Shih Bin Su

N-Acetylcysteine Attenuates Hexavalent Chromium-Induced Hypersensitivity through Inhibition of Cell Death, ROS-Related Signaling and Cytokine Expression

Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor κB (NF-κB), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

Long-term Mortality Risk After Hyperglycemic Crisis Episodes in Geriatric Patients With Diabetes: A National Population-Based Cohort Study

OBJECTIVE Hyperglycemic crisis is one of the most serious diabetes-related complications. The increase in the prevalence of diabetes in the geriatric population leads to a large disease burden, but previous studies of geriatric hyperglycemic crisis were focused on acute hyperglycemic crisis episode (HCE). This study aimed to delineate the long-term mortality risk after HCE. RESEARCH DESIGN AND METHODS This retrospective national population-based cohort study reviewed, in Taiwan’s National Health Insurance Research Database, data from 13,551 geriatric patients with new-onset diabetes between 2000 and 2002, including 4,517 with HCE (case subjects) (ICD-9 code 250.1 or 250.2) and 9,034 without HCE (control subjects). The groups were compared and followed until 2011. RESULTS One thousand six hundred thirty-four (36.17%) case and 1,692 (18.73%) control subjects died (P < 0.0001) during follow-up. Incidence rate ratios (IRRs) of death were 2.82 times higher in case subjects (P < 0.0001). The mortality risk was highest in the first month (IRR 26.56; 95% CI 17.97–39.27) and remained higher until 4–6 years after the HCE (IRR 1.49; 95% CI 1.23–1.81). After adjustment for age, sex, selected comorbidities, and monthly income, the mortality hazard ratio was still 2.848 and 4.525 times higher in case subjects with one episode and two or more episodes of hyperglycemic crisis, respectively. Older age, male sex, renal disease, stroke, cancer, chronic obstructive pulmonary disease, and congestive heart failure were independent mortality predictors. CONCLUSIONS Patients with diabetes had a higher mortality risk after HCE during the first 6 years of follow-up. Referral for proper education, better access to medical care, effective communication with a health care provider, and control of comorbidities should be done immediately after HCE.

Lack of Pupil Reflex and Loss of Consciousness Predict 30-Day Neurological Sequelae in Patients with Carbon Monoxide Poisoning

Background Predicting the neurological sequelae of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of neurological sequelae in patients with COP and combined these predictors to predict the prognosis. Methods This study was conducted at four hospitals in Shandong Province, China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. Thirty-day neurological sequelae were the primary endpoints. Results A lack of pupil reflex and a loss of consciousness appear to be independent predictors for neurological sequelae in patients with COP. The presence of either one had a sensitivity of 77.0% (95% confidence interval [CI]: 69.3–83.2), a specificity of 47.1% (95% CI: 38.3–56.0), positive predictive value (PPV) of 62.9% (95% CI: 55.2–70.1), and a negative predictive value (NPV) of 63.6% (95% CI: 52.6–73.4). With both predictors present, the sensitivity was 11.5% (95% CI: 6.9 to 18.3), the specificity was 99.2 (95% CI: 94.7–100.0), the PPV was 94.1% (95% CI: 69.2–99.7), and the NPV was 49.0% (95% CI: 42.5–55.5). Conclusions The risk for neurological sequelae apparently increased with the number of independent predictors. In patients with both predictors, the risk for neurological sequelae was 94.1%. Almost all (99.2%) patients with neither predictor had no neurological sequelae. This finding may help physicians make decisions about and dispositions for patients with COP. For patients with a higher risk, earlier treatment and more appropriate utilization of health care services, including hyperbaric oxygen, should be considered.

Acute Anticholinesterase Pesticide Poisoning Caused a Long-term Mortality Increase: A Nationwide Population-based Cohort Study

Abstract Acute anticholinesterase pesticide (organophosphate and carbamate) poisoning (ACPP) often produces severe complications, and sometimes death. We investigated the long-term mortality of patients with ACPP because it is not sufficiently understood. In this retrospective nationwide population-based cohort study, 818 patients with ACPP and 16,360 healthy comparisons from 1999 to 2010 were selected from Taiwans National Health Insurance Research Database. They were followed until 2011. Ninety-four (11.5%) ACPP patients and 793 (4.9%) comparisons died (P < 0.01) during follow-up. The incidence rate ratios (IRRs) of death were 2.5 times higher in ACPP patients than in comparisons (P < 0.01). The risk of death was particularly high in the first month after ACPP (IRR: 92.7; 95% confidence interval [CI]: 45.0–191.0) and still high for ∼6 months (IRR: 3.8; 95% CI: 1.9–7.4). After adjusting for age, gender, selected comorbidities, geographic area, and monthly income, the hazard ratio of death for ACPP patients was still 2.4 times higher than for comparisons. Older age (≥35 years), male gender, diabetes mellitus, coronary artery disease, hypertension, stroke, mental disorder, and lower monthly income also predicted death. ACPP significantly increased long-term mortality. In addition to early follow-up after acute treatment, comorbidity control and socioeconomic assistance are needed for patients with ACPP.

Hypotension, bedridden, leukocytosis, thrombocytopenia and elevated serum creatinine predict mortality in geriatric patients with fever

The geriatric population (aged ≥65 years) accounts for 12–24% of all emergency department (ED) visits. Of them, 10% have a fever, 70–90% will be admitted and 7–10% of will die within a month. Therefore, mortality prediction and appropriate disposition after ED treatment are of great concern for geriatric patients with fever. We tried to identify independent mortality predictors of geriatric patients with fever, and combine these predictors to predict their mortality.

Infection, Absent Tachycardia, Cancer History, and Severe Coma Are Independent Mortality Predictors in Geriatric Patients With Hyperglycemic Crises

Hyperglycemic crises present a disease continuum of diabetic emergency. There are three types of hyperglycemic crisis in clinical practice: 1 ) diabetic ketoacidosis (DKA), 2 ) hyperosmolar hyperglycemic state (HHS), and 3 ) mixed DKA/HHS (1,2). The prevalence of diabetes in the elderly is extremely high and growing (3–5). The elderly also have a higher mortality risk for hyperglycemic crises; therefore, it is particularly important to identify patients at risk within the geriatric population because early detection and intervention are beneficial (3–5). We investigated independent mortality predictors in geriatric patients with hyperglycemic crises and combined these predictors to predict the prognosis. This study was conducted in a university-affiliated medical center. Consecutive elderly (≥65 years) patients who visited our emergency department between January 2004 and December 2010 were prospectively enrolled when they met the criteria of a hyperglycemic crisis (1). One hundred and …

Peptic Ulcer Disease in Healthcare Workers: A Nationwide Population-Based Cohort Study

Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on-call, and have rotating nightshifts, all of which might contribute to peptic ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not clear. Using Taiwan’s National Health Insurance Research Database, we identified 50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs (dieticians, technicians, rehabilitation therapists, and social workers) as the study cohort, and randomly selected an identical number of non-HCW patients (i.e., general population) as the comparison cohort. Conditional logistical regression analysis was used to compare the PUD risk between them. Subgroup analysis for physician specialties was also done. Nurses and other HCWs had a significantly higher PUD risk than did the general population (odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.433–1.521 and OR: 1.328; 95% CI: 1.245–1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828–0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI: 0.987–1.072). In the physician specialty subgroup analysis, internal medicine, surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other physicians (OR: 1.579; 95% CI: 1.441–1.731, OR: 1.734; 95% CI: 1.565–1.922, OR: 1.336; 95% CI: 1.151–1.550, and OR: 1.615; 95% CI: 1.425–1.831, respectively). In contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359–0.822). Heavy workloads, long working hours, workplace stress, rotating nightshifts, and coping skills may explain our epidemiological findings of higher risks for PUD in some HCWs, which might help us improve our health policies for HCWs.

Risk of Retinal Artery Occlusion in Patients With End-Stage Renal Disease A Retrospective Large-Scale Cohort Study

AbstractThere is globally increasing prevalence and incidence in end-stage renal disease (ESRD). These patients are frequently reported to have retinal abnormalities and both diseases share some systemic risk factors. Hence, it is clinically relevant to determine whether ESRD is a predictor of retinal artery occlusion (RAO).To investigate the risk of RAO in ESRD patients.A retrospective, nationwide, matched cohort study. The study included 93,766 ESRD patients recruited between 2000 and 2009 from the Taiwan National Health Insurance Research Database. The same number control group included age- and sex-matched patients without ESRD selected from the Taiwan Longitudinal Health Insurance Database, 2000. Data for each patient were collected from the index date until December 2011.The incidence and risk of RAO were compared between the 2 groups. The hazard ratio (HR) for RAO after adjustment for potential confounders was calculated using Cox proportional hazards regression. Kaplan–Meier analysis was used to calculate the cumulative RAO incidence rate.In total, 237 ESRD patients and 73 controls exhibited RAO during follow-up; thus, the RAO incidence rate in ESRD patients was 4.49 times (95% confidence interval (CI), 3.45–5.83) that in the control patients. After adjustment for potential confounders, including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 2.78 times (95% CI, 2.02–3.84) more likely to develop RAO in cohort for the total sample. Among patients with hypertension, the RAO incidence rate was significantly higher in the ESRD group, and hypertension significantly increased RAO risk even after adjustment for other confounders in the cohort.ESRD increases the risk of RAO, particularly in ESRD patients with hypertension. Therefore, clinicians should educate ESRD patients about RAO and ensure appropriate blood pressure control.

Cancer Incidence in Physicians: A Taiwan National Population-based Cohort Study.

AbstractCancer has been the leading cause of death in Taiwan since 1982. Physicians have many health-related risk factors which may contribute to cancer, such as rotating night shift, radiation, poor lifestyle, and higher exposure risk to infection and potential carcinogenic drugs. However, the cancer risk in physicians is not clear. In Taiwans National Health Insurance Research Database, we identified 14,889 physicians as the study cohort and randomly selected 29,778 nonmedical staff patients as the comparison cohort for this national population-based cohort study. Cox proportional-hazard regression was used to compare the cancer risk between physicians and comparisons. Physician subgroups were also analyzed. Physicians had a lower all-cancer risk than did the comparisons (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.76–0.97). In the sex-based analysis, male physicians had a lower all-cancer risk than did male comparisons (HR 0.82, 95% CI 0.73–0.94); and female physicians did not (HR 1.29, 95% CI 0.88–1.91). In the cancer-type analysis, male physicians had a higher risk of prostate cancer (HR 1.72, 95% CI 1.12–2.65) and female physicians had twice the risk of breast cancer (HR 2.00, 95% CI 1.11–3.62) than did comparisons. Cancer risk was not significantly associated with physician specialties. Physicians in Taiwan had a lower all-cancer risk but higher risks for prostate and breast cancer than did the general population. These new epidemiological findings require additional study to clarify possible mechanisms.

Increased risk for diabetes mellitus in patients with carbon monoxide poisoning

Carbon monoxide poisoning (COP) causes hypoxic injury and inflammatory and immunological reactions in the brain and local organs including the pancreas. Therefore, it is plausible that COP may increase the risk for developing diabetes mellitus (DM), but studies on this possible association are limited. We conducted a nationwide study in Taiwan to fill the data gap. We used the Nationwide Poisoning Database and the Longitudinal Health Insurance Database 2000 to identify all COP patients diagnosed between 1999 and 2012 (the study cohort) and then construct a comparison cohort of patients without COP through matching at 1:3 by the index date and age. The risk for DM between the two cohorts was compared by following up until 2013. We also investigated the independent predictors for DM in all the patients. During the study period, 22,308 COP patients were identified, and 66,924 non-COP patients were included in the comparison cohort accordingly. Patients with COP had an increased risk for DM with an adjusted hazard ratio (AHR) of 1.92 (95% confidence interval [CI]: 1.79-2.06) after adjusting for age, sex, comorbidities, and monthly income, especially in the subgroups of age <35 years, age ≥ 65 years, female sex, and comorbidities with congestive heart failure, hyperthyroidism, and polycystic ovary syndrome. Cox proportional hazard regression analysis showed that the increased risk for DM was highest in the first month after COP (AHR= 3.38; 95% CI: 2.29-4.99) and lasted even after 4 years (AHR= 1.82; 95% CI: 1.62-2.04). We found that COP, older age, male sex, hypertension, hyperlipidemia, hyperuricemia, and low monthly income were independent predictors for DM. Intervention studies are needed to validate the results and delineate the detailed mechanisms.Carbon monoxide poisoning (COP) causes hypoxic injury and inflammatory and immunological reactions in the brain and local organs including the pancreas. Therefore, it is plausible that COP may increase the risk for developing diabetes mellitus (DM), but studies on this possible association are limited. We conducted a nationwide study in Taiwan to fill the data gap. We used the Nationwide Poisoning Database and the Longitudinal Health Insurance Database 2000 to identify all COP patients diagnosed between 1999 and 2012 (the study cohort) and then construct a comparison cohort of patients without COP through matching at 1:3 by the index date and age. The risk for DM between the two cohorts was compared by following up until 2013. We also investigated the independent predictors for DM in all the patients. During the study period, 22,308 COP patients were identified, and 66,924 non-COP patients were included in the comparison cohort accordingly. Patients with COP had an increased risk for DM with an adjusted hazard ratio (AHR) of 1.92 (95% confidence interval [CI]: 1.79–2.06) after adjusting for age, sex, comorbidities, and monthly income, especially in the subgroups of age <35 years, age ≥ 65 years, female sex, and comorbidities with congestive heart failure, hyperthyroidism, and polycystic ovary syndrome. Cox proportional hazard regression analysis showed that the increased risk for DM was highest in the first month after COP (AHR= 3.38; 95% CI: 2.29–4.99) and lasted even after 4 years (AHR= 1.82; 95% CI: 1.62–2.04). We found that COP, older age, male sex, hypertension, hyperlipidemia, hyperuricemia, and low monthly income were independent predictors for DM. Intervention studies are needed to validate the results and delineate the detailed mechanisms.