Poisoning by toxic plants in Hong Kong: a 15-year review.

INTRODUCTION: Hong Kong has a great diversity of plants, many of which are toxic to humans. The aim of this study was to identify the plant species most commonly involved in cases of plant poisoning in Hong Kong and to provide clinicians with a reference tool for the diagnosis and management of plant poisoning. METHODS: We retrospectively reviewed all plant poisoning cases referred to the Hospital Authority Toxicology Reference Laboratory from 1 January 2003 to 31 December 2017. Demographics, clinical presentation, laboratory findings, treatment and outcomes of patients, as well as morphological identification and analytical testing of the plant specimens, were investigated. RESULTS: A total of 62 cases involving 26 poisonous plant species were identified, among which Alocasia macrorrhizos (Giant Alocasia), Gelsemium elegans (Graceful Jessamine), and Rhododendron (Azalea) species were the three most commonly encountered. Gastrointestinal toxicity (n=30, 48%), neurological toxicity (n=22, 35%), and hepatotoxicity (n=6, 10%) were the three most common clinical problems. Forty-nine (79%) and eight (13%) patients had mild and moderate toxicity, respectively; they all recovered shortly with supportive treatment. The remaining five (8%) patients experienced severe toxicity requiring intensive care support. Most patients (n=61, 98%) used the plants intentionally: as a medicinal herb (n=31), as food (n=29), and for attempting suicide (n=1). Reasons for using the poisonous plants included misidentification (n=34, 55%), unawareness of the toxicity (n=20, 32%), and contamination (n=6, 10%). CONCLUSIONS: Although most plant exposure resulted in a self-limiting disease, severe poisonings were encountered. Epidemiology of plant poisonings is geographically specific. Clinicians should be aware of local poisonous plants and their toxicities.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.

Effects of a plasma heating procedure for inactivating Ebola virus on common chemical pathology tests.

OBJECTIVES: The recent declaration of Ebola virus disease as epidemic by the World Health Organization indicates urgency for affected countries and their laboratories to evaluate and provide treatment to patients potentially infected by the Ebola virus. A heat inactivation procedure involving treating specimens at 60°C for 60 minutes has been suggested for inactivation of the Ebola virus. This study aimed at evaluating the effect of plasma heating on common biochemical tests. DESIGN: Comparative experimental study. SETTING: A regional chemical pathology laboratory in Hong Kong. METHODS: Forty consecutive plasma specimens for general chemistry analytes on Beckman Coulter AU5822 and another 40 plasma specimens for troponin I analysis on Access 2 Immunoassay System were obtained, anonymised, and divided into two aliquots. One aliquot was analysed directly and the other was analysed after heating at 60°C for 60 minutes. RESULTS: A total of 20 chemical pathology tests were evaluated. Nine tests (sodium, potassium, chloride, urea, creatinine, total calcium, phosphate, total protein, and glucose) were not significantly affected by the heat inactivation procedure and remained clinically interpretable. Results for magnesium (15% mean increase), albumin (41% mean increase), bilirubin (8% mean decrease), amylase (27% mean decrease), and troponin I (76% mean decrease) were still interpretable using regression estimation with proportional bias. However, all enzymes studied except amylase (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, and lactate dehydrogenase) were inactivated to a significant degree. Their Pearson r or Spearman rho values ranged from no significant correlation (P≥0.05) to 0.767, and most normality was rejected. CONCLUSION: Heat inactivation results in no significant change in electrolytes, glucose, and renal function tests, but causes a significant bias for many analytes. Recognition of the relationship between pre- and post-heat inactivation specimens allows clinical interpretation of affected values and contributes to patient care. For safety and diagnostic accuracy, we recommend use of a point-of-care device for blood gases, electrolytes, troponin, and liver and renal function tests within a class 2 or above biosafety cabinet with level 3 or above biosafety laboratory practice.

Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

OBJECTIVE: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. DESIGN: Cross-sectional study. SETTING: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. PARTICIPANTS: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. MAIN OUTCOME MEASURES: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. RESULTS: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. CONCLUSIONS: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

Recipes and general herbal formulae in books: causes of herbal poisoning.

Traditional Chinese medicine is commonly used locally, not only for disease treatment but also for improving health. Many people prepare soups containing herbs or herbal decoctions according to recipes and general herbal formulae commonly available in books, magazines, and newspapers without consulting Chinese medicine practitioners. However, such practice can be dangerous. We report five cases of poisoning from 2007 to 2012 occurring as a result of inappropriate use of herbs in recipes or general herbal formulae acquired from books. Aconite poisoning due to overdose or inadequate processing accounted for three cases. The other two cases involved the use of herbs containing Strychnos alkaloids and Sophora alkaloids. These cases demonstrated that inappropriate use of Chinese medicine can result in major morbidity, and herbal formulae and recipes containing herbs available in general publications are not always safe.

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.

Emergence of new psychoactive substance 2-fluorodeschloroketamine: Toxicology and urinary analysis in a cluster of patients exposed to ketamine and multiple analogues.

New psychoactive substances (NPS) emerge continually, amongst which is a growing class of ketamine analogues with an arylcyclohexylamine backbone. Recently we reported a poisoning outbreak associated with 2-oxo-PCE (deschloro-N-ethyl-ketamine). The present report describes the emergence of another ketamine analogue, 2-fluorodeschloroketamine (2F-DCK). The compound was first detected in a patient's urine, its identity confirmed by accurate mass analysis and comparison with reference standard. Four putative metabolites were identified, including nor-2F-DCK, dehydronor-2F-DCK (major metabolite) and two hydroxylated derivatives of nor-2F-DCK. Between January and July 2019, 20 cases of analytically confirmed 2F-DCK exposure were encountered. In 19 out of 20 cases, at least one more ketamine-type drug was detected concurrently with 2F-DCK, including ketamine (90%), deschloroketamine (DCK, 50%), 2-oxo-PCE (45%) and tiletamine (10%). In particular, six of the cases showed the presence of 4 ketamine-type drugs in the same urine sample. The clinical effects observed in patients exposed to 2F-DCK are predominantly neurological (impaired consciousness, agitation, abnormal behaviour) and cardiovascular (hypertension, tachycardia); five patients had loss of consciousness or convulsion. Management was mainly supportive; all patients recovered uneventfully. This is the first clinical case series involving 2F-DCK and frontline medical personnel are urged to be aware of this rapidly expanding class of NPS, in particular the co-ingestion of multiple ketamine analogues.

MiR-652-3p promotes bladder cancer migration and invasion by targeting KCNN3.

OBJECTIVE: Increasing evidence indicated that microRNAs (miRNAs) are crucial regulators for cancer development. Bladder cancer (BCa) is a major threat to human health. The aim of this study was to analyze the roles of miR-652-3p in BCa, and to explore the associated mechanisms. MATERIALS AND METHODS: MiR-652-3p expression in BCa cell lines was explored using Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) method. MiR-652-3p expression level in BCa tissues was explored at StarBase. Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and transwell invasion assay were conducted to investigate the biological roles of miR-652-3p. The underlying mechanisms of miR-652-3p in NSCLC were investigated using luciferase activity reporter assay and rescue experiments. RESULTS: We showed that miR-652-3p expression level was upregulated in both BCa tissues and cell lines. The knockdown of miR-652-3p significantly inhibited BCa cell proliferation, migration, and invasion in vitro. Moreover, we showed that potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 (KCNN3) was a functional target for miR-652-3p. Besides, the expression of KCNN3 in BCa tissues was negatively correlated with miR-652-3p. CONCLUSIONS: Collectively, these results showed that miR-652-3p could promote BCa cell proliferation, migration, and invasion via directly regulating KCNN3, which may provide a novel therapeutic target for BCa treatment.