Joint effects of risk factors on adverse events associated with adult blood donations.

The process for blood donation is considered safe, but some adverse events have been reported. Risk factors for adverse events were assessed in this study.A retrospective case-control study was conducted to investigate the risk factors for adverse events after blood donation between 2010 and 2013. Variables such as gender, age, body mass index (BMI), donation status, donation volume, donation site, pre-donation systolic blood pressure (SBP), and pre-donation diastolic blood pressure were compared between donors with and without adverse events. Multiple logistic regression analysis was performed to assess the joint effects of age, gender, and donation status on adverse events.The incidence of adverse events among adult blood donations was 1287/1,253,678 (0.1%). On multivariate logistic regression analysis, blood donors aged <35 years (odds ratio [OR], 2.99, 95% confidence interval [CI], 2.57-3.48), of female gender (OR, 3.30, 95% CI, 2.62-4.15), and with first-time donor status (OR, 6.40, 95% CI, 5.17-7.93), donation of 500 mL (OR, 2.22, 95% CI, 1.83-2.69), predonation SBP <124 mm Hg (OR, 1.25, 95% CI,1.05-1.48) and BMI <24 kg/m (OR, 1.67, 95% CI, 1.42-1.96) were associated with increased likelihood of adverse event. Further analysis with joint effects method revealed that first-time female donors aged <35 years are associated with the highest odds of adverse events when compared with repeat male donors aged ≧35 years (OR, 100.57, 95% CI, 48.45-208.75).The findings of our study should prove useful in identifying donors at risk and planning appropriate strategies for the prevention of adverse effects.

Dermoscopic assessment of xerosis severity, pigmentation pattern and vascular morphology in subjects with physiological aging and photoaging.

BACKGROUND: Skin aging can be classified as either physiological or pathological aging. Pathological aging is most often due to chronic sunlight exposure (photoaging). Age-dependent changes in dermoscopic features of normal skin have not previously been well defined. OBJECTIVES: We compared the dermoscopic features of skin from non-elderly subjects, elderly subjects with physiological aging, and elderly subjects with photoaging. MATERIALS AND METHODS: We enrolled 40 non-elderly subjects aged 20-60 years, 40 elderly subjects aged >60 years with physiological aging, and 40 elderly subjects aged >60 years with photoaging. Skin from the lower legs of subjects was examined by dermoscopy. RESULTS: Compared with non-elderly subjects, dermoscopic examination of elderly subjects with physiological aging and photoaging revealed various degrees of xerosis (mild: scaling limited to skin furrows; moderate: scaling extending beyond skin furrows with accentuation of skin markings; severe: plate-like scaling extending beyond skin furrows with formation of deep skin fissures). In addition, dermoscopic examination of skin from elderly subjects with photoaging showed increased prevalence of uneven pigmentation (small brown globules, reticular pigmentation, and homogeneous pigmentation in a patchy distribution) and vascular telangiectasia (linear and branching vessels). CONCLUSION: This study provides a novel dermoscopic grading system to evaluate the severity of xerosis and demonstrates the application of dermoscopy for the accurate assessment of subtle morphological changes (including pigmentation pattern and vascular structures) associated with physiological aging and photoaging.

Clinical features of Kaposi's sarcoma: experience from a Taiwanese medical center.

BACKGROUND: Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center. METHODS: Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed. RESULTS: There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy. CONCLUSIONS: The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan.

Inclusion complex of saikosaponin-d with hydroxypropyl-ß-cyclodextrin: Improved physicochemical properties and anti-skin cancer activity.

BACKGROUND: Saikosaponin-d (SSD) is a triterpene saponin isolated from Bupleurum plants. It has been shown to exhibit antioxidant, anti-inflammatory, and anticancer activities. However, its biomedical applications are limited by its poor water solubility. Cyclodextrins are highly water soluble oligosaccharide compounds which can form inclusion complexes with lipophilic drugs. PURPOSE: We complexed SSD with hydroxypropyl-ß-cyclodextrin (HPBCD) in various ratios to form SSD-HPBCD inclusion complexes. The inclusion complexes were evaluated for their solubility, physicochemical properties and cytotoxic effects in cutaneous squamous cell carcinoma cells. METHODS: Surface morphology of pure SSD and SSD-HPBCD inclusion complexes was evaluated by scanning electron microscopy. Crystalline structure was determined by X-ray diffractometry. Intermolecular hydrogen bond formation between SSD and HPBCD was investigated by Fourier transform infrared spectroscopy. Human cutaneous squamous cell carcinoma HSC-1 cell viability was determined by the MTS assay, and cell apoptosis by the caspase 3/7 assay. Signal transduction pathways were investigated by Western blotting. RESULTS: SSD-HPBCD inclusion complexes showed greatly increased water solubility. This was associated with an improvement in physicochemical properties, including transformation of crystalline structure to amorphous form, and formation of hydrogen bonds between SSD and HPBCD. In addition, SSD-HPBCD inclusion complexes induced apoptosis in HSC-1 cells, and this was mediated through activation of MAPK and suppression of Akt-mTOR signaling pathways. CONCLUSION: SSD-HPBCD inclusion complex shows improvement in water solubility and physicochemical properties, and exhibits anticancer effects against cutaneous squamous cell carcinoma cells. Therefore, it may be a potential drug formulation for the treatment of skin cancer.

Dermoscopic features of livedoid vasculopathy.

Livedoid vasculopathy (atrophie blanche) is a form of thrombotic vasculopathy. It is characterized by small ulcers that become crusted, and heal after several months to produce white atrophic scars. The most commonly affected sites are the lower legs, in particular the dorsum of the feet and ankles. To date, the dermoscopic features of livedoid vasculopathy have not been clearly described in the literature. In this observational study, we sought to evaluate the dermoscopic patterns of livedoid vasculopathy and determine whether the dermoscopic features are associated with certain histopathological characteristics. We evaluated 9 patients with livedoid vasculopathy by dermoscopy. Skin biopsy specimens were stained with hematoxylin and eosin for histopathologic examination, and dermoscopic features were correlated with histopathological characteristics. In the majority of patients with livedoid vasculopathy, examination with dermoscopy revealed central crusted ulcers or ivory white areas associated with peripheral pigmentation in a reticular pattern. In addition, increased vascular structures including linear and glomerular vessels were found. On histopathological examination, the central ivory white areas correlated with dermal fibrosis, the reticular pigmentation corresponded to epidermal basal layer hyperpigmentation or melanin within melanophages in the dermal papillae, and the vascular structures correlated with dilatation and proliferation of capillaries in the upper dermis. In summary, the most common dermoscopic features of livedoid vasculopathy identified in this study were central crusted ulcers or ivory white scar-like areas associated with peripheral reticular pigmentation and increased vascular structures. The characterization of dermoscopic criteria for livedoid vasculopathy may improve the accuracy in the clinical diagnosis and follow-up of this disease.

Neutrophil extracellular trap formation is increased in psoriasis and induces human ß-defensin-2 production in epidermal keratinocytes.

Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human ß-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes, and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections.

Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study.

BACKGROUND: The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined. OBJECTIVE: We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants. METHODS: A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development. RESULTS: Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose. LIMITATIONS: This study is retrospective in nature. CONCLUSION: Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy.

Dermal desmoplastic fibroblastoma presenting as a large sacral mass.

Desmoplastic fibroblastoma (collagenous fibroma) is a rare and recently recognised benign tumour. Most desmoplastic fibroblastomas arise in the subcutaneous tissue or skeletal muscle. Involvement of the dermis is extremely rare. We describe an unusual case of dermal desmoplastic fibroblastoma presenting as a large sacral mass in a 16-year-old male. An awareness of this entity is necessary to avoid confusion with other benign and malignant soft tissue neoplasms.

Artocarpin Induces Apoptosis in Human Cutaneous Squamous Cell Carcinoma HSC-1 Cells and Its Cytotoxic Activity Is Dependent on Protein-Nutrient Concentration.

Artocarpin, a natural prenylated flavonoid, has been shown to have various biological properties. However, its effects on human cutaneous squamous cell carcinoma (SCC) have not been previously investigated. We set out to determine whether artocarpin has cytotoxic effects on SCC cells and whether its pharmacological activity is dependent on protein-nutrient concentration. Our results showed that treatment of HSC-1 cells (a human cutaneous SCC cell line) with artocarpin decreased cell viability and induced cell apoptosis by increasing caspase 3/7 activity. These effects were more pronounced at low fetal bovine serum (FBS) concentrations. Artocarpin induced an increase in the level of phospho-p38 and a decrease in the levels of phospho-ERK, phospho-JNK, phospho-Akt, phospho-mTOR, and phospho-S6K. High FBS concentrations in the culture media inhibited and delayed the uptake of artocarpin from the extracellular compartment (culture media) into the intracellular compartment, as determined by high performance liquid chromatography (HPLC) analysis. In conclusion, artocarpin induces apoptosis in HSC-1 cells through modulation of MAPK and Akt/mTOR pathways. Binding of artocarpin to proteins in the FBS may inhibit cellular uptake and reduce the cytotoxic activity of artocarpin on HSC-1 cells. Therefore, artocarpin may have potential use in the future as a form of treatment for cutaneous SCC.

CCR7 expression correlates with subcutaneous involvement in mycosis fungoides skin lesions and promotes migration of mycosis fungoides cells (MyLa) through mTOR activation.

BACKGROUND: The molecular pathogenesis of mycosis fungoides (MF) is currently poorly understood. The chemokine receptor CCR7 has been demonstrated to be involved in the development and progression of certain cancers, but its role in MF has rarely been investigated. OBJECTIVES: We seek to determine whether CCR7 is expressed in MF skin lesions. In addition, we evaluate whether CCR7 plays a role in MF cell proliferation and migration, and which signaling pathways are involved. METHODS: Immunohistochemical staining of 21 cases of MF pathology specimens with CCR7 was performed. Medical charts and pathology slides of these cases were reviewed. Surface expression of CCR7 on MyLa cells (MF cell line) and peripheral blood mononuclear cells (PBMCs) was assessed by flow cytometry. Cell proliferation and migration were evaluated with the Alamar Blue assay and transwell chemotaxis assay, respectively. RESULTS: CCR7 was found to be expressed in 62% (13 out of 21) of MF pathology specimens, and its expression correlated with subcutaneous extension of lymphoma cells. CCR7 expression was increased on the surface of MyLa cells compared to that on PBMCs. Addition of CCL21 (CCR7 agonist) enhanced MyLa cell migration but not proliferation. The CCL21-induced MyLa cell migration was found to be mediated by the mTOR pathway. CONCLUSIONS: CCR7 is more likely to be expressed in MF skin lesions with subcutaneous involvement. Activation of CCR7 promotes migration of MyLa cells (MF cell line) through the mTOR pathway. These findings provide new insights into the significance of CCR7 in the pathophysiology of MF.

Lymphopaenia, anti-Ro/anti-RNP autoantibodies, renal involvement and cyclophosphamide use correlate with increased risk of herpes zoster in patients with systemic lupus erythematosus.

Herpes zoster occurs with increased frequency in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify and evaluate clinical and laboratory risk factors associated with development of herpes zoster in patients with SLE. A retrospective case-control study was performed in a population of patients with SLE. Patients were identified as cases if their first episode of herpes zoster occurred after diagnosis of SLE. Patients with SLE who never developed herpes zoster were enrolled as controls. Medical charts and laboratory data for both cases and control patients were comprehensively reviewed. A total of 65 cases and 105 controls were included. Risk factors associated with the development of herpes zoster in patients with SLE were found to be lymphopaenia, anti-Ro antibodies, anti-RNP antibodies, neuropsychiatric manifestations, renal involvement and cyclophosphamide use. Therefore, the presence of certain disease manifestations in patients with SLE represents risk factors for the development of herpes zoster.

Prevalence of adult atopic dermatitis among nursing staff in a Taiwanese medical center: a pilot study on validation of diagnostic questionnaires.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous studies have focused mostly on pediatric patients, and investigations emphasizing adult AD have been limited. OBJECTIVE: We set out to determine the 1-year prevalence and evaluate the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD questionnaires of adult AD in Taiwan. METHODS: We conducted a cross-sectional study among nursing staff at a university hospital. The 1-year prevalence of AD was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists' diagnosis based on Hanifin and Rajka criteria was used as a reference for validation. RESULTS: The overall response rate was 92.9%, equivalent to 1131 complete questionnaires. Ninety adult patients with AD (8%) were identified by dermatologists' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%) patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively. Using the receiver operating characteristic curve analysis, the UKWP criteria performed significantly better than its ISAAC counterpart. Further analysis indicated that modification of these criteria resulted in significant improvement in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and 55.2% sensitivity and specificity, respectively, whereas modified UKWP demonstrated 82.2% and 94.2% sensitivity and specificity, respectively. LIMITATION: Most of the study subjects were female with a high educational background. CONCLUSION: Currently available questionnaire instruments do not perform well in the identification of adult patients with AD. Modification of the original questionnaires may allow for future large-scale epidemiologic studies.

Treatment of idiopathic prurigo nodularis in Taiwanese patients with low-dose thalidomide.

Prurigo nodularis is an intensely pruritic dermatosis characterized by lichenified and excoriated papules and nodules. The course of prurigo nodularis is often chronic, and some patients respond very poorly to the standard therapeutic modalities. Because the pathogenesis of this disease remains obscure, the treatment of prurigo nodularis can be disappointing and frustrating for both the patients and physicians. Thalidomide, a tumor necrosis factor-alpha antagonist, has been suggested as an alternative treatment option for recalcitrant prurigo nodularis. In the past, the regimen for treatment of prurigo nodularis often required thalidomide at 200 mg/day. We recruited patients with intractable prurigo nodularis and treated them with low-dose thalidomide. Six patients with idiopathic prurigo nodularis were successfully treated with low-dose thalidomide (50-100 mg/day) without clinical development of peripheral neuropathy. In summary, our preliminary results suggest that low-dose thalidomide may be a safe and effective treatment option for patients with recalcitrant idiopathic prurigo nodularis.

The prevalence of SEN virus infection in blood donors in Taiwan.

OBJECTIVES: To determine the prevalence of SENV infections among blood donors in central Taiwan and to clarify the relationship between these infections and elevated alanine aminotransaminase (ALT) values. METHODS: DNA was extracted from plasma of 200 blood donors and amplified by seminested PCR. RESULTS: For all donors, the prevalence of SENV-D was 32%, and of SENV-H was 30.5%. Prevalence of mixed SENV-D/H infection was 11.5% and of SENV-D and/or SENV-H (SENV-D/H) was 51%. Infections were not associated with age, gender, or raised ALT values. CONCLUSIONS: SENV-D and SENV-H infections are common among blood donors in central Taiwan but are unlikely to contribute to abnormal ALT values.