SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults.

BACKGROUND: In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. METHODS: We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. RESULTS: A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. CONCLUSIONS: Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).

Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway.

The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

Clinical significance of serum YKL-40 in Behçet disease.

BACKGROUND: Serum YKL-40 is an inflammatory biomarker of endothelial dysfunction and may play a role in the inflammatory process of Behçet disease (BD). OBJECTIVES: Serum YKL-40 levels were evaluated in patients with BD in order to identify associations with other inflammatory cytokines and establish laboratory parameters. Serum YKL-40 levels were also compared with BD clinical features and disease activity. METHODS: In total, 112 patients with BD and 45 age- and sex-matched healthy volunteers were included. Disease activity was assessed with BD Current Activity Form score and Electronic Medical Record-based Activity Index (EMRAI) score. RESULTS: Serum YKL-40 levels were significantly higher in patients with BD (median 41·88, range 12·52-171·30 ng mL(-1) ) than in healthy volunteers (median 20·92, range 5·01-64·20 ng mL(-1) ; P < 0·01). The cut-off value for YKL-40 (30·005 ng mL(-1) ) was determined from the receiver operating characteristic curve. EMRAI scores and the proportion of patients in the active phase of BD presenting with two or more major criteria were significantly higher in patients with elevated YKL-40 levels (P = 0·04 and P = 0·04, respectively). A statistically significant elevation in YKL-40 levels was observed in patients with active BD compared with patients with inactive BD (P = 0·05). Serum YKL-40 values were positively correlated with interleukin-6 and EMRAI scores (both P = 0·04), indicating that serum YKL-40 levels are increased in patients with BD and positively correlate with disease activity. CONCLUSIONS: YKL-40 may play a role in the pathophysiology of BD and provide a useful marker for monitoring patients with BD.

External validation of bloodstream infection mortality risk score in a population-based cohort.

A risk score was recently derived to predict mortality in adult patients with Gram-negative bloodstream infection (BSI). The aim of this study was to provide external validation of the BSI mortality risk score (BSIMRS) in a population-based cohort. All residents of Olmsted County, Minnesota, with Escherichia coli and Pseudomonas aeruginosa BSI from 1 January 1998 to 31 December 2007 were identified. Logistic regression was used to examine the association between BSIMRS and mortality. Area under receiver operating characteristic curve (AUC) was calculated to quantify the discriminative ability of the BSIMRS to predict a variety of short-term and long-term outcomes. Overall, 424 unique Olmsted County residents with first episodes of E. coli and P. aeruginosa BSI were included in the study. Median age was 68 (range 0-99) years, 280 (66%) were women, 61 (14%) had cancer and 9 (2%) had liver cirrhosis. The BSIMRS was associated with 28-day mortality (p <0.001) with an AUC of 0.86. There was an almost 56% increase in 28-day mortality for each point increase in BSIMRS (OR 1.56, 95% CI 1.40-1.78). A BSIMRS ≥ 5 had a sensitivity of 74% and a specificity of 87% to predict 28-day mortality with a negative predictive value of 97%. The BSIMRS had AUC of 0.85, 0.85 and 0.81 for 7-, 14- and 365-day mortality, respectively. BSIMRS stratified mortality with high discrimination in a population-based cohort that included patients of all age groups who had a relatively low prevalence of cancer and liver cirrhosis.

CD11a, CD11c, and CD18 gene polymorphisms and susceptibility to Behçet's disease in Koreans.

Lesions of Behçet's disease (BD) show vascular infiltrates of immune cells expressing integrins. ß2 integrins (CD11/CD18) play a major role in cell migration to the inflammatory lesion and also induce cytokine production. Thus, genetic polymorphisms of CD11/CD18 may be associated with the pathogenesis of BD. In this study, nine single nucleotide polymorphisms (SNPs) of the CD11a, CD11c, and CD18 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype analysis in 305 BD patients and 266 healthy controls. The frequencies of genotype rs11574944 CC and haplotype rs11574944C-rs2230433G-rs8058823A in CD11a were significantly lower in BD patients. The frequencies of genotype rs2230429 CC, rs2929 GG, and haplotype rs2230429C-rs2929G in CD11c were higher in BD patients. The frequencies of genotype rs235326CC and haplotype rs2070946A-rs235326C-rs760456G-rs684G in CD18 were significantly higher in the BD patients than in the controls. Other SNPs in CD11a, CD11c, and CD18 gene were not significantly different. Therefore, the major genotype and haplotype of CD11a/CD18 may play a role in decreasing the susceptibility of BD, whereas the major genotype and haplotype of CD11c/CD18 may play a role in increasing the susceptibility of BD.

Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis.

Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.

Immunopathogenic characterization of cutaneous inflammation in Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic inflammatory disease characterized by recurrent oral aphthous and genital ulcers, ocular lesions and cutaneous lesions. Although many studies of cytokine levels in sera of BD patients have been conducted, there are only limited number of studies about the cytokine expression and cellular infiltration in the BD-related skin lesions. OBJECTIVES: To investigate the immunophenotypes and cytokine profiles of BD-related skin lesions. METHODS: Twenty patients who fulfilled the diagnostic criteria for BD with BD-related skin lesions were enrolled in this study. We assessed the histopathological features of BD-related skin lesions by immunohistochemical studies with anti-human CD4, CD8, CD68, FoxP3, CD-11b, IFN-γ and IL-4 antibodies. RESULTS: Immunophenotyping of inflammatory infiltrating cells showed that CD68+ macrophages were the most common type of infiltrated cells in erythema nodosum-like lesions, erythema multiforme-like lesions and Sweet's syndrome-like lesions, whereas neutrophils were the main population of inflammatory infiltrating cells in papulopustular lesions. In all of the four types of BD-related skin lesions, the percentage of CD8+ T cells was higher than that of CD4+ T cells (P < 0.05), and IL-4 expression was stronger than IFN-γ expression (P < 0.05). CONCLUSION: In this study, we assessed the infiltrating inflammatory cells and cytokine expression of acute cutaneous lesions in BD through immunohistochemical staining of BD-related skin lesions. Further studies about the disease activity and the molecular biology underlying the cutaneous inflammation are needed to understand the detailed pathogenesis of BD.

Changing clinical expression of Behçet disease in Korea during three decades (1983-2012): chronological analysis of 3674 hospital-based patients.

BACKGROUND: Behçet disease (BD) is a chronic multisystemic vasculitis affecting blood vessels of any calibre or type. Recent evidence suggests that the clinical expression of BD is lessening. OBJECTIVES: To examine the clinical expression of BD in Korea during the past three decades via a large patient registry. METHODS: Initial manifestations of patients with BD seen at a tertiary referral hospital between 1983 and 2012 were reviewed retrospectively, stratifying patients by decade to compare epidemiological data and cardinal symptoms. RESULTS: In total 3674 patients with BD were reviewed. Significant proportional declines occurred with respect to male sex, complete type BD and major presenting features (genital ulcers, ocular involvement and skin lesions), whereas the mean patient age rose progressively, as did the frequencies of joint, gastrointestinal and central nervous system manifestations (all P < 0·0001). CONCLUSIONS: During the past three decades, clinical expression of BD in Korea has changed, resulting in fewer instances of complete type disease, declining male propensity, and shifting patterns of organ involvement.

Both the sera of patients with Behçet's disease and Streptococcus sanguis stimulate membrane expression of hnRNP A2/B1 in endothelial cells.

OBJECTIVES: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been identified as a target antigen of anti-endothelial cell immunglobulin (Ig)A antibodies in patients with Behçet's disease (BD). The aim was to investigate the effects of the sera from BD patients and Streptococcus sanguis on the subcellular expression of hnRNP A2/B1 in human dermal microvascular endothelial cells (HDMECs). METHOD: The sera of BD patients and healthy controls (HC) as well as cultured S. sanguis were used to stimulate HDMECs. Subcellular fractions were obtained from stimulated HDMECs and were subjected to immunoblot analyses. The distribution of hnRNP A2/B1 was investigated by immunocytochemistry and direct immunofluorescence study was performed in biopsy specimens of mucosal ulcers from BD patients. RESULTS: BD patients' sera increased the membrane expression of hnRNP A2/B1 in HDMECs after 12 and 24 h of incubation compared with HDMECs incubated with endothelial cell culture media and HC sera. S. sanguis also increased hnRNP A2/B1 in the cellular membrane. hnRNP A2/B1 mRNA level was also significantly upregulated in HDMECs incubated with BD patients' sera and S. sanguis. Immunocytochemistry demonstrated marked expression of hnRNP A2/B1 in the cytoplasm and cellular membrane of HDMECs incubated with BD patients' sera or S. sanguis. In addition, direct immunofluorescence experiments revealed the co-localization of serum IgA antibodies and monoclonal antibodies (mAbs) against hnRNP A2/B1 in tissue sections from ulcers of BD patients. CONCLUSIONS: Our data indicate that both the sera of BD patients with active disease and S. sanguis infection are inflammatory stimuli that can induce membranous hnRNP A2/B1 expression in HDMECs.

Behçet's disease in concurrence with psoriasis.

BACKGROUND: Behçet's disease (BD) and psoriasis are chronic inflammatory diseases characterized by multisystemic vasculitis and epidermal hyperplasia respectively. Although it has been found that the pathogenesis of BD and psoriasis share common perspectives, reports of patients who have both diseases in concurrence are rare. OBJECTIVES: To analyse and evaluate the clinical manifestations of BD patients who have psoriasis together. METHODS: Retrospective evaluation of the medical records of nine BD patients who were also diagnosed with psoriasis at the BD Specialty Clinic of Severance Hospital was carried out. We analysed the characteristics of patients and the clinical activity of both diseases, and also the effect of the treatment of one disease against the other. RESULTS: Of the nine BD patients who also had psoriasis, male to female ratio was 1 : 2. Two (22.2%) patients had a complete type of BD and seven (77.8%) patients had an incomplete type of BD. For the psoriatic lesions, all nine (100%) patients were diagnosed as psoriasis vulgaris. Five (55.6%) patients had BD as the preceding disease and four (44.4%) patients had psoriasis as the preceding. All five patients who formerly developed BD followed by psoriasis had an active state of BD, but the activity of psoriasis of all nine patients was minimal to average. CONCLUSION: In this study, we evaluated the clinical manifestations of nine patients who had BD and psoriasis together. Although the exact pathogenesis remains unclear, there might be some influence by each disease to the other between BD and psoriasis.

Serum IgA reactivity against GroEL of Streptococcus sanguinis and human heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behçet disease.

BACKGROUND: Infectious agents, especially Streptococcus sanguinis and herpes simplex virus, have long been postulated as major triggering factors for Behçet disease (BD). OBJECTIVES: To identify an anti-S. sanguinis antigen reacting with serum IgA antibody in patients with BD. METHODS: We detected a target protein by proteomics analysis and evaluated serum IgA reactivity of 100 patients with BD against the identified streptococcal target protein and human heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1. Homologous epitope sequences between the streptococcal target protein and human hnRNP A2/B1 were also evaluated. RESULTS: Four protein bands were detected by immunoprecipitation, and chaperonin GroEL was identified by a proteomics analysis. Reactivity of serum IgA against recombinant S. sanguinis GroEL was detected in 77 of 100 patients with BD (77%) and in 21 of 70 healthy controls (30%). In addition, reactivity of serum IgA against human recombinant hnRNP A2/B1 was seen in 79 of 100 patients with BD (79%) and in eight of 70 healthy controls (11%). Among the eight distinctive epitopes with significant homology between S. sanguinis GroEL and human hnRNP A2/B1, the serum IgA reactivity of patients with BD was markedly higher with epitope 3 (hnRNP A2/B1 peptide 33-46 and GroEL peptide 57-70) and epitope 6 (hnRNP A2/B1 peptide 177-188 and GroEL peptide 347-358). CONCLUSION: We identified an S. sanguinis GroEL protein as a target of serum anti-S. sanguinis IgA antibody reactivity in patients with BD. In addition, patients with BD exhibited serum IgA reactivity against homologous epitope regions between S. sanguinis GroEL and human hnRNP A2/B1.

Learning from HSV-infected mice as a model of Behçet's disease.

Several animal models of Behçet's disease (BD) have been proposed according to putative etiology. Among these models, the herpes simplex virus (HSV)-induced model produced the most similar disease attributes observe in patients. Inoculation of HSV type 1 to the scratched earlobe of mice produced the appropriate symptoms, including oral, genital, and skin ulcers, eye lesions, arthritis, and intestinal involvement. This HSV-induced BD model is the only continuously used model, to which various therapeutic modalities have been applied.

Diagnosis of tuberculosis and drug resistance: what can new tools bring us?

This is an exciting time for tuberculosis (TB) diagnostics. The technology for rapid diagnosis of TB and rifampicin (RMP) resistance in pulmonary sputum smear-positive specimens is well advanced, and assays have high specificity with good sensitivity. Nevertheless, the current sensitivity of TB detection means that these assays still cannot replace the standard diagnostic methods for TB or conventional drug susceptibility testing (DST). In extra-pulmonary specimens, the performance of molecular tools varies and should be considered separately for each specimen type. Evidence for the use of these assays for TB and drug resistance detection in individuals co-infected with TB and the human immunodeficiency virus (HIV) is limited. As the positive predictive value for RMP resistance reaches ≥ 90% only when the prevalence of RMP resistance in new TB patients is >15%, which is rare globally, many cases with such resistance will be false-resistant, emphasising the need for a secondary confirmative test. Similarly, increased (or incorrect) diagnosis of TB may compromise programme effectiveness by increasing the numbers of individuals requiring anti-tuberculosis treatment, unless it is carefully planned. For the future, 1) assays with greater sensitivity for TB detection are needed; 2) rapid diagnostics for paediatric TB are important, and there is a need for carefully designed studies, including those involving HIV-positive children; 3) more clinical data need to be obtained from longitudinal studies, especially related to the influence of rapid diagnostics on disease outcome; and 4) point-of-care tests using untreated sputum, blood or urine and little or no equipment would be of immeasurable benefit. Although great progress has been made, we are not there yet.

Matrix metalloproteinase-2, -9, -12, and tissue inhibitor of metalloproteinase 2 gene polymorphisms and cutaneous expressions in patients with Behçet's disease.

Matrix metalloproteinases (MMPs) induce leukocyte migration into inflammation sites that lead to either promotion or repression of inflammation by activating or inactivating cytokines. An increased level of MMP-9 and a decreased level of MMP-2 have been observed in Behçet's disease (BD). This study was performed to analyze the relationship between MMP-2, -9, -12 and the tissue inhibitor of metalloproteinase-2 (TIMP-2) promoter polymorphisms in developing BD. The expression of MMP-2 and -9 was also evaluated in the skin of BD. The MMPs and TIMP-2 polymorphisms were confirmed by using polymerase chain reaction-restriction fragment length polymorphism in 251 BD and 312 controls. Cutaneous expression of MMP-2 and -9 in 17 BD patients with erythema nodosum (EN) or EN-like lesion was compared with 14 patients with idiopathic EN by immunohistochemical stains. The frequency of MMP-2-1575*G/*G and MMP-2-735*C/*C genotypes was shown to be lower in BD, whereas MMP-9-1562*C/*C was significantly higher in BD compared with the controls. The frequency of common haplotype MMP-2-1575*G -735*C was significantly lower in BD patients than in controls (P = 0.0046, permutation P = 0.009). No significant differences were observed between BD and controls in the allele and genotype frequencies of MMP-12-82A>G or TIMP-2-418G>C polymorphisms. The tissue expression of MMP-2, shown by immunohistochemistry, was significantly lower in BD compared with the controls. However, the expression of MMP-9 was significantly higher in BD. These results suggest that MMP-2 and -9 could each modulate the development of BD in opposite directions. Major genotypes of the MMP-2-1575*G/*G and MMP-2-735*C/*C and the common MMP-2-1575*G -735*C haplotype may provide some protection against development of BD, while MMP-9-1562*C/*C may promote the disease. The reciprocal expression of MMP-2 and -9 in the skin tissue of BD was also confirmed.

Increased retinol-binding protein (RBP) 4 and anti-RBP4 antibody in alopecia areata.

BACKGROUND: Neither the underlying pathogenesis of alopecia areata (AA) nor the molecular mechanisms leading to hair loss have been fully elucidated. OBJECTIVES: To compare the protein profiles of sera obtained from patients with AA with those from healthy controls. METHODS: Protein profiles of sera obtained from subjects with AA and healthy controls were compared using proteomics techniques. Serum levels of the identified protein were quantified by specific enzyme-linked immunosorbent assay (ELISA). The relative serum reactivities of the recombinant human protein were compared between patients with AA and healthy controls using Western blots and double indirect immunofluorescence. RESULTS: The upregulated expression of retinol-binding protein (RBP) 4 was identified, and RBP4 ELISA demonstrated significantly increased serum levels of RBP4 among subjects with AA when compared with healthy controls. Western blots using recombinant human RBP4 and the sera from both groups presented serum reactivity of antihuman recombinant RBP4 IgG antibodies in 10/15 subjects with AA (67%) and 2/15 healthy controls (13%). Double indirect immunofluorescence demonstrated merged fluorescence signals of serum anti-RBP4 IgG antibodies and monoclonal antibodies to RBP4 in subjects with AA on the outer root sheath and companion layer. CONCLUSIONS: Our data demonstrate that AA is associated with increased serum levels of RBP4 and positive IgG immunoreactivity against recombinant human RBP4. These results suggest that the major components for the retinoic acid biosynthesis pathway may be crucially involved in the pathogenic process of AA.

Major arterial aneurysms and pseudoaneurysms in Behçet's disease: results from a single centre.

OBJECTIVE: Behçet's disease (BD) with arterial involvement is closely correlated with mortality and morbidity due to life-threatening complications such as arterial occlusion and aneurysm rupture. We aimed to determine the clinical characteristics of BD patients with aneurysms and pseudoaneurysms in the major arterial systems. METHODS: Medical records of 30 BD patients diagnosed with aneurysms or pseudoaneurysms in the major arterial systems were reviewed to determine the clinical characteristics of BD, the sites and types of arterial aneurysms or pseudoaneurysms, laboratory test results, and response to treatment. RESULTS: A total of 47 aneurysms and pseudoaneurysms (32 saccular aneurysms, eight fusiform aneurysms, and seven pseudoaneurysms) were detected in 30 patients. Most aneurysms and pseudoaneurysms (27 patients, 90%) had not ruptured. Symptomatic lesions presented in 21 patients (70%), and asymptomatic lesions were incidentally detected in nine (30%). Ten of the 30 patients (33.3%) presented two or more aneurysmal lesions. Recurrence was observed in five patients (16.7%) after treatment with stent graft (n = 3), graft interposition (n = 1), or graft embolization (n = 1). CONCLUSION: We suggest that BD patients diagnosed with major arterial aneurysms should be further evaluated to detect possible associated venous or arterial thrombosis formations or aneurysmal lesions at other sites.

Recurrent tuberculosis in Denmark: relapse vs. re-infection.

SETTING: Denmark, a country with a low-incidence of tuberculosis (TB). OBJECTIVE: To analyse the proportion of relapse vs. re-infection and to compare selected characteristics between the two subgroups. DESIGN: A population-based cohort study. All 4154 Mycobacterium tuberculosis isolates from patients in Denmark genotyped by insertion sequence 6110 restriction fragment length polymorphism were followed for recurrent TB over 13.5 years. Recurrent cases were classified as relapse or re-infection by genotype patterns in initial and serial disease episodes. RESULTS: Recurrent TB was found in 73 (1.8%) cases. Identical M. tuberculosis genotypes in initial and serial episodes were found in 54 (1.3%), indicating relapse, whereas different genotypes, representing re-infection, were found in 19 (0.5%) cases. Cavitary TB in the initial episode was significantly associated with relapse (OR 4.6, 95%CI 1.1-26.9) compared to re-infection. CONCLUSION: The rate of recurrent TB is low in Denmark. Comparing selected characteristics between the relapse and re-infection subgroups revealed that only the presence of cavitary disease was associated with relapse. Although recurrent TB was rarely due to re-infection, the risk of re-infection increased with time.

Efficacy and safety of 1064-nm Q-switched Nd:YAG laser with low fluence for keloids and hypertrophic scars.

BACKGROUND: Several treatment modalities using laser devices have been used for the treatment of keloids and hypertrophic scars with various therapeutic outcomes. OBJECTIVE: The purpose of this study was to describe the efficacy and safety of 1064-nm Q-switched (QS) Nd:YAG laser with low fluence on keloids and hypertrophic scars. METHODS: Keloids and hypertrophic scars located at 21 anatomic sites in 12 Korean patients (10 men and 2 women; mean age 23.8 years, range 21-33) were treated using 1064-nm QS Nd:YAG laser with low fluence at 1-2 week intervals. Treatment settings were 1.8-2.2 J/cm(2), 7-mm spot size and 5-6 passes with appropriate overlapping. RESULTS: Follow-up data collected 3 months after the final treatment revealed decreases in the mean score for the following lesion characteristics: pigmentation from 1.8 to 1.2; vascularity from 1.4 to 1.0; pliability from 3.0 to 2.0 and height from 2.3 to 1.8. The modified Vancouver General Hospital Burn Scar Assessment score decreased from 8.6 to 5.9 (P < 0.0001). Observed side-effects were a mild prickling sensation during treatment, and mild post-treatment erythema, both of which resolved within few hours. CONCLUSION: Our results demonstrate that QS Nd:YAG laser with low fluence may be used for the treatment of keloids and hypertrophic scars.