The quality of reporting randomized controlled trials in the dermatology literature in an era where the CONSORT statement is a standard.

BACKGROUND: The quality of reporting randomized controlled trials (RCTs) in the dermatology literature has not received much consideration since the late 2000s. OBJECTIVES: We aimed to assess the quality of recently reported RCTs published in dermatology journals, focusing on randomization processes, blinding and trial registration. METHODS: We reviewed 2042 original articles and identified 141 primary reports of RCTs in four dermatology journals (Journal of the American Academy of Dermatology, JAMA Dermatology, Journal of Investigative Dermatology and British Journal of Dermatology) from January 2015 to December 2017. Details were extracted from articles, supplements and public trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with optimal reporting quality. RESULTS: Among the 141 RCTs, 99 (70·2%), 82 (58·2%) and 69 (48·9%) described methods used for randomization, allocation concealment and implementation, respectively. Most trials (126, 89·4%) reported blinding status; however, one-third did not state the similarity of the intervention. Furthermore, 52 RCTs (36·9%) were not registered prospectively. Trials published in the British Journal of Dermatology and using central randomization were significantly associated with optimal reporting quality after adjusting for covariates. CONCLUSIONS: Several critical items in reporting RCTs, including allocation concealment, similarity of interventions in blinded trials and prospective trial registration, have remained unsatisfactory in the recent dermatology literature.

Claudin-1 expression decreases with increasing pathological grade in actinic keratosis and may be a marker of high-risk actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common sun-induced skin disorder that can progress to invasive squamous cell carcinoma. However, there is still no reliable method to predict high-risk AK. AIM: To identify markers that reflect the biological behaviour of AK and to understand the pathogenesis of AK. METHODS: In total, 52 patients with AK and 17 site-matched healthy controls (HCs) were enrolled. We evaluated solar elastosis and immunohistochemical features using antibodies to p53, vitamin D receptor (VDR), claudin-1 and Langerin (CD207). Comparisons between AK and HC skin were performed and analyses carried out according to the pathological grade of AK. RESULTS: We found that in both patients and HCs, solar elastosis increased and Langerhans cell (LC) density decreased with ageing. Solar elastosis and p53 expression were higher and VDR expression was lower in patients than in HCs; however, there was no statistical difference between them in relation to the pathological grade of AK. Claudin-1 expression gradually decreased from HC skin to severe AK, and particularly decreased in areas with epidermal atypia. LC density in severe AK was significantly lower than in HC skin and mild AK, while there was no difference in LC density between HC skin, mild AK and moderate AK. CONCLUSIONS: Claudin-1 could be a useful marker of the pathological severity of AK. In addition, p53 increases and VDR decreases in AK, not in a gradual manner but in the early steps of carcinogenesis. LC density is relatively maintained in AK until it reaches severe dysplasia.

CD34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea.

BACKGROUND: Fibrosis is thought to be the main pathophysiology of scleroderma, and myofibroblasts play the main role in abnormal fibrotic pathologies. Altered distribution of dermal dendritic cells (DDCs) and vascular abnormalities has been reported to relate to the pathogenesis of scleroderma. OBJECTIVE: To investigate fibrotic pathogenesis of morphea (localized scleroderma) by demonstrating the relative expression and distribution of DDCs and myofibroblasts, we performed immunohistochemical stains using several relevant antibodies. METHODS: Skin lesions of 50 patients with morphea and age-, sex- and site-matched normal skin of 50 subjects were evaluated for the following antibodies: CD34, factor XIIIa (FXIIIa), smooth muscle actin (SMA), CD31 and vascular cell adhesion molecule-1 (VCAM-1). RESULTS: CD34 stromal stain was significantly lower in patients than controls (P = 0.000), while FXIIIa, SMA and VCAM-1 stains were significantly higher in patients than controls (P = 0.043, P = 0.000 and P = 0.027, respectively). In subtype analysis within patients, CD34 stromal stain showed decreasing trends with increasing disease extent and increasing fibrosis, respectively. CD34 stromal stain showed an inverse correlation and mutually exclusive spatial expression pattern with SMA stain (r = -0.286, P = 0.044). The inverse relationship was maintained in each dermal layer analysis, upper and lower dermis (r = -0.397, P = 0.004 and r = -0.281, P = 0.048, respectively). CONCLUSIONS: Mutually exclusive staining patterns of CD34 stromal and SMA stains suggest a phenotypic change of CD34+ DDCs into SMA+ myofibroblasts with increasing disease extent and fibrosis in morphea. Degree of loss of CD34+ DDCs can be a useful marker in predicting the extent and severity of morphea.

Lipid profile in patients with androgenetic alopecia: a meta-analysis.

BACKGROUND: Many studies have reported that androgenetic alopecia (AGA) might be a risk factor for cardiovascular disorders, and the association of AGA with dyslipidaemia has been studied. However, the results were controversial and previous meta-analyses had several critical limitations. OBJECTIVE: We performed a meta-analysis to clarify whether AGA patients have abnormal lipid profiles. METHODS: A literature search was performed using the MEDLINE, EMBASE, The Cochrane Library and KOREA MED databases. RESULTS: We pooled 19 observational studies and performed a meta-analysis to compare serum total cholesterol, serum triglyceride (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) and the cholesterol levels between AGA and control groups. The serum total cholesterol, TG and LDL cholesterol levels were significantly higher in the AGA group than in the control group, and the standardized mean differences were 0.377 (95% confidence interval [CI]: 0.182-0.572, P < 0.001), 0.426 (95% CI: 0.164-0.688, P = 0.001) and 0.450 (95% CI: 0.171-0.728, P = 0.002) respectively. In addition, HDL cholesterol level was significantly lower in the AGA group than in the control group, and the standardized mean difference was -0.248 (95% CI: -0.472 to -0.023, P = 0.030). CONCLUSIONS: AGA patients showed statistically significant abnormal lipid profiles, and this might partly explain the association between AGA and cardiovascular diseases.

A case of perforating dermatofibroma with floret-like giant cells.

Dermatofibromas are slow-growing solitary nodules, composed mostly of a dermal proliferation of spindle cells and epithelioid cells. Some dermatofibromas present with multinucleated giant cells, such as Touton, foreign body, and osteoclast-like cells. We report a case of dermatofibroma containing both Touton giant cells and floret-type cells. A 12-year-old boy presented with a 6-mm, firm, nontender, dusky-red to greyish dermal nodule on his left popliteal fossa. As suggested clinically by the central opening, perforation of the epidermis with partial extrusion of the dermal components, including macrophages and vertically oriented collagen bundles, via transepidermal elimination, were detected. In the upper dermis, collagen trapping and mostly epithelioid cells with many giant cells were seen, while the lower part contained mainly spindle cells in a storiform pattern. Multinucleated giant cells scattered in the upper dermis were mainly floret-type multinucleated giant cells with star-shaped cytoplasmic projections, associated with some Touton giant cells. To our knowledge, this is the first report of a perforating dermatofibroma with floret-type multinucleated giant cells.

Metabolic syndrome and sex-specific socio-economic disparities in childhood and adulthood: the Korea National Health and Nutrition Examination Surveys.

AIMS: To examine whether adulthood and/or childhood sex-specific socio-economic disparities are associated with metabolic syndrome and its components in a developed non-Western setting. METHODS: Based on the Fourth Korea National Health and Nutrition Examination Surveys, 14 888 people aged ≥ 20 years were analysed to evaluate the effect of adult and childhood socio-economic status on metabolic syndrome. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Logistic regression analyses were conducted to calculate the odds ratios for metabolic syndrome and each component of metabolic syndrome in later life. RESULTS: The age-standardized prevalence of metabolic syndrome was 26.6% for men and 21.3% for women. Compared with the highest level of education, men with the lowest education level were significantly less likely to have metabolic syndrome (odds ratio 0.76, 95% CI 0.60-0.96), whereas the opposite association was found in women (odds ratio 3.29, 95% CI 2.45-4.42). Men who were manual labourers and economically inactive had a lower prevalence of metabolic syndrome compared with those with non-manual jobs (odds ratio 0.82, 95% CI 0.69-0.98 and odds ratio 0.79, 95% CI 0.64-0.99, respectively), but the reverse association was observed in women (odds ratio 1.34, 95% CI 1.04-1.73 and odds ratio 1.40, 95% CI 1.09-1.81, respectively). A significant interaction between combined adulthood and childhood socio-economic status on the presence of metabolic syndrome was observed (P < 0.05). CONCLUSIONS: Our findings suggest that sex-specific socio-economic disparities in childhood and adulthood have differential effects on the prevalence of metabolic syndrome and its individual components in Korea.

Emergence of Enterococcus species in the infectious microorganisms cultured from patients with endophthalmitis in South Korea.

PURPOSE: To investigate the microorganisms in culture-proven endophthalmitis and their susceptibilities to antimicrobial agents commonly used in South Korea. METHODS: Medical records of consecutive patients with culture-proven endophthalmitis at eight institutions between 1 January 2004 and 31 July 31 2010 were reviewed. Four categories of endophthalmitis were studied: postoperative, posttraumatic, endogenous, and unspecified. Outcome measures were culture-proven infectious organisms, antimicrobial susceptibilities, and final visual acuity in the patients. RESULTS: A total of 93 microorganisms were identified from 103 patients during the study period. The positive culture rate was 59.2 % (103/174). The most common organisms identified were Enterococcus faecalis (in 20.8 % of patients, 20/96), Staphylococcus epidermidis (18.8 %, 18/96), other coagulase-negative staphylococci (10.4 %, 10/96), Pseudomonas aeruginosa (6.3 %, 6/96), and Klebsiella pneumoniae (6.3 %, 6/96). Two cases of Enterococcus faecium (2.1 %) were recognized. Overall, 70 of 96 (73.0 %) isolates were Gram-positive bacteria, 22 (23.0 %) were Gram-negative bacteria, and 4 (4.2 %) were fungi. The most common organisms resulting in reduced light perception were E. faecalis and K. pneumoniae. CONCLUSIONS: The emergence of E. faecalis in endophthalmitis is mainly caused by the high incidence of E. faecalis in postoperative endophthalmitis. This increase also impacts the final visual acuity of the patients.

Psoriasis concurrent with inflammatory bowel disease.

BACKGROUND: Previous studies have indicated an association between psoriasis and inflammatory bowel disease (IBD), and the concurrence of the two diseases reportedly has higher morbidities in Caucasian populations. However, reports on the concurrence of psoriasis with IBD in the Asian population in the literature are scarce. Objective To analyse the characteristics of psoriasis concurrent with IBD and investigate the associated morbidity in the Asian population. METHODS: We retrospectively examined the medical records of 15 patients with a confirmed diagnosis of both psoriasis and IBD. Sixty age-, gender-, and ethnicity-matched patients with a confirmed diagnosis of only psoriasis were included as controls. Both cases and controls had visited the Seoul National University Hospital or Seoul National University Boramae Hospital between 1990 and 2012. The characteristics of psoriasis, presence of comorbidity and laboratory parameters were compared between the two groups. RESULTS: Compared to controls with psoriasis only, cases of psoriasis concurrent with IBD had a younger age of onset, longer duration of psoriasis and a higher Psoriasis Area Severity Index (PASI) score. A larger proportion of cases was treated with phototherapy, systemic therapy and biologics. However, all these differences above were not statistically significant. Cases of psoriasis with concurrent IBD showed higher erythrocyte sedimentation rate and C-reactive protein levels compared with the controls (both P = 0.000). Furthermore, this case group had a higher proportion of patients with psoriatic arthritis and with more than one autoimmune disease as compared with the control group (P = 0.007 and 0.005 respectively). CONCLUSION: Asian patients having psoriasis concurrent with IBD exhibited different characteristics as compared with those having psoriasis only, particularly in terms of psoriasis severity, risk of psoriatic arthritis, systemic inflammatory parameters and presence of autoimmune comorbidity. However, further studies elucidating the exact pathogenesis and including a larger number of patients are required.

External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long-chain triglyceride emulsion propofol in beagle dogs.

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

High-concentration all-trans retinoic acid induces dermal inflammation and reduces the accumulation of type I procollagen in human skin in vivo.

BACKGROUND: Because inflammation is a factor promoting ageing, all-trans retinoic acid (RA)-induced irritation may have a negative influence on collagen accumulation in human skin despite its stimulation of collagen production. OBJECTIVES: To determine whether RA-induced irritation detrimentally affects RA efficacy as represented by new collagen synthesis. METHODS: Retinoic acid (0·01%, 0·025% or 0·05%) or vehicle was applied to the buttock skin of elderly male volunteers three times a week for 8 weeks under continuous occlusion. Every 2 weeks, biopsy specimens were obtained and immunohistochemical analysis was performed to determine levels of type I procollagen expression and inflammatory cell infiltration. RESULTS: Topical RA regardless of concentration increased type I procollagen expression in human skin in vivo after 2 weeks. However, only 0·01% RA continuously increased type I procollagen expression up to 8 weeks. After 4 weeks, significant infiltrations of macrophages and neutrophils were observed in 0·025% and 0·05% RA-treated skin, and procollagen expression had returned to baseline. CONCLUSIONS: Excessive RA-induced inflammation might prevent collagen accumulation in aged skin despite the positive effect of RA on collagen production.

Meningitis in Korean patients with systemic lupus erythematosus: analysis of demographics, clinical features and outcomes; experience from affiliated hospitals of the Catholic University of Korea.

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified ('septic meningitis'), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.

Degradation of organic dye using zero-valent iron prepared from by-product of pickling line.

In this study, zero-valent iron (ZVI) was produced using iron oxide that is a by-product of a pickling line at a steel works. The reaction activity of the produced ZVI was evaluated through a series of decomposition experiments of Orange II aqueous solution. The size of ZVI particles increased with reduction temperature due to coalescence. Correspondingly, the specific surface area of ZVI decreased with increasing reduction temperature. The decomposition efficiency of synthesized ZVI particles was higher at a lower pH. In particular, no significant decomposition reaction was observed at pH of 4 and higher. The rate of the ZVI-assisted decomposition of Orange II was increased by addition of H2O2 at pH of 3, whereas it was reduced by addition of H2O2 at a higher pH of 6. Nevertheless, simultaneous use of ZVI, UV and H2O2 led to a considerable increase in the decomposition rate even at a high pH condition (pH = 6).

Deregulation of E-cadherin by human papillomavirus is not confined to high-risk, cancer-causing types.

BACKGROUND: E-cadherin is a tumour suppressor protein, which is normally expressed on keratinocytes and antigen-presenting Langerhans cells (LCs) in the epidermis. We have previously shown that E-cadherin is lost from tissues infected with the high-risk cancer-causing human papillomavirus (HPV) type 16. OBJECTIVES: To test if E-cadherin dysregulation is associated with the cancer risk of the infecting HPV and to establish if it is conserved among HPVs in the α, ß, γ and µ genera. METHODS: Forty-seven lesions infected with low- or high-risk HPV types spanning four HPV genera were stained for E-cadherin, P-cadherin and CD1a to detect LCs. RESULTS: Surface E-cadherin was reduced in tissues infected with members of the α4, α7 and α9 species and the γ and µ genera but was equivalent to normal epidermis in the ß only-infected lesions tested and patchy in α10-infected tissues. There was a direct relationship between atypical E-cadherin expression and a significant reduction in LCs. Expression of P-cadherin, a protein that is increased in the E-cadherin constitutive knockout mouse, was increased in lesions with reduced E-cadherin. CONCLUSIONS: These data show that E-cadherin dysregulation by HPV is widely conserved across the majority of HPV genera. E-cadherin expression was reduced or lost in epidermis irrespective of the cancer risk of the infecting HPV type or the ability of the virus to degrade retinoblastoma protein or p53. A correlation between dysregulated E-cadherin and reduced numbers of LCs supports viral regulation of surface E-cadherin contributing to viral evasion of the host immune system.

Slow proliferation as a biological feature of colorectal cancer metastasis.

BACKGROUND: We have recently reported an inverse relationship between colon cancer progression and tumour proliferative activity. Here, we extend our findings by evaluating the proliferative activity of liver metastatic lesions and primary colorectal cancers (CRC) that differ in their metastatic potential. METHODS: Using an earlier established multi-gene proliferation signature (GPS), proliferative levels were analysed in 73 primary CRCs and 27 liver metastases. RESULTS: Compared with primary CRCs, we observed a significantly lower expression of the GPS in liver metastases and confirmed their lower proliferative levels by quantitative RT-PCR and Ki-67 immunostaining. No difference could be detected in apoptotic indices as assessed by M30 immunostaining, indicating that the net growth rate is lower in metastases relative to primary tumours. Notably, relapsed primaries or those with established metastases had significantly lower proliferative activity than CRCs that were non-metastatic and did not relapse. CONCLUSION: Our results suggest that slow proliferation is a biological characteristic of both liver metastases and those primary tumours with the ability to metastasise. The delineation of the mechanisms underlying the inverse association between proliferation and CRC aggressiveness may be important for the development of new therapeutic strategies.

Slow compressional wave propagation in wet human and bovine cortical bone.

Ultrasonic wave propagation in bovine plexiform and human Haversian bone was studied in the range 0.5 to 15 megahertz. A new longitudinal wave was observed which traveled more slowly than the ordinary longitudinal wave. The slow wave was associated with the dynamics of fluid motion in the pores of bone.

Heterocyst pattern formation controlled by a diffusible peptide.

Many filamentous cyanobacteria grow as multicellular organisms that show a developmental pattern of single nitrogen-fixing heterocysts separated by approximately 10 vegetative cells. Overexpression of a 54-base-pair gene, patS, blocked heterocyst differentiation in Anabaena sp. strain PCC 7120. A patS null mutant showed an increased frequency of heterocysts and an abnormal pattern. Expression of a patS-gfp reporter was localized in developing proheterocysts. The addition of a synthetic peptide corresponding to the last five amino acids of PatS inhibited heterocyst development. PatS appears to control heterocyst pattern formation through intercellular signaling mechanisms.

Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.

Heterodimerization between members of the Bcl-2 family of proteins is a key event in the regulation of programmed cell death. The molecular basis for heterodimer formation was investigated by determination of the solution structure of a complex between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak. The structure and binding affinities of mutant Bak peptides indicate that the Bak peptide adopts an amphipathic alpha helix that interacts with Bcl-xL through hydrophobic and electrostatic interactions. Mutations in full-length Bak that disrupt either type of interaction inhibit the ability of Bak to heterodimerize with Bcl-xL.