Purpose: We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). Methods: A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48–72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. Results: Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). Conclusion D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
Apoptosis ; Arm ; Bevacizumab ; Capecitabine ; Cell Aging ; Colorectal Neoplasms ; Creatine Kinase ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Liver ; Simvastatin ; Tablets ; Treatment Outcome

Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT. Whereas the initial QF-CMV results during the early phase of CMV infection did not correlate with the course of the corresponding infection, the QF-CMV results post resolution of the first CMV infection correlated with the recurrence of CMV infection until 12 months post allo-HSCT; no recurrent infections occurred in the four QF-CMV-positive patients, while recurrent infections manifested in five of eight QF-CMV-negative (62.5%) and all three QF-CMV-indeterminate patients (P=0.019). In spite of the small number of patients examined, this study supports the potential application of monitoring CMV-specific T-cell immunity using the QF-CMV assay to predict the recurrence of CMV infection in pediatric allo-HSCT recipients.
Cytomegalovirus ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Mortality ; Pilot Projects ; Prospective Studies ; Recurrence ; T-Lymphocytes

Cerebral air embolism is an uncommon disorder, but it can result in significant morbidity and even mortality. Cerebral air embolism during esophago-gastro-duodenoscopy is also rare, but has in recent years been repeatedly reported. We report here a patient with cerebral infarction due to air embolism during endoscopic variceal ligation in liver cirrhosis. The patient was later confirmed to have patent foramen ovale. To our knowledge, this is the first report of such a complication with underlying patent foramen ovale and portal hypertension, who did no have underlying malignancy

BACKGROUND: Asthma patients may experience acute episodic exacerbation. The guidelines recommend that written action plan should be given to asthma patients. However, no one can predict when and where acute exacerbation will happen. As people carry smart phone almost anytime and anywhere, smartphone application could be a useful tool in asthma care. We evaluated the feasibility of the ubiquitous healthcare system of asthma care using a smartphone application (snuCare) based on the self-management guideline or action plan. METHODS: Forty-four patients including fragile asthmatics were enrolled from Seoul National University Bundang Hospital between December 2011 and February 2012. They were randomly assigned into application user (n = 22) or application nonuser group (n = 22). We evaluated user-satisfaction, and clinical parameters such as asthma control, Quality of Life Questionnaire for Adult Korean Asthmatics, and the adherence of patients. RESULTS: The characteristics were similar at baseline between the 2 groups except those who treated with short-term systemic steroid or increased dose of systemic steroid during previous 8 weeks (user vs. nonuser: 31.8% vs. 4.5%, p = 0.020). Total of 2,226 signals was generated during 8 weeks including 5 risky states. After eight weeks, the users answered that it was very easy to use the application, which was shown in highest scores in terms of satisfaction (mean ± standard deviation, 4.3 ± 0.56). Seventy-three percent of patients answered that the application was very useful for asthma care. User group showed improved the adherence scores (p = 0.017). One patient in application user group could avoid Emergency Department visit owing to the application while a patient in nonuser group visited Emergency Department. CONCLUSION: The ubiquitous healthcare system using a smartphone application (snuCare) based on the self-management guideline or action plan could be helpful in the monitoring and the management of asthma.
Adult ; Asthma ; Delivery of Health Care ; Emergency Service, Hospital ; Humans ; Morinda ; Quality Control ; Self Care ; Seoul ; Smartphone ; Telemedicine

Yokenella regensburgei, a member of the family Enterobacteriaceae, is rarely isolated in humans. Here, we report a 71-year-old man with diabetic foot infection from which Y. regensburgei was isolated. Following debridement and disarticulation of the foot, an exudate specimen was obtained, from which Gramnegative bacilli were recovered. The organism was identified as Y. regensburgei using the Vitek 2 system (bioMerieux, USA) and 16S rRNA and gyrB gene sequencing. To our knowledge, this is the first case of Y. regensburgei isolation in Korea.
Aged ; Debridement ; Diabetic Foot* ; Disarticulation* ; Enterobacteriaceae ; Exudates and Transudates* ; Foot ; Humans ; Korea* ; Sequence Analysis, DNA ; Wounds and Injuries*

OBJECTIVE: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea. METHODS: Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system. RESULTS: A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%). CONCLUSION: Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.
Adrenal Cortex Hormones ; Anti-Bacterial Agents ; Back Pain ; Betamethasone ; Calcium Channel Blockers ; Dexamethasone ; Diagnosis ; Female ; Humans ; Korea ; Magnesium Sulfate ; Muscle Cramp ; Obstetric Labor, Premature* ; Physician's Practice Patterns ; Pregnancy ; Pregnancy Outcome ; Pregnant Women ; Premature Birth ; Retrospective Studies* ; Tocolysis ; Tocolytic Agents ; Uterine Contraction ; Vaginal Discharge

BACKGROUND: Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation. OBJECTIVE: We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor. METHODS: Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing. RESULTS: The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci. CONCLUSION: The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.
Adult ; Asthma ; Child ; DNA Methylation ; DNA ; Healthy Volunteers ; Humans ; Interferon Type I ; Interferons ; Male ; Methylation ; Polymerase Chain Reaction ; Rhinovirus ; RNA, Messenger

Stenotrophomonas maltophilia is an emerging pathogen associated with morbidity and mortality in hospitalized patients. The treatment of S. maltophilia infection is challenging because clinical isolates are frequently resistant to most antimicrobial agents except trimethoprim-sulfamethoxazole (TMP-SMX). S. maltophilia osteomyelitis is a rare disease and requires a prolonged treatment with TMP-SMX. Here, we report an interesting case of a patient with S. maltophilia osteomyelitis who developed a delayed hypersensitivity reaction during TMP-SMX treatment and successfully treated after desensitization. TMP-SMX desensitization should be considered in patients with hypersensitivity to TMP-SMX, especially when there are no effective alternative drugs in S. maltophilia infection.
Anti-Infective Agents ; Desensitization, Immunologic ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Mortality ; Osteomyelitis* ; Rare Diseases ; Stenotrophomonas maltophilia ; Trimethoprim, Sulfamethoxazole Drug Combination*