Cerebral hemodynamics and stroke risks in symptomatic intracranial atherosclerotic stenosis with internal versus cortical borderzone infarcts: A computational fluid dynamics study.

There may be different mechanisms underlying internal (IBZ) and cortical (CBZ) borderzone infarcts in intracranial atherosclerotic stenosis. In 84 patients with symptomatic, 50-99% atherosclerotic stenosis of M1 middle cerebral artery (MCA-M1) with acute borderzone infarcts in diffusion-weighted imaging, we classified the infarct patterns as isolated IBZ (n = 37), isolated CBZ (n = 31), and IBZ+CBZ (n = 16) infarcts. CT angiography-based computational fluid dynamics models were constructed to quantify translesional, post-stenotic to pre-stenotic pressure ratio (PR) in the MCA-M1 lesion. Those with IBZ infarcts were more likely to have a low PR (indicating impaired antegrade flow across the lesion) than those without (p = 0.012), and those with CBZ infarcts were more likely to have coexisting small cortical infarcts (indicating possible embolism) than those without (p = 0.004). In those with isolated IBZ or CBZ infarcts, low PR was independently associated with isolated IBZ infarcts (adjusted odds ratio = 4.223; p = 0.026). These two groups may also have different trajectories in the stroke risks under current medical treatment regimen, with a higher risk of same-territory ischemic stroke recurrence within 3 months in patients with isolated IBZ infarcts than isolated CBZ infarcts (17.9% versus 0.0%; log-rank p = 0.023), but similar risks later in 1 year.

Hemodynamic significance of intracranial atherosclerotic disease and ipsilateral imaging markers of cerebral small vessel disease.

INTRODUCTION: Cerebral small vessel disease (CSVD) commonly exists in patients with symptomatic intracranial atherosclerotic disease (sICAD). We aimed to investigate the associations of hemodynamic features of sICAD lesions with imaging markers and overall burden of CSVD. PATIENTS AND METHODS: Patients with anterior-circulation sICAD (50%-99% stenosis) were analyzed in this cross-sectional study. Hemodynamic features of a sICAD lesion were quantified by translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) via CT angiography-based computational fluid dynamics modeling. PR ⩽median was defined as low ("abnormal") PR, and WSSR ⩾ fourth quartile as high ("abnormal") WSSR. For primary analyses, white matter hyperintensities (WMHs), lacunes, and cortical microinfarcts (CMIs) were assessed in MRI and summed up as overall CSVD burden, respectively in ipsilateral and contralateral hemispheres to sICAD. Enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) were assessed for secondary analyses. RESULTS: Among 112 sICAD patients, there were more severe WMHs, more lacunes and CMIs, and more severe overall CSVD burden ipsilaterally than contralaterally (all p < 0.05). Abnormal PR and WSSR (vs normal PR and WSSR) was significantly associated with moderate-to-severe WMHs (adjusted odds ratio = 10.12, p = 0.018), CMI presence (5.25, p = 0.003), and moderate-to-severe CSVD burden (12.55; p = 0.033), ipsilaterally, respectively independent of contralateral WMHs, CMI(s), and CSVD burden. EPVSs and CMBs were comparable between the two hemispheres, with no association found with the hemodynamic metrics. DISCUSSION AND CONCLUSION: There are more severe WMHs and CMI(s) in the hemisphere ipsilateral than contralateral to sICAD. The hemodynamic significance of sICAD lesions was independently associated with severities of WMHs and CMI(s) ipsilaterally.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

Impact of Cold Snare vs Cold Forceps Resection of Diminutive Adenomas on Segmental Incomplete Resection Rate.

INTRODUCTION: Polypectomy technique, for diminutive lesion resection, is variable among colonoscopists using either cold snare polypectomy (CSP) or cold forceps polypectomy (CFP). While it is well described that CSP is a preferred technique to resect small lesions, there is little data evaluating the impact resection techniques have on metachronous adenoma burden. The aim of this study was to evaluate the rate of incomplete resection attributable to CSP and CFP of diminutive adenomas. METHODS: This is a 2-center retrospective cohort study evaluating the segmental incomplete resection rate (S-IRR) of diminutive tubular adenomas (TA). S-IRR was calculated by subtracting the segmental metachronous adenoma rate in a specific colonic segment without adenoma from segments with adenoma on index colonoscopy. The primary outcome was the S-IRR of diminutive TA resected by CSP or CFP on index colonoscopy. RESULTS: A total of 1,504 patients were included in the analysis: 1,235 with TA <6 mm and 269 with TA 6-9 mm as the most advanced lesion. The S-IRR in a segment that had a <6-mm TA incompletely resected by CFP on index colonoscopy was 13%. The S-IRR in a segment that had a <6-mm TA incompletely resected by CSP was 0%. Among 12 included colonoscopists, the range of overall S-IRR was 1.1%-24.4% with an average S-IRR of 10.3%. DISCUSSION: S-IRR was 13% higher with CFP resection of diminutive TA than with CSP. A proposed S-IRR metric of <5% is a target goal for all diminutive polyp resection because 3/12 colonoscopists achieved this low rate. S-IRR can be used as a methodology to compare and quantify the difference in segmental metachronous adenoma burden across various polypectomy removal methods.

Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape.

OBJECTIVE: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. METHODS: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. RESULTS: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. CONCLUSION: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

Ciprofloxacin resistance and tolerance of Pseudomonas aeruginosa ocular isolates.

PURPOSE: Tolerance to antibiotics may occur due to changes in bacterial growth patterns and can be a precursor to development of resistance. However, there is a lack of information on the ability of ocular bacteria isolates to develop tolerance. This paper explores the tolerance to 8 different antibiotics of 61 microbial keratitis isolates of Pseudomonas aeruginosa from Australia and India using the MBC/MIC ratio, with tolerance defined by a ratio ≥ 32, and tolerance to ciprofloxacin by an agar diffusion assay. METHODS: Antibiotics used were ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin, imipenem, ceftazidime and polymyxin B. Isolates were sourced from microbial keratitis infections in Australia and India. Minimum bactericidal and minimum inhibitory concentration (MBC and MIC) were obtained using broth microdilution and compared to breakpoints from the Clinical Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) to determine bacterial susceptibility. Tolerance was assessed as MBC/MIC ≥ 32. An alternative method for tolerance detection (TD) was assessed with 13P. aeruginosa sensitive isolates by agar disk diffusion assay of ciprofloxacin followed by application of glucose to the agar and observation of re-growth of colonies. RESULTS: Thirty-three isolates were resistant to imipenem, 20 to ciprofloxacin, 14 to tobramycin and piperacillin, 12 to levofloxacin and ceftazidime, 8 to gentamicin, and 5 to polymyxin B. The percentage of strains resistant to levofloxacin (7 vs 30 %; p = 0.023), gentamicin (0 vs 24 %; p = 0.005) and tobramycin (4 vs 33 %; p = 0.004) was significantly greater in isolates from India.On average, strains from India exhibited notably greater MIC and MBC values compared to strains obtained from Australia. Out of 61 isolates, none displayed an MBC/MIC ratio ≥ 32. However, three sensitive isolates had low tolerance, nine had medium tolerance and one had high tolerance to ciprofloxacin with the TDtest. CONCLUSIONS: This study used two methods to determine whether P. aeruginosa strains could show tolerance to antibiotics. Using the MBC/MIC criteria no strain was considered tolerant to any of the eight antibiotics used. When 13 strains were tested for tolerance against ciprofloxacin, the most commonly used monotherapy for keratitis, one had high tolerance and nine had medium tolerance. This demonstrates the capacity of P. aeruginosa to develop tolerance which may result in therapeutic failures if inappropriate dosing regimens are used to treat keratitis.

Review: School-based interventions to improve mental health literacy and reduce mental health stigma - a systematic review.

BACKGROUND: The steadily increasing prevalence of mental disorders in children and adolescents presents itself as a public health challenge, especially given the health, social and economic burden of mental disorders. School-based interventions aimed at improving mental health literacy and reducing mental health stigma have the potential to prevent mental disorders and promote mental well-being, thus reducing the burden of mental disorders. This review identified and synthesised evidence on the effectiveness of school-based interventions designed to improve mental health literacy and reduce mental health stigma. METHODS: Electronic bibliographic databases including MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Child Development and Adolescent Studies, British Education Index and Applied Social Sciences Index and Abstracts (ASSIA) were searched. Randomised controlled trials (RCTs) were included if they assessed the effectiveness or cost-effectiveness of school-based intervention aimed at improving mental health literacy and reducing mental health stigma for children and young people aged 4-18 years. Quality of studies was appraised using the EPHPP tool. A numerical summary and a narrative description of the findings in relation to the research questions were synthesised. This systematic review was registered with PROSPERO (CRD42020191265). RESULTS: We identified 21 studies describing 20 unique school-based mental health interventions. Overall, there is moderate evidence suggesting that school-based mental health interventions can be effective in improving mental health literacy and reducing mental health stigma defined as attitudes and beliefs regarding mental disorders. However, there is less evidence for their long-term effectiveness, as most studies did not include follow-ups. CONCLUSIONS: Despite exclusively including studies with randomised designs, intervention and methodological heterogeneity poses uncertainties to any conclusions made. Future research should focus on resolving methodological issues concerning how outcomes are assessed and include process evaluations to better inform the design of an intervention in term of its delivery and implementation.

Review: School-based mental health literacy interventions to promote help-seeking - a systematic review.

BACKGROUND: School-based mental health literacy interventions aim to prevent mental disorders and promote mental wellbeing through improving the knowledge and understanding of mental health, mental disorders, and reducing stigma. Evidence suggests that good mental health literacy helps young people recognise mental health difficulties in themselves and in others, and seek help for mental health problems. Improved help-seeking can allow for early intervention, which prevents the progression of mental disorders and ultimately reduces the burden of mental disorders. The aim of this review is to identify and synthesise evidence on the effectiveness of school-based mental health literacy interventions in improving help-seeking outcomes. METHODS: We searched MEDLINE, Embase, PsycINFO, ERIC, Child Development and Adolescent Studies, British Education Index and ASSIA (June 2020). Additional searches were conducted a year later to identify any new publications (June 2021). We included randomised controlled trials (RCTs) assessing the effectiveness or cost-effectiveness of school-based interventions to improve help-seeking outcomes for children and young people aged 4-18 years. Included studies were critically appraised. RESULTS: We identified 11 studies investigating help-seeking outcomes of school-based mental health literacy interventions including a total of 7066 participants from 66 secondary schools. Overall, there is no strong evidence for the effectiveness of school-based mental health literacy interventions in improving help-seeking outcomes, including general attitudes towards help-seeking, personal intentions to seek help, knowledge of when and how to seek help for mental disorders, confidence to seek help, and actual help-seeking behaviours. None of the studies investigated the cost-effectiveness of the interventions. CONCLUSION: The lack of standardised measures with established reliability and validity for help-seeking outcomes, and the incomprehensive consideration of the multi-faceted concepts of MH literacy and MH stigma have contributed to the scarcity of evidence for the effectiveness. Future research should focus on developing standardised measurement tools and including economic evaluations to understand pragmatic and financial aspects of school-based mental health literacy interventions.

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

INTRODUCTION: The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1 year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1 year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. RESULTS: A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1 year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). CONCLUSION: Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.

A cross-sectional study of COVID-19 vaccination patterns among patients with epilepsy in Hong Kong.

OBJECTIVE: As Hong Kong faced the 5th wave of the COVID-19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination gap among patients with epilepsy. METHODS: A cross-sectional, pragmatic study of COVID-19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI). RESULTS: A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up-to-date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects. SIGNIFICANCE: A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.

Risk of total metachronous advanced neoplasia in patients with both small tubular adenomas and serrated polyps.

BACKGROUND AND AIMS: The impact of concomitant small serrated polyps (SPs) on the risk of subsequent neoplasia when small tubular adenomas (TAs) are found is uncertain. METHODS: Patients who on index colonoscopy had ≤2 TAs of <10 mm in size in isolation were compared with those with concomitant ≤2 small-sized SPs. SP was inclusive of polyps described by pathology as sessile serrated lesions (SSLs) or proximal hyperplastic polyps (HPs) <10 mm in size. The primary endpoint was the rate of total metachronous advanced neoplasia (T-MAN) compared among the TAs in the isolation group and the groups inclusive of SPs (SSLs or proximal HPs). RESULTS: For patients with TAs and small SPs found concomitantly, the rate of T-MAN was 9.6% (24/251), which was significantly higher than the rate of T-MAN in patients with isolated small TAs (5.2% [59/1138], P = .011). Within the concomitant SP cohort, the rate of T-MAN in the proximal HP subgroup remained significantly increased (9% [19/212]) compared with the isolated small TA group (P = .037). CONCLUSIONS: When small TAs are found concomitantly with small SPs, there is an increase in the rate of T-MAN in comparison with isolated TAs. This increase in T-MAN also occurs when small TAs are found in conjunction with small proximal HPs. The presence of concomitant small SPs should be considered in determining surveillance intervals when small TAs are identified in colonoscopy screening programs.

A bibliometric analysis of polycystic ovary syndrome research in Southeast Asia: Insights and implications.

BACKGROUND AND AIMS: There has been an increased understanding in the pathophysiology and management of polycystic ovary syndrome (PCOS) in recent years. This study aimed to evaluate the trends and characteristics of PCOS publications in Southeast Asia (SEA) through a bibliometric analysis. METHODS: Systematic review of literature on PCOS in SEA countries between 1975 and 2020 was performed using the Scopus database. All published studies on PCOS conducted in or published by authors from any of the countries in SEA were included in this analysis. Bibliographic information was obtained, and visualization of collaboration networks of countries and keywords was conducted using VOSviewer software. RESULTS: A total of 260 articles were included in this analysis. The number of PCOS publications in SEA continued to increase through the years. The country with the highest number of publications was Thailand while Singapore produced the most publications with the greatest impact. The focus of research in SEA was on PCOS prevalence, risk factors, infertility, and metabolic complications. A country's fertility rate, research and development expenditures (%GDP), number of researchers per million people, and international research collaborations significantly correlated with PCOS research impact in SEA. CONCLUSION: This is the first bibliometric analysis in PCOS research in SEA. Despite the continuing increase in PCOS publications in SEA, it still lags compared to other regions. Countries in SEA should consider policies and strategies directed at increasing research support and encouraging international collaborations for local researchers to produce more meaningful publications and augment PCOS knowledge in the region.

Evolving ischemic stroke subtypes in 15 years: A hospital-based observational study.

BACKGROUND: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. AIM: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. METHODS: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes. RESULTS: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0-9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9-45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001). CONCLUSION: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.

Assessing potential trade-offs between the lower back and shoulders: influence of lift training intervention on joint demands.

Background. Many of the approaches available for modifying manual materials handling (MMH) exertion emphasize lower back protection but often do not consider how interventions affect other body regions. This study focused on the influence of lift training on resultant joint moments and muscular demand trade-offs between the lower back and shoulders during MMH tasks. Methods. Three recommended lifting techniques (straddle lift, pivot technique and tripod lift) were compared to a priori (untrained) self-selected lifting techniques. Results. Mean and cumulative resultant moments indicated that using the lifting techniques evaluated in this investigation protected the shoulders more than the lower back. Mean and peak shoulder muscle activity also decreased following training (p < 0.05). Although there were no peak and mean changes to lower back muscle activity (p>0.05), there was a significant decrease in cumulative lower back muscle activity (p < 0.05). Reported perceived exertion values decreased following training across the lifting techniques for all evaluated body regions (p < 0.05). Conclusion. Overall, the recommended MMH techniques protected both the lower back and the shoulders, and no exposure trade-offs between them were identified.

A retrospective comparison of cognitive performance in individuals with advanced Parkinson's Disease in Hong Kong and Canada.

A deeper understanding of the cross-cultural applicability of cognitive tests across countries and cultures is needed to better equip neuropsychologists for the assessment of patients from diverse backgrounds. Our study compared cognitive test scores in patients with advanced Parkinson's disease (PD) at the Prince of Wales Hospital (n = 63; Hong Kong) and the Foothills Medical Center (n = 20; Calgary, Canada). The groups did not differ in age or sex (p > .05), but Western patients had significantly more years of education (M = 14.2, SD = 2.7) than Asian patients (M = 10.33, SD = 4.4). Cognitive tests administered to both groups included: digit span, verbal fluency (animals), the Boston Naming Test, and verbal memory (California Verbal Learning Test or Chinese Auditory Verbal Learning Test). Testing was completed before and 12 months after deep brain stimulation surgery. Results showed cognitive performance was similar across time, but significant group differences were found on digit span forward (longer among patients from Hong Kong; F(1, 75) = 44.155, p < .001) and the Boston Naming Test (higher percent spontaneous correct among patients from Canada; F(1, 62) = 7.218, p = .009, η2 = 0.104), after controlling for age, sex, and years of education. In conclusion, our findings provide preliminary support for the similarity of Chinese versions of tests originally developed for Western populations. Also, we caution that some aspects of testing may be susceptible to cultural bias and therefore warrant attention in clinical practice and refinement in future test development for Asian patients.

Risk factors for delayed-onset dementia after stroke or transient ischemic attack-A five-year longitudinal cohort study.

BACKGROUND: Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. AIM: We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. METHODS: This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. RESULTS: In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. CONCLUSION: The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease.

OBJECTIVES: The predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD. METHODS: Unrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis. RESULTS: Among 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process. CONCLUSIONS: Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Cricopharyngeal peroral endoscopic myotomy improves oropharyngeal dysphagia in patients with Parkinson's disease.

Background and study aims Oropharyngeal dysphagia (OPD) is prevalent in patients with Parkinson's disease (PD). Upper esophageal sphincter (UES) dysfunction is an important pathophysiological factor for OPD in PD. The cricopharyngeus (CP) is the main component of UES. We assessed the preliminary efficacy of cricopharyngeal peroral endoscopic myotomy (C-POEM) as a treatment for dysphagia due to UES dysfunction in PD. Patients and methods Consecutive dysphagic PD patients with UES dysfunction underwent C-POEM. Swallow metrics derived using high-resolution pharyngeal impedance manometry (HRPIM) including raised UES integrated relaxation pressure (IRP), raised hypopharyngeal intrabolus pressure (IBP), reduced UES opening caliber and relaxation time defined UES dysfunction. Sydney Swallow Questionnaire (SSQ) and Swallowing Quality of Life Questionnaire (SWAL-QOL) at before and 1 month after C-POEM measured symptomatic improvement in swallow function. HRPIM was repeated at 1-month follow-up. Results C-POEM was performed without complications in all (n = 8) patients. At 1 month, there was an improvement in both the mean SSQ (from 621.5 to 341.8, mean difference -277.3, 95 %CI [-497.8, -56.7], P  = 0.02) and SWAL-QOL (from 54.9 to 68.3, mean difference 9.1, 95 %CI [0.7, 17.5], P  = 0.037) scores. Repeat HRPIM confirmed a decrease in both the mean UES IRP (13.7 mm Hg to 3.6 mm Hg, mean difference -10.1 mm Hg, 95 %CI [-16.3, -3.9], P  = 0.007) and the mean hypopharyngeal IBP (23.5 mm Hg to 10.4 mm Hg, mean difference -11.3 mm Hg, 95 %CI [-17.2, -5.4], P  = 0.003). Conclusions In dysphagic PD patients with UES dysfunction, C-POEM is feasible and enhances UES relaxation and reduces sphincteric resistance to flow during the swallow, thereby improving dysphagia symptoms.

Correlation of LINE-1 Hypomethylation With Size and Pathologic Extent of Dysplasia in Colorectal Tubular Adenomas.

INTRODUCTION: Conventional adenomas (tubular adenoma [TA] or tubulovillous adenoma) and sessile serrated lesions (SSLs) are neoplastic precancerous lesions frequently detected in patients undergoing average risk screening colonoscopy and polyp surveillance. Metachronous risk stratification of adenomas is currently limited to histologic features and size of polyps. We report long interspersed nucleotide element-1 (LINE-1) methylation levels in SSL in comparison to TA and the impact of TA size and presence of high-grade dysplasia (HGD) on LINE-1 methylation. METHODS: LINE-1 methylation was assessed by pyrosequencing of bisulfite-converted DNA. We compared LINE-1 methylation between TA and SSL, among varying sizes of TA, and between TA with HGD and low-grade dysplasia (LGD). RESULTS: LINE-1 methylation declined with increasing polyp size in TA when comparing those <5 mm (72.31 ± 6.11), 5 to <10 mm (67.50 ± 7.00), and ≥10 mm (66.75 ± 11.89). There were lower LINE-1 methylation levels in TA with LGD (n = 119) compared with SSLs (n = 29) (69.11 ± 8.62 vs 81.41 ± 2.43, P < 0.001). TA containing HGD (n = 26) had lower LINE-1 methylation levels than those with LGD (n = 119) (59.86 ± 7.93 vs 69.11 ± 8.62, P < 0.001). DISCUSSION: HGD and increasing size of TA/tubulovillous adenoma were associated with lower LINE-1 methylation. This supports a hypothesis that LINE-1 hypomethylation in TAs indicates advancement along the CRC tumorigenesis pathway. Lower LINE-1 methylation and greater variance of global DNA methylation was seen in TA compared with SSL. LINE-1 methylation in adenomas correlates with polyp size and degree of dysplasia and deserves further study as a predictor of metachronous colorectal cancer risk.

Super-refractory status epilepticus in autoimmune encephalitis treated with interleukin-1 receptor antagonist, anakinra.

Autoimmune encephalitis is increasingly recognised as a major cause of new-onset refractory status epilepticus. Early immunotherapy with agents such as methylprednisolone is recommended. Anakinra is an interleukin-1 receptor antagonist used for various inflammatory disorders. It has been used successfully in the treatment of febrile infection-related epilepsy syndrome in children and in one adult case. In this case report, we describe a case of super-refractory status epilepticus in a 38-year-old female due to autoimmune encephalitis who was treated successfully with anakinra after 16 weeks of therapeutic coma and failing multiple immunotherapies. Despite a prolonged period of therapeutic coma, this patient made a reasonable recovery with effective communication and ability to walk with assistance upon discharge. We propose that the successful treatment with anakinra in our case could be due to elevated inflammatory cytokines in the pathogenesis of autoimmune encephalitis, although we acknowledge that interleukin levels were unfortunately not available. We conclude that anakinra can be a valuable alternative option in patients with autoimmune encephalitis refractory to conventional immunotherapies.