Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Association between Introduction of the Diagnosis-Related Groups System for Anal Operation and Length of Stay: Higher Effectiveness at Hospitals with Longer Length of Stay / 보건행정학회지

BACKGROUND: We investigated association between introduction of the diagnosis-related groups (DRG) system for anal operation and length of stay. Also, we investigated how it is different among hospitals with longer length of stay and among hospitals with shorter length of stay before introduction of the DRG system. METHODS: We used data from Health Insurance Review and Assessment which were national health insurance claim data. Total 13,111 cases of anal surgery cases were included which were claimed by hospitals since July 2012 to June 2014. Two-level multivariable regression was conducted to analysis the association between length of stay and characteristics of hospital and patient. RESULTS: Before introducing DRGs, the average length of stay was 5.41 days. After introducing DRGs, average length of stay was decreased to 3.92 days. After introducing DRGs, length of stay has decreased (β=−1.0450, p < 0.0001) and it was statistically significant. Among hospitals which had short length of stay (shorter than mean of length of stay) before introducing DRGs, effect of introducing DRGs was smaller (β=−0.4282, p < 0.0001). On contrary, among hospitals which had long length of stay (longer than mean of length of stay) before introducing DRGs, effect of introducing DRGs was bigger (β=−1.8280, p < 0.0001). CONCLUSION: Introducing DRGs was more effective to hospitals which had long length of stay before introducing DRGs.

The Ability of the Acute Physiology and Chronic Health Evaluation (APACHE) IV Score to Predict Mortality in a Single Tertiary Hospital / 대한중환자의학회지

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) II model has been widely used in Korea. However, there have been few studies on the APACHE IV model in Korean intensive care units (ICUs). The aim of this study was to compare the ability of APACHE IV and APACHE II in predicting hospital mortality, and to investigate the ability of APACHE IV as a critical care triage criterion. METHODS: The study was designed as a prospective cohort study. Measurements of discrimination and calibration were performed using the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test respectively. We also calculated the standardized mortality ratio (SMR). RESULTS: The APACHE IV score, the Charlson Comorbidity index (CCI) score, acute respiratory distress syndrome, and unplanned ICU admissions were independently associated with hospital mortality. The calibration, discrimination, and SMR of APACHE IV were good (H = 7.67, P = 0.465; C = 3.42, P = 0.905; AUROC = 0.759; SMR = 1.00). However, the explanatory power of an APACHE IV score >93 alone on hospital mortality was low at 44.1%. The explanatory power was increased to 53.8% when the hospital mortality was predicted using a model that considers APACHE IV >93 scores, medical admission, and risk factors for CCI >3 coincidentally. However, the discriminative ability of the prediction model was unsatisfactory (C index <0.70). CONCLUSIONS: The APACHE IV presented good discrimination, calibration, and SMR for hospital mortality.

The Ability of the Acute Physiology and Chronic Health Evaluation (APACHE) IV Score to Predict Mortality in a Single Tertiary Hospital / 대한구급학회지

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) II model has been widely used in Korea. However, there have been few studies on the APACHE IV model in Korean intensive care units (ICUs). The aim of this study was to compare the ability of APACHE IV and APACHE II in predicting hospital mortality, and to investigate the ability of APACHE IV as a critical care triage criterion. METHODS: The study was designed as a prospective cohort study. Measurements of discrimination and calibration were performed using the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test respectively. We also calculated the standardized mortality ratio (SMR). RESULTS: The APACHE IV score, the Charlson Comorbidity index (CCI) score, acute respiratory distress syndrome, and unplanned ICU admissions were independently associated with hospital mortality. The calibration, discrimination, and SMR of APACHE IV were good (H = 7.67, P = 0.465; C = 3.42, P = 0.905; AUROC = 0.759; SMR = 1.00). However, the explanatory power of an APACHE IV score >93 alone on hospital mortality was low at 44.1%. The explanatory power was increased to 53.8% when the hospital mortality was predicted using a model that considers APACHE IV >93 scores, medical admission, and risk factors for CCI >3 coincidentally. However, the discriminative ability of the prediction model was unsatisfactory (C index <0.70). CONCLUSIONS: The APACHE IV presented good discrimination, calibration, and SMR for hospital mortality.

The Effect of Mandatory Diagnosis-Related Groups Payment System / 보건행정학회지

BACKGROUND: The voluntary diagnosis-related groups (DRG)-based payment system was introduced in 2002 and the government mandated participation in the DRG for all hospitals from July 2013. The main purpose of this study is to examine the independent effect of mandatory participation in DRG on various outcomes of patients. METHODS: This study collected 1,809,948 inpatient DRG data from the Health Insurance Review and Assessment database which contains medical information for all patients for the period 2007 to 2014 and examined patient outcomes such as length of stay (LOS), total medical cost, spillover, and readmission rate according to hospital size. RESULTS: LOS of patients decreased after DRGs (large hospitals: adjusted odds ratio [aOR], 0.87; 95% confidence interval [CI], 0.78-0.97; small hospitals: aOR, 0.91; 95% CI, 0.91-0.92). The total medical cost of patients increased after DRGs (large hospitals: aOR, 1.22; 95% CI, 1.14-1.30; small hospitals: aOR, 1.22; 95% CI, 1.21-1.23). The results reveals that spillover of patients increased after DRGs (large hospitals: aOR, 1.27; 95% CI, 0.70-2.33; small hospitals: aOR, 1.18; 95% CI, 1.16-1.20). Finally, we found that readmission rates of patients decreased significantly after DRGs (large hospitals: aOR, 0.28; 95% CI, 0.26-0.29; small hospitals: aOR, 0.59; 95% CI, 0.56-0.63). CONCLUSION: The DRG payment system compared to fee-for-service payment in South Korea may be an alternative medical price policy which can reduce the LOS. However, government need to monitor inappropriate changes such as spillover increase. Since this study also is the results based on relatively simple surgery, insurer needs to compare or review bundled payment like new DRG for expansion of various inpatient-related diseases including internal medicine.

Severe Nail Fold Psoriasis Extending from Nail Psoriasis Resolved with Ustekinumab: Suggestion of a Cytokine Overflow Theory in the Nail Unit

Because nail psoriasis is difficult to treat, therapy with many biological drugs has been attempted. Ustekinumab is approved for chronic plaque psoriasis and psoriatic arthritis (PsA), with some trials reporting nail improvement using this agent. A 51-year-old man with severe chronic plaque psoriasis had severe involvement of all fingernails and toenails, with accompanying nail fold psoriasis. He also had PsA of the small joints of the fingers. Despite multiple conventional therapies, the nail lesions did not improve, and his nail psoriasis severity index score was 97. After a fourth ustekinumab injection, most of the fingernail psoriasis was resolved, and only hyperkeratosis remained on both large toenails. Because the nail plate, nail fold, and small joints of the fingers are closely apposed structures within a small area, cytokines produced from the nail units overflow to the nail fold and small joints and can induce nail fold psoriasis and PsA.

Multiple Cavitary Pulmonary Nodules Caused by Mycobacterium intracellulare / 가정의학회지

Nontuberculous mycobacteria (NTM) have been increasingly recognized as an important cause of chronic pulmonary infections. The Mycobacterium avium complex (MAC), which is composed of two species, Mycobacterium avium and Mycobacterium intracelluare, is the most commonly encountered pathogen associated with NTM lung disease. MAC pulmonary infection typically presents in a fibrocavitary form or a nodular bronchiectatic form. However, there have been atypical presentations of MAC pulmonary infections, including solitary pulmonary nodules (SPN). There have been several previous reports of SPN due to MAC infection in the United States, Japan, and Korea. In 2009, Sekine and colleagues reported a case of MAC pulmonary infection presenting with multiple nodules. To date, however, there have been no cases of NTM lung infection with multiple cavitary pulmonary nodules, and neither a fibrotic change nor nodular bronchiectasis. The present case showed a multiple cavitating nodular lung infection due to MAC, which is very rare and different from the typical presentation of MAC pulmonary infections. We also showed that percutaneous transthoracic needle aspiration can be a useful diagnostic tool to evaluate a case of multiple cavitary nodules.

Pumpless extracorporeal interventional lung assist for bronchiolitis obliterans after allogenic peripheral blood stem cell transplantation for acute lymphocytic leukemia / 영남의대학술지

Bronchiolitis obliterans (BO), which is associated with graft-versus-host disease after allogenic hematopoietic stem cell transplantation, is a major obstacle to survival after bone marrow transplantation due to its gradual progress, eventually leading to respiratory failure. Pumpless extracorporeal interventional lung assist (iLA) is effective in treatment of reversible hypercapnic respiratory failure. In this paper, we present a 23-year-old female patient who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia. After 6 months, she complained of shortness of breath and was diagnosed with BO. Five months later, she developed an upper respiratory tract infection that worsened her BO and caused life-threatening hypercapnia. Since mechanical ventilation failed to eliminate CO2 effectively, iLA was applied as rescue therapy. Her hypercapnia and respiratory acidosis showed significant improvement within a few hours, and she was successfully weaned off iLA after 12 days. This is the first case report of iLA application for temporarily aggravated hypercapnia of PBSCT-associated BO followed by successful weaning. This rescue therapy should be considered in ventilator-refractory reversible hypercapnia in BO patients.

Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy / 결핵및호흡기질환

Malignant mesothelioma is a rare malignant neoplasm that arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium. Typically, pleural fluid cytology or closed pleural biopsy, surgical intervention (video thoracoscopic biopsy or open thoracotomy) is conducted to obtain pleural tissue specimens. However, endobronchial lesions are rarely seen and cases diagnosed from bronchoscopic biopsy are also rarely reported. We reported the case of a 77-year-old male who was diagnosed as malignant mesothelioma on bronchoscopic biopsy from obstructing masses of the endobronchial lesion.

Histopathological Findings Are Associated with the Clinical Types of Psoriasis but Not with the Corresponding Lesional Psoriasis Severity Index

BACKGROUND: The assessment of the severity of psoriasis is often subjective because of the lack of quantitative laboratory diagnostic tools. Histopathological examination is the most commonly performed procedure for psoriasis diagnosis; however, it is usually descriptive. Thus, there is currently no quantitative method of determining psoriasis severity. The clinical types of psoriasis are correlated with the severity of the disease, and a lesional severity index, such as the psoriasis severity index (PSI), could be used as a quantitative tool for assessing gross severity. OBJECTIVE: To correlate the histopathological findings of psoriasis with the PSI. METHODS: Psoriatic lesions in 98 patients were evaluated. The lesions were classified into the guttate, papular, small plaque, and large plaque types according to morphology, and were scored according to the PSI. Ten common histopathological features of psoriasis were evaluated for correlation with gross severity. RESULTS: The clinical types of psoriasis showed significant correlations with the histopathological severity. However, the PSI score showed no correlation with histopathological severity. CONCLUSION: In the future, subjective gross assessment should be modified by using objective measuring devices with detailed scales, in order to correlate the findings with the histological severity.

Association of Demographic and Socioeconomic Factors With Risk Factors for Chronic Kidney Disease / 예방의학회지

OBJECTIVES: The goal of this study was to examine the association of various demographic and socioeconomic factors with risk factors for chronic kidney disease (CKD). METHODS: We used nationally representative pooled data from the Korea National Health and Nutrition Examination Survey (KNHANES), 2007-2013. We estimated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation. We defined CKD as a GFR <60 mL/min/1.73 m2, and 1304 of the 45 208 individuals included in the KNHANES were found to have CKD by this definition. The outcome variable was whether individual subjects adhered to the CKD prevention and management guidelines recommended by the Korea Centers for Disease Control and Prevention. The guidelines suggest that individuals maintain a normal weight, abstain from alcohol consumption and smoking, manage diabetes and hypertension, and engage in regular exercise in order to prevent and manage CKD. RESULTS: This study found that individuals with CKD were more likely to be obese and have hypertension or diabetes than individuals without CKD. In particular, male and less-educated CKD patients were less likely to adhere to the guidelines. CONCLUSIONS: Although the prevalence of CKD, as indicated by the KNHANES data, decreased from 2007 to 2013, the prevalence of most risk factors associated with CKD fluctuated over the same time period. Since a variety of demographic and socioeconomic factors are related to the successful implementation of guidelines for preventing and managing CKD, individually tailored prevention activities should be developed.

The Effect of Economic Participatory Change on Unmet Needs of Health Care among Korean Adults / 보건행정학회지

BACKGROUND: The objective of this research is to investigate and provide analysis of the economic participatory change affecting the unmet needs of health care in Korean adults. METHODS: We used Korea health panel 4th and 5th data of 10,261 adults. The method of investigation is threefold. First, We identified the regional factors affecting unmet needs of health care. Second, we analyzed the effect of economic participatory change as it affects the unmet needs of health care. Third, we also investigated whether there were discernable differences between the age subgroups. RESULTS: It was determined that influencing factors included sex, education, economic level, and health status. And after the subgroup analysis of age, we found that the economic participatory change was associated with the economical unmet needs of health care especially for those over 40 years of age. Also the population are facing unemployment enduring particular economic hardship in meeting their medical needs. CONCLUSION: This study finds that there are some policy recommendations for the sake of medical service equality. Medical welfare policy for those 40 years of age and older has been identified as an area that needs improvement. And considering that those 40 years of age and older are facing unemployment enduring particular economic hardship in meeting their medical needs, this study finds a need for government sponsored medical stipends or subsidizing of medical premiums, co-payment, and other fees.

A Case of Malignant Transformation in a Congenital Cystic Adenomatoid Malformation / 대한내과학회지

Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare condition with the potential for malignant transformation. Several cases that presented with malignant changes have been reported worldwide. However, no report about a malignant transformation case in a CCAM in Korea has been published. We report the first patient who had a malignant change in a CCAM. A 32-year-old female underwent a bilobectomy for a cystic lung lesion that was a type 1 CCAM associated with malignant transformation. A biopsy specimen from the resected cystic lesion showed foci of adenocarcinoma.

Differences in the Known Cellular Composition of Benign Pigmented Skin Lesions Reflected in Computer-Aided Image Analysis

BACKGROUND: Computer-aided image analysis (CAIA) has been suggested as an effective diagnostic tool for pigmented skin lesions (PSLs), especially melanoma. However, few studies on benign PSLs have been reported. OBJECTIVE: The purpose of this study was to evaluate benign PSLs with our CAIA software and analyze the differences between the parameters of those lesions. METHODS: By using homegrown CAIA software, we analyzed 3 kinds of PSLs-nevus, lentigo, and seborrheic keratosis. The group of seborrheic keratosis was divided into pigmented seborrheic keratosis, sebolentigine, and hyperkeratotic seborrheic keratosis. The CAIA was used to extract the color, as well as the morphological, textural, and topological features from each image. RESULTS: In line with clinical observations, the objective parameters indicated that nevus was dark and round, lentigo was small and bright, and seborrheic keratosis was large and spiky. The surface of nevus showed the highest contrast and correlation. In topological analysis, the concentricity clearly separated melanocytic lesions from seborrheic keratosis. The parameters of pigmented seborrheic keratosis were between those of typical nevus and seborrheic keratosis. CONCLUSION: We confirmed that definite correlations exist between the subjective differentiation by experts' examination and the objective evaluation by using CAIA. We also found that the morphological differences observed in CAIA were greatly influenced by the composition ratios of keratinocytes and melanocytes, which are already known histopathological characteristics of each PSL.

Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. METHODS: A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. RESULTS: The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. CONCLUSION: In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients.

Tinea Incognito Simulating Herpes Simplex Virus Infection

No abstract available.

The Pattern of Hair Dyeing in Koreans with Gray Hair

BACKGROUND: Hair graying is considered as a part of normal ageing process. Nonetheless, this process raises a significant cosmetic concern, especially among ethnic Korean elderly whose baseline hair color is black. For this reason, Korean elderly dye their hair with frequency despite the risk of dermatologic problems such as allergic contact dermatitis. OBJECTIVE: In this study, the authors investigate the prevalence and pattern of hair dyeing and its relation with scalp diseases in Korea. METHODS: Six hundred twenty subjects (330 men and 290 women) with graying hair were given a questionnaire survery and underwent a physical examination. RESULTS: Of the 620 total, 272 subjects (43.9%) dyed their hair. Hair dyeing was significantly more frequent among women than among men (p<0.001). Subjects from 50 to 69 years of age showed higher prevalence of hair dyeing when compared to either younger or older groups. Subjective self-assessment of the extent of hair graying was associated with increased prevalence of hair dyeing, that is, individuals who feel graying has advanced by more than 20% of the overall hair were much more likely to dye their hair (p<0.001). Hair dyeing did not correlate with either alopecia or scalp disease. CONCLUSION: Our survey has found that the prevalence of hair dyeing is higher among Korean women than men. People in their fifties and sixties and people with more than 20% extent of grayness were more likely to dye their hair than otherwise. Hair dyeing was not associated with any increase in the prevalence of scalp diseases.

Intractable Tufted Angioma Associated with Kasabach-Merritt Syndrome

No abstract available.

Intractable Tufted Angioma Associated with Kasabach-Merritt Syndrome

No abstract available.

Differentiation of Benign Pigmented Skin Lesions with the Aid of Computer Image Analysis: A Novel Approach

BACKGROUND: The differential diagnosis of common pigmented skin lesions is important in cosmetic dermatology. The computer aided image analysis would be a potent ancillary diagnostic tool when patients are hesitant to undergo a skin biopsy. OBJECTIVE: We investigated the numerical parameters discriminating each pigmented skin lesion from another with statistical significance. METHODS: For each of the five magnified digital images containing clinically diagnosed nevus, lentigo and seborrheic keratosis, a total of 23 parameters describing the morphological, color, texture and topological features were calculated with the aid of a self-developed image analysis software. A novel concept of concentricity was proposed, which represents how closely the color segmentation resembles a concentric circle. RESULTS: Morphologically, seborrheic keratosis was bigger and spikier than nevus and lentigo. The color histogram revealed that nevus was the darkest and had the widest variation in tone. In the aspect of texture, the surface of the nevus showed the highest contrast and correlation. Finally, the color segmented pattern of the nevus and lentigo was far more concentric than that of seborrheic keratosis. CONCLUSION: We found that the subtle distinctions between nevus, lentigo and seborrheic keratosis, which are likely to be unrecognized by ocular inspection, are well emphasized and detected with the aid of software.