•Ischemic brain injury impaired cognitive function at 28 days post-stroke in mice.•Ischemic brain injury triggered AIM2 inflammasome-mediated inflammation within 7 days post-stroke.•Microglia- or ...endothelial cell-induced AIM2 production mediated PSCI pathogenesis.•AIM2 inflammasome-induced pyroptosis may contribute to acute and chronic neuronal death after stroke.•AIM2 KO and administration of the caspase-1 inhibitor, Ac-YVAD-CMK, attenuated long-term cognitive deficits.
Although over one-third of stroke patients may develop post-stroke cognitive impairment (PSCI), the mechanisms underlying PSCI remain unclear. We explored here, the involvement of post-stroke inflammasomes in long-term PSCI development, using a 45 min-middle cerebral artery occlusion (MCAO)/reperfusion-induced PSCI model. Immunohistological assessment on day 1, 3, and 7 was followed by cognitive function test 28 days post-stroke. Evaluation of inflammasome sensor gene expression in aged mouse brains showed dominant expression of absent in melanoma 2 (Aim2) in 6-, 12-, and 18-month-old mouse brains. AIM2 mRNA and protein increased until 7 days post-stroke. PSCI decreased anxiety in elevated plus maze test and impaired spatial learning and memory functions in Morris water maze test 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1β, and IL-18, were higher in the hippocampus and cortex of the PSCI than in those of the sham group 7 days post-stroke. AIM2 immunoreactivity of the PSCI group was primarily co-localized with Iba-1 (microglial marker) and CD31 (endothelial cell marker) immunoreactivities but not NeuN (neuronal marker) and GFAP (astrocyte marker) immunoreactivities, suggesting that microglia or endothelial cell-induced AIM2 production mediated PSCI pathogenesis. Additionally, inflammasome-induced pyroptosis might contribute to acute and chronic neuronal death after stroke. AIM2 knockout (KO) and Ac-YVAD-CMK-induced caspase-1 inhibition in mice significantly improved cognitive function and reversed brain volume in the hippocampus relative to those in stroke mice. Conclusively, AIM2 inflammasome-mediated inflammation and pyroptosis likely aggravated PSCI; therefore, targeting and controlling AIM2 inflammasome could potentially treat PSCI.
The sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce the incidence of macrovascular complications of diabetes, while their effect on diabetic retinopathy has not been clarified. We compared ...the effects of SGLT2is with those of dipeptidyl peptidase-4 inhibitors (DPP4is) on the risk of diabetic retinopathy and its progression in people with type 2 diabetes. We performed a retrospective cohort study among people with type 2 diabetes who started on a SGLT2i or DPP4i from 2014 to 2016 according to the Korean National Health Insurance Service database. Subjects initiated on a SGLT2i or DPP4i were matched on a 1:1 basis according to their propensity scores, and Cox proportional hazards regression models were used to calculate the hazard ratios for the risk of diabetic retinopathy and its progression. After propensity score-matching, 41,430 patients without a history of diabetic retinopathy were identified as new users of a SGLT2i (n = 20,175) or DPP4i (n = 20,175). The hazard ratio (95% CI) for diabetic retinopathy was 0.89 (0.83-0.97) for SGLT2i initiators compared with DPP4i initiators. In patients with a history of diabetic retinopathy (n = 4,663 pairs), there was no significant difference in diabetic retinopathy progression between SGLT2i initiators and DPP4i initiators (hazard ratio 0.94, 95% CI 0.78-1.13). This real-world cohort study showed that SGLT2is might be associated with lower risk of diabetic retinopathy compared with DPP4is. Randomized controlled trials are needed to investigate the long-term effect of SGLT2is in diabetic retinopathy in people with diabetes.
Aims/Introduction
This study aimed to determine whether sodium–glucose cotransporter 2 inhibitors (SGLT2i) were related to increased fracture risk in adults with type 2 diabetes compared with ...dipeptidyl peptidase‐4 inhibitors (DPP‐4i).
Materials and Methods
Between 1 May 2016 and 31 December 2018, we carried out a new‐user cohort study using the Korean National Health Insurance Service database. Propensity score matching was carried out on 478,826 new users of an SGLT2i or DPP‐4i. After propensity score matching on >80 covariates, 84,460 individuals were initiated on SGLT2i or DPP‐4i, with 42,230 individuals in each treatment group. The time to first fracture event was compared between the SGLT2i and DPP‐4i groups using Cox proportional hazards models, and the results are reported as hazard ratios with 95% confidence intervals for fracture occurrence. Subgroup analyses investigated fractures between treatment groups according to baseline characteristics.
Results
Individuals who were started on SGLT2i were not linked with increased fracture risk in both as‐treated and intention‐to‐treat analyses (as‐treated: hazard ratio 0.98, 95% confidence interval 0.92–1.04; intention‐to‐treat: hazard ratio 0.94, 95% confidence interval 0.89–1.00). We identified no significant interaction between the individuals' age, sex, fracture history or thiazolidinedione use in any subgroup analyses, showing that none of these variables appeared to be impact modifiers in the connection between SGLT2i and fractures.
Conclusions
Our study found no increase in the risk of fracture among individuals treated with SGLT2i in a real‐world clinical setting for type 2 diabetes.
This study showed no increase in the fracture risk with real‐world clinical use of sodium–glucose cotransporter 2 inhibitors in patients with type 2 diabetes. This study provided important clinical information by increasing the understanding of the fracture safety of sodium–glucose cotransporter 2 inhibitors.
An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting ...with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.
Abstract Background There is currently insufficient evidence to confirm the effect of ambient air pollution on mental disorders, especially among susceptible populations. This study investigated the ...short-term effect of ambient air pollution on the risk of depressive episode and the effect modification across disease subpopulations. Methods Subjects who visited the emergency department (ED) for depressive episode from 2005 to 2009 ( n =4985) in Seoul, Republic of Korea were identified from medical claims data. We conducted a time-stratified case-crossover study using conditional logistic regression. Subgroup analyses were conducted after the subjects were stratified by underlying disease (cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, asthma, and depressive disorder). The risk was expressed as an odds ratio (OR) per 1 standard deviation of each air pollutant. Results SO2 , PM10 , NO2 , and CO were positively associated with ED visits for depressive episode. The maximum risk was observed in the distributed lag 0–3 model for PM10 (OR, 1.120; 95% confidence interval, 1.067–1.176). PM10 , NO2 , and CO significantly increased the risks of ED visits for depressive episode in subjects with either underlying cardiovascular disease, diabetes mellitus, asthma, or depressive disorder. Limitations Our data may include a misclassification bias due to the validity of a diagnosis determined from medical services utilization data. Conclusions SO2 , PM10 , NO2 , and CO significantly increased the risk of ED visits for depressive episode, especially among individuals with pre-existing cardiovascular disease, diabetes mellitus, or asthma.
Abstract
This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors ...affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (
P
= 0.018). However, it significantly declined by − 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (
P
< 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio OR = 0.98; 95% confidence interval CI 0.96–1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16–5.50), and pneumonia (OR = 2.59, 95% CI 1.08–6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.
The "obesity paradox" has not been elucidated in the long-term outcomes of acute coronary syndrome (ACS). We investigated the association between obesity and cardiovascular (CV) outcomes in ACS ...patients with and without diabetes.
We identified 6978 patients with ACS aged 40-79 years from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2015. Baseline body mass index (BMI) was categorized as underweight (< 18.5 kg/m
), normal weight (18.5-22.9 kg/m
), overweight (23.0-24.9 kg/m
), obese class I (25.0-29.9 kg/m
), and obese class II (≥ 30.0 kg/m
). The primary outcome was major adverse CV events (MACE)-CV death, myocardial infarction (MI), and stroke. The secondary outcomes were the individual components of MACE, hospitalization for heart failure (HHF), and all-cause death.
After adjustment for confounding variables, compared to normal-weight patients without diabetes (reference group), obese class I patients with and without diabetes had a lower risk of MACE, but only significant in patients without diabetes (with diabetes: hazard ratio HR 0.95, 95% confidence interval CI 0.78-1.14; without diabetes: HR 0.78, 95% CI 0.62-0.97). Obese class II patient with diabetes had a higher risk of MACE with no statistical significance (HR 1.14, 95% CI 0.82-1.59). Underweight patients with and without diabetes had a higher risk of MACE, but only significant in patients with diabetes (with diabetes: HR 1.79, 95% CI 1.24-2.58; without diabetes: HR 1.23, 95% CI 0.77-1.97).
In ACS patients, obesity had a protective effect on CV outcomes, especially in patients without diabetes.
The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.
This study used 2013 to 2016 data from the Korea ...National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.
In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets.
This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.
Diabetes mellitus is a leading cause of mortality and increased disability-adjusted life years worldwide. In Korea, the prevalence of diabetes increased from 8.6% to 11.0% in 2001 to 2013 and the ...prevalence of adult obesity, which is the most important risk factor of diabetes, increased from 29.2% to 31.8% during the same period. There has been a dramatic increase in the number of obese Koreans with diabetes in recent decades and the prevalence of diabetes in people aged 40 years and older also increased in 2001 to 2013. Nevertheless, the mean age at the first diagnosis of diabetes was very similar for men in 2005 and 2013, while the mean age for women decreased slightly. There is an inverse linear relationship between body mass index and age at the diagnosis of diabetes among those who are newly diagnosed. Accordingly, the prevalence of diabetes is increasingly shifting to younger individuals and those who are obese. Therefore, public efforts should focus on healthy lifestyle changes, primary prevention measures, screening for the early detection of diabetes, and long-term management.
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