Mechanical stretch induces hair regeneration through the alternative activation of macrophages.

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.

Cancer Risks in Vitiligo Patients: A Nationwide Population-Based Study in Taiwan.

Vitiligo is an autoimmune disease characterized by destruction of melanocytes and associated with other autoimmune disease. Whether the dysregulation of immune system enhances oncogenesis or not remains obscure. Until now, no nationwide population-based study has been conducted regarding this. As such, this paper aims to clarify cancer risk in vitiligo patients. A retrospective nationwide population-based cohort study between 2000 and 2010 was performed based on data from the National Health Insurance Research Database of Taiwan. Standardized incidence ratios (SIRs) of cancers were analyzed. Among the 12,391 vitiligo patients (5364 males and 7027 females) and 48,531.09 person-years of observation, a total of 345 cancers were identified. Significantly increased SIRs were observed for prostate cancer in male patients, thyroid cancer and breast cancer in female patients and bladder cancers in both male and female patients. Unfortunately, the low incidence rate of certain cancers limited the power of our statistical analyses. This study demonstrated the patterns of malignancies in vitiligo patients of Taiwan. Compared with the general population, male patients had higher risks of prostate cancer and female patients had higher risks of thyroid cancer and breast cancer. The risks of bladder cancer were also increased in both male and female patients.

Atopic dermatitis and risk of ischemic stroke: a nationwide population-based study.

BACKGROUND: Epidemiological studies have shown a strong association between systemic inflammatory diseases, particularly allergic diseases, and cardiovascular diseases. However, the relationship between atopic dermatitis (AD) and ischemic stroke remains unclear. METHOD: The study identified 20,323 AD patients and 20,323 comorbidity-matched subjects between 2005 and 2008. The two cohorts were followed until 31 December 2009. Ischemic stroke and other cardiovascular events were determined. RESULTS: During the follow-up period, 301 (1.48%) patients in the AD cohort and 228 (1.12%) matched subjects experienced ischemic stroke. After multivariate adjustment, patients with AD had a 1.33-fold (95% confidence interval (CI), 1.12-1.59; P = 0.001) increased incidence of ischemic stroke. Adjusted hazard ratios for the risk of ischemic stroke in patients with mild, moderate, and severe AD were 1.20 (95% CI, 1.00-1.45; P = 0.052), 1.64 (95% CI, 1.23-2.19; P = 0.001), and 1.71 (95% CI, 1.15-2.56; P = 0.008), respectively. The log-rank test showed a higher cumulative incidence of ischemic stroke in the severe AD group than in the moderate and mild AD groups during the follow-up period (P < 0.001). CONCLUSIONS: AD may be an independent risk factor for ischemic stroke, and risk of ischemic stroke increases with AD severity.

Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study.

PURPOSE: Systemic sclerosis is a life-threatening autoimmune disease characterized by vasculopathy, which results in myocardial involvement in an extremely high percentage of patients. Nevertheless, there have been no large-scale epidemiological studies about the risk of acute myocardial infarction in patients with systemic sclerosis. The aims of this study were to evaluate the hazard ratio (HR) and risk factors of acute myocardial infarction in patients with systemic sclerosis, as well as to compare the risks of acute myocardial infarction among systemic sclerosis patients taking different immunosuppressors. METHODS: The study cohort included 1344 patients with systemic sclerosis and 13,440 (1:10) age-, sex-, and comorbidity-matched controls during the period between 1997 and 2006, from the National Health Insurance Research Database. We compared the risk of acute myocardial infarction between patients with systemic sclerosis and controls and calculated the adjusted HRs for acute myocardial infarction in systemic sclerosis patients taking immunosuppressors and not taking immunosuppressors. RESULTS: The incidence rates of acute myocardial infarction were 535 and 313 cases per 100,000 person-years for systemic sclerosis cohort and reference cohort, respectively (P <.001, unadjusted). After adjusting for age, sex, and underlying medical diseases on Cox proportional hazards model, systemic sclerosis was found to be an independent risk factor for acute myocardial infarction (HR 2.45). Other risk factors included hypertension (HR 2.08) and diabetes (HR 2.14). The multivariate adjusted HR for acute myocardial infarction did not decrease among the systemic sclerosis patients taking systemic steroids, penicillamine, cyclophosphamide, azathioprine, methotrexate, or cyclosporine. CONCLUSION: Systemic sclerosis is independently associated with an increased risk of acute myocardial infarction. Immunosuppressors do not lower the risk of acute myocardial infarction in our study.

Increased risk of sexual dysfunction in male patients with psoriasis: a nationwide population-based follow-up study.

INTRODUCTION: An association between psoriasis and sexual dysfunction (SD) has been explored. However, the risk of SD after the diagnosis of psoriasis relative to the age-matched general population remains unknown. Aim. To clarify the risk of developing SD in male patients with psoriasis. METHODS: From 2000 to 2001, we identified 12,300 male patients with newly diagnosed psoriasis and 61,500 matching controls from National Health Insurance Database in Taiwan. MAIN OUTCOME MEASURES: The two cohorts were followed up until 2008, and we observed the occurrence of SD by registry of SD diagnosis in the database. Stratified Cox proportional hazard regressions were used to calculate the 7-year SD risk for these two groups. RESULTS: Of the 73,800 sampled patients, 1,812 patients (2.46%) experienced SD during the 7-year follow-up period, including 373 (3.03% of patients with psoriasis) in the study group and 1,439 (2.34% of patients without psoriasis) in the comparison group. The hazard ratio (HR) for SD for patients with psoriasis was 1.27 times (95% confidence interval [CI], 1.11-1.46; P = 0.001) as high as that for patients without psoriasis after adjusting for age, monthly income, number of health-care visits, systemic treatment, and other comorbidities. Stratified analysis showed that the risk of SD was higher in patients older than 60 years old (HR: 1.42, 95% CI: 1.12-1.81) and patients with psoriatic arthritis (HR: 1.78, 95% CI: 1.08-2.91). However, the risk of SD was not significantly elevated in patients receiving systemic treatment, including retinoid, methotrexate, and cyclosporine. CONCLUSIONS: Male patients with psoriasis are at increased risk of developing SD. Physicians should pay attention to the impact of psoriasis on psychosocial and sexual health, especially in old-aged patients.

Cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in Taiwan.

It has long been a debate that whether atopy is a risk factor or protective factor for cancer. However, no large-scale study of different cancers in patients with atopic diseases has been conducted among Asians. Here, we conducted a nationwide study to evaluate the cancer risk in patients with allergic rhinitis (AR), asthma and atopic dermatitis (AD). Drawing on Taiwan's National Health Insurance Research Database, 225,315 patients with AR, 107,601 patients with asthma and 34,263 patients with AD without prior cancers were identified in the period from 1996 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. Although the overall cancer risks in patients with atopic symptoms were not increased, the risks were slightly elevated in female patients with AR or asthma (SIR: 1.13 and 1.08, AR and asthma, respectively) and slightly decreased in males patients with AR. Those aged 20-39 years-old possessed the highest risk. A higher risk of developing brain cancer was found in patients with atopic diseases, and patient with AR or asthma also had an elevated risk of developing cancer of kidney and urinary bladder. In contrast, the risk of nonmelanoma skin cancer was lower in patients with AR and asthma. Compared to patients with only one atopic disease, those with more than one atopic disease had lower cancer risks. Our data suggests that the association between atopy and cancer is site-specific.

Malignancies after renal transplantation in Taiwan: a nationwide population-based study.

BACKGROUND: Renal transplantation has been regarded as the treatment of choice for end-stage renal disease. Renal transplantation increases the risk of cancers due to long-term immunosuppression. The types of post-transplantation malignancies may vary among different geographic regions and ethnic populations. To date, large population-based studies of post-transplantation malignancies in Asian renal transplant recipients (RTRs) have rarely been reported. METHODS: To investigate the patterns of post-transplantation malignancies in Chinese RTRs, we performed a nationwide population-based cohort study between 1997 and 2008 based on data from the National Health Insurance Database in Taiwan. Patterns of cancer incidence in RTRs were compared with those of the general population using standardized incidence ratios (SIRs). RESULTS: Among the 4716 RTRs (2475 males and 2241 females; mean age 44.1 ± 12.4 years) and 22 556 person-years of observation, 320 post-transplant cancers were diagnosed. The SIR of all cancers was 3.75 (95% confidence interval 3.36-4.18). Women had a higher risk than men for the development of malignancies (SIR 5.04 for women and SIR 2.88 for men). Renal, bladder and liver cancers were the most common cancers, with SIRs of 44.29, 42.89 and 5.07, respectively. When stratified by age, RTRs of young age at transplant (<20 years) had the highest risk of post-transplantation malignancies. CONCLUSIONS: This study demonstrates different patterns of malignancies after renal transplantation in Chinese RTRs, with higher incidences of kidney and bladder cancers. Physicians should be more vigilant in examining RTRs for post-transplantation malignancies especially in younger patients.

Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study.

BACKGROUND: Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by onset age has rarely been reported. OBJECTIVE: We sought to clarify the role of atopic and autoimmune diseases in AA, thereby better understanding its pathogenesis. METHODS: A total of 4334 patients with AA were identified from the National Health Insurance Database in Taiwan from 1996 to 2008. A national representative cohort of 784,158 persons served as control subjects. RESULTS: Among patients with AA, there were significant associations with vitiligo, lupus erythematosus, psoriasis, atopic dermatitis, autoimmune thyroid disease, and allergic rhinitis. Different ages at onset resulted in disparate comorbidities. Increased risk of atopic dermatitis (odds ratio [OR] 3.82, 95% confidence interval 2.67-5.45) and lupus erythematosus (OR 9.76, 95% confidence interval 3.05-31.21) were found in childhood AA younger than 10 years. Additional diseases including psoriasis (OR 2.43) and rheumatoid arthritis (OR 2.57) appeared at onset age 11 to 20 years. Most atopic and autoimmune diseases were observed at onset ages of 21 to 60 years. With onset age older than 60 years, thyroid disease (OR 2.52) was highly related to AA. Moreover, patients with AA had higher risk for more coexisting diseases than control subjects. LIMITATIONS: We could not differentiate hypothyroidism from hyperthyroidism. CONCLUSIONS: AA is related to various atopic and autoimmune diseases. Different associated diseases in each onset age group of AA can allow clinician to efficiently investigate specific comorbidities.

The risk of cancer in patients with psoriasis: a population-based cohort study in Taiwan.

BACKGROUND: An association between psoriasis and malignancy has been explored. However, no studies have been reported regarding cancer risk in Asian psoriasis populations. OBJECTIVES: The aim of this study was to investigate the risk of cancer development in association with psoriasis. The effects of age at diagnosis, treatment modalities, and observation time were also evaluated. METHODS: Data for this retrospective population-based cohort study were obtained from the Taiwan National Health Insurance Research Database (NHIRD). This study included 3,686 patients with first-time diagnosis of psoriasis between 1996 and 2000. Another 200,000 patients without psoriasis served as the comparison group. All enrolled subjects were followed-up until the end of 2007. Cumulative incidences and hazard ratios (HRs) of cancer development were determined. RESULTS: Among the 3,686 psoriasis patients, 116 had incident cancers. The 7-year cumulative incidence of cancer among psoriasis patients was 4.8%. The adjusted HR for developing a cancer in association with psoriasis was 1.66 (95% confidence interval [CI], 1.38-2.00). Cancer risk was higher in male patients than in female patients (adjusted HR 1.86 vs.1.14, respectively). Certain cancers were significantly associated with psoriasis, including those of the urinary bladder and skin, followed by oropharynx/larynx, liver/gallbladder, and colon/rectum. Patients with psoriasis had an increased adjusted HR for cancer that varied by age. Younger patients with psoriasis tended to have the greatest risk of cancer. Finally, systemic phototherapy and oral medication did not significantly increase the risk of cancer. Phototherapy with UVB appeared to reduce the risk of cancer in psoriasis (adjusted HR, 0.52; 95% CI, 0.29-0.95; P = .03). LIMITATIONS: NHIRD did not contain information regarding severity of psoriasis, status of smoking, alcohol use, family history of cancer, or diet. Misclassification of disease cannot be ruled out in a registry-based database. CONCLUSIONS: Psoriasis carries an elevated risk of malignancies, especially in younger and in male patients. This effect is independent of systemic treatment for psoriasis. Finally, phototherapy with UVB did not increase, but rather reduced, the risk of cancer in psoriasis.

Prevalence of atopic dermatitis, allergic rhinitis and asthma in Taiwan: a national study 2000 to 2007.

To study the prevalence of atopic dermatitis, allergic rhinitis, and asthma in Taiwan, we analysed the claims data of a nationally representative cohort of 997,729 enrolees from the National Health Insurance register from 2000 to 2007. Overall, 66,446 patients were diagnosed with atopic dermatitis, and 49.8% of them had concomitant allergic rhinitis and/or asthma. The overall 8-year prevalences of atopic dermatitis, allergic rhinitis, and asthma were 6.7%, 26.3% and 11.9%, respectively. Children and adolescents had significantly higher prevalences of these atopic diseases. The prevalence of atopic dermatitis in females was lower than that in males before the age of 8 years, but became higher after that. Patients with atopic dermatitis were more likely to have allergic rhinitis and asthma. Those having both atopic dermatitis and allergic rhinitis possessed an even higher risk for asthma (odds ratio 9.04). The numbers of visits for atopic dermatitis were highest in late spring to mid-summer. These data suggest that atopic diseases are common in Taiwan.

Elevated risk of second primary cancer in patients with cutaneous malignant melanoma: a nationwide cohort study in Taiwan.

BACKGROUND: It has been described that Caucasian patients with cutaneous malignant melanoma (CMM) are at an increased risk of developing second primary cancer. However, no large-scale study of second primary cancer in CMM patients has been conducted among Asians, who have distinctly different skin types. OBJECTIVE: We sought to access the risk of second primary cancer among CMM patients based on data from a nationwide database in Taiwan. METHODS: Utilizing the catastrophic illness database of Taiwan's National Health Insurance Research Database, we identified 2665 CMM patients without prior cancers in the period from 1997 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. RESULTS: The mean age ± standard deviation at diagnosis of CMM was 62.2 ± 17.4 years. The mean annual incidence was 0.9 cases per 100,000 people. The overall cancer risk was elevated (SIR: 2.54), with younger patients having a higher risk. The risk remained elevated during the first five years after the CMM diagnosis. CMM patients had a higher risk of developing cancers of eye (SIR: 275.68), connective tissue (SIR: 43.45), brain (SIR: 21.03), and non-melanoma skin cancer (SIR: 17.71). CONCLUSION: CMM patients have a 2.54-fold risk of second primary cancer, with younger patients at increased risk. The risk remains elevated during the first five years after the diagnosis of CMM. The sites with highest risk of second primary cancer are eye, connective tissue, brain, and non-melanoma skin cancer.

Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome.

OBJECTIVE: To evaluate the role of leptin, a 16-kDa adipocyte-derived hormone, in the development of metabolic dysregulation of psoriasis. DESIGN: Case-control study. SETTING: Referral centers. Patients Seventy-seven patients with psoriasis and 81 age- and sex-matched control subjects were included in the study. Intervention Enzyme-linked immunoassay of serum samples from study subjects. MAIN OUTCOME MEASURES: Serum leptin levels and proportions of comorbidities (including hypertension, diabetes mellitus, metabolic syndrome, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol concentrations) in cases vs controls were compared using chi(2) and Mann-Whitney tests. The clinical significance of leptin in psoriasis was analyzed using logistic regression models. RESULTS: Significantly more obesity (odds ratio [OR], 2.67) and hypertension (2.17) (P =.04 for both) were observed in subjects with psoriasis. High serum leptin levels (>or=7397.43 pg/mL) were found in female subjects (OR, 6.05; P < .001) and in subjects with obesity (3.45; P =.01), hypertension (2.19; P =.04), metabolic syndrome (3.58; P =.008), and psoriasis (2.25; P =.02). On multivariate analysis, psoriasis (OR, 4.57; P =.009) was significantly associated with hyperleptinemia independent of female sex (26.36; P < .001), metabolic syndrome (4.37; P =.04), and obesity (2.83; P =.12). Finally, patients with psoriasis who had hyperleptinemia tended to be female (P < .001) and manifested obesity (P =.002) and metabolic syndrome (P =.003). CONCLUSIONS: Hyperleptinemia is associated with psoriasis independent of female sex and other conventional cardiovascular risk factors such as obesity and metabolic syndrome. Hyperleptinemia in psoriasis may contribute to metabolic syndrome.