A Case of Generalized Lichen Sclerosus et Atrophicus

A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow-band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient.     

Educational and decision-support tools for asthma-management guideline implementation

Many international and national asthma guidelines are now available in large parts of the world, but they are not yet implemented appropriately. There is a gap between scientific evidence-based medicine and real clinical practice. Implementation of guidelines is highly complex. Special strategies are needed to encourage guideline-based, high-quality care. It is important to understand the contents, the format, and the learning strategies which physicians prefer for the dissemination of guidelines. Physicians prefer more concise and immediately available guidelines that are practical to use. Thus, asthma guidelines should be disseminated as convenient and easily accessible tools. Various education programs and decision-support tools have been designed and applied to the clinical management of asthma to solve these challenging problems. Many of them have been shown to be effective at increasing physicians' knowledge and adherence to asthma guidelines and improving patients' clinical outcomes. These educational and decision-support tools are expected to contribute to a narrowing of the gap between asthma guidelines and practice/implementation of the guidelines.     

Comparison of the Child-Turcotte-Pugh classification and the model for end-stage liver disease score as predictors of the severity of the systemic inflammatory response in patients undergoing living-donor liver transplantation

The aim of this study was to evaluate and compare the Child-Turcotte-Pugh (CTP) classification system and the model for end-stage liver disease (MELD) score in predicting the severity of the systemic inflammatory response in living-donor liver transplantation patients. Recipients of liver graft were allocated to a recipient group (n = 39) and healthy donors to a donor group (n = 42). The association between the CTP classification, the MELD scores and perioperative cytokine concentrations in the recipient group was evaluated. The pro-inflammatory cytokines measured included interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; the anti-inflammatory cytokines measured included IL-10 and IL-4. Cytokine concentrations were quantified using sandwich enzyme-linked immunoassays. The IL-6, TNF-α, and IL-10 concentrations in the recipient group were significantly higher than those in healthy donor group patients. All preoperative cytokine levels, except IL-6, increased in relation to the severity of liver disease, as measured by the CTP classification. Additionally, all cytokine levels, except IL-6, were significantly correlated preoperatively with MELD scores. However, the correlations diminished during the intraoperative period. The CTP classification and the MELD score are equally reliable in predicting the severity of the systemic inflammatory response, but only during the preoperative period.     

Predictive accuracy of a health risk appraisal program using mortality risk age in 116,927 Korean men

Health risk appraisal (HRA) is a tool for determining health risk factors and motivating individuals to maintain a healthy lifestyle. We performed this study to describe the HRA algorithm and evaluate the accuracy of an HRA program for 10-yr mortality prediction in Korean men. We used data derived from periodic health examinations of 116,927 male public officials and school personnel aged 20 or older. Risk age and the difference between risk age and calendar age were calculated. We obtained the hazard ratio (HR) of 10-yr mortality according to the calculated age difference. Of the 116,927 subjects, 1,900 (1.6%) died during the 10 yr after the 1992 medical examinations. The HR of 10-yr mortality increased significantly with age difference. Compared with the HR in the reference group (age difference below 2 yr), the HR in the group with a 2- to 6-yr age difference was 1.20 (95% confidence interval [CI]: 1.05 to 1.38) and HR in the group with more than 7-yr age difference was 1.35 (95% CI: 1.14 to 1.75). Risk age is a relatively good predictor of 10-yr mortality in Korean men and may be useful in identifying high-risk middle-aged men for health interventions.     

Therapy-related myelodysplastic syndrome/acute myeloid leukemia with del(7)(q22) in a patient with de novo AML

A 55-year-old Korean woman was initially diagnosed with acute myelomonocytic leukemia (AML). After induction chemotherapy was performed using cytarabine, idarubicin, and G-CSF, complete remission (CR) was subsequently achieved following reinduction chemotherapy using the same chemotherapeutic agents. Thirty-six months after the initial CR, an increase in immature cells (up to 12.0%) was observed in the patient's bone marrow. Because chromosome analysis revealed a karyotype of 46,XX,del(7)(q22) in all of the analyzed cells, the patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Although the patient subsequently received chemotherapy and G-CSF for neutropenia, t-MDS rapidly progressed after 3 months to therapy-related acute myeloid leukemia (t-AML). Although very rare, de novo AML can progress to a secondary MDS/AML with del(7q) after chemotherapy with cytarabine, idarubicin, and G-CSF. Further investigation into the role of genes located in 7q22 may provide more information about the mechanisms of leukemogenesis.     

DNA methylation profile during multistage progression of pulmonary adenocarcinomas

Multiple genetic and epigenetic alterations are known to be involved in the carcinogenesis of peripheral pulmonary adenocarcinoma (ADC). However, epigenetic abnormalities have not been extensively investigated in the following multistage progression sequence: atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to invasive ADC. To determine the potential role of promoter methylation during ADC development of the lung, we examined methylation status in 20 normal, 20 AAH, 30 AIS, and 60 ADC lung tissues and compared methylation status among the lesions. The MethyLight assay was used to determine the methylation status of 18 CpG island loci, which were hypermethylated in ADC compared to noncancerous lung tissues. The mean number of methylated CpG island loci was significantly higher in ADC than in AAH and AIS, (p < 0.003 between ADC and AAH, p < 0.005 between ADC and AIS). Aberrant methylation of HOXA1, TMEFF2, and RARB was frequently observed in preinvasive lesions, including AAH and AIS. Furthermore, methylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was significantly more frequent in invasive ADC than AAH or AIS. Our results indicate that epigenetic alterations are involved in the multistep progression of pulmonary ADC development, and aberrant CpG island methylation accumulates during multistep carcinogenesis. In addition, aberrant methylation of HOXA1, TMEFF2, and RARB occurred in preinvasive lesions, which indicates that epigenetic alterations of these genes are involved in the early stages of pulmonary ADC development. In contrast, hypermethylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was more frequent in invasive ADC than in preinvasive lesions, which indicates that methylation of these genes occurs later during tumor invasion in the AAH–AIS–ADC sequence.     

Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC) class I expression by increasing interferon-gamma (IFN-gamma)

Tumor immunity is primarily mediated by cells as CD8+ cytotoxic T lymphocytes (CTL) recognize tumor antigen by MHC class I molecules. But most tumors are associated with a decreased expression of MHC class I to escape the antitumor immunity of the host. Our previous data have demonstrated that MPL has an antitumor effect on metastatic lung cancer of B16 melanoma with enhancing cytotoxicity due to increase of IFN-gamma and IL-2, and decrease of IL-4, which indicates the stimulation of type 1 helper T cells (Th1). To determine the effects of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha on MHC class I expression of B16 melanoma cells, we evaluated the expression of MHC class I molecules with treatments of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha by flow cytometry. The supernatant of MPL-treated spleen cells in vitro upregulated the expression of MHC class I molecules of B16 melanoma cells compared to the control supernatant of spleen cells. The MHC class I expression of B16 melanoma cells treated with IFN-gamma, but not TNF-alpha or IL-1 alpha, increased in a time-dependent manner. In conclusion, MPL upregulated MHC class I expression of B16 melanoma cells by activating spleen cells via IFN-gamma. These data suggest that increased IFN-gamma by MPL is responsible for the upregulation of MHC class I expression to augment cytotoxicity. Therefore, we suggest that MPL could play an important role in immunotherapy.     

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome

BackgroundThe mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS.MethodsThe RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls.ResultsPatients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered.ConclusionThe patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Deformation-induced ω phase in modified Ti–29Nb–13Ta–4.6Zr alloy by Cr addition

For spinal-fixation applications, implants should have a high Young’s modulus to reduce springback during operations, though a low Young’s modulus is required to prevent stress shielding for patients after surgeries. In the present study, Ti–29Nb–13Ta–4.6Zr alloy (TNTZ) with a low Young’s modulus was modified by adding Cr to obtain a higher deformation-induced Young’s modulus in order to satisfy these contradictory requirements. Two newly designed alloys, TNTZ–8Ti–2Cr and TNTZ–16Ti–4Cr, possess more stable β phases than TNTZ. These alloys consist of single β phases and exhibit relatively low Young’s moduli of <65 GPa after solution treatment. However, after cold rolling, they exhibit higher Young’s moduli owing to a deformation-induced ω-phase transformation. These modified TNTZ alloys show significantly less springback than the original TNTZ alloy based on tensile and bending loading–unloading tests. Thus, the Cr-added TNTZ alloys are beneficial for spinal-fixation applications.