Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has affected all medical fields, including neurosurgery. Particularly, performing preoperative screening tests has become mandatory, potentially extending the time from admission to the emergency room and operating room, thus possibly affecting patients’ prognosis. This study aimed to determine the influence of COVID-19 screening time on patients’ postoperative prognosis. Methods: From September 10, 2020, to May 31, 2021, we retrospectively evaluated 54 patients with cerebral hemorrhage who underwent emergency surgery in the emergency room after the screening test. The control group included 89 patients with cerebral hemorrhage who underwent emergency surgery between January 2019 and March 2020, i.e., the period before the COVID-19 pandemic. Prognosis was measured using the Glasgow Coma Scale scores, which were obtained preoperatively, postoperatively, and at discharge, and the modified Rankin Scale (mRS). Additionally, unfavorable outcomes (mRS score 3–6) and in-hospital mortality rates were investigated for postoperative prognostic assessments. Results: No remarkable differences were observed in the time to surgical intervention and prognostic evaluation scores between patients with cerebral hemorrhage who underwent COVID-19 screening tests and subjects in the control group. Conclusion This study confirmed that patient treatment and prognosis were not significantly affected by additional preoperative screening testing times during the pandemic. We believe that our results are informative for the evaluation and performance of emergency neurosurgery during the pandemic.

Objective: : Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). Methods: : This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. Results: : The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. Conclusion : This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.
Anti-Infective Agents ; Betaine ; Cell Membrane ; Cryptococcus ; Cryptococcus neoformans ; Dandruff ; Ergosterol ; Fungi ; Gene Deletion ; Genetic Testing ; Genomics ; Humans ; Malassezia ; Methods ; Skin ; Transcriptome

OBJECTIVE: The aim of this nationwide study was to analyze the current state of patients with newly diagnosed metastatic spine tumors according to surgical methods.METHODS: Data was extracted from the Korean Health Insurance Review and Assessment Service database. Surgery was categorized into three methods : fusion, decompression, and vertebroplasty. Data included patient age, sex, health insurance type, and co-morbidities. Survival rates of metastatic spine tumor patients according to each surgical method were evaluated.RESULTS: Among 1677 patients who had an operation, 823 patients were treated by fusion, 141 patients underwent decompression, and 713 patients were treated by vertebroplasty. The three most prevalent primary tumor sites were the lung, breast, and liver & biliary. On the other hand, the three most prevalent primary tumor sites of patients who underwent surgery were the lung, liver & biliary, and the prostate. The median survival periods for each surgical method in the metastatic spine tumor patients were 228 days for those who underwent surgery, 249 days for decompression, and 154 days for vertebroplasty. Age, sex, and comorbidities significantly affected survival rate.CONCLUSION: For every primary tumor site, decompression was the least common surgical method during the study period. Although the three surgical methods did not significantly affect the survival period, patients with a poor prognosis tended to undergo vertebroplasty.
Breast ; Comorbidity ; Decompression ; Hand ; Humans ; Insurance, Health ; Liver ; Lung ; Methods ; Neoplasm Metastasis ; Prognosis ; Prostate ; Spine ; Survival Rate ; Vertebroplasty

BACKGROUND: This study was conducted to identify the sleep status of daytime workers who do not work in shifts. This study analyzed factors affecting sleep duration and sleep quality. METHODS: This study was conducted on 1171 daytime workers at a manufacturing workshop. We used a self-administered questionnaire to investigate demographic variables, work type, working period, musculoskeletal symptoms and the Pittsburgh Sleep Quality Index to assess sleep. Regular health checkup was conducted for the worker’s clinical examination. RESULTS: The mean sleep duration was 6.36 h and the mean score on the Pittsburgh Sleep Quality Index was 4.46. Work type and obesity were related to sleep duration. Age, obesity and musculoskeletal pain were significantly related to sleep quality. The prevalence ratio of researcher group for short sleep duration was 1.27 (95% confidence interval: 1.02–1.58). The prevalence ratio of those aged 50 years and over was 0.47 (0.25–0.91) and of those in their 40s was 0.56 (0.35–0.91) for poor sleep quality compared to those in their 20s. The prevalence ratio of the obesity group for poor sleep quality was 1.53 (1.10–2.12). The prevalence ratio of musculoskeletal pain group for poor sleep quality was 1.92 (1.29–2.84). CONCLUSIONS: Age, obesity and musculoskeletal pain were factors affecting the poor quality on sleep of daytime workers. In addition, work type related to short sleep duration.
Education ; Musculoskeletal Pain ; Obesity ; Prevalence

PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. RESULTS: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. CONCLUSION: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Disease-Free Survival ; Drug Therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Multivariate Analysis ; Platinum ; Prognosis ; Reactive Oxygen Species* ; Smoke ; Smoking

It is well established that TGF-beta1 and retinoic acid (RA) cause IgA isotype switching in mice. We recently found that lactoferrin (LF) also has an activity of IgA isotype switching in spleen B cells. The present study explored the effect of LF on the Ig production by mouse peritoneal B cells. LF, like TGF-beta1, substantially increased IgA production in peritoneal B1 cells but little in peritoneal B2 cells. In contrast, LF increased IgG2b production in peritoneal B2 cells much more strongly than in peritoneal B1 cells. LF in combination with RA further enhanced the IgA production and, interestingly, this enhancement was restricted to IgA isotype and B1 cells. Similarly, the combination of the two molecules also led to expression of gut homing molecules alpha4beta7 and CCR9 on peritoneal B1 cells, but not on peritoneal B2 cells. Thus, these results indicate that LF and RA can contribute to gut IgA response through stimulating IgA isotype switching and expression of gut-homing molecules in peritoneal B1 cells.
Animals ; B-Lymphocytes ; Immunoglobulin A* ; Immunoglobulin Class Switching ; Immunoglobulin G ; Lactoferrin* ; Mice ; Spleen ; Transforming Growth Factor beta1 ; Tretinoin*

Ten dogs were enrolled in this study: two healthy dogs, two obese dogs without other medical issues and six obese dogs with underlying diseases including pemphigus, chronic active hepatitis, hyperadrenocorticism, narcolepsy, otitis media and heartworm infection. Pyrosequencing of the 16S rRNA gene to explore the gut bacterial diversity revealed that distal gut bacterial communities of samples from patients with pemphigus, otitis media and narcolepsy consisted primarily of Firmicutes, while the major phylum of the distal gut bacterial communities in patients with chronic active hepatitis and hyperadrenocorticism was Fusobacteria. Proteobacteria were the dominant phylum in heartworm infected obese patients.
Adrenocortical Hyperfunction ; Animals ; Dogs* ; Fusobacteria ; Genes, rRNA ; Hepatitis, Chronic ; Humans ; Microbiota* ; Narcolepsy ; Otitis Media ; Pemphigus ; Pilot Projects* ; Proteobacteria

OBJECTIVE: The purpose of this study was to evaluate the surgical technique and outcome of mini-open posterior lumbar interbody fusion (PLIF) under circumferential releasing technique. METHODS: Fourty patients who underwent mini-open PLIF using the percutaneous screw fixation system for Meyerding Grade II spondylolisthesis or more were retrospectively studied. After complete circumferential release, the slipped vertebrae would tend to obtain spontaneous reduction, and with compressive force by percutaneous screw fixation, additional reduction could be achieved. The radiological measurements including slippage reduction, disc height, restoration of lumbar lordotic angle and focal segmental angle were analyzed. The clinical outcome was assessed using the visual analog scale (VAS) and low back outcome score (LBOS), and procedure related complications were also analyzed. RESULTS: Slippage percentage was improved from 38.0+/-12.6% to 9.3+/-7.8% and lumbar lordotic angle was changed from 43.0+/-13.8degrees to 48.2+/-10.3degrees. Focal segmental angle improved from 10.1+/-8.5degrees to 15.9+/-6.0degrees. The mean LBOS and mean pain score were also improved significantly. Complications included one case of medial penetration of pedicle border and two cases of transient radiculopathy. However, there were no signs of neurological aggravation or fusion failure during the follow-up period. CONCLUSION: Mini-open PLIF using the percutaneous screw fixation following complete circumferential release can be safe and effective treatment for even moderate to severe grade spondylolisthesis.
Follow-Up Studies ; Humans ; Radiculopathy ; Retrospective Studies ; Spine ; Spondylolisthesis* ; Visual Analog Scale