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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.

Despite their proven efficacy for treating lung cancer, the cardiovascular risks associated with programmed cell death protein 1 (PD-1) inhibitors and their combinations with chemotherapy (chemo-immunotherapy) are unclear. This study aimed to investigate these associations.This retrospective cohort study included Hong Kong patients with lung cancer receiving PD-1 inhibitors during 2013-2021. Patients with non-concurrent use of PD-1 inhibitors and chemotherapy, any use of tyrosine kinase inhibitors or other immunotherapy agents, and those with prior stroke, heart failure, or myocardial infarction were excluded. PD-1 inhibitors and chemo-immunotherapy were compared for major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, heart failure, stroke, and myocardial infarction. All patients were followed up until the end of 2021. Inverse probability of treatment weighting was used to balance covariates between the two treatment groups.In total, 713 patients (333 PD-1 inhibitors users and 380 chemo-immunotherapy users) were analysed. Over a mean follow-up of 1.4 ± 1.3 years, 24 had MACE, with an observed incidence of 2.8 [1.6-4.8] events per 100 person-year for patients on PD-1 inhibitors, and 2.1 [1.2-3.8] per 100 person-year for patients on chemo-immunotherapy. No significant between-group difference in MACE incidence was observed (log-rank p = 0.641).The cardiovascular risks associated with PD-1 inhibitors and chemo-immunotherapy may not be significantly different amongst patients with lung cancer. Cardiovascular events associated with either regimen may be uncommon.

ImportanceThe use of warfarin as an anticoagulant to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks.ObjectiveThis study compared the risks of ischemic stroke, death and bleeding in patients with IE with and without warfarin use.DesignProspective cohort study.SettingPopulation-based.ParticipantsPatients aged 18 or older and diagnosed with IE in Hong Kong between January 1st1997 and August 31st2020 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.ExposureWarfarin use within 14 days of IE diagnosis.Main outcomes and measuresPatients 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.ResultsThe 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). From Cox regression, 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 haemorrhage (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 haemorrhage 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 relevanceIn patients with IE, warfarin use initiated within 14 days of IE diagnosis may be associated with significantly decreased risks of mortality but higher risks of intracranial haemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis.Key pointsQuestionIs warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe?FindingsIn 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 haemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding.MeaningIn patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial haemorrhage.

PurposeThis study aimed to compare the effects of sodium glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset hip fractures.MethodsThis was a retrospective population-based cohort study including type-2 diabetes mellitus patients treated with either SGLT2I or DPP4I between January 1st2015 and December 31st2020 in Hong Kong. The primary outcome was new-onset hip fracture and the secondary outcome was all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regression were applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed.ResultsThis cohort included 56393 patients with type-2 diabetes mellitus (median age: 62.1 years old [interquantile range, IQR]: 54.2-71.1; 57.45% males), of which 20432 patients ([incidence rate, IR]: 36.23%) used SGLT2I and 35961 patients (IR: 63.77%) used DPP4I. After the 1:1 propensity score matching, 449 (IR: 1.09%) patients had hip fractures, and 2012 patients (IR: 4.92%) died. SGLT2I was associated with significantly lower risks of hip fractures after adjusting for the demographics, past comorbidities, non-SGLT2I/DPP4I medications and laboratory results (hazard ratio: 0.55; 95% confidence interval: 0.42-0.89; P=0.0036). The results were consistent in the competing risk models and the different propensity matching approaches.ConclusionsSGLT2I was associated with lower risks of new-onset hip fractures after propensity score matching and adjustments.SummaryThis study compared the risks of hip fractures in between users of sodium glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors in type-2 diabetes mellitus. After propensity score matching, SGLT2I was associated with lower risks of hip fractures adjusting for confounders (hazard ratio: 0.55; 95% confidence interval: 0.42-0.89; P=0.0036).

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 β-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/β-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.

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.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.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).NLR is a significant predictor of new-onset ischaemic stroke after adjusting for significant confounders in Chinese type 2 diabetes patients.

IntroductionThe understanding of healthcare resource utilisation and its related costs is crucial for optimizing resource allocation in the healthcare setting. There is currently a paucity of published studies investigating healthcare costs related to long QT syndrome (LQTS).MethodThis was a retrospective study of LQTS patients from Hong Kong, China. The healthcare resource utilisation for Accident and Emergency (A&E), inpatient and specialist outpatient settings across a 19-year period was extracted and analysed. Costs in US dollars were calculated using unit costs.ResultsThe cohort consists of 125 LQTS patients with a mean presentation age of 26.7 ± 22.0 years old. Of these, 45 patients presented with ventricular tachycardia/ventricular fibrillation (VT/VF) and 44 patients had an implantable cardioverter-defibrillator (ICD) implementation. At the individual patient level, the median annualised costs were $69 (30-183) at the A&E setting, $10270 (2248-64006) at the inpatient setting and $675 (393-1329) at the special outpatient setting. Patients who presented with VT/VF initially had significantly higher annualised median costs in the inpatient ($59843 [13812-214930] vs. $5480 [1162-23111], pConclusionThere is an increasing healthcare demand in the inpatient and specialist outpatient settings for LQTS patients. The most expensive attendance type was inpatient setting stay at $10270 per year. The total median annualised cost of LQTS patients without VT/VF was 90% lower compared to patients with VT/VF.

IntroductionHealthcare resource utilisation and costs are important metrics of healthcare burden, but they have rarely been explored in the setting of cardiac ion channelopathies.PurposeThe aim of this study is to compare HCRUs and costs between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS) in a single city of China.MethodsThis was a territory-wide retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for accident and emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analysed over a 19-year period (2001-2019) at the cohort level. Comparisons were made between BrS and LQTS cohorts using incidence rate ratios (IRRs [95% confidence intervals]).ResultsOver the 19-year study period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. BrS patients had lower total costs compared to LQTS patients (2,008,126 [2,007,622-2,008,629] vs. 2,343,864 [2,342,828-2,344,900]; IRR: 0.857 [0.855-0.858]). For specific attendance types, BrS patients had higher costs for A&E attendances (83,113 [83,048-83,177] vs. 70,604 [70,487-70,721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]). However, they had lower costs for inpatient stay (1,391,624 [1,391,359-1,391,889] vs. 1,713,742 [1,713,166-1,714,319]; IRR: 0.812 [0.810-0.814]) and to a smaller extent, lower costs for specialist outpatient services (531213 [531049-531376] vs. 558597 [558268-558926]; IRR: 0.951 [0.947-0.9550]) compared to LQTS patients.ConclusionOverall, BrS patients consume 14% less healthcare resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients. Further studies are needed to examine patient-based attendances and costs to identify subgroups of high HCRU users for both cohorts.

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 (AE), 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 (AE) 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],P0.0001) 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.

BackgroundThe association between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are currently unknown.MethodsThis was a retrospective population-based cohort study including type-2 diabetes mellitus (T2DM) patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. Patients with concurrent DPP4I and SGLT2I usage were excluded. The primary outcomes were NAFLD and HCC. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Univariable and multivariable Cox regression was applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed.ResultsThis cohort included 62699 patients with T2DM, amongst which 22154 patients were on SGLT2I and 40545 patients were on DPP4I. After matching (44308 patients), 1090 patients developed new-onset NAFLD (Incidence: 4.6; 95% Confidence interval [CI]: 4.3-4.9) and 187 patients developed HCC (Incidence: 0.8; 95% CI: 0.7-0.9). Overall, SGLT2I was associated with lower risks of NAFLD (Hazard ratio [HR]: 0.39; 95% CI: 0.34-0.46), and HCC (HR: 0.46; 95% CI: 0.29-0.72) compared to DPP4I after adjustments. SGLT2I was also associated with lower risks of cancer-related mortality (HR: 0.29; 95% CI: 0.23-0.37) and all-cause mortality (HR: 0.28; 95% CI: 0.25-0.31). However, amongst patients with hepatitis B virus infection, SGLT2I was associated with higher risks of HCC (HR: 3.28; 95% CI: 1.21-8.90). The results were consistent in competing risk models and different matching approaches.ConclusionSGLT2I was associated with lower risks of NAFLD, and HCC compared to DPP4I after propensity scores matching and adjustments.Lay summaryThe association between two antidiabetic medications, SGLT2I and DPP4I, and the risks of fatty liver disease and liver cancer have not been explored. In our study, SGLT2I was associated with a lower risk of fatty liver disease and liver cancer compared to DPP4I amongst patients with type 2 diabetes. However, DPP4I was associated with lower risks of liver cancer compared to SGLT2I among patients with hepatitis B virus infectionCentral illustration

BackgroundBoth Coronavirus Disease-2019 (COVID-19) infection and COVID-19 vaccination have been associated with the development of acute myocardial infarction (AMI). This study compared the rates of AMI after COVID-19 infection and among the COVID-19 vaccinated populations in Hong Kong.MethodsThis was a population-based cohort study from Hong Kong, China. Patients with positive real time-polymerase chain reaction (RT-PCR) test for COVID-19 between January 1st, 2020 and June 30th, 2021 were included. The data of the vaccinated and unvaccinated population was obtained from the “Reference Data of Adverse Events in Public Hospitals” published by the local government. The individuals who were vaccinated with COVID-19 vaccination prior the observed period (December 6th, 2021 to January 2nd, 2022) in Hong Kong were also included. The vaccination data of other countries were obtained by searching PubMed using the terms [“COVID-19 vaccine” AND “Myocardial infarction”] from its inception to February 1st, 2022. The main exposures were COVID-19 test positivity or previous COVID-19 vaccination. The primary outcome was the development of AMI within 28 days observed period.ResultsThis study included 11441 COVID-19 patients, of whom 25 suffered from AMI within 28 days of exposure (rate per million: 2185; 95% confidence interval [CI]: 1481-3224). The rates of AMI were much higher than those who were not vaccinated by the COVID-19 vaccine before December 6th, 2021 (rate per million: 162; 95% CI: 147-162) with a rate ratio of 13.5 (95% CI: 9.01-20.2). Meanwhile, the rate of AMI was lower amongst the vaccinated population (rate per million: 47; 95% CI: 41.3-53.5) than COVID-19 infection with a rate ratio of 0.02 (0.01, 0.03). Regarding post-vaccination AMI, COVID-19 infection was associated with a significantly higher rate of AMI than post-COVID-19 vaccination AMI in other countries.ConclusionsCOVID-19 infection was associated with a higher rate of AMI than the vaccinated general population, and those immediately after COVID-19 vaccination.

BackgroundThere is much uncertainty regarding the comparative risks of cancer for T2DM patients on SGLT2I versus DPP4I.MethodsThis population-based cohort study patients included T2DM patients who were administered with either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020 in Hong Kong.ResultsAmongst 60112 T2DM patients (mean baseline age: 62.1±12.4 years, male: 56.36%), 18167 patients were SGLT2I users and 41945 patients were DPP4I users. Multivariate cox regression analysis revealed that SGLT2I usage was associated with a decreased risk of all-cause mortality (HR:0.92; 95%CI:0.84-0.99; P=0.04), cancer-related mortality (HR:0.58; 95%CI:0.42-0.80; P≤0.001) and a 30% risk reduction of new-onset overall cancer (HR:0.70; 95%CI:0.59-0.84; P≤0.001). Dapagliflozin and ertugliflozin both demonstrated superiority in relation to new-onset cancer development, with the former demonstrating a lowered risk of breast cancer (HR:0.48; 95%CI:0.27-0.83; P=0.001).ConclusionSGLT2I was associated with lower risk of all-cause mortality, cancer-related mortality and new-onset overall cancer compared to DPP4I.

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.

BackgroundDiabetes mellitus is associated with the development of colorectal cancer (CRC). There have been a lack of study comparing the risk of colorectal cancer in sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i), both of which commonly prescribed second line agents for diabetes.MethodsWe conducted a territory wide retrospective cohort study on patients with type 2 diabetes who was prescribed either of the two agents. Baseline demographics, use of other medications, comorbidities and biochemical parameters were extracted. Propensity score matching was performed to reduce the impacts of cofounders. Cause specific Cox regression was used to evaluate the risk of incident colorectal cancer in SGLT2i users, as compared to DPP4i users. Subgroup analyses based on age, gender and estimated glomerular filtration rate were performed.ResultsAfter propensity score matching, we included 13029 subjects who were prescribed SGLT2i and DPP4i respectively. Incidence rate ratio of CRC was 0.566 (0.418-0.766) in SGLT2i users. Overall, use of SGLT2i was associated with a lower risk of incident CRC (HR: 0.526; 95% CI: 0.382-0.724; P 2 (HR: 0.560; 95% CI: 0.395-0.792; P =0.001).ConclusionUse of SGLT2i may reduce risk of incident CRC as compared to use of DPP4i, especially in younger male patients with fairly preserved renal function.

Context Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. Objective The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. Methods This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. Results This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25-2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond. Conclusion Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs.

Background Coronavirus Disease-2019 (COVID-19) vaccination has been associated with the development of carditis, especially in children and adolescent males. However, the rates of these events in the global setting have not been explored in a systematic manner. The aim of this systematic review and meta-analysis is to investigate the rates of carditis in children and adolescents receiving COVID-19 vaccines. Methods PubMed, Embase and several Latin American databases were searched for studies. The number of events, and where available, at-risk populations were extracted. Rate ratios were calculated and expressed as a rate per million doses received. Subgroup analysis based on the dose administered was performed. Subjects ≤ 19 years old who developed pericarditis or myocarditis following COVID-19 vaccination were included. Results A total of 369 entries were retrieved. After screening, 39 articles were included. Our meta-analysis found that 343 patients developed carditis after the administration of 12,602,625 COVID-19 vaccination doses (pooled rate per million: 37.76; 95% confidence interval [CI] 23.57, 59.19). The rate of carditis was higher amongst male patients (pooled rate ratio: 5.04; 95% CI 1.40, 18.19) and after the second vaccination dose (pooled rate ratio: 5.60; 95% CI 1.97, 15.89). In 301 cases of carditis (281 male; mean age: 15.90 (standard deviation [SD] 1.52) years old) reported amongst the case series/reports, 261 patients were reported to have received treatment. 97.34% of the patients presented with chest pain. The common findings include ST elevation and T wave abnormalities on electrocardiography. Oedema and late gadolinium enhancement in the myocardium were frequently observed in cardiac magnetic resonance imaging (CMR). The mean length of hospital stay was 3.91 days (SD 1.75). In 298 out of 299 patients (99.67%) the carditis resolved with or without treatment. Conclusions Carditis is a rare complication after COVID-19 vaccination across the globe, but the vast majority of episodes are self-limiting with rapid resolution of symptoms within days. Graphical abstract Central illustration. Balancing the benefits of vaccines on COVID-19-caused carditis and post-vaccination carditis.

BackgroundDipeptidyl peptidase-4 inhibitors (DPP4I) may be associated with higher risks of acute pancreatitis and pancreatic cancer. This study compared the risks of acute pancreatitis and pancreatic cancer between sodium glucose cotransporter 2 inhibitors (SGLT2I) and DPP4I users.MethodsThis was a retrospective population-based cohort study of patients with type-2 diabetes mellitus on either SGLT2I or DPP4I between January 1st 2015 and December 31st 2020 in Hong Kong. The primary outcome was new-onset acute pancreatitis and pancreatic cancer. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regressions were applied to identify significant predictors.ResultsThis cohort included 31609 T2DM patients (median age: 67.4 years old [SD: 12.5]; 53.36% males). 6479 patients (20.49%) used SGLT2I, and 25130 patients (70.50%) used DPP4I. After matching, the incidence of acute pancreatitis was significantly lower in SGLT2I users (incidence rate, IR: 0.6; 95% confidence interval, CI: 0.2-1.4) than in DPP4I (IR: 2.1; CI: 1.3-3.0). The incidence of pancreatic cancer was also lower among SGLT2I users (IR: 1.4; 95% CI: 0.7-2.6 vs. 3.6; 95% CI: 2.6-4.9). SGLT2I was associated with lower risks of acute pancreatitis (hazard ratio, HR: 0.11; 95% CI: 0.02-0.51; P=0.0017) and pancreatic cancer (HR: 0.22; 95% CI: 0.039-0.378; P=0.0003) after adjustments. The results were consistent in the competing risk models and the different matching approaches.ConclusionsSGLT2I may be associated with lower risks of new-onset acute pancreatitis and pancreatic cancer after matching and adjustments, underscoring the need for further evaluation in the prospective setting.Key messagesWhat is already known on this topicT2DM was associated with higher risks of pancreatic cancer. Meanwhile, second-line anti-diabetic drugs were suggested to reduce the risks of pancreatic cancer, although DPP4I was suggested to be associated with acute pancreatitis.What this study addsSGLT2I was associated with an 89% lower risk of acute pancreatitis and 78% lower risk of pancreatic cancer than DPP4I users.How this study might affect research, practice or policyThe findings of this study may influence the choice of second-line antidiabetic therapy in T2DM patients in terms of the pancreatic safety profile. This study may inspire more studies on the long-term cancer benefits of SGLT2I.

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 Conclusions SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

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 gt; 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.

To gain insights on the cardiovascular effects of metformin and sulphonylurea, the present study compares the rates of incident atrial fibrillation, stroke, cardiovascular mortality and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus. This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1, 2000, and December 31, 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, past comorbidities and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analyses using propensity score stratification, high-dimensional propensity score and inverse probability of treatment weighting were conducted. Subgroup analyses were conducted for age and gender in the matched cohort. A total of 36,228 sulphonylurea users and 72,456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75-3.77; P

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.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.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).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.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI.

BackgroundDyslipidaemia is associated with adverse cardiovascular outcomes. However, the long-term prognostic value of visit-to-visit cholesterol variability for the risks of heart failure (HF) is uncertain. We investigated the associations between cholesterol variability and the risk of HF and adverse cardiovascular events.MethodsThis retrospective cohort study included patients attending family medicine clinics in Hong Kong during 2000-2003 with follow-up until 2019. Patients with at least three sets of blood cholesterol (low-density (LDL-C) and high-density (HDL-C) lipoprotein cholesterol) levels available at different visits were included. Patients with prior HF, myocardial infarction (MI), use of HF medications, and pregnancy were excluded. Visit-to-visit variability was calculated using standard deviation and coefficient of variation (CV). The primary outcome was HF. The secondary outcomes were cardiovascular mortality, and myocardial infarction.ResultsA total of 5662 patients were included (2152 males; mean age 63.3±12.4 years; mean follow-up 15.3±4.6 years). Higher variability of HDL-C (hazard ratio (HR) for CV: 13.757 [6.261, 30.226], pConclusionHigher visit-to-visit cholesterol variability was varyingly associated with significantly increased long-term risks of HF and adverse cardiovascular events. Such associations may be negated by using lipid-lowering medication(s).

The three direct oral anticoagulants (DOAC), rivaroxaban, apixaban and dabigatran have been associated with lower risks of fractures compared to warfarin. However, no large scale studies have explored the associations with the newest DOAC, edoxaban, with fracture risk. The present study aims to elucidate the effects of edoxaban on the risk of hip fracture amongst elderly patients by comparing the incidence of new onset hip fracture between edoxaban and warfarin users in a Chinese population.This was a retrospective population-based cohort study of patients with edoxaban or warfarin use between January 1st, 2016 and December 31st, 2019 in Hong Kong, China. Patients with less than one-month exposure, medication switching between warfarin and edoxaban, those who died within 30 days after drug exposure, prior human immunodeficiency virus infection, age50 years old, and those with prior hip fractures were excluded. Propensity score matching (1:2) between edoxaban and warfarin users using the nearest neighbour method was performed based on demographics, prior comorbidities, and use of different medications. The study outcomes were new onset hip fractures, medically attended falls and all-cause mortality.A total of 5014 patients including 579 edoxaban users and 4435 warfarin users (median age: 70 years old [interquartile range (IQR): 62-79], 56.66% males) with a median follow-up of 637.5 (IQR: 320-1073) days were included. In the matched cohort, edoxaban users had significantly lower rates of new onset hip fractures, medically attended falls and all-cause mortality. The protective value of edoxaban use against new onset hip fracture (hazard ratio [HR]: 0.13, 95% confidence interval [CI]: [0.03-0.54], p = 0.0051), medically attended falls (HR: 0.47, [0.29-0.75], p = 0.0018) and all-cause mortality (HR: 0.61, [0.42-0.87], p = 0.0059) in comparison to warfarin use persisted after matching. The significant relationship between edoxaban use and lower fracture risk was preserved in all sensitivity analyses using different approaches using the propensity score.Edoxaban use is associated with lower risks of new onset hip fractures, medically attended falls and mortality risks compared to warfarin after propensity score matching.

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.