The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Targeted Metabolomic Biomarkers for Stroke Subtyping.

BACKGROUND AND PURPOSE: Ischemic stroke is a heterogeneous disease with various etiologies. The current subtyping process is complicated, time-consuming, and costly. Metabolite-based biomarkers have the potential to improve classification and deliver optimal treatments. We here aimed to identify novel, targeted metabolomics-based biomarkers to discriminate between large-artery atherosclerosis (LAA) and cardioembolic (CE) stroke. METHODS: We acquired serum samples and clinical data from a hospital-based acute stroke registry (ischemic stroke within 3 days from symptom onset). We included 346 participants (169 LAA, 147 CE, and 30 healthy older adults) and divided them into training and test sets. Targeted metabolomic analysis was performed using quantitative and quality-controlled liquid chromatography with tandem mass spectrometry. A multivariate regression model using metabolomic signatures was created that could independently distinguish between LAA and CE strokes. RESULTS: The training set (n = 193) identified metabolomic signatures that were different in patients with LAA and CE strokes. Six metabolomic biomarkers, i.e., lysine, serine, threonine, kynurenine, putrescine, and lysophosphatidylcholine acyl C16:0, could discriminate between LAA and CE stroke after adjusting for sex, age, body mass index, stroke severity, and comorbidities. The enhanced diagnostic power of key metabolite combinations for discriminating between LAA and CE stroke was validated using the test set (n = 123). CONCLUSIONS: We observed significant differences in metabolite profiles in LAA and CE strokes. Targeted metabolomics may provide enhanced diagnostic yield for stroke subtypes. The pathophysiological pathways of the identified metabolites should be explored in future studies.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). METHODS: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). FINDINGS: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. INTERPRETATION: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. FUNDING: Bristol Myers Squibb and Janssen Research & Development.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

Aim: While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. Material and methods: This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. Results: The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). Conclusion: The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

BACKGROUND: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. METHODS: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. RESULTS: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). CONCLUSION: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes.

OBJECTIVE: The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated. METHODS: Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days. RESULTS: In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (ß = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011). INTERPRETATION: CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.

U-shaped associations between glycated albumin and obesity and role of IL-10 in hyperacute ischemic stroke.

OBJECTIVE: There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). MATERIALS AND METHODS: We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1ß, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. RESULTS: The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). CONCLUSION: GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations.

Brain-Only Metastasis and 10-Year Survival after Curative Gastric Cancer Resection: A Case Report.

Gastric cancer (GC) usually metastasizes to locoregional lymph nodes, the peritoneum causing ascites, or to the liver and lungs but rarely to the brain. Few cases of brain-only GC metastases have been reported, and the prognosis is very poor. We present a case of brain-only metastasis 2 years after curative GC surgery and chemotherapy, who visited the ER due to a headache. The patient underwent operative tumor resection of the brain with additional chemotherapy and is still alive and disease free 10 years after initial curative treatment. This case shows that brain-only metastasis may have a better prognosis than that of systemic metastasis; thus, aggressive treatment with radiotherapy or surgery with chemotherapy may be needed.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

BACKGROUND: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. AIMS: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. METHODS: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. RESULTS: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. CONCLUSION: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Gastric Ischemia after SARS-CoV-2 Infection.

Gastric ischemia is uncommon because the stomach has multiple collateral blood supplies. The etiology of gastric ischemia is vascular insufficiency caused by systemic hypotension, vasculitis, or disseminated thromboembolism. Mechanical causes include gastric volvulus and acute gastric distention. Uncommon as gastric ischemia is, we are the first to report a 65-year-old male who developed gastric ischemia leading to gastric pneumatosis 26 days after initial treatment for severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV-2), via laparoscopic imaging. We conclude that physicians should be suspicious of gastric ischemia when the patient is infected with SARS-CoV-2 with severe abdominal pain and should proceed with medical conservative care instead of surgery.

Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210-6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027-9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship.

Risk Allele Frequency Analysis and Risk Prediction of Single-Nucleotide Polymorphisms for Prostate Cancer.

The incidence of prostate cancer (PCa) varies by ethnicity. This study aimed to provide insights into the genetic cause of PCa, which can result in differences in incidence among individuals of diverse ancestry. We collected data on PCa-associated single-nucleotide polymorphisms (SNPs) from a genome-wide association study catalog. Fisher's exact tests were used to analyze the significance of enrichment or depletion of the effect on the allele at a given SNP. A network analysis was performed based on PCa-related SNPs that showed significant differences among ethnicities. The SNP-based polygenic risk score (PRS) was calculated, and its correlation with PCa incidence was evaluated. European, African, and East Asian populations had different heatmap patterns. Calculated PRS from the allele frequencies of PCa was the highest among Africans, followed by Europeans, and was the lowest among East Asians. PRS was positively correlated with the incidence and mortality of PCa. Network analysis revealed that AR, CDKN1B, and MAD1L1 are genes related to ethnic differences in PCa. The incidence and mortality of PCa showed a strong correlation with PRS according to ethnicity, which may suggest the effect of genetic factors, such as the AR gene, on PCa pathogenesis.

A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts.

Dyslipidemia is an important independent risk factor for cardiovascular disease (CVD). Specifically, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and the ApoB/A1 ratio have been linked to CVD. We conducted a genome-wide association study meta-analysis of two Korean cohorts containing a total of 12,924 patients to identify novel single nucleotide polymorphisms (SNPs) associated with ApoA1 and ApoB levels and the ApoB/A1 ratio. Additionally, an expression quantitative trait locus (eQTL) and differentially expressed genes (DEGs) analysis were performed. The statistically significant eQTL, DEG, and Gene Ontology (GO) results were used to explore the predicted interaction networks and retrieve the interacting genes and proteins. We identified three novel SNPs (rs11066280, p = 3.46 × 10−21; rs1227162, p = 2.98 × 10−15; rs73216931, p = 5.62 × 10−9) associated with ApoA1. SNP rs73216931 was an eQTL for KMT5A in the pancreas and whole blood. The network analysis revealed that HECTD4 and MYL2:LINC1405 are associated with AKT1. Our in silico analysis of ApoA1 genetic variants revealed heart muscle-related signals. ApoA1 also correlated positively with vitamin D, and genes associated with ApoA1 and vitamin D were found. Our data imply that more research into ApoA1 is needed to understand the links between dyslipidemia and CVD and vitamin D and CVD.

Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson's Disease: 10 Years and Beyond.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. OBJECTIVE: To investigate the survival rate and long-term outcome of DBS. METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma.

BACKGROUND: The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. METHODS: The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. RESULTS: In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e-6 and 1.55e-7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e-12 and 2.55e-6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e-17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e-8). CONCLUSIONS: The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.