Cardiovascular Safety of COVID-19 Vaccination in Patients With Cancer: A Self-Controlled Case Series Study in Korea.

BACKGROUND: Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea. METHODS: We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI). RESULTS: Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis. CONCLUSION: For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.

Growth and Electronic Structure of Copper Oxide Monolayer Epitaxial Films.

Copper-based high-temperature superconductors share a common feature in their crystal structure, which is the presence of a CuO2 plane, where superconductivity takes place. Therefore, important questions arise as to whether superconductivity can exist in a single layer of the CuO2 plane and, if so, how such superconductivity in a single CuO2 plane differs from that in a bulk cuprate system. To answer these questions, studies of the superconductivity in cuprate monolayers are necessary. In this study, we constructed a heterostructure system with a La2-xSrxCuO4 (LSCO) monolayer containing a single CuO2 plane and measured the resulting electronic structures. Monolayer LSCO has metallic and bulk-like electronic structures. The hole doping ratio of the monolayer LSCO is found to depend on the underlying buffer layer due to the interface effect. Our work will provide a platform for research into ideal two-dimensional cuprate systems.

Effect of Smoking Cessation on the Risk of Subarachnoid Hemorrhage: A Nested Case-Control Study in Korean Men.

BACKGROUND: Smoking is a well-established risk factor for subarachnoid hemorrhage (SAH), and current smokers have an increased risk of SAH. However, there are insufficient data on whether smoking cessation in current smokers reduces the risk of SAH. METHODS: A nested case-control study was conducted based on the National Health Insurance Service-National Health Screening Cohort, which comprises nationwide health claims data and a national health screening program in Korea (2002-2019). We constructed a cohort of current male smokers without a history of stroke at the baseline health screening (2002-2003). From this cohort, cases were defined as individuals who experienced a nontraumatic SAH during the follow-up period up to 2019. Five controls were matched to each case using incidence density sampling. Smoking status (continuation or cessation) before the occurrence of SAH was evaluated using the repeated national health screening program. We conducted a multivariable conditional logistic regression analysis, adjusting for alcohol consumption, physical activity, body mass index, systolic blood pressure, and fasting blood glucose levels, to evaluate the association between SAH risk and smoking cessation. RESULTS: At baseline, there were 112 142 current male smokers. After excluding individuals with prior stroke or insufficient data, the cohort consisted of 105 223 eligible participants (mean age, 50.3±8.5 years). Among them, we identified 318 cases of SAH and 1590 matched controls. Those who quit smoking had a significantly lower risk of SAH compared with current smokers (adjusted odds ratio, 0.55 [95% CI, 0.41-0.73]). The risk of SAH decreased with a longer period of smoking cessation. The risk reduction with smoking cessation was consistent even among prior heavy smokers. CONCLUSIONS: Smoking cessation in current male smokers reduced the risk of SAH, and the risk reduction was greater as the cessation period increased. These findings warrant intensive efforts to encourage smokers, even heavy smokers, to quit.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study.

BACKGROUND: Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS: We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS: During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS: Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study.

INTRODUCTION: Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. METHODS: This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. RESULTS: From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492). CONCLUSIONS: In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Proton Pump Inhibitors and Risk of Cardiovascular Disease: A Self-Controlled Case Series Study.

INTRODUCTION: We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control. METHODS: We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables. RESULTS: In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome. DISCUSSION: Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

Association of atrial fibrillation with infectivity and severe complications of COVID-19: A nationwide cohort study.

Infection is associated with the occurrence, recurrence, and progression of atrial fibrillation (AF), and is also closely related to poor prognosis. However, studies of the relationship between infectivity and severe complications of coronavirus infectious disease-19  (COVID-19) with a history of AF are limited. To estimate infectivity and severity of complications in COVID-19 patients with a history of AF, this study was done. From the Korean nationwide COVID-19 dataset, 212 678 participants with at least one severe acute respiratory syndrome coronavirus 2 (COVID-19) test were included between January 1 and June 4, 2020. AF was defined according to at least two outpatient hospital visits or one admission with an ICD-10 code of "I48" before the COVID-19 test. To investigate the association of AF with infectivity and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) was performed. Severe complications of COVID-19 were defined as a composite outcome of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. Among 212 678 participants who underwent the COVID-19 test, there were 7713 COVID-19 positive patients. After PSM, COVID-19 PCR positivity did not show a significant difference according to the presence of AF (odds ratio [OR]: 0.79, 95% confidence interval [CI]: [0.60-1.04]). Of 7713 COVID-19 patients, 62 (0.8%) had a history of AF and severe complications occurred in 444 (5.7%) patients. After PSM, AF was associated with the development of severe complications (OR: 2.04, 95% CI: [1.10-3.79]) and mortality (OR: 2.09, 95% CI: [1.01-4.31]) of COVID-19. We found that AF was associated with an increased risk of severe complications in COVID-19 infected patients.

Associations of heart failure with susceptibility and severe complications of COVID-19: A nationwide cohort study.

Infection is associated with occurrence and worsening of heart failure (HF). However, studies on the association of susceptibility and severe complications of coronavirus disease 2019 (COVID-19) with HF history are limited. From the Korean nationwide COVID-19 data set, 212,678 participants with at least one severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction (RT-PCR) test were included between January 1 and June 4, 2020. To investigate the association of HF with susceptibility and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) and logistic regression analysis were performed. The primary outcome was a composite outcome of mechanical ventilation, intensive care unit (ICU) admission, and death. After PSM, COVID-19 PCR positivity did not show a significant difference according to HF history in multivariable analysis (odds ratio [OR]: 0.91, 95% confidence interval (CI) (0.79-1.04), p = 0.146). Of 7630 individuals with confirmed COVID-19 infection, 310 (4.1%) had HF history. The overall primary outcome occurred in 426 (5.6%) individuals, including 159 (2.1%) cases of mechanical ventilation, 254 (3.3%) cases of ICU admission, and 215 (2.8%) cases of death. In multivariate logistic analysis, presence of HF history was associated independently with primary outcome (OR: 1.99, 95% CI: 1.42-2.79, p < 0.001), particularly mortality (OR: 2.02, 95% CI: 1.36-3.00, p < 0.001). Our study demonstrated that HF history is associated poor prognosis, particularly mortality, in COVID-19. Patients with HF can have severe complication if infected with COVID-19; therefore, careful management are necessary.

Association between the fatty liver index and the risk of severe complications in COVID-19 patients: a nationwide retrospective cohort study.

BACKGROUND: Research on the association of non-alcoholic fatty liver disease (NAFLD) with prognosis in COVID-19 has been limited. We investigated the association between the fatty liver index (FLI), a non-invasive and simple marker of NAFLD, and the severe complications of COVID-19 patients in South Korea. METHODS: We included 3122 COVID-19-positive patients from the nationwide COVID-19 cohort dataset in South Korea between January and June 2020. The FLI was calculated using triglyceride, body mass index, glutamyl transpeptidase, and waist circumference, which were obtained from the national health screening program data. Severe complications related to COVID-19 were defined as the composite of mechanical ventilation, intensive care unit treatment, high-oxygen flow therapy, and death within 2 months after a COVID-19 infection. We performed a multivariate logistic regression analysis for the development of severe complications in COVID-19 patients. RESULTS: The mean ± standard deviation of FLI were 25.01 ± 22.64. Severe complications from COVID-19 occurred in 223 (7.14%) patients, including mechanical ventilation in 82 (2.63%) patients, ICU admission in 126 (4.04%), high-flow oxygen therapy in 75 (2.40%), and death in 94 (3.01%) patients, respectively. The multivariate analysis indicated that the highest tertile (T3) of FLI was positively associated with severe complications from COVID-19 (adjusted odds ratio (OR): 1.77, 95% confidence interval (CI) (1.11-2.82), P = 0.017) compared with the lowest tertile (T1). CONCLUSIONS: Our study demonstrated that FLI, which represents NAFLD, was positively associated with an increased risk of severe complications from COVID-19. FLI might be used as a prognostic marker for the severity of COVID-19.

Superconducting Sr2RuO4 Thin Films without Out-of-Phase Boundaries by Higher-Order Ruddlesden-Popper Intergrowth.

Ruddlesden-Popper (RP) phases (An+1BnO3n+1, n = 1, 2,···) have attracted intensive research with diverse functionalities for device applications. However, the realization of a high-quality RP-phase film is hindered by the formation of out-of-phase boundaries (OPBs) that occur at terrace edges, originating from lattice mismatch in the c-axis direction with the A'B'O3 (n = ∞) substrate. Here, using strontium ruthenate RP-phase Sr2RuO4 (n = 1) as a model system, an experimental approach for suppressing OPBs was developed. By tuning the growth parameters, the Sr3Ru2O7 (n = 2) phase was formed in a controlled manner near the film-substrate interface. This higher-order RP-phase then blocked the subsequent formation of OPBs, resulting in nearly defect-free Sr2RuO4 layer at the upper region of the film. Consequently, the Sr2RuO4 thin films exhibited superconductivity up to 1.15 K, which is the highest among Sr2RuO4 films grown by pulsed laser deposition. This work paves the way for synthesizing pristine RP-phase heterostructures and exploring their unique physical properties.

Association Between the Risk for Cardiovascular Events and Antiviral Treatment for Herpes Zoster.

BACKGROUND: Cardiovascular risk increases following herpes zoster. We investigated whether treatment with antiviral agents, steroids, and common cardiovascular medications was associated with the risk of postherpetic cardiovascular events. METHODS: This was a nationwide population-based, retrospective, cohort study using the National Health Insurance Service health claims data in Korea. We included patients with a first-ever diagnosis of herpes zoster in 2003-2014 and no prior cardiovascular event. The primary outcome was the occurrence of composites of myocardial infarction (International Statistical Classification of Diseases, Tenth Revision, code I21) and stroke (codes I60-I63) since the herpes zoster. We analyzed the exposure (intravenous or oral administration) to antiviral agents, steroids, antithrombotics, and statins within ±7 days from the index date of herpes zoster diagnosis. Follow-up was performed until occurrence of the primary outcome, death, or 31 December 2015, whichever came first. RESULTS: Of 84 993 patients with herpes zoster, the proportions of patients who received the treatment with antiviral agents, steroids, antithrombotics, and statins were 90.5%, 48.0%, 9.1%, and 7.9%, respectively. During the mean (standard deviation) follow-up period of 5.4 (3.1) years, 1523 patients experienced the primary outcome. Multivariate Cox regression analysis demonstrated that treatment with antiviral agents (adjusted hazard ratio, 0.82; 95% confidence interval, .71-.95) and statins (0.71; .59-.85) were significantly associated with the lower risk of primary outcome. Use of antithrombotics and steroids were not associated with the risk. CONCLUSIONS: After herpes zoster, treatment with antiviral agents was significantly associated with lower risk of cardiovascular events. We need more information on the cardiovascular protective role of herpes zoster treatments.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Dipstick proteinuria and risk of type 2 diabetes mellitus: a nationwide population-based cohort study.

BACKGROUND: Proteinuria has been recognized as a marker of systemic inflammation and endothelial dysfunction associated with insulin resistance and ß-cell impairment, which can contribute to the development of type 2 diabetes mellitus (T2DM). However, it is unknown whether the dipstick proteinuria test has a predictive value for new-onset T2DM. METHODS: This retrospective cohort study analyzed 239,287 non-diabetic participants who participated in the Korean nationwide health screening program in 2009-2010. Proteinuria was determined by the urine dipstick test at the baseline health screening. We performed multivariate Cox proportional regression analyses for the development of new-onset T2DM. Follow-up was performed until December 2015. RESULTS: During the mean follow-up period of 5.73 years, 22,215 participants were diagnosed with new-onset T2DM. The presence of proteinuria was significantly associated with an increased risk of T2DM (adjusted hazard ratio: 1.19, 95% confidence interval: 1.10, 1.29). There was a positive dose-response relationship between the degree of dipstick proteinuria and T2DM risk. This significant association between proteinuria and T2DM risk was consistent regardless of the fasting glucose level at baseline. CONCLUSIONS: Dipstick proteinuria is a significant risk factor for new-onset T2DM. Therefore, proteinuria might be a useful biomarker to identify those at a high risk for developing T2DM.

Initial Stroke Severity in Patients With Atrial Fibrillation According to Antithrombotic Therapy Before Ischemic Stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the leading cause of ischemic stroke. Preventive antithrombotic use, especially for anticoagulation, reduces the incidence of ischemic stroke in patients with AF. Using data from the nationwide multicenter stroke registry, we investigated the trends of preceding antithrombotic medication use in patients with acute ischemic stroke (AIS) with AF and its association with initial stroke severity and in-hospital outcomes. METHODS: This study included 6786 patients with AIS with known AF before stroke admission across 39 hospitals between June 2008 and December 2018. We collected the data on antithrombotic medication use (no antithrombotic/antiplatelet/anticoagulant) preceding AIS. Initial stroke severity was measured using the National Institutes of Health Stroke Scale, and in-hospital outcome was determined by modified Rankin Scale score at discharge. RESULTS: During the study period, anticoagulant use continued to increase. However, nearly one-third of patients with AIS with known AF did not receive antithrombotics before stroke. Initial National Institutes of Health Stroke Scale scores varied according to preceding antithrombotic therapy (P<0.001). It was higher in patients who did not receive antithrombotics than in those who received antiplatelets or anticoagulants (median National Institutes of Health Stroke Scale score: 8 versus 7 and 8 versus 6, respectively). Favorable outcome at discharge (modified Rankin Scale score, 0-2) was more prevalent in patients who received antiplatelets or anticoagulants (P<0.001). Use of antiplatelets (odds ratio, 1.23 [95% CI, 1.09-1.38]) and anticoagulants (odds ratio, 1.31 [95% CI, 1.15-1.50]) was associated with a mild initial neurological deficit (National Institutes of Health Stroke Scale score ≤5) in patients with AIS with AF. CONCLUSIONS: Throughout the study period, the proportion of patients taking anticoagulants increased among patients with AIS with known AF. However, a large portion of AF patients still did not receive antithrombotics before AIS. Furthermore, prehospitalization use of anticoagulants was associated with a significantly higher likelihood of a mild initial neurological deficit and favorable outcome at discharge.

Polar Metal Phase Induced by Oxygen Octahedral Network Relaxation in Oxide Thin Films.

ABO3 perovskite materials and their derivatives have inherent structural flexibility due to the corner sharing network of the BO6 octahedron, and the large variety of possible structural distortions and strong coupling between lattice and charge/spin degrees of freedom have led to the emergence of intriguing properties, such as high-temperature superconductivity, colossal magnetoresistance, and improper ferroelectricity. Here, an unprecedented polar ferromagnetic metal phase in SrRuO3 (SRO) thin films is presented, arising from the strain-controlled oxygen octahedral rotation (OOR) pattern. For compressively strained SRO films grown on SrTiO3 substrate, oxygen octahedral network relaxation is accompanied by structural phase separation into strained tetragonal and bulk-like orthorhombic phases, and the asymmetric OOR evolution across the phase boundary allows formation of the polar phase, while bulk metallic and ferromagnetic properties are maintained. From the results, it is expected that other oxide perovskite thin films will also yield similar structural environments with variation of OOR patterns, and thereby provide promising opportunities for atomic scale control of material properties through strain engineering.

Oral health and changes in lipid profile: A nationwide cohort study.

AIM: We aimed to investigate the association of periodontitis and oral hygiene indicators with changes in blood lipid parameters in a nationwide, population-based cohort in a longitudinal setting. MATERIALS AND METHODS: We included nationwide health screening program participants who underwent oral health examination in 2009-2010 and follow-up examinations for lipid profile without exposure to lipid-lowering agents. RESULTS: During the 5.19-year median follow-up, 65,078 individuals (mean age at baseline examination: 55.41 ± 7.30 years) underwent 286,218 health examinations. The prevalence of periodontitis was 39%. In the multivariate mixed model analysis, periodontitis and tooth loss were associated with decreased high-density lipoprotein cholesterol levels (ß = -0.0066 mmol/L, standard error = 0.0026, p = .013) and increased triglyceride levels (ß=0.0307, mmol/L, standard error = 0.0049, p < .001), respectively. Compared with tooth brushing ≤1 time/day, tooth brushing ≥3 times/day was associated with increased high-density lipoprotein cholesterol levels (ß = 0.0176 mmol/L, standard error = 0.0052, p = .006) and decreased triglyceride levels (ß = -0.0285 mmol/L, standard error = 0.0090, p = .001). CONCLUSIONS: Periodontitis and tooth loss may be attenuating factors for blood high-density lipoprotein cholesterol and triglyceride levels, respectively. Frequent tooth brushing may improve dyslipidaemia, particularly blood high-density lipoprotein cholesterol and triglyceride levels. Oral hygiene improvement may reduce the risk of dyslipidaemia.

Oral health and gastrointestinal cancer: A nationwide cohort study.

AIMS: Poor oral hygiene is closely associated with bacteraemia and systemic inflammation, which are known mediators of cancer development. We investigated the relationship between oral hygiene indicators and the risk of gastrointestinal cancer in a nationwide population-based cohort. MATERIALS AND METHODS: This study was conducted on data from 150,774 subjects from the Korean National Health Screening Cohort. The occurrence of gastrointestinal cancer was analysed according to the presence of periodontal disease and oral hygiene indicators: frequency of toothbrushing, dental visits for any reason, professional dental cleanings and number of missing teeth. Gastrointestinal cancer was defined using International Statistical Classification of Diseases-10 codes C15-C26. RESULTS: During a median 11.6 years of follow-up, the estimated 10-year event rate for gastrointestinal cancer was 6.76%. In a multivariable analysis, after adjusting for age, sex, income level, regular exercise, alcohol consumption, smoking status, body mass index, history of comorbidities, systolic blood pressure and laboratory findings, frequent toothbrushing (≥3/day) was significantly associated with a reduced risk for gastrointestinal cancer (hazard ratio: 0.91, 95% confidence interval (0.86-0.96), p < .001, p for trend < .001). CONCLUSIONS: Good oral hygiene behaviour, especially frequent toothbrushing, could be associated with a lower risk of gastrointestinal cancer.