Purpose: Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed. Materials and Methods: The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor. Results: The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells. Conclusion HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

Purpose: To compare the results of lacrimal syringing performed in clinical practice and under general anesthesia, and the clinical efficacy of lacrimal syringing under general anesthesia before endoscopic dacryocystorhinostomy and dacryoscintigraphy. Methods: The study included 148 eyes of 82 patients who underwent endoscopic dacryocystorhinostomy and silicone tube intubation from August 2018 to April 2019. The patients were examined with lacrimal syringing in clinical practice and re‐examined under general anesthesia. Based on the change in lacrimal syringing, the patients were assigned to inconsistent and consistent groups. The inconsistent group was subclassified into complete (‘regurgitation’ of lacrimal syringing changes to a ‘passage’ pattern) and partial improvement groups (the degree of regurgitation improves under general anesthesia). Results: Twenty (13.5%) eyes showed inconsistent results of lacrimal syringing performed in clinical practice and under general anesthesia; all showed improved passage under general anesthesia. The surgical results did not differ significantly (p = 0.336) between the consistent and inconsistent groups, but did between the complete and partial improvement groups (p < 0.01). Conclusions Lacrimal syringing under general anesthesia may enable an accurate preoperative diagnosis of the degree of obstruction. The combined results of dacryoscintigraphy and lacrimal syringing performed in clinical practice and under general anesthesia allow surgeons to evaluate the lacrimal drainage anatomy precisely and may be useful for predicting the functional success of endoscopic dacryocystorhinostomy.

Objective: Decompressive craniectomy (DC) is one of the treatment modalities in severe traumatic brain injury (TBI), however, there was a lack of evidence for optimal craniectomy size. The authors aimed to investigate optimal DC size and analyze clinical outcome according to craniectomy size. Methods: We retrospectively reviewed the medical data of 87 patients with a space occupying lesion following TBI who underwent unilateral DC. Craniectomy size was measured by anterior-posterior (AP) diameter and surface estimate (SE). Mortality, clinical outcome, and complications were collected and analyzed according to craniectomy size. Results: Nineteen patients (21.8%) died and 35 patients (40.2%) had a favorable outcome at last follow-up (a mean duration, 30.3±39.4 months; range, 0.2–132.6 months). Receiver operating curve analyses identified AP diameter more than 12.5 cm (area under the curve [AUC]=0.740; p=0.002) and SE more than 98.0 cm2 (AUC=0.752;p=0.001) as cut-off values for survival, and AP diameter more than 13.4 cm (AUC=0.650; p=0.018) and SE more than 107.3 cm2 (AUC=0.685; p=0.003) for favorable outcome. Large craniectomy resulted in a significantly lower mortality rate and a higher rate of favorable outcome than small craniectomy (p=0.005 and p=0.014, respectively). However, procedure related bleeding occurred more frequently in the large craniectomy group (p=0.044). Conclusion Unilateral DC size is associated with clinical outcome of patients with a space occupying lesion following severe TBI. Large craniectomy is needed for survival and favorable outcome.

PURPOSE: This study was to investigate the effect of instability on the activation of lower limb muscles during lunge exercise. METHODS: The study subjects were healthy twenties and were selected to have no orthopedic or neurological diseases. 1) Flat lunge exercise (Lunge 1, 2) Lunge exercise on TOGU (Lunge 2, 3) Holding the olympic bar and moving the lunge on TOGU (Lunge 3, 4) Holding the Surge and moving the lunge on TOGU (Lunge 4). Through the above four actions, we can see how the top-down instability influences the lower limb unlike the Bottom-up instability. EMG attachment sites were gluteus medius, vastus medialis, gastrocnemius, tibialis anterior. RESULTS: These result suggest that exercise using Lunge 4 activity was the highest in muscle activity compared to other exercises, but vastus medialis showed the highest muscle activity in Lunge 2 exercise(p<0.05). CONCLUSION This study showed the muscular activity of the lower extremities according to the lunge exercise using the instability tools.

PURPOSE: To analyze the causes, success rate, and the changes of Jones tube length in endoscopic conjunctivodacryocystorhinostomy (CDCR) reoperation cases. METHODS: The medical records of 40 patients (41 eyes, a total of 52 cases) who underwent reoperation of CDCR with Jones tube reinsertion using an endoscope from January 2013 to December 2018 were retrospectively reviewed. We analyzed the success rate, causes of reoperation, changes in lengths of used tubes, and the average interval times between operations. RESULTS: The most common cause of reoperation was medial tube migration (53.8%). As in other causes, tube loss (17.3%), obstructions related with conjunctival overgrowth or granulation (13.46%), lateral tube migration (11.53%), iatrogenic removal (1.92%), and acute dacryocystitis (1.92%) followed. In patients with medial tube migration, the average tube length used in reoperations decreased by approximately 1.11 mm compared to prior operations. In cases of lateral tube migration, the average tube length increased approximately 1.00 mm after the reoperation. The success rate of reoperations was 78.04%. The average interval time between the initial operation and the first reoperation was 52 months. In cases with several reoperations, the interval time decreased as the number of reoperations increased. CONCLUSIONS Because medial tube migration was found to be the most common cause of reoperations, it should be considered as a potential problem when performing surgery. The changes in the lengths of inserted Jones tubes were related to certain types of complication, which affected the prognoses. In endoscopic CDCR reoperations, the success rate was favorable. In recurrent cases, the average interval time between reoperations decreased as the number of operations increased.

Intramural hematoma of the gastrointestinal tract is a rare disease entity. Pancreatitis-induced intramural gastric hematoma (IGH) is far more seldom reported. Here, we report a rare case of a giant IGH occurring as a delayed complication of pancreatitis in a 51-year-old man. The diagnosis was made using computed tomography (CT) and endoscopic ultrasonography. The patient was conservatively managed, and follow-up abdominal CT showed marked decreases in the size of the IGH.

PURPOSE: Breast cancer has a high prevalence in Korea. To achieve personalized therapy for breast cancer, long-term follow-up specimens are needed for next-generation sequencing (NGS) and multigene analysis. Formalin-fixed paraffin-embedded (FFPE) samples are easier to store than fresh frozen (FF) samples. The objective of this study was to optimize RNA extraction from FFPE blocks for NGS. METHODS: RNA quality from FF and FFPE tissues (n=5), expected RNA amount per unit area, the relationship between archiving time and quantity/quality of FFPE-extracted RNA (n=14), differences in quantitative real-time polymerase chain reaction (qRT-PCR) and NGS results, and comparisons of both techniques with tissue processing at different institutions (n=96) were determined in this study. RESULTS: The quality of RNA did not show any statistically significant difference between paired FF and FFPE specimens (p=0.49). Analysis of tumor cellularity gave an expected RNA amount of 33.25 ng/mm2. Archiving time affected RNA quality, showing a negative correlation with RNA integrity number and a positive correlation with threshold cycle. However, RNA from samples as old as 10 years showed a 100% success rate in qRT-PCR using short primers, showing that the effect of archiving time can be overcome by proper experiment design. NGS showed a higher success rate than qRT-PCR. Specimens from institution B (n=46), which were often stored in a refrigerator for more than 6 hours and fixed without slicing, showed lower success rates and worse results than specimens from the other institutes. CONCLUSION: Archived FFPE tissues can be used to extract RNA for NGS if they are properly processed before fixation. The expected amount of RNA per unit size calculated in this study will be useful for other researchers.
Academies and Institutes ; Breast Neoplasms ; Estrogens ; Follow-Up Studies ; Humans ; Korea ; Prevalence ; Real-Time Polymerase Chain Reaction ; RNA* ; Sequence Analysis

BACKGROUND/OBJECTIVES: Folic acid supplementation before pregnancy is known to significantly reduce the risk of having a baby with neural tube defects (NTDs). Therefore, it is important for women to be aware of the effects of folic acid supplementation before pregnancy. The purpose of this study was to investigate the awareness and preconceptional use of folic acid and to assess the current knowledge about folic acid among low-income pregnant women in Korea. SUBJECTS/METHODS: A questionnaire survey was conducted in 2012. Five hundred pregnant women were selected from the waiting list for the Nutriplus program implemented in public health centers using a multistage clustered probability sampling design. Data from 439 women were analyzed after excluding ones with incomplete answers. RESULTS: Among women who responded to the questionnaire, 65.6% had heard of folic acid before pregnancy, and 26.4% reported on the preconceptional use of folic acid. Women with a university degree or higher education were more likely to be aware of folic acid and to take folic acid in the preconception period. In a multivariate logistic regression, when age, education level, household income, employment status, gravidity, parity, and folic acid awareness were included in the model, folic acid awareness was a strong predictor of preconceptional folic acid use. As of interview, 85.4% and 77.7% of women were aware of the NTD-preventive role of folic acid and the appropriate time to take folic acid, respectively. The main sources of information on folic acid were healthcare professionals (41.2%), friends and family members (31.2%), and the media (26.5%). CONCLUSIONS: Our results suggest that public health strategies are needed to increase the preconceptional use of folic acid among Korean women.
Delivery of Health Care ; Dietary Supplements ; Education ; Employment ; Family Characteristics ; Female ; Folic Acid* ; Friends ; Gravidity ; Humans ; Korea* ; Logistic Models ; Neural Tube Defects ; Parity ; Pregnancy ; Pregnant Women* ; Public Health ; Waiting Lists

BACKGROUND: Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast. METHODS: Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers. RESULTS: The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I² = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity. CONCLUSIONS: These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.
Breast Neoplasms* ; Breast* ; Carcinogenesis ; Case-Control Studies ; Humans* ; Nipples ; Odds Ratio ; Oncogenic Viruses ; Oropharyngeal Neoplasms ; Papilloma ; Papilloma, Intraductal ; Paraffin ; Prevalence ; Real-Time Polymerase Chain Reaction*

Neurological deficits after brain surgery are not uncommon, and correct and prompt differential diagnosis is essential to initiate appropriate treatment. We describe a patient suffering from loss of consciousness due to hyperammonemia, following valproic acid treatment after surgery for an unruptured cerebral aneurysm. A 57-year-old female patient underwent successful aneurysmal neck clipping to correct an unruptured aneurysm. Her postoperative course was good, and she received anti-epileptic therapy (valproic acid) and a soft diet. Within a few days the patient experienced mental deterioration. Her serum valproic acid reached toxic levels (149.40 mg/L), and serum ammonia was fifteen times the upper normal limit (553 mmol/L; normal range, 9-33 mmol/L). After discontinuation of valproic acid and with conservative treatment, the patient recovered without any complications. Valproate-induced hyperammonemic encephalopathy is an unusual but serious neurosurgical complication, and should not be disregarded as a possible cause of neurological deficits after neurovascular surgery. Early diagnosis is crucial, as discontinuation of valproic acid therapy can prevent serious complications, including death.
Ammonia ; Aneurysm* ; Brain ; Diagnosis, Differential ; Diet ; Early Diagnosis ; Female ; Humans ; Hyperammonemia ; Intracranial Aneurysm ; Middle Aged ; Neck ; Reference Values ; Unconsciousness ; Valproic Acid