Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.

OBJECTIVE: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). DESIGN: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. RESULTS: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23-0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03-1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19-0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. CONCLUSIONS: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes.

OBJECTIVES: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. METHODS: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. RESULTS: This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21-71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches. CONCLUSIONS: SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy - a systematic review of the literature.

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients > 18 years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3 months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation.

Clinical Characteristics, Genetic Basis and Healthcare Resource Utilisation and Costs in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia: A Retrospective Cohort Study.

Background: This study examined the clinical characteristics, genetic basis, healthcare utilisation and costs of catecholaminergic ventricular tachycardia (CPVT) patients from a Chinese city. Methods: This was a territory-wide retrospective cohort study of consecutive CPVT patients at public hospitals or clinics in Hong Kong. Healthcare resource utilisation for accident and emergency (A&E), inpatient and outpatient attendances were analysed over 19 years (2001-2019) followed by calculations of annualised costs (in USD). Results: Sixteen patients with a median presentation age (interquartile range (IQR) of 11 (9-14) years old) were included. Fifteen patients (93.8%) were initially symptomatic. Ten patients had both premature ventricular complexes (PVCs) and ventricular tachycardia/fibrillation (VT/VF). One patient had PVCs without VT/VF. Genetic tests were performed on 14 patients (87.5%). Eight (57.1%) tested positive for the ryanodine receptor 2 (RyR2) gene. Seven variants have been described elsewhere (c.14848G > A, c.12475C > A, c.7420A > G, c.11836G > A, c.14159T > C, c.10046C > T and c.7202G > A). c.14861C > G is a novel RyR2 variant not been reported outside this cohort. Patients were treated with beta-blockers (n = 16), amiodarone (n = 3) and verapamil (n = 2). Sympathectomy (n = 8) and implantable-cardioverter defibrillator implantation (n = 3) were performed. Over a median follow-up of 13.3 years (IQR: 8.4-18.1) years, six patients exhibited incident VT/VF. At the patient level, the median (IQR) annualised costs for A&E, inpatient and outpatient attendances were $ 66 (40-95), $ 10521 (5240-66887) and $ 791 (546-1105), respectively. Conclusions: All patients presented before the age of 19. The yield of genetic testing was 57%. The most expensive attendance type was inpatient stays, followed by outpatients and A&E attendances.

Isogenic Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes Reveal Activation of Wnt Signaling Pathways Underlying Intrinsic Cardiac Abnormalities in Rett Syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in MeCP2mutant iPSC-CMs. Treatment of MeCP2mutant iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the ß-catenin protein level and CACN1AC expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/ß-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.

Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies.

Inherited cardiomyopathies are among the major causes of heart failure and associated with significant mortality and morbidity. Currently, over 70 genes have been linked to the etiology of various forms of cardiomyopathy, some of which are X-linked. Due to the lack of appropriate cell and animal models, it has been difficult to model these X-linked cardiomyopathies. With the advancement of induced pluripotent stem cell (iPSC) technology, the ability to generate iPSC lines from patients with X-linked cardiomyopathy has facilitated in vitro modelling and drug testing for the condition. Nonetheless, due to the mosaicism of the X-chromosome inactivation, disease phenotypes of X-linked cardiomyopathy in heterozygous females are also usually more heterogeneous, with a broad spectrum of presentation. Recent advancements in iPSC procedures have enabled the isolation of cells with different lyonisation to generate isogenic disease and control cell lines. In this review, we will summarise the current strategies and examples of using an iPSC-based model to study different types of X-linked cardiomyopathy. The potential application of isogenic iPSC lines derived from a female patient with heterozygous Danon disease and drug screening will be demonstrated by our preliminary data. The limitations of an iPSC-derived cardiomyocyte-based platform will also be addressed.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

IMPORTANCE: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. EXPOSURE: Warfarin use within 14 days of IE diagnosis. MAIN OUTCOMES AND MEASURES: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. RESULTS: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. CONCLUSIONS AND RELEVANCE: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. KEY POINTS: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? FINDINGS: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study.

BACKGROUND AND AIMS: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope. METHODS AND RESULTS: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline. CONCLUSION: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.

Healthcare Big Data in Hong Kong: Development and Implementation of Artificial Intelligence-Enhanced Predictive Models for Risk Stratification.

Routinely collected electronic health records (EHRs) data contain a vast amount of valuable information for conducting epidemiological studies. With the right tools, we can gain insights into disease processes and development, identify the best treatment and develop accurate models for predicting outcomes. Our recent systematic review has found that the number of big data studies from Hong Kong has rapidly increased since 2015, with an increasingly common application of artificial intelligence (AI). The advantages of big data are that i) the models developed are highly generalisable to the population, ii) multiple outcomes can be determined simultaneously, iii) ease of cross-validation by for model training, development and calibration, iv) huge numbers of useful variables can be analyzed, v) static and dynamic variables can be analyzed, vi) non-linear and latent interactions between variables can be captured, vii) artificial intelligence approaches can enhance the performance of prediction models. In this paper, we will provide several examples (cardiovascular disease, diabetes mellitus, Brugada syndrome, long QT syndrome) to illustrate efforts from a multi-disciplinary team to identify data from different modalities to develop models using territory-wide datasets, with the possibility of real-time risk updates by using new data captured from patients. The benefit is that only routinely collected data are required for developing highly accurate and high-performance models. AI-driven models outperform traditional models in terms of sensitivity, specificity, accuracy, area under the receiver operating characteristic and precision-recall curve, and F1 score. Web and/or mobile versions of the risk models allow clinicians to risk stratify patients quickly in clinical settings, thereby enabling clinical decision-making. Efforts are required to identify the best ways of implementing AI algorithms on the web and mobile apps.

Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: a population-based cohort study.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients. This study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective population-based cohort study of prospectively recorded data on male patients with T2DM who were prescribed either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 from Hong Kong. METHODS: The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbor search was performed and multivariable Cox regression was applied. A three-arm analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted. RESULTS: This study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n = 17,120; DPP4I: n = 25,009). In the propensity score matched cohort, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). Over a follow-up duration of 5.61 years, SGLT2I was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) than DPP4I after adjustments. The subgroup analyses showed that the interactions between SGLT2I and age, hypertension, heart failure, and GLP-1a were not statistically significant. The result remained consistent in the sensitivity analysis. CONCLUSION: The study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after propensity score matching and adjustments compared to DPP4I amongst T2DM patients.

The Association Between Systemic Arterial Hypertension and Chronic Obstructive Pulmonary Disease. Results from the U.S. National Health and Nutrition Examination Survey 1999-2018: A Cross-sectional Study.

Background: Systemic arterial hypertension (HTN) is one of the common comorbidities among patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association between HTN and COPD. Methods: A total of 46,804 eligible non-pregnant participants aged ≥ 20 years examined in the Mobile Examination Center of the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this cross-sectional study. Participants with invalid data on covariates, HTN, and COPD were excluded. The association between HTN and COPD was studied using logistic regression upon adjusting the potential covariates. Results: Among the participants, 46.1% (95% confidence interval [CI], 45.3-46.9) had HTN, and 6.8% (95% CI, 6.4-7.2) had self-reported COPD. COPD was associated with HTN (OR [odds ratio]=1.18, 95% CI [1.05-1.31], P<0.01) after adjusting for demographics, socioeconomic factors, smoking, diabetes, body mass index, and medication use, including inhaled corticosteroids and methylxanthines. The association between HTN and COPD was significant among adults younger than 60 years (P<0.01). Stratified by smoking status, there was a significant association between HTN and COPD in current heavy smokers (1.25, 95% CI [1.01-1.58]; P=0.04). Conclusions: In this nationwide survey, COPD was associated with HTN. The association was more robust among adults younger than 60 years and current heavy smokers. Future prospective studies are needed to examine the relationship between HTN and COPD.

The Effects of Human Papillomavirus Infection and Vaccination on Cardiovascular Diseases, NHANES 2003-2016.

BACKGROUND: Human papillomavirus (HPV) infection has been proposed to be an unconventional risk factor for cardiovascular diseases. We investigated the association between HPV infection and cardiovascular diseases among women with or without HPV vaccination. METHODS: This cross-sectional study included 9,353 women aged between 20 to 59 years old who were tested for vaginal HPV DNA in the National Health and Nutrition Examination Survey (NHANES) 2003-2016. Cardiovascular diseases were defined as the presence of self-reported coronary heart diseases, heart attacks, angina pectoris, and stroke. The association between HPV and cardiovascular diseases was studied using logistic regression, with adjustment for the potential confounders. RESULTS: A total of 40.8% of women were HPV DNA positive; 3.0% had cardiovascular diseases; and 9.0% of women received the HPV vaccine. The presence of vaginal HPV infection was associated with cardiovascular diseases (odd ratio [OR] = 1.66, 95% confidence interval [CI] 1.28-2.16), which remained significant (OR = 1.54, 95% CI 1.15-2.08) after adjustment for sociodemographic characteristics, lifestyle behaviors, medical history, family history of cardiovascular diseases, and antihypertensive drugs. The association was absent among those who were vaccinated against HPV (OR= 0.50, 95% CI 0.07-3.51) but present among those who were not (OR = 1.63, 95% CI 1.18-2.25). CONCLUSIONS: There was an association between HPV infection and cardiovascular diseases. This association was not significant among women vaccinated against HPV. The effect of HPV vaccination on cardiovascular diseases requires further investigation.

X-linked dystonia parkinsonism: epidemiology, genetics, clinical features, diagnosis, and treatment.

X-linked dystonia parkinsonism (XDP) is a rare X-linked recessive degenerative movement disorder that only affects Filipino descent, predominantly males. Its underlying cause is associated with the genetic alterations in the TAF1/DYT3 multiple transcription system. SINE-VNTR-Alu (SVA) retrotransposon insertion was suggested to be the responsible genetic mutation. Clinically, it initially presents as focal dystonia and generalizes within years. Parkinsonism arises years later and coexists with dystonia. Nonmotor symptoms like cognitive impairment and mood disorders are also common among XDP patients. XDP diagnosis relies on clinical history and physical examination. On imaging, abnormalities of the striatum, such as atrophy, are widely seen and can explain the clinical presentations with a three-model pathway of the striatum. Treatments aim for symptomatic relief of dystonia and parkinsonism and to prevent complications. Oral medications, chemo-denervation, and surgery are used in XDP patients. This review summarizes the currently important information regarding XDP, providing a synoptic overview and understanding of XDP for future studies.

Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong.

INTRODUCTION: The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users. METHODS: This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression. RESULTS: The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23-5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses. CONCLUSION: SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Precision medicine in catecholaminergic polymorphic ventricular tachycardia: Recent advances toward personalized care.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy where the initial disease presentation is during childhood or adolescent stages, leading to increased risks of sudden cardiac death. Despite advances in medical science and technology, several gaps remain in the understanding of the molecular mechanisms, risk prediction, and therapeutic management of patients with CPVT. Recent studies have identified and validated seven sets of genes responsible for various CPVT phenotypes, including RyR2, CASQ-2, TRDN, CALM1, 2, and 3, and TECRL, providing novel insights into the molecular mechanisms. However, more data on atypical CPVT genotypes are required to investigate the underlying mechanisms further. The complexities of the underlying genetics contribute to challenges in risk stratification as well as the uncertainty surrounding nongenetic modifiers. Therapeutically, although medical management involving beta-blockers and flecainide, or insertion of an implantable cardioverter defibrillator remains the mainstay of treatment, animal and stem cell studies on gene therapy for CPVT have shown promising results. However, its clinical applicability remains unclear. Current gene therapy studies have primarily focused on the RyR2 and CASQ-2 variants, which constitute 75% of all CPVT cases. Alternative approaches that target a broader population, such as CaMKII inhibition, could be more feasible for clinical implementation. Together, this review provides an update on recent research on CPVT, highlighting the need for further investigation of the molecular mechanisms, risk stratification, and therapeutic management of this potentially lethal condition.

Attendance-related Healthcare Resource Utilisation and Costs in Patients With Brugada Syndrome in Hong Kong: A Retrospective Cohort Study.

Understanding health care resource utilisation and its associated costs are important for identifying areas of improvement regarding resource allocations. However, there is limited research exploring this issue in the setting of Brugada syndrome (BrS).This was a retrospective territory-wide study of BrS patients from Hong Kong. Healthcare resource utilisation for accident and emergency (A&E), inpatient and specialist outpatient attendances were analyzed over a 19-year period, with their associated costs presented in US dollars. A total of 507 BrS patients with a mean presentation age of 49.9 ± 16.3 years old were included. Of these, 384 patients displayed spontaneous type 1 electrocardiographic (ECG) Brugada pattern and 77 patients had presented with ventricular tachycardia/ventricular fibrillation (VT/VF). At the individual patient level, the median annualized costs were $110 (52-224) at the (A&E) setting, $6812 (1982-32414) at the inpatient setting and $557 (326-1001) for specialist outpatient attendances. Patients with initial VT/VF presentation had overall greater costs in inpatient ($20161 [9147-189215] vs $5290 [1613-24937],P < 0.0001) and specialist outpatient setting ($776 [438-1076] vs $542 [293-972],P = 0.015) compared to those who did not present VT. In addition, patients without Type 1 ECG pattern had greater median costs in the specialist outpatient setting ($7036 [3136-14378] vs $4895 [2409-10554],p=0.019). There is a greater health care demand in the inpatient and specialist outpatient settings for BrS patients. The most expensive attendance type was inpatient setting stay at $6812 per year. The total median annualized cost of BrS patients without VT/VF presentation was 78% lower compared to patients with VT/VF presentation.

Predictive value of neutrophil-to-lymphocyte ratio for atrial fibrillation and stroke in type 2 diabetes mellitus: The Hong Kong Diabetes Study.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus. METHODS: This was a population-based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government-funded hospitals/clinics in Hong Kong. Follow-up was until 31 December, 2019, or death. RESULTS: A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow-up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new-onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20-1.37], p < .001, HR: 1.41 [1.32-1.51], p < .001 and HR: 1.38 [1.29-1.47], p < .001) and AF (HR: 1.09 [1.02-1.17], p < .015; HR: 1.28 [1.20-1.37], p < .001; HR: 1.39 [1.31-1.49], p < .001) compared to quartile 1. On multivariable analysis, NLR remained a significant predictor of ischemic stroke risk for quartiles 2 and 3 (quartile 2: HR: 1.14 [1.05, 1.22], p = .001; quartile 3: HR: 1.14 [1.06, 1.23], p < .001) but not quartile 4 (HR: 1.08 [0.994, 1.17], p = .070). NLR was not predictive of AF after adjusting for confounders (quartile 2: HR: 0.966 [0.874, 1.07], p = .499; quartile 3: HR: 0.978 [0.884, 1.08], p = .661; quartile 4: HR: 1.05 [0.935, 1.16], p = .462). CONCLUSION: NLR is a significant predictor of new-onset ischaemic stroke after adjusting for significant confounders in Chinese type 2 diabetes patients.