Evaluating the Impact of Nutritional Risk on Stress-Induced Hyperglycemia and Trauma Patient Outcomes.

INTRODUCTION: Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. METHODS: A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. RESULTS: SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). CONCLUSION: SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival.

Evaluating the prognostic value of the stress index in trauma patients.

Background: The stress index (SI), defined as the serum glucose to potassium ratio, has emerged as a potential prognostic indicator in some patient populations. This study aims to evaluate the predictive value of SI on the trauma patients sustained by all trauma causes. Methods: A retrospective analysis was conducted on 20,040 adult trauma patients admitted to a single trauma center from January 1, 2009, to December 31, 2022. The SI was calculated according to the serum levels of glucose (mg/dL) and potassium (mEq/L) upon patients' arrival to emergency room. The enrolled patients were stratified into two groups based on an optimal SI cutoff value determined by receiver operating characteristic (ROC) curve analysis. The association between SI and in-hospital mortality, as well as other clinical outcomes, was assessed using multivariate logistic regression, adjusting for potential confounders. Results: The mortality patients had a significantly higher SI (59.7 ± 30.6 vs. 39.5 ± 17.5, p < 0.001) than those who survived. The SI was identified as a significant independent predictor of mortality (odds ratio [OR] 4.65, 95 % confidence interval [CI]: 2.61-8.27, p < 0.001) in the multivariate analysis. In addition, patients in the high SI group (≥42.7) demonstrated significantly worse outcomes, including higher in-hospital mortality (7.5 % vs. 1.4 %, p < 0.001), longer hospital stays compared to the low SI group (<42.7). Conclusion: The SI serves as a simple and valuable prognostic tool in risk stratification of the trauma patients.

Comparative Efficacy of Fractional CO2 Laser Combined with Topical Steroid Cream versus Solution for Post-Thyroidectomy Scar Treatment: A Prospective Study.

BACKGROUNDS: Post-thyroidectomy scarring is a common illness impacting patient quality of life. Fractional carbon dioxide (CO2) lasers and topical steroids delivered via laser-assisted drug delivery (LADD) have shown potential for scar treatment. However, ideal steroid formulations (cream vs. solution) when combined with laser therapy remain unclear. METHODS: This study included 12 patients receiving fractional CO2 laser on post-thyroidectomy scars. After laser treatment, one scar half received topically applied steroid cream, while the other half received steroid solution. The Patient and Observer Scar Assessment Scale (POSAS) was used to measure the scar conditions at the time prior to the first treatment and one year later by the patients themselves and by the surgeon who did the laser treatment. Scar appearance was photographically assessed at baseline and 6 months post-treatment by four blinded evaluators using scales. RESULTS: This study discovered a modest improvement in the appearance of post-thyroidectomy scars when combining fractional CO2 laser treatment with either topical steroid cream or solution. Patients and treating physicians examined the POSAS scores one year after treatment found significant improvements in all aspects of the scar conditions, with high efficacy and satisfaction levels reported by patients. CONCLUSIONS: Fractional CO2 laser combined with topical steroid delivery, either cream or solution form, significantly enhanced post-thyroidectomy scar appearance with modest effect and high patient satisfaction. This approach may represent a promising scar management strategy along with current scar treatment for the post-thyroidectomy scar.

Geriatric Trauma Outcome Score as a Mortality Predictor in Isolated Moderate to Severe Traumatic Brain Injury: A Single-Center Retrospective Study.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, with severe cases significantly increasing the risk of complications and long-term mortality. The Geriatric Trauma Outcome Score (GTOS), based on age, injury severity, and transfusion need, has been validated for predicting mortality in older trauma patients, but its utility in predicting mortality for TBI patients remains unexplored. METHODS: This retrospective study included 5543 adult trauma patients with isolated moderate to severe TBI, defined by head Abbreviated Injury Scale (AIS) scores of ≥ 3, from 1998 to 2021. GTOS was calculated with the following formula: age + (Injury Severity Score × 2.5) + 22 (if transfused within 24 h). The area under the receiver operating characteristic curve (AUROC) assessed GTOS's ability to predict mortality. The optimal GTOS cutoff value was determined using Youden's index. Mortality rates were compared between high- and low-GTOS groups, separated by the optimal GTOS cutoff value, including a propensity score-matched analysis adjusting for baseline characteristics. RESULTS: Among 5543 patients, mortality was 8.3% (462 deaths). Higher mortality is correlated with male sex, older age, higher GTOS, and comorbidities like hypertension, coronary artery disease, and end-stage renal disease. The optimal GTOS cut-off for mortality prediction was 121.5 (AUC = 0.813). Even when the study population was matched by propensity score, patients with GTOS ≥121.5 had much higher odds of death (odds ratio 2.64, 95% confidence interval 1.93-3.61, p < 0.001) and longer hospital stays (mean 16.7 vs. 12.2 days, p < 0.001) than those with GTOS < 121.5. CONCLUSIONS: These findings support the idea that GTOS is a useful tool for risk stratification of in-hospital mortality in isolated moderate to severe TBI patients. However, we encourage further research to refine GTOS for better applicability in TBI patients.

Effects of Lymphaticovenous Anastomosis on Quality of Life, Body Image, and Spiritual Health in Lymphedema Patients: A Prospective Cohort Study.

BACKGROUND: Lymphedema is a debilitating condition that significantly affects quality of life due to its chronic nature and visible symptoms. Lymphaticovenous anastomosis (LVA) has emerged as a promising surgical intervention, yet its effects on body image and spiritual health alongside physical symptoms have not been thoroughly examined. This study evaluates the efficacy of LVA in improving symptoms, quality of life (QOL), body image, and spiritual well-being in lymphedema patients. METHODS: A prospective cohort study was conducted at Kaohsiung Chang Gung Memorial Hospital, Taiwan, involving 44 patients with lymphedema undergoing LVA surgery. Evaluations were made pre-surgery, one month post-surgery, and six months post-surgery using the 36-Item Short Form Health Survey (SF-36), Multidimensional Body-Self Relations Questionnaire-Appearance Scales (MBSRQ-AS), and a spiritual health scale. Statistical analysis was performed using one-way repeated measures ANOVA. RESULTS: Significant improvements were observed in lymphedema symptoms and QOL measures at six months post-operation. SF-36 results showed enhanced scores in nearly all domains, particularly in physical functioning and role-physical. The appearance orientation scores from the MBSRQ-AS significantly increased, indicating improved perceptions in some dimensions of body image. CONCLUSIONS: LVA surgery significantly enhances physical and psychological outcomes in patients with lymphedema, with marked improvements in symptoms, QOL, and body image perceptions. The findings suggest that while LVA is effective in addressing the physical and psychological aspects of lymphedema, it does not impact spiritual dimensions. This underscores the need for holistic approaches in the management of lymphedema to address all facets of patient well-being.

Role of the Stress Index in Predicting Mortality among Patients with Traumatic Femoral Fractures.

BACKGROUND: Traumatic femoral fractures, often resulting from high-energy impacts such as traffic accidents, necessitate immediate management to avoid severe complications. The Stress Index (SI), defined as the glucose-to-potassium ratio, serves as a predictor of mortality and adverse outcomes in various trauma contexts. This study aims to evaluate the prognostic value of the SI in patients with traumatic femoral fractures. METHODS: This retrospective cohort study included adult trauma patients aged 20 or above with traumatic femoral fractures from the Trauma Registry System at a level 1 trauma center in southern Taiwan between 1 January 2009 and 31 December 2022. At the emergency room, serum electrolyte levels were assessed using baseline laboratory testing. By dividing blood glucose (mg/dL) by potassium (mEq/L), the SI was calculated. The best cut-off value of the SI for predicting mortality was determined using the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). RESULTS: A total of 3717 patients made up the final group, of which 3653 survived and 64 died. In comparison to survivors, deceased patients had substantially higher blood glucose levels (199.3 vs. 159.0 mg/dL, p < 0.001) and SIs (53.1 vs. 41.6, p < 0.001). The optimal SI cut-off value for predicting mortality was 49.7, with a sensitivity of 53.1% and a specificity of 78.7% (AUC = 0.609). High SI was associated with increased mortality (4.2% vs. 1.0%, p < 0.001) and longer hospital stays (12.8 vs. 9.5 days, p < 0.001). The adjusted odds ratios of mortality, controlled by comorbidities, the Glasgow Coma Scale, and the Injury Severity Score, were significantly higher in patients with a higher SI (AOR 2.05, p = 0.016) than those with a lower SI. CONCLUSIONS: Elevated SI upon admission correlates with higher mortality and extended hospital stay in patients with traumatic femoral fractures. Although the SI has a moderate predictive value, it remains a useful early risk assessment tool, necessitating further prospective, multi-center studies for validation and standardization.

The Stress Index as a Predictor of Mortality in Patients with Isolated Moderate to Severe Traumatic Brain Injury.

BACKGROUND: The Stress Index (SI), calculated as the ratio of blood glucose to serum potassium levels, is a promising prognostic marker in various acute care settings. This study aimed to evaluate the utility of the SI for predicting mortality in patients with isolated moderate-to-severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included adult trauma patients (aged ≥ 20 years) with isolated moderate to severe TBI (Abbreviated Injury Scale ≥ 3 for only head region) treated from 2009-2022. The SI was computed from the initial glucose and potassium levels upon arrival at the emergency department. Logistic regression models were used to assess the association between the SI and mortality after adjusting for relevant covariates. The most effective threshold value of the SI for predicting mortality was identified using receiver operating characteristic (ROC) analysis. RESULTS: Among the 4357 patients with isolated moderate and severe TBI, 463 (10.6%) died. Deceased patients had a significantly higher SI (61.7 vs. 44.1, p < 0.001). In multivariate analysis, higher SI independently predicted greater mortality risk (odds ratio (OR) 6.70, 95% confidence interval (CI) 1.66-26.99, p = 0.007). The optimal SI cutoff for predicting mortality was 48.50 (sensitivity 62.0%, specificity 71.4%, area under the curve 0.724). Patients with SI ≥ 48.5 had nearly two-fold higher adjusted mortality odds compared to those below the threshold (adjusted OR 1.94, 95% CI 1.51-2.50, p < 0.001). CONCLUSIONS: SI is a useful predictor of mortality in patients with isolated moderate-to-severe TBI. Incorporating SI with standard clinical assessments could enhance risk stratification and management approaches for this patient population.

The Association Between Antidepressant Use and Drug-Induced Liver Injury: A Nationwide, Population-Based Case-Control Study in Taiwan.

BACKGROUND AND OBJECTIVE: The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. METHODS: The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. RESULTS: The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95% CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). CONCLUSION: SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders.

AIMS: Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice. MAIN METHODS: C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed. KEY FINDINGS: In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders. SIGNIFICANCE: This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.

Determinants of the success in flap reconstruction-Outcome analysis of 120 flaps in 484 procedures for pressure injury.

Pressure injury (PI) mainly occurs in bedridden older adults or those with physical limitations. Here, we aimed to determine the appropriate timing to conduct flap reconstruction in patients with PIs and identify factors affecting surgical outcomes. We retrospectively reviewed the data of all patients who received debridement or flap reconstruction surgery for PIs in our hospital from January 2016 to December 2021. The extracted data included patient demographics, surgical records, blood test results, vital signs, and flap outcomes. In total, 484 surgical procedures (364 debridements and 120 flaps) were performed on 216 patients. Serum albumin level of ≥2.5 g/dL remarkably increased the likelihood of complete wound healing (odds ratio [OR] = 4.12, P = .032) and reduced the risk of postoperative complications (OR = 0.26, P = .040). In contrast, advanced age (OR = 1.04, P = .045) and serum creatinine level ≥2 mg/dL (OR = 5.07, P = .016) increased the risk of postoperative complications. Thus, patients with a favourable nutrition status have a higher likelihood of achieving complete wound healing. By contrast, patients who are older and have serum creatinine ≥2 mg/dL and serum albumin <2.5 g/dL tend to develop more postoperative complications. Overall, thorough correction for patient inflammation, infection, anaemia, and malnutrition status can provide optimal flap surgery outcomes.

Effectiveness of Botulinum Toxin Injection on Bruxism: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The present study compiled evidence on the efficacy of botulinum toxin A (BTX) for management of bruxism. METHODS: A literature review that included randomized control, cohort, as well as observational studies published between January 2000 and November 2022 was conducted. All studies related to BTX injections administered into the masseters of patients with bruxism were included. Primary outcomes were measured by performing a meta-analysis of changes in maximal biting forces and pain severity and meta-regression of the effects of the BTX dose. RESULTS: Ten studies were included for quantitative analysis. The analysis of the maximal biting force after BTX injections demonstrated a significant reduction at 1 month or less compared with both oral splints (P < 0.000001) and saline injections (P = 0.01). BTX continued to outperform oral splinting (P = 0.001) and saline placebos (P = 0.03) at 3 months. Between 3 and 6 months, a significantly higher maximal biting strength was observed in the BTX group than the oral splinting group (P < 0.00001). No significant differences in the maximal biting force were observed between the BTX and saline placebo groups (P = 0.50). A similar trend was observed in the analysis of pain reduction after botulinum treatment. Additionally, for every unit increase in the BTX dose, pain severity decreased by 0.0831 points (P = 0.0011). CONCLUSION: BTX is effective in reducing biting strength and pain severity. BTX effects are evident at less than 4 weeks, peak between 5 and 8 weeks, and last for up to 24 weeks. Higher BTX doses result in greater improvement in pain. Although BTX benefits manifest earlier, they gradually diminish, and oral splinting exerts a more enduring effect, especially after 9-12 weeks. BTX injections into masseters are recommended as management options for bruxers, especially for those having difficulties complying with wearing oral splints or those seeking earlier symptom relief. However, future studies should determine BTX effects beyond 24 weeks and after repetitive injections and how bruxers of different ages or genders respond to treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The change of clinical features and surgical outcomes in patients with pressure injury during the COVID-19 pandemic.

This retrospective study aims to explore whether the COVID-19 pandemic altered patient conditions and surgery outcomes by studying 213 pressure injury (PI) patients who underwent surgery during 2016 to 2019 (pre-COVID) and 2020 to 2021 (COVID) in Taiwan. We extracted patient demographics, surgical and blood test records, preoperative vital signs, and flap surgery outcomes. In total, 464 surgeries were performed, including 308 pre-COVID and 156 COVID. During the COVID period, there were more patients presenting with dementia, and it had significantly more patients with >12 000 white blood cells/µL (24.03% vs 15.59%, P = 0.029), higher C-reactive protein levels (7.13 ± 6.36 vs 5.58 ± 5.09 mg/dL, P = 0.014), pulse rates (86.67 ± 14.76 vs 81.26 ± 13.66 beats/min, P < 0.001), and respiratory rates (17.87 ± 1.98 vs 17.31 ± 2.39 breaths/min, P = 0.009) but lower haemoglobin levels (9.75 ± 2.02 vs 10.43 ± 1.67 mg/dL, P < 0.001) preoperatively. There were no between-group differences in flap surgery outcomes but had fewer flap surgeries during COVID-19. Thus, PI patient condition was generally poor during the COVID-19 pandemic because of reduced access to medical treatment; this problem may be resolved through holistic care during a future pandemic or pandemic-like situation.

Nanofiber-Based Odor-Free Medical Mask Fabrication Using Polyvinyl Butyral and Eucalyptus Anti Odor Agent.

Following the 2020 COVID-19 worldwide outbreak, many countries adopted sanitary and safety measures to safeguard public health such as wearing medical face mask. While face masks became a necessity for people, disadvantages impede their long period wearing such as uncomfortable breathability and odor. The intermediate layer of the medical face mask is composed of porous non-woven fabric to block external particles while maintaining breathability. To overcome aforementioned limitation, this study uses electrospinning to design and fabricate odorless face masks via the use of aromatic oil. Eucalyptus essential oil is encapsulated through mixing and layer-by-layer by hydrophobic polyvinyl butyral and further used to fabricate the medical mask intermediate layer. We found that adding 0.2 g of eucalyptus into polyvinyl butyral fabric through mixing results in the deodorization rate of 80% after 2 h, with fabric thickness of 440.9 µm, and melt-blown non-woven fabric thickness of 981.7 µm. The Particle Filtration Efficiency of 98.3%, Bacterial Filtration Efficiency above 99.9%, and the differential pressure of 4.7 mm H2O/cm2 meet the CNS 14774 standard on medical face masks. Therefore, this study successfully proved that this type of masks' middle layer not only effectively protects against coronavirus, but also provides better scents and makes it more comfortable for consumers.

Folium Sennae Increased the Bioavailability of Methotrexate through Modulation on MRP 2 and BCRP.

Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0-2880, AUC720-2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720-2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

Exploring the Relationship Between Colorectal Cancer and Allopurinol: A Taiwanese Population-Based Propensity-Matched Case-Control Study.

The role of allopurinol usage in colorectal cancer (CRC) has no definite conclusion. The aim of this study was to explore the correlation between allopurinol usage and CRC risk in Taiwan. Using the National Health Insurance Database, we conducted a case-control study of cases who were ≥20 years old and had newly diagnosed CRC for the period from 2000 to 2013. The controls were matched to cases by age, sex, index year, comorbidities, and socioeconomic status using propensity scores. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were measured by the conditional logistic regression model. We examined 4372 cases and 4372 matched controls. A statistically significant correlation was noted between allopurinol usage and CRC risk (OR, 0.79; 95%CI, 0.69-0.90). We used the cumulative-defined daily doses (cDDDs) in a further subgroup analysis, the ORs decreased from tertile 1 (T1; low dose, <12 cDDDs), T2 (medium dose, 12 to 88.5 cDDDs), to T3 (high dose, >88.5 cDDDs). These values were 0.85 (95%CI, 0.69-1.06), 0.77 (95%CI, 0.62-0.95), to 0.76 (95%CI, 0.61-0.94). The results indicated a dose-response relationship between allopurinol usage and CRC risk (P for trend < .001). We thus inferred that patients with medium and high doses of allopurinol (≥12 cDDDs) had a statistically significantly decreased CRC risk.

Effects of hearing impairment and hearing aid use on the incidence of cognitive impairment among community-dwelling older adults: evidence from the Taiwan Longitudinal Study on Aging (TLSA).

BACKGROUND: Previous studies have reported associations between hearing impairment (HI) and cognitive impairment, but the evidence is not conclusive while considering concurrent geriatric syndromes. Especially, evidence from previous studies rarely came from Asian studies. This study aimed to evaluate the independent effects of HI and hearing aid use on the incidence of cognitive impairment while considering most geriatric confounders. METHODS: This population-based, propensity-score matched cohort study used cohort from Waves IV-VII (1999-2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive impairment was identified based on Short Portable Mental Status Questionnaire (SPMSQ) scores. The hazard ratio (HR) was calculated using the Cox proportional hazard regression adjusting for age, sex, comorbidities, socioeconomic status, Center for Epidemiologic Studies Depression (CES-D) scores, the instrumental activities of daily living scale, mobility condition and quality of life. In addition, social support and participation were also considered as confounders in the analysis. To assess the robustness of our findings, we conducted a sensitivity analysis designed to access unmeasured confounding factors by calculating E-values. RESULTS: After 1:1 propensity-score matching, we included 709 participants in both the HI and non-HI groups with a mean age of 73.4 years and 39.4% of participants were female. The mean follow-up was 8.9 ± 3.9 years. The HI group had a higher incidence of cognitive impairment than the non-HI group (74.5% vs. 69.1%, respectively), with an adjusted HR of 1.16 (95% confidence interval [CI], 1.03-1.32) based on a 12-year follow up. The E-value was 1.45 for the estimate, which provided evidence for this study's robustness. Although, a subgroup analysis showed that hearing aid use was associated with lower incidences of cognitive impairment (66.3% vs. 75.6%) when compared to non-users in the HI group, the adjusted HR of 0.82 (95% CI, 0.61-1.09) revealed no significant differences. CONCLUSIONS: HI was an independent risk factor of incident cognitive impairment on top of concurrent geriatric syndromes. Early HI detection may thus be effective for preventing cognitive decline. Further studies are needed to evaluate the effect of hearing aid use on the prevention of cognitive decline.

SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility.

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.

Potential benefits of biologics on stroke and mortality in patients with rheumatoid arthritis: A nationwide population-based cohort study in Taiwan.

AIM: To examine the changes in the risks of death and cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients treated with conventional synthetic or biologic disease-modifying antirheumatic drugs (csDMARD or bDMARD) during 1997-2013. METHODS: Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database. There were 1569 patients in the csDMARD cohort who received cyclosporine ≥50 mg/d with concomitant usage of ≥2 csDMARDs during 1997-2003. There were 1530 patients in the bDMARD cohort if patients had ≥1 claim for bDMARD during 2003-2011. Adjusted hazard ratios (aHRs) for the risk of death, myocardial infarction, and stroke, were assessed using the Kaplan-Meier survival curves and the Cox proportional hazards models. RESULTS: Compared with matched cohorts, the incidence of death was higher with csDMARD with a more than 6-fold increase (csDMARD vs controls: 33% vs 5%); while it only increased with a much smaller magnitude with bDMARD (bDMARD vs controls: 15% vs 11%). In addition, an increase in the reduction of incidence rate of stroke with bDMARD (bDMARD vs controls: 2% vs 5%) than that with csDMARD (csDMARD vs controls: 3% vs 4%) was found. Results from multivariate analysis showed that RA patients receiving bDMARD had a significantly lower increase in the risk of deaths (aHR 1.05; 95% CI 0.84-1.33) compared with those receiving csDMARD (aHR 8.75; 95% CI 7.43-10.31). In addition, bDMARD was associated with a higher reduction in the risk of stroke compared with csDMARD (bDMARD: aHR 0.37; 95% CI 0.22-0.62; csDMARD: aHR 0.73; 95% CI 0.51-1.05). CONCLUSION: Biologics used in RA patients have been shown to have a beneficial impact on improving clinical outcomes, including decreased risks of death and stroke. The economic burden from costs of biologics may be alleviated by improving outcomes.

Activation of P-glycoprotein and CYP 3A by Coptidis Rhizoma in vivo: Using cyclosporine as a probe substrate in rats.

Coptidis Rhizoma (CR), the rhizome of Coptis chinensis FRANCH, is a popular Chinese herb. CR contains plenty of isoquinoline alkaloids such as berberine, coptisine and palmatine. Cyclosporine (CSP), an important immunosuppressant with narrow therapeutic window, is employed as a probe substrate of P-glycoprotein (P-gp) and CYP3A4 in order to investigate the in vivo modulation effect of CR on P-gp and CYP3A4. Three groups of rats were orally administered CSP without and with single dose or repeated dosing of CR in a parallel design. Blood samples were collected at specific time points and the blood CSP concentration was determined by a specific monoclonal fluorescence polarization immunoassay. The results showed that a single dose (1.0 g/kg) and the 7th dose (1.0 g/kg) of CR significantly decreased the Cmax of CSP by 56.9% and 70.4%, and reduced the AUC0-540 by 56.4% and 68.7%, respectively. Cell study indicated that CR decoction, berberine, coptisine, palmatine all activated the efflux transport of P-gp. Ex-vivo study showed that the serum metabolites of CR activated CYP 3A4. In conclusion, through using CSP as an in vivo probe substrate, we have verified that oral intake of CR activated the functions of P-gp and CYP3A based on in vivo and in vitro studies.

Transporter-mediated interaction of indican and methotrexate in rats.

Indican (indoxyl-ß-D-glucoside) is present in several Chinese herbs e.g. Isatis indigotica, Polygonum tinctorium and Polygonum perfoliatum. The major metabolite of indican was indoxyl sulfate (IS), an uremic toxin which was a known substrate/inhibitor of organic anion transporter (OAT) 1, OAT 3 and multidrug resistance-associated protein (MRP) 4. Methotrexate (MTX), an important immunosuppressant with narrow therapeutic window, is a substrate of OAT 1, 2, 3, 4 and MRP 1, 2, 3, 4. We hypothesized that IS, the major metabolite of oral indican, might inhibit the renal excretion of MTX mediated by OAT 1, OAT 3 and MRP 4. Therefore, this study investigated the effect of oral indican on the pharmacokinetics of MTX. Rats were orally given MTX with and without indican (20.0 and 40.0 mg/kg) in a parallel design. The serum MTX concentration was determined by a fluorescence polarization immunoassay. For mechanism clarification, phenolsulfonphthalein (PSP, 5.0 mg/kg), a probe substrate of OAT 1, OAT 3, MRP 2 and MRP 4, was intravenously given to rats with and without a intravenous bolus of IS (10.0 mg/kg) to measure the effect of IS on the elimination of PSP. The results indicated that 20.0 and 40.0 mg/kg of oral indican significantly increased the area under concentration-time curve0-t (AUC0-t) of MTX by 231% and 259%, prolonged the mean residence time (MRT) by 223% and 204%, respectively. Furthermore, intravenous IS significantly increased the AUC0-t of PSP by 204% and decreased the Cl by 68%. In conclusion, oral indican increased the systemic exposure and MRT of MTX through inhibition on multiple anion transporters including OAT 1, OAT 3 and MRP 4 by the major metabolite IS.