integrin is associated with disease. It has recently been shown that this amino acid substitution results in a dysfunctional integrin, which is deficient in mediating cell adhesion to integrin ligands, phagocytosis and in addition cannot restrict inflammatory cytokine production in macrophages. In this review, we discuss immunological functions of the Mac-1 integrin and how defects in the genetic variant of Mac-1 may relate to SLE development.