The association between chronic obstructive pulmonary disease and dementia: a population-based retrospective cohort study.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is frequently associated with various comorbidities. However, the proportion of COPD patients with dementia has not been adequately examined. This retrospective cohort study investigated the association between COPD and dementia by using a nationwide population-based database in Taiwan. METHODS: Data were retrieved from the Taiwanese National Health Insurance Research Database and analyzed using multivariate Cox proportional hazards regression models to assess the effects of COPD on the risk of dementia after adjusting for demographic characteristics and comorbidities. RESULTS: The COPD cohort exhibited a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline than did the non-COPD cohort (P < 0.0001). After adjusting for covariates, the COPD patients exhibited a 1.27-fold higher risk of developing dementia (hazard ratio 1.27, 95% confidence interval 1.20-1.36). The incidence rate was higher in patients with frequent acute exacerbations than in the non-COPD patients regardless of whether a hospital admission or emergency room visit was required (hazard ratio 196.8 vs. 41.7, 95% confidence intervals 145.9-265.5 and 22.3-78.0). CONCLUSION: This study shows that COPD is associated with a subsequent higher risk of dementia after adjusting for comorbidities. Specifically, the association between COPD and dementia is greater in patients with more frequent acute exacerbation events of COPD.

Increased risk of cancer for patients with ankylosing spondylitis: a nationwide population-based retrospective cohort study.

OBJECTIVES: Few studies have investigated the relationship between ankylosing spondylitis (AS) and other inflammatory spondyloarthritis and subsequent cancer. The aim of this study was to determine whether AS is associated with cancer risk. METHOD: We used data from the National Health Insurance (NHI) system of Taiwan to investigate this association. The AS cohort included 4133 patients, and each patient was randomly frequency matched with four persons without AS based on sex, age, and entry year (control cohort). We conducted a Cox proportional hazards regression analysis to estimate the influence of AS on cancer risk. RESULTS: Among patients with AS, the overall risk of developing cancer was 38% higher than that of people without AS, and the difference was significant [adjusted hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.18-1.60]. This phenomenon held true even when we analysed males and females separately. The risk of developing lung or head and neck cancer among patients with AS was significantly higher; and risks for liver, bladder, and uterus cancers were marginally significantly higher. CONCLUSIONS: This nationwide population-based cohort study shows that Taiwanese patients with AS have a higher risk of developing cancer, particularly lung or head and neck cancer.

A population-based cohort study in Taiwan--use of insulin sensitizers can decrease cancer risk in diabetic patients?

BACKGROUND: The purpose of the study was to explore the possible association between the use of insulin sensitizers (thiazolidinediones, TZDs) and the risk of cancer in Taiwanese diabetic patients. PATIENTS AND METHODS: From the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22 910 diabetic patients newly diagnosed from 2001 to 2009 and 91 636 non-diabetic comparisons frequency matched with age, sex, and calendar year, excluding those with cancer at the baseline. Among the diabetics, 4159 patients were treated with TZDs and the rest of 18 752 patients were on other anti-diabetic medications (non-TZDs). RESULTS: In comparison to the non-diabetes group, the non-TZDs group had an increased risk of developing cancer [the adjusted hazard ratio (HR): 1.20 and 95% confidence interval (CI) = 1.11-1.30]. The TZDs group had a HR of 1.18 (95% CI = 0.98-1.42). Analysis of site-specific cancer risks showed that both TZDs and non-TZDs groups with elevated risks of colorectal and pancreatic cancer. However, the non-TZDs group had an increased risk of liver cancer when comparing with TZD and non-diabetes groups. CONCLUSION: This study suggests that patients with diabetes are at an elevated risk of cancer (especially in colorectal and pancreatic cancers), and the use of TZDs might decrease the liver cancer risk in diabetic patients. Further investigation using large samples and rigorous methodology is warranted.

Bisphosphonate treatment may reduce osteoporosis risk in female cancer patients with morphine use: a population-based nested case-control study.

UNLABELLED: Chronic use of morphine is a risk factor for endocrinopathy and osteoporosis. Bisphosphonates accentuated the protective effect to develop osteoporosis in female patients with malignancy with morphine treatment. INTRODUCTION: This study investigates the risk of osteoporosis associated with morphine use by comparing the incidence of osteoporosis in female cancer patients treated with and without morphine. METHODS: A population-based nested case-control retrospective analysis was performed using the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. A malignancy cohort of 12,467 female patients without a history of osteoporosis during 1998-2010, and then 639 patients who subsequently developed osteoporosis as the osteoporosis group, were evaluated. Control-group patients were selected from the malignancy cohort without osteoporosis and frequency matched to each osteoporosis case 2:1 for age, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age. RESULTS: Female cancer patients who received morphine had a 10% lower risk of developing osteoporosis than non-morphine users, but this risk reduction was not significant. For patients treated with bisphosphonates, the morphine group had significantly lower odds in developing osteoporosis than the non-morphine group. CONCLUSION: Morphine treatment is not associated with the incidence of osteoporosis, and bisphosphonates accentuated the protective effect of morphine in the development of osteoporosis in female patients with malignancy in Taiwan.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Risk of coronary artery disease is not linked to head and neck cancers: a population-based retrospective cohort study.

OBJECTIVES: To explore the possible association between the risk of coronary artery disease and head or neck cancer based on some possible shared risk factors and/or treatment-related complications. DESIGN AND SETTING: A population-based retrospective cohort study. PARTICIPANTS: All new 729 patients with head and neck cancer diagnosed between 2000 and 2003 were followed up till 2009, and the risk of subsequent coronary artery disease was calculated. For each patient, the risk was calculated in 4 age-and sex-matched population controls. Matching was not possible for factors including socio-economic group and smoking. MAIN OUTCOME MEASURES: Cox's proportional hazard regression analysis was conducted to estimate the relationship between head or neck cancer and risk of coronary artery disease. RESULTS: For patients with head or neck cancer, the overall risk for developing coronary artery disease was almost the same as that of the control group [adjusted hazard ratio (but without control for some lifestyle factors): 0.95; 95% confidence interval: 0.65-1.35]. Overall, we found no increased risk of coronary artery disease for patients with head or neck cancer when the data were categorised either by treatment methods or by cancer subsites. CONCLUSIONS: This population-based study indicated that patients with head or neck cancer were at no higher risk of developing coronary artery disease than was the general population over a 6- to 9-year period; however, we cannot exclude the risk over a longer period of time.

A Nationwide Study on Outcomes for the Offspring of Renal Transplant Recipients in Taiwan.

OBJECTIVE: Hormonal changes, in either men or women experiencing chronic kidney disease, cause decreased libido, erectile dysfunction, dysmenorrhea, and ovarian dysfunction, all of which may contribute to infertility. Patients' endocrinal and sexual function could be rapidly restored after successful renal transplantation (RTx), which may assist in achieving a successful pregnancy. However, fetuses will be exposed to the immunosuppressive agents passed on from the female recipients, which may be another potential factor leading to a poor fetal outcome. This nationwide study examined the perinatal status of offspring from RTx recipients in Taiwan. METHODS: The National Health Insurance (NHI) program is a mandatory universal health insurance program in Taiwan which provides coverage for 99.6% of its population. Nationwide, births totaled 2,562,253 between 2001 and 2012. Of that total, 97 births were from mothers who had had a RTx prior to delivery. A total of 2,561,973 births from the general population was then determined by combining the NHI database with the National Birth Registry database. Offspring from the RTx recipients and the general population was at a ratio of 1:10 matched by both birth year and birth month, where 77 offspring were from RTx recipients, while 770 served as a control. RESULTS: The offspring from the RTx group displayed significant statistical differences from the general population regarding low birth weight (< 2500 g) (53.3% vs 9.9%, P < .001), premature delivery (< 37 weeks) (46.8% vs 10.7%, P < .001), and high cesarean section delivery rate (50.7% vs 38.2%, P = .033). Regarding the Apgar score, which was assessed 1 minute and 5 minutes after each birth, fewer than 7 disclosed rates of 21.3% and 6.7% respectively in offspring of the RTx group; the corresponding numbers were 5.1% (P < .001) and 2.3% (P = .028) respectively in the other group. CONCLUSION: Upon restoration of fertility after RTx, most female recipients wish to have their own child; therefore, we as doctors have the responsibility to provide the necessary information we possess regarding the outcomes of offspring of female surgery recipients of childbearing age. Consequently, as the outcomes may not be satisfactory, we will continue to require more studies on the long-term outcome of offspring from RTx recipients in order to provide a more rational conclusion.

C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study.

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L-1 versus 2.43 ± 2.00 mg L-1 ), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.

Long-Term Outcome of Liver Transplant Recipients After the Development of Renal Failure Requiring Dialysis: A Study Using the National Health Insurance Database in Taiwan.

BACKGROUND: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients. METHODS: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients. RESULTS: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9). CONCLUSIONS: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes.

cDNA cloning of the 210-kDa paraneoplastic pemphigus antigen reveals that envoplakin is a component of the antigen complex.

Although the 210 and 190-kDa proteins are the most frequently detected antigens reacting with sera of patients with paraneoplastic pemphigus (PNP) in immunoblot analysis, there is still uncertainty as to the nature of these PNP antigens. To isolate and characterize a cDNA clone encoding the 210-kDa PNP antigen, we screened a human keratinocyte lambda gt 11 cDNA expression library by the immunoperoxidase method with serum IgG from a PNP patient. The IgG used for the immunoscreening of a keratinocyte cDNA expression library recognized 210- and 190-kDa antigens by immunoblotting. A single clone, called here the PNP clone, producing a fusion protein that reacted strongly with the patient's IgG, was further characterized. Only the PNP patient's IgG, but not IgG from a normal control, pemphigus foliaceus, or pemphigus vulgaris patients, bound the plaques of this positive clone. Furthermore, PNP IgG affinity purified on plaques of this clone, but not unrelated clones, bound to keratinocyte cell surfaces by immunofluorescence and reacted with the 210-kDa PNP antigen by immunoblotting. EcoRI digestion of the clone's cDNA insert demonstrated a 1.4-kbp fragment. This cDNA insert was placed into a M13 mp 18 vector and sequenced. Sequence analysis revealed that the cDNA insert of the PNP clone encodes a part of the central rod domain and the COOH-terminal C domain of envoplakin, a newly defined precursor of the cornified envelope that is homologous to desmoplakin. This result demonstrates that the 210-kDa PNP antigen is envoplakin and PNP is an autoimmune disease that produces autoantibodies against intermediate filament-associated proteins in desmosomes and hemidesmosomes, desmoplakin, bullous pemphigoid antigen 1 (BPAG 1), and envoplakin.

Characteristics and potency of an acellular pertussis vaccine composed of pertussis toxin, filamentous hemagglutinin, and pertactin.

In an attempt to develop a safer pertussis vaccine, we successfully purified 3 pertussis protective antigens-pertussis toxin, filamentous hemagglutinin, and a 69-kDa outer membrane protein (also named pertactin), from Bordetella pertussis strain ATCC 9340. The toxicity of pertussis toxin could be effectively reduced by the treatment with formaldehyde 0.07% while preserving of a high degree of immunogenicity. By mixing purified pertussis antigens with diphtheria and tetanus toxoids (DT), we have formulated a DT acellular pertussis (DTaP) vaccine. Toxicity studies on body-weight gain in mouse, histamine sensitization, lymphocyte promoting, and Chinese hamster ovary cell clustering tests suggested that this DTaP vaccine is safer than a whole cell vaccine produced in France (DTP[F]). The formulated vaccine elicited high levels of anti-pertussis toxin antibodies in both mice and monkeys. In mice, a 2-fold neutralization of anti-pertussis toxin antibodies was produced by DTaP compared with DTP(F) vaccine and an acellular vaccine manufactured in Japan (DTaP[J]). More importantly, in intracerebral challenge assay in mouse, this vaccine also provided a better protection than DTaP(J).

A clinical analysis of 11 patients with chronic actinic dermatitis in Korea.

Chronic actinic dermatitis is a rare disease worldwide and also in Korea. However there has been no clinicohistologic and photobiological analysis of chronic actinic dermatitis in Korea. We examined 11 patients who were diagnosed as chronic actinic dermatitis and the results of this study were compared with previous reports. Most patients were elderly men who had erythematous papules or lichenified plaques on sun-exposed areas such as the face, neck, and dorsum of the hands with severe itching sensation. All patients had severe sensitivity to UVB and biopsied specimens showed findings of chronic eczema. Five patients had positive photopatch test materials. The patients were treated with systemic and topical steroid, cyclosporine and antihistamine.

Epidermolysis bullosa simplex (Dowling-Meara type) associated with pyloric atresia and congenital urologic abnormalities.

We report a case of epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM), which was associated with congenital pyloric atresia (PA) and various urologic abnormalities, a diagnosis confirmed by immunofluorescence mapping and electron microscopic findings. Immunofluorescent mapping showed the serum from a patient with bullous pemphigoid faintly binding to the floor of the blister, and monoclonal antibodies against type IV and VII collagens were also stained on the floor of the blister. Electron microscopy showed epidermolytic cleavage and prominent clumping of tonofilaments in the basal and suprabasal keratinocytes. An abdominal radiograph and barium swallow showed a complete obstruction at the pyloric channel level. The widespread bullae healed without any scar formation and the bullae formation was localized on the extremities after 3 months of age without any specific treatment. Multiple urologic abnormalities such as bilateral hydronephrosis, hydroureter and a distended bladder with trabeculation were observed at 12 months of age. Currently, with the patient at 4 years of age, bullae still appear on the hands and feet and nail shedding can be observed. The patient's father, a paternal uncle and a paternal aunt had had similar bullous eruptions in infancy, all of which had improved spontaneously by the age of one.

Cutaneous mesenchymal hamartoma.

A case of a cutaneous mesenchymal hamartoma occurring on the thigh of a newborn infant is reported. Microscopically, the solitary tumorous lesion consisted of an intimate mixture of fibrocollagenous bundles, islands of mature fat cells, distorted blood vessels, and eccrine sweat glands. Many mast cells were scattered throughout the fibrocollagenous bundles. Ultrastructurally, most tumor cells were suggestive of undifferentiated mesenchymal cells.

A case of classical Kaposi's sarcoma of the penis showing a good response to high-energy pulsed carbon dioxide laser therapy.

Isolated Kaposi's sarcoma (KS) of the glans penis is rare; only 37 cases are reported in the literature. Treatment of KS consists mostly of old modalities, some old methods in updated improved versions, and some new and experimental therapies. We report a case of isolated classical Kaposi's sarcoma involving multiple sites of the penis in a 54-year-old man who was treated with high-energy pulsed carbon dioxide (CO2) laser therapy, resulting in complete resolution of the lesions and no evidence of recurrence.

A case of multiple nevoid hypertrichosis.

Nevoid hypertrichosis is an uncommon congenital disorder consisting of terminal hair growth in a localized distribution on flesh-colored skin; it is not associated with any other systemic abnormalities. A 21-year-old male patient had a circumscribed area of depigmented terminal hairs on his chest which had been present since 1 year of age. At the age of 18, similar lesions developed on his left shoulder and upper arm. The underlying skin was slightly hypopigmented, and no other systemic abnormalities were found. Histologic examination demonstrated terminal hair follicles in otherwise normal skin. The number of HMB 45 positive melanocytes was markedly decreased in the affected skin. This case of multiple nevoid hypertrichosis is reported with a review of previously reported cases.

A case of acinic cell adenocarcinoma on the left hemifacial area.

Acinic cell adenocarcinoma is a rare salivary gland tumor which predominantly occurs in the parotid gland. A 46-year-old man presented with a left preauricular mass of one month duration; the pathologic report showed acinic cell adenocarcinoma. He was transferred to the oral and maxillofacial surgery department, and a total parotidectomy was performed. We present this interesting case of acinic cell adenocarcinoma from the parotid gland with cutaneous involvement.

A case of primary cutaneous actinomycosis.

Primary cutaneous actinomycosis is very uncommon because of the exclusively endogenous habitat of the organism. We report a case of primary cutaneous actinomycosis characterized by histopathological "sulfur granules". The patient had a well-defined subcutaneous nodule on the left thigh without any other lesion and was treated with surgical excision and subsequent oral ampicillin for six weeks. There has been no recurrence during a 1-year period of follow-up.