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.

Effects of virtual reality on anxiety and pain in adult patients undergoing wound-closure procedures: A pilot randomized controlled trial.

Background: In emergency departments, suturing is a typical procedure for closing lacerated wounds but is invasive and often causes anxiety and pain. Virtual reality (VR) intervention has been reported as a relaxing measure. Objective: The study aims to examine the effects of VR intervention on anxiety, pain, physiological parameters, local anesthesia requirements and satisfaction in Chinese adult patients undergoing wound closure in emergency departments in Hong Kong. Methods: Adult patients who had lacerated wounds and were undergoing wound closure by suturing can communicate in Chinese and were hemodynamically stable were invited for this trial. Eighty patients were randomly assigned to the VR group, which received VR intervention and standard care, or to the control group, which received standard care only. The primary outcome was anxiety, and the secondary outcomes included pain, blood pressure, pulse rate, satisfactory with pain management, service satisfactory, and extra local analgesia requirement. Outcomes were conducted at baseline, during the procedure and 5 min after the procedure. Results: The VR group had a significantly greater reduction in anxiety (p < 0.001), pain (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), pulse rate (p = 0.003) and requested less amount of additional local anesthesia (p = 0.025). The satisfactory level with pain management (p = 0.019) and service (p = 0.002) were significantly higher in participants who received VR intervention. In addition, most participants preferred to have VR in the future, and no major adverse events associated with the use of VR were reported. Conclusion: This pilot study provides insight into the use of VR and the direction of future studies. It may effectively improve psychological and physiological outcomes in adult patients during wound-closure procedures in emergency departments.

N,N-dimethylpentylone poisoning: Clinical manifestations, analytical detection, and metabolic characterization.

INTRODUCTION: The proliferation of new psychoactive substances (NPS) poses a significant challenge to clinical and forensic toxicology laboratories. N,N-dimethylpentylone, a novel synthetic cathinone, has emerged as a public health concern. The aims of this study are to describe the clinical presentation of N,N-dimethylpentylone poisoning, to describe detection methods, and to deduce its metabolic pathways. METHODS: Clinical data was collected and reviewed retrospectively from patients with confirmed N,N-dimethylpentylone exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify N,N-dimethylpentylone and its metabolites in urine samples. The metabolic pathway was characterised by comparison of the detected substances with reference standards. RESULTS: Eight cases were included in the case series. Seven different metabolites of N,N-dimethylpentylone were identified in in vivo patient urine samples, where the two major metabolic pathways were proposed to be opening of the 5-membered ring and reduction of carboxide. All patients presented with neuropsychiatric and/or cardiovascular symptoms. Co-ingestion with other substances was reported in all cases. One patient requiring intensive care was described in detail. All patients eventually recovered. The analytical method allowed the simultaneous identification of N,N-dimethylpentylone, pentylone and bisdesmethyl-N,N-dimethylpentylone, as well as other drugs of abuse in patient samples. CONCLUSION: N,N-dimethylpentylone appears to be less potent than its metabolite pentylone. Co-ingestion with other drugs of abuse is common. Poisoning cases have neuropsychiatric and cardiovascular manifestations. An updated and comprehensive laboratory method is needed for its detection.

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.

SARS-CoV-2-specific antibodies and neutralization capacity in breast milk following infection vs vaccination.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been found in breast milk following both natural SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination. This was a prospective study to evaluate the temporal changes in amount and neutralization capacity of anti-SARS-CoV-2 antibodies in breast milk stimulated by natural infection and by vaccination. Serial breast milk samples were collected from postnatal women who were recruited through convenience sampling. We found a rapid increase in neutralizing SARS-CoV-2-specific antibodies in breast milk from both study groups. Amongst the infection group, the median immunoglobulin A (IgA) level was 16.99 (range, 0-86.56) ng/mL and median binding capacity was 33.65% (range, 0-67.65%), while in the vaccination group these were 30.80 (range, 0-77.40) ng/mL and 23.80% (range, 0-42.80%), respectively. In both groups, both binding capacity and IgA levels decreased progressively over time after peaking. Neutralizing activity had become undetectable by about 150 days after the first dose of the vaccine, but a vaccine booster dose restored secretion of neutralizing IgA, albeit with different levels of response in different individuals. This highlights the importance of the vaccine booster dose in sustaining neutralizing antibody levels in breast milk, which may potentially provide protection for very young children, who cannot receive the COVID-19 vaccine. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging considerations for salvage surgery in nasopharyngeal carcinoma: what surgeons need to know.

Nasopharyngeal carcinoma is frequently an undifferentiated squamous cell carcinoma, which is primarily treated with radiotherapy with or without chemotherapy; however, for residual or recurrent cancer, salvage surgery is the treatment of choice for resectable disease because it reduces the significant morbidity associated with re-irradiation. This review highlights the current surgical approach, mapping the extent of disease with an emphasis on magnetic resonance imaging (MRI) and integrated positron-emission tomography (PET)/computed tomography (CT), imaging features that determine operability for nasopharyngectomy and neck dissection, and need for a succinct radiological report and multidisciplinary team discussion, which are of paramount importance for successful surgical planning.

Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death.

Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.

Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.

Since the publication of the Hong Kong Epilepsy Guideline in 2009, there has been significant progress in antiepileptic drug development. New AEDs have emerged, and data about their uses have been published. Women require special attention in epilepsy care. Drug teratogenicity, pregnancy, breastfeeding, contraception, reproduction technology, menopause, and catamenial epilepsy are major topics. Antiepileptic drugs should be chosen individually for patients who are pregnant or may become pregnant with consideration of their teratogenicity and seizure control properties. Folate is commonly prescribed for women of childbearing age who are taking antiepileptic drugs. Spontaneous vaginal delivery and breastfeeding are not contra-indicated in most cases but need to be considered individually based on the patient's medical condition and wishes. Serum drug level monitoring of certain antiepileptic drugs during pregnancy and puerperium can guide dosage adjustment. For catamenial epilepsy, intermittent benzodiazepines such as clobazam during the susceptible phase of the menstrual cycle could be a treatment option.

Examining the Moderating Role of Patient Enablement on the Relationship Between Health Anxiety and Psychosomatic Distress: A Cross-Sectional Study at a Traditional Chinese Medicine Outpatient Clinic in Hong Kong.

BACKGROUND: Little research effort has been devoted to examining the role of patient enablement in alleviating health anxiety in primary care. In this study, we examined the role of patient enablement as a moderator in the relationship between health anxiety, psychological distress, and treatment seeking in traditional Chinese medicine (TCM). METHODS: The participants were 634 patients of a government-subsidized Chinese medicine outpatient clinic in Hong Kong. They were asked to complete a series of questionnaires on patient enablement, health anxiety, anxiety, depression, physical distress, annual clinic visits, and service satisfaction and provided various demographic details. Descriptive statistics, correlations, and general linear models were used to analyze the data. RESULTS: We found that patient enablement correlated positively with service satisfaction. Patient enablement also interacted significantly with health anxiety in affecting indices of psychological distress (depression, anxiety) and treatment seeking (annual visits). Among highly enabled patients, the positive association between health anxiety and indices of psychological distress was weakened, and they also showed more health anxiety-driven treatment seeking as measured by annual clinic visits. CONCLUSION: These findings suggest a moderating mechanism by which patient enablement weakens the relationship between health anxiety on psychological well-being and increases treatment-seeking behavior in TCM. Practitioners are encouraged to provide sufficient information to patients to foster self-care and disease self-management using complementary and alternative medicine (CAM).

A retrospective study on risk assessment and management of forensic psychiatric inpatients in Hong Kong.

The Department of Forensic Psychiatry of Castle Peak Hospital is the only facility in Hong Kong that provides territory-wide forensic psychiatric services for patients with criminal involvement. This retrospective study aimed to explore whether the rehabilitation programs provided by the department could significantly reduce the risks of forensic psychiatric inpatients as measured by the Short-Term Assessment of Risk and Treatability (START). START ratings of inpatients who were hospitalized in the department for more than 3 months and were discharged to the community during the period from 11 April 2015 to 31 March 2019 were analyzed. A total of 79 patients were assessed, of whom 61 (77.2%) were males. Fifty-four (68.4%) patients suffered from schizophrenia. START scores upon admission (strength score = 5.67; vulnerability score = 17.43) and upon discharge (strength score = 6.87, vulnerability score = 11.18) indicated significant reduction of risks among inpatients (p < 0.05).

A clinical prediction score using age at diagnosis and saline infusion test parameters can predict aldosterone-producing adenoma from idiopathic adrenal hyperplasia.

PURPOSE: Accurate subtyping of the primary aldosteronism into aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH) is important to direct for specific treatment modalities. The objective of the study was to compare the clinical and biochemical parameters of APA and IAH patients to derive a Clinical Prediction Score reliably predicting APA from IAH. METHODS: This was a retrospective multi-centre study recruiting 38 APA patients and 42 IAH patients from four major hospitals in Hong Kong using database from Surgical Outcomes Monitoring and Improvement Programme and Clinical Data Analysis and Reporting System. Their clinical and biochemical parameters were evaluated. RESULTS: Patients in APA group were younger than IAH group (mean age 48.6 ± 9.2 vs. 57.1 ± 7.3 years old, p < 0.001), had more suppressed renin before saline infusion in saline infusion test (SIT) (median 0.19 [IQR 0.15-0.37] vs. 0.39 [IQR 0.19-0.69] ng/mL/h, p = 0.01), and higher aldosterone level after saline infusion in SIT (median 674 [IQR 498-1000] vs. 327 [IQR 242-483] pmol/L, p < 0.001). A clinical prediction score using three parameters was devised, comprising age at diagnosis < 50 years, PRA before saline infusion in SIT ≤ 0.26 ng/mL/h, and aldosterone level after saline infusion in SIT ≥ 424 pmol/L. A score of 2 would predict APA with a sensitivity of 84.2% and specificity of 88.1%, and a score of 3 would predict APA with a sensitivity of 31.6% and specificity of 100%. CONCLUSIONS: Clinical Prediction Score based on the combination of age at diagnosis, PRA, and aldosterone level in the saline infusion tests could reliably predict APA from IAH.