Cardiorenal outcomes and mortality after sodium-glucose cotransporter-2 inhibitor initiation in type 2 diabetes patients with percutaneous coronary intervention history.

AIMS: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. RESULTS: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. CONCLUSIONS: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin.

AIM: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. RESULTS: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. CONCLUSIONS: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

Diabetes severity and the risk of depression: A nationwide population-based study.

BACKGROUND: In consideration of the substantial occurrence rates of diabetes mellitus (DM) and depression, it is imperative to identify patients with DM who are at an elevated risk of developing depression. Accordingly, this study aimed to examine whether the risk of depression escalated proportionally with the severity of diabetes. METHODS: 2,067,017 adults diagnosed with type 2 DM, with the exception of those diagnosed with depression either before or within one year of the index date, were identified from a nationwide population-based cohort in Korea. Severity scores for DM were established based on various factors, including insulin use, DM duration of at least 5 years, use of three or more oral hypoglycemic agents, the presence of chronic kidney disease (CKD), cardiovascular diseases (CVD), or diabetic retinopathy. Each of these attributes was assigned a score of one point for diabetes severity, and their cumulative sum was defined as a diabetes severity score, ranging from 0 to 6. RESULTS: During a median follow-up of 6.2 years, 407,047 cases of major depression were identified. Each component contributing to the DM severity score was significantly associated with an increased risk of depression (all P-values <0.001), with insulin use and the presence of CVD demonstrating the most significant correlation with depression risk. As the DM severity score increased, the risk of depression was observed to significantly escalate (P for trend <0.001). After adjusting for potential confounding variables, the hazard ratios (95% confidence intervals) of depression were 1.15 (1.14-1.16) in 1 point, 1.28 (1.27-1.29) in 2 points, 1.45 (1.43-1.47) in 3 points, 1.70 (1.67-1.73) in 4 points, 1.91 (1.84-1.98) in 5 points, and 2.01 (1.79-2.26) in 6 points, respectively. CONCLUSION: The results of this study indicate that diabetes severity is positively associated with an elevated risk of developing major depression. Based on these findings, it is feasible to consider targeting depression screening efforts towards individuals with higher diabetes severity scores.

Metabolic dysfunction-associated fatty liver disease increases the risk of type 2 diabetes mellitus in young Korean adults.

AIMS: To investigate the impact of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) on the risk of type 2 diabetes mellitus in young Korean adults. METHODS: Data were sourced from the Korean National Health Insurance Service-Health Screening Cohort, comprising adults aged 20-39 who underwent health examinations between 2009 and 2012. Participants were grouped based on the presence of MAFLD and nonalcoholic fatty liver disease (NAFLD), both individually and in combination. The categorizations included Neither-FLD, NAFLD-only, MAFLD-only, or Both-FLD. Incident diabetes was identified through claims data during the follow-up period. RESULTS: Among 6,232,656 participants, 676,747 (10.8 %) had MAFLD. During a median follow-up of 9.5 years, 182,291 incident diabetes cases were identified. Multivariate analysis revealed a significantly higher diabetes risk in the MAFLD group compared to those in the Non-MAFLD group (HR = 6.148, 95 % CI, 6.084-6.212). Notably, diabetes incidence was highest in FLI ≥ 60 subgroup with BMI ≥ 23 and metabolic syndrome. CONCLUSIONS: MAFLD is associated with a 6.1-fold increased diabetes risk in young adults, underscoring the urgent need for early intervention to mitigate this risk.

Weight change in patients with new-onset type 2 diabetes mellitus and its association with remission: Comprehensive real-world data.

AIMS: We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults. MATERIALS AND METHODS: We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication. RESULTS: In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25. CONCLUSION: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals.

Advances in laser speckle imaging: From qualitative to quantitative hemodynamic assessment.

Laser speckle imaging (LSI) techniques have emerged as a promising method for visualizing functional blood vessels and tissue perfusion by analyzing the speckle patterns generated by coherent light interacting with living biological tissue. These patterns carry important biophysical tissue information including blood flow dynamics. The noninvasive, label-free, and wide-field attributes along with relatively simple instrumental schematics make it an appealing imaging modality in preclinical and clinical applications. The review outlines the fundamentals of speckle physics and the three categories of LSI techniques based on their degree of quantification: qualitative, semi-quantitative and quantitative. Qualitative LSI produces microvascular maps by capturing speckle contrast variations between blood vessels containing moving red blood cells and the surrounding static tissue. Semi-quantitative techniques provide a more accurate analysis of blood flow dynamics by accounting for the effect of static scattering on spatiotemporal parameters. Quantitative LSI such as optical speckle image velocimetry provides quantitative flow velocity measurements, which is inspired by the particle image velocimetry in fluid mechanics. Additionally, discussions regarding the prospects of future innovations in LSI techniques for optimizing the vascular flow quantification with associated clinical outlook are presented.

Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults.

AIM: This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. MATERIALS AND METHODS: In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. RESULTS: The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. CONCLUSIONS: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.

Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study.

BACKGRUOUND: Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population. METHODS: This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis. RESULTS: Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers. CONCLUSION: Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers.

The Risk of Shoulder Adhesive Capsulitis in Individuals with Prediabetes and Type 2 Diabetes Mellitus: A Longitudinal Nationwide Population-Based Study.

BACKGRUOUND: This study aimed to investigate the association between type 2 diabetes mellitus (T2DM) and shoulder adhesive capsulitis (AC) using a large-scale, nationwide, population-based cohort in the Republic of Korea. METHODS: A total of 3,471,745 subjects aged over 20 years who underwent a National Health Insurance Service medical checkup between 2009 and 2010 were included in this study, and followed from the date of their medical checkup to the end of 2018. Subjects were classified into the following four groups based on the presence of dysglycemia and history of diabetes medication: normal, prediabetes, newly diagnosed T2DM (new-T2DM), and T2DM (claim history for antidiabetic medication). The endpoint was new-onset AC during follow-up. The incidence rates (IRs) in 1,000 person-years and hazard ratios (HRs) of AC for each group were analyzed using Cox proportional hazard regression models. RESULTS: The IRs of AC were 9.453 (normal), 11.912 (prediabetes), 14.933 (new-T2DM), and 24.3761 (T2DM). The adjusted HRs of AC in the prediabetes, new-T2DM, and T2DM groups were 1.084 (95% confidence interval [CI], 1.075 to 1.094), 1.312 (95% CI, 1.287 to 1.337), and 1.473 (95% CI, 1.452 to 1.494) compared to the normal group, respectively. This secular trend of the HRs of AC according to T2DM status was statistically significant (P<0.0001). CONCLUSION: This large-scale, longitudinal, nationwide, population-based cohort study of 3,471,745 subjects confirmed that the risk of AC increases in prediabetic subjects and is associated with T2DM status.

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

BACKGRUOUND: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. METHODS: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. RESULTS: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. CONCLUSION: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Optimal LDL cholesterol levels in young and old patients with type 2 diabetes for secondary prevention of cardiovascular diseases are different.

Objective: Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce. Methods: From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55-69 mg/dL, 70-99 mg/dL, 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL. Results: Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55-69 mg/dL were 0.97 (95% CI: 0.85-1.11) and 0.96 (95% CI: 0.79-2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70-99 mg/dL and LDL-C = 55-69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91-1.08 and HR: 0.91, 95% CI: 0.81-1.01). Conclusion: LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55-69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.

Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy - a nationwide cohort study.

Objectives: Levothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer. Methods: We enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation. Results: We evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771-0.932), 0.703 (0.591-0.836), and 0.405 (0.224-0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648-0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients. Conclusion: We suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy.

Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020.

BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis.

BACKGRUOUND: The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results. METHODS: This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis. RESULTS: During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure. CONCLUSION: In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Association between regular physical activity and lower incidence of colorectal cancer in patients with diabetes mellitus: a nationwide cohort study.

AIM: The aim of this work was to investigate the association between changes in physical activity (PA) status and the development of colorectal cancer (CRC) in patients with diabetes. METHOD: This nationwide population study included 1 439 152 patients with diabetes who underwent a health screening provided by the Korean National Health Insurance Service between January 2009 and December 2012 and a follow-up screening after 2 years. Based on changes in PA status, participants were categorized into four groups: remained inactive, remained active, active-to-inactive and inactive-to-active. RESULTS: During the median follow-up period of 5.2 years, 38 244 new cases of CRC were diagnosed. Compared with the remained inactive group, among the three other groups, the remained active group had the lowest risk of CRC [adjusted hazard ratio (aHR) 0.93; 95% CI 0.90-0.96], followed by the inactive-to-active group (aHR 0.97; 95% CI 0.94-1.00) and active-to-inactive group (aHR 0.99; 95% CI 0.96-1.02), after adjusting for confounding variables (p = 0.0007). This reduction in cancer incidence in the remained active group was observed for both rectal cancer (aHR 0.87, 95% CI 0.79-0.95) and colon cancer (aHR 0.93, 95% CI 0.90-0.97), irrespective of sex. In terms of the intensity and amount of PA, moderate intensity PA was the most effective, and a positive correlation was found between the amount of PA and the reduction in CRC incidence. CONCLUSION: Regular PA was independently associated with a decreased risk of CRC in patients with diabetes. The intensity and amount of physical activity both play a role in reducing the risk.

Photobiomodulation Therapy Restores Olfactory Function Impaired by Photothrombosis in Mouse Olfactory Bulb.

An ischemic stroke typically accompanies numerous disorders ranging from somatosensory dysfunction to cognitive impairments, inflicting patients with various neurologic symptoms. Among pathologic outcomes, post-stroke olfactory dysfunctions are frequently observed. Despite the well-known prevalence, therapy options for such compromised olfaction are limited, likely due to the complexity of olfactory bulb architecture, which encompasses both the peripheral and central nervous systems. As photobiomodulation (PBM) emerged for treating ischemia-associated symptoms, the effectiveness of PBM on stroke-induced impairment of olfactory function was explored. Novel mouse models with olfactory dysfunctions were prepared using photothrombosis (PT) in the olfactory bulb on day 0. The post-PT PBM was performed daily from day 2 to day 7 by irradiating the olfactory bulb via an 808 nm laser with a fluence of 40 J/cm2 (325 mW/cm2 for 2  smin per day). The buried food test (BFT) was used to score behavioral acuity in food-deprived mice to assess the olfactory function before PT, after PT, and after PBM. Histopathological examinations and cytokine assays were performed on the mouse brains harvested on day 8. The results from BFT were specific to an individual, with positive correlations between the baseline latency time measured before PT and its alteration at the ensuing stages for both the PT and PT + PBM groups. Also, the correlation analysis in both groups showed highly similar, significant positive relationships between the early and late latency time change independent of PBM, implicating a common recovery mechanism. Particularly, PBM treatment accelerated the recovery of impaired olfaction following PT by suppressing inflammatory cytokines and enhancing both glial and vascular factors (e.g., GFAP, IBA-1, and CD31). PBM therapy during the acute phase of ischemia improves the compromised olfactory function by modulating microenvironments and inflammation status of the affected tissue.

Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study.

BACKGRUOUND: Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures. METHODS: We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider's medical specialty, the proximity to the medical center, and financial burdens of treatment. RESULTS: Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over -2.5, and in five (2.3%) patients due to expected dental procedures. CONCLUSION: Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study.

BACKGROUND/AIMS: A re-increasing trend of thyroid cancer since 2015 has been observed despite a similar examination rate, and the incidence of thyroid cancer among young adults continues to rise. METHODS: This study used data from the Korean National Health Insurance Service. Individuals 20-39 years of age who underwent ≥ 4 health checkups from 2009-2013 were enrolled and followed throughout 2019. To quantify the metabolic burden, groups were divided by the number of diagnoses of metabolic syndrome across four consecutive health examinations. RESULTS: Among the study population (n = 1,204,646), 5,929 (0.5%) were diagnosed with thyroid cancer during a follow- up period of 5 years. The hazard ratio (95% confidence interval) values of thyroid cancer occurrence according to the number (1-4) of diagnoses of metabolic syndrome across the four health examinations compared to the group without metabolic syndrome were significantly greater, as follows: 1.12 (1.02-1.23), 1.25 (1.10-1.42), 1.33 (1.15-1.55), and 1.48 (1.25-1.75) (p for trend < 0.01), respectively. Each component of metabolic syndrome showed a significant increase in hazard ratio according to the number of diagnoses except for impaired fasting glucose criteria. CONCLUSION: Cumulative exposure to metabolic syndrome was associated with thyroid cancer risk in young adults.