The Presence of Diabetes Mellitus or Pre-diabetes Mellitus Increases Mortality from Heart Disease in a Taiwanese Population: A 10-year Follow-Up Study.

BACKGROUND: We evaluated hyperglycemia-associated mortality in the Taiwanese population by conducting a 10-year retrospective cohort study. METHODS: From 2007 to 2017, all participants, regardless of their age or underlying diseases, were identified at a Health Screening Center in Taiwan. Overall, 114,534 participants were included in the analysis. They were classified into three subgroups according to glycemia and smoking status by combining survival for data analysis. RESULTS: The mean follow-up time, age, and body mass index (BMI) were 8.14 ± 2.22 years, 40.95 ± 12.14 years, and 23.24 ± 3.65 kg/m2, respectively. The cumulative death rate increased from 0.9% in the normal fasting blood glucose(FBG) subgroup to approximately 6% in the diabetes FBG subgroup. After adjusting for age, gender, BMI, high-density lipoprotein, triglycerides, waist circumference(WC), and smoking status, the hazard ratio (HR) for all-cause, cancer, and heart disease mortality in the diabetes mellitus(DM) subgroup was 1.560, 1.381, and 1.828, respectively.HR was 0.989 in all-cause, 0.940 in cancer, and 1.326 in heart disease in the pre-DM subgroup. CONCLUSION: Being tested for pre-DM is related to a higher risk of death from heart disease in the Taiwanese population at baseline. Therefore, cardiovascular risk must be actively measured among diabetes patients every visit.

Troponin I Cutoff for Non-ST-Segment Elevation Myocardial Infarction in Sepsis.

The diagnostic value and optimal cutoff level of cardiac troponin I in patients with sepsis have not been studied. In this single hospital retrospective study, we assessed the optimal cutoff value of troponin I for diagnosing non-ST-segment elevation myocardial infarction (NSTEMI) with type 1 myocardial infarction (MI) in patients with sepsis who had undergone a percutaneous coronary intervention from 2009 to 2019. In total, 5,341 patients (excluding patients with chronic kidney disease) were included, of whom 277 had sepsis or septic shock. Of the 123 patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and sepsis, 77 (62.6%) were diagnosed with NSTEMI with type 1 MI. The receiver-operating characteristic curve showed an area under the curve (AUC) of 0.705 for diagnosis of NSTEMI with type 1 MI with a troponin I cutoff of >300 ng/L (sensitivity: 68.4%, specificity: 70.2%, Youden index: 0.386). Multiple linear regression showed no significant predictors of NSTEMI with type 1 MI. Troponin level and the Global Registry of Acute Coronary Events (GRACE) scores were correlated (R 2 = 0.0625, p = 0.032) and showed comparable predictive value for 6-month mortality (AUC: 0.637 and 0.611, respectively, p = 0.7651). The optimal troponin I cutoff to effectively diagnose NSTEMI with type 1 MI in patients with sepsis was 300 ng/L.

Testosterone Level Reduction Increases the 10-Year Risk of Cardiovascular Diseases: A Retrospective Cohort Study in a Taiwanese Young Male Population.

Low testosterone levels are associated with increased risk of cardiovascular disease; however, most previous studies assessed the relationship of testosterone levels with a history of cardiovascular (CV) events rather than with CV risk prediction scores consequently neglecting the effect of testosterone on CV risk in healthy young individuals. The aim of this study was to investigate the relationship between testosterone levels and predict the 10-year risk of cardiovascular disease. This retrospective cohort study was conducted through a large medical health examination system in four metropolises in Taiwan. Two risk scores were used to predict the 10-year cardiovascular risk of participants: the Framingham Risk Score (FRS) (2008) and the Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator (2013). Multivariate-adjusted logistic regression was used to calculate odds ratios (ORs) for the correlation of testosterone level reduction with the increase in predicted CV risk. We used the MJ Health Research Foundation database to collect reports of 125,414 individuals who underwent medical checkups between 2007 and 2016. The final sample size included 1,253 male participants. A reduction in testosterone level between two subsequent medical checkups was associated with higher CV risk estimated by the FRS and ASCVD Risk Estimator in young participants aged 30-49 years (OR = 0.804, 95% CI: 0.711-0.909, p < 0.01 and OR = 0.841, 95% CI: 0.742-0.953, p < 0.01, respectively). Reduction in total testosterone levels increases CV risk in men aged 30 to 49 years, while the CV risk is not influenced by low testosterone levels at baseline.

The Association between Serum Testosterone and Hyperuricemia in Males.

Gout is a common systemic inflammatory disease with a male predominance. This study aimed to determine the relationship between serum total testosterone level and hyperuricemia. Data on 1899 men, collected from 2007 to 2017, were included in the analysis. Serum testosterone and urate (SU) were measured on enrolment. The primary endpoints were SU levels ≥ 7 mg/dL and ≥9 mg/dL. On enrolment, participants had a mean age of 45.6 years and mean total testosterone and SU levels of 510 ng/dL and 6.6 mg/dL, respectively. The mean total testosterone levels were 533 and 470 ng/dL in patients with SU levels < 7 mg/dL and ≥7 mg/dL, respectively (p < 0.001); and 515 and 425 ng/dL in patients with SU levels < 9 mg/dL and ≥9 mg/dL, respectively (p < 0.001). After adjusting for age, body mass index, creatinine, serum lipid, fasting blood glucose, systolic blood pressure, and diastolic blood pressure, low testosterone level (<400 ng/dL) was significantly associated with an SU level ≥ 7 mg/dL (hazard ratio: 1.182, 95% confidence interval: 1.005−1.39) and ≥9 mg/dL (hazard ratio: 1.905, 95% confidence interval: 1.239−2.928). In men, a low testosterone level may be associated with an increased risk of hyperuricemia.

Association between hypertriglyceridemic waist phenotype and hypogonadism in Taiwanese adult men.

BACKGROUND: Aging-related hypogonadism in men is related to the deterioration of overall health. Those with this disease rarely receive treatment. The hypertriglyceridemic waist (HTGW) phenotype is a tool for predicting abnormalities of cardiovascular metabolism. However, the relationship between the HTGW phenotype and hypogonadism remains undetermined. This study aimed to determine the association between HTGW phenotype and hypogonadism in different age groups. METHODS: Data of this cross-sectional study were obtained from MJ Health Screening Center in Taiwan from 2007 to 2016. The HTGW phenotype was divided into four categories based on whether the waist circumference (WC) and triglyceride levels were normal. WC of <90 cm and triglyceride level of <150 mg/dL were defined as normal. Hypogonadism was defined as a testosterone level of <300 ng/dL. RESULTS: Overall, 6442 male participants were divided into three age groups: <50, 50-64, and ≥65 years (n = 4135, 1958, and 349; age groups 1, 2, and 3, respectively). The overall prevalence of hypogonadism was 10.6%. In group 1, participants with HTGW (odds ratio, 1.98; 95% confidence interval (CI), 1.354-2.896) had a higher risk of hypogonadism than those with normal WC and normal triglyceride levels after adjustment for body mass index and fasting blood glucose level. In group 2, participants with HTGW (odds ratio, 1.873; 95% CI, 1.099-3.193) had an increased risk of hypogonadism after adjustment for body mass index, fasting blood glucose level, Cholesterol levels, high-density lipoprotein (HDL) levels, low-density lipoprptein (LDL) levels and smoking status. However, no relationship was observed between HTGW phenotype and hypogonadism in group 3. CONCLUSION: HTGW phenotype was highly associated with hypogonadism in Taiwanese adult men. More attention should be paid to men aged <50 years with HTGW.

Waist Circumference Is More Closely Associated with Hypogonadism than Is Hyperglycemia, Independent of BMI in Middle-Aged Men.

INTRODUCTION: To evaluate whether waist circumference (WC) or hyperglycemia is more closely associated with hypogonadism in middle-aged men. Research Design and Methods. This cross-sectional study analyzed male participants under 65 years old from the MJ Health Screening Center in Taiwan from 2007 to 2016. Basic patient characteristics with relevant parameters were obtained. We used the chi-square test to perform a correlation analysis for HbA1c and WC between participants with and without hypogonadism. A one-way ANOVA with post hoc Scheffe's method was applied to compare the mean testosterone (T) among the HbAlc and WC groups (normal blood sugar with normal WC (NBSNW), abnormal blood sugar with normal WC (ABSNW), normal blood sugar with abnormal WC (NBSAW), and abnormal blood sugar with abnormal waist circumference (ABSAW)). RESULTS: The 5,680 participants were divided into two groups based on the presence (n = 599) or absence of hypogonadism (n = 5,081), which was defined as total testosterone (TT) < 300 ng/dL. The mean TT of group NBSAW (443.71 ± 220.59 ng/dl) was significantly lower than that of group ABSNW (506.64 ± 191.08 ng/dl, p < 0.001). Moreover, the mean TT of group ABSAW (398.89 ± 146.24 ng/dl) was significantly lower than that of group ABSNW (506.64 ± 191.08 ng/dl, p < 0.001). The ORs after adjusting for BMI, TG, HDL, SBP, and DBP were statistically significant when comparing NBSAW vs. NBSNW (OR = 2.846; 95%CI = 2.266-3.575; p < 0.001), ABSNW vs. NDNW (OR = 1.693; 95%CI = 1.309-2.189; p < 0.001), and ABSAW vs. NBSNW (OR = 4.613; 95%CI = 3.634-5.856; p < 0.001). CONCLUSION: The current study showed that WC should be the risk factor that is more closely associated with hypogonadism than hyperglycemia in middle-aged men.

Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss.

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

Ultrasound Microbubble-Facilitated Inner Ear Delivery of Gold Nanoparticles Involves Transient Disruption of the Tight Junction Barrier in the Round Window Membrane.

The application of ultrasound microbubbles (USMBs) enhances the permeability of the round window membrane (RWM) and improves drug delivery to the inner ear. In this study, we investigated the efficiency of USMB-aided delivery of chitosan-coated gold nanoparticles (CS-AuNPs) and the mechanism of USMB-mediated enhancement of RMW permeability. We exposed mouse inner ears to USMBs at an intensity of 2 W/cm2 and then filled the tympanic bulla with CS-AuNPs or fluorescein isothiocyanate-decorated CS-AuNPs (FITC-CS-AuNPs). The membrane uptake of FITC-CS-AuNPs and their depth of permeation into the three-layer structure of the RWM, with or without prior USMB treatment, were visualized by z-stack confocal laser scanning microscopy. Ultrastructural changes in the RWM due to USMB-mediated cavitation appeared as sunburn-like peeling and various degrees of depression in the RWM surface, with pore-like openings forming in the outer epithelium. This disruption of the outer epithelium was paralleled by a transient reduction in tight junction (TJ)-associated protein levels in the RWM and an enhanced delivery of FITC-CS-AuNPs into the RWM. Without prior USMB exposure, the treatment with CS-AuNPs also caused a noticeable reduction in TJ proteins of the RWM. Our findings indicated that the combined treatment with USMBs and CS-AuNPs represents a promising and efficient drug and gene delivery vehicle for a trans-RWM approach for inner ear therapy. The outer epithelial layer of the RWM plays a decisive role in controlling the transmembrane transport of substances such as CS-AuNPs following the administration of USMBs. Most importantly, the enhanced permeation of AuNPs involved the transient disruption of the TJ-created paracellular barrier in the outer epithelium of the RWM.

The Immediate and Long-Term Impact of Military Aircraft Noise on Hearing: A Cross-Sectional Comparison of Fighter Pilots and Ground Staff.

We examined the immediate and long-term impacts of military aircraft noise exposure on noise-induced hearing loss (NIHL) in fighter pilots and ground staff. We recruited 40 pilots, 40 ground staff, and 136 age-matched controls; all participants underwent hearing tests, including conventional pure-tone audiometry (PTA) (0.25-8.0 kHz), extended high-frequency (EHF) audiometry (9.0-18.0 kHz), and distortion-product otoacoustic emission (DPOAE) as a recent reference. A subsequent hearing test immediately after flight-mission noise exposure was requested. The results revealed higher recent hearing thresholds in pilots and ground staff than in controls. Threshold shifts at many octave band frequencies were also significantly elevated in ground staff. The grouped frequency threshold was significantly elevated in the 4-8 kHz high-frequency range. After a single flight-mission noise exposure, both ground staff and pilots showed decreased signal-to-noise ratios for DPOAE (1-8 kHz), whereas only ground staff showed significantly elevated left-ear hearing thresholds at 3, 11.2, and 12.5 kHz by conventional and EHF PTA. Fighter pilots and ground staff serve in hazardous noise-exposed environments that cause hearing damage and subsequent NIHL, but ground staff may be more vulnerable. A comprehensive hearing conservation program should be implemented to protect high-risk service members, and especially ground staff, from high-intensity noise exposure.

Association Between Low Serum Testosterone and the Development of Metabolic Syndrome in Elderly Taiwanese Men.

PURPOSE: To assess the association between serum testosterone (T) and metabolic syndrome (MS) in different age groups in Taiwanese men. MATERIALS AND METHODS: Male participants, regardless of age or any underlying disease, were identified from MJ Health Screening Center in Taiwan from 2007 to 2016 for this cross-sectional study. They were divided into three groups according to age, and further classified according to MS diagnosis. Basic patient characteristics with relevant parameters were obtained. One-way ANOVA of mean T values between different numbers of measures that exceeds the cut-off values of MS components was performed to assess the relationship of T and MS. Logistic regression analysis was also used to estimate the risk for MS with each increment in T, age, and BMI. RESULTS: A total of 4,931 men were included. The MS group had significantly lower serum T levels compared to the non-MS group in each age group. The one-way ANOVA found the mean value of T was significantly higher in patients without MS component (6.19±2.12 ng/mL) than those with 1-5 MS components (with one MS component: 5.48±2.13 ng/mL, two MS components: 4.93±2.03 ng/mL, three MS components: 4.37±1.60 ng/mL, four MS components: 4.13±2.89 ng/mL, five MS components: 3.74±1.27 ng/mL, and P<0.001). There was no significant difference between the patients with three components and the patients with four or five components. Logistic regression models with age stratification showed T with lower odds ratio (OR) for MS after adjusting for BMI in those ≥65 years old (OR=0.693; 95% CI=0.559-0.858; P<0.001); 50-64 years old (OR=0.868; 95% CI=0.802-0.940; P<0.001) and <50 years old (OR=0.810; 95% CI=0.758-0.865; P<0.001). CONCLUSION: Lower serum T was strongly associated with MS, with the predictive value increasing with age in Taiwanese men.

Naja atra venom-spit ophthalmia in Taiwan: An epidemiological survey from 1990 to 2016.

BACKGROUND: Venomous snakebites are common during hot seasons in Taiwan. However, rarely is venom spat directly into the subject's eyes, causing eye injury. Despite being uncommon, analytical data regarding venom-spit ophthalmia in Taiwan have been lacking. This study thus aimed to conduct an epidemiological survey on Naja atra venom-spit ophthalmia in Taiwan during the past decades to improve future care of such patients. METHODS: Registered records of cases with snake venom injuries at the Taiwan National Poison Control Center from 1990 to 2016 were retrospectively reviewed, enrolling those with records of cobra venom-spit eye injuries and excluding exotic species. Demographic data, clinical symptoms, snake species, ocular conditions, management, and outcomes were recorded and analyzed. RESULTS: A total of 39 cases suffering from Naja atra venom-spit ophthalmia were enrolled. The overall incidence rate was 1.6 cases per million people from 1990 to 2016. Among the included cases, most were unilaterally injured (82%), male (95%), aged 18 to 59 years (90%), injured during catching (51%), and injured in spring and summer (92%). Ocular symptoms occurred in 90% of the cases, majority of which included ocular pain (90%) and redness (85%). Conjunctivitis (67%) and corneal injury (59%) of involved eyes were common. Immediate water irrigations were done in all cases, most of whom received further topical eye drops, including antibiotics, corticosteroids, and vasoconstrictors. Although topical or intravenous antivenoms were administered in 11 cases, no obviously superior outcome was observed. Most cases (77%) were symptom free after the acute stage. CONCLUSION: Although Naja atra venom-spit ophthalmia in Taiwan is uncommon, the risk for transient ocular symptoms and corneal/conjunctival injury does exists. Prompt ocular irrigation and professional ophthalmic care after envenomation help prevent serious ocular sequelae. Moreover, superior outcomes were not achieved with the use of antivenom. Nonetheless, further studies are required to clarify the role antivenoms play in venom-spit ophthalmia.

Ultrastructural Changes Associated With the Enhanced Permeability of the Round Window Membrane Mediated by Ultrasound Microbubbles.

The round window membrane (RWM) is the most common entryway for local drug and gene delivery into the inner ear, but its permeability can change the treatment outcome. We previously demonstrated a feasible and highly efficient approach using ultrasound-aided microbubble (USMB) cavitation to enhance the permeability of the RWM. Here, we investigated the safety of USMB exposure and the association between temporal changes in RWM permeability and ultrastructure. Experimental guinea pigs were divided into two treatment groups: a control group receiving round window soaking (RWS) with MBs and treatment (USM) groups undergoing 3 (USM-3) or 5 (USM-5) consecutive USMB exposures (1 min/exposure) at an acoustic intensity of 3 W/cm2 and 1 MHz frequency. The trans-RWM delivery efficiency of biotin-fluorescein isothiocyanate conjugates, used as permeability tracers, revealed a greater than 7-fold higher delivery efficiency for the USM groups immediately after 3 or 5 exposures than for the RWS group. After 24 h, the delivery efficiency was 2.4-fold higher for the USM-3 group but was 6.6-fold higher for the USM-5 group (and 3.7-fold higher after 48 h), when compared to the RWS group. Scanning electron microscopy images of the RWM ultrastructure revealed USMB-induced sonoporation effects that could include the formation of heterogeneous pore-like openings with perforation diameters from 100 nm to several micrometers, disruption of the continuity of the outer epithelial surface layer, and loss of microvilli. These ultrastructural features were associated with differential permeability changes that depended on the USMB exposure course. Fourteen days after treatment, the pore-like openings had significantly decreased in number and the epithelial defects were healed either by cell expansion or by repair by newly migrated epithelial cells. The auditory brainstem response recordings of the animals following the 5-exposure USMB treatment indicated no deterioration in the hearing thresholds at a 2-month follow-up and no significant hair cell damage or apoptosis, based on scanning electron microscopy, surface preparations, and TUNEL assays. USMBs therefore appear to be safe and effective for inner ear drug delivery. The mechanism of enhanced permeability may involve a disruption of the continuity of the outer RWM epithelial layer, which controls transmembrane transport of various substances.