BACKGROUND: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA).METHODS: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected.CONCLUSION: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

BACKGROUND: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). METHODS: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected. CONCLUSION NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

BACKGROUND: Arthroscopic stabilization of torn coracoclavicular (CC) ligaments gained popularity recently. However, loss of reduction after the operation and complications unique to this technique involving tunnel placement through the distal clavicle and coracoid process are concerns. The purpose of this study was to report intraoperative and early postoperative complications associated with this procedure. METHODS: This study retrospectively evaluated 18 consecutive patients who had undergone arthroscopic stabilization for torn CC ligaments between 2014 and 2015. The indications for surgery were acute or chronic acromioclavicular dislocation and acute fracture of the distal clavicle, associated with CC ligament disruption. Clinical outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) and the University of California, Los Angeles (UCLA) scores. Intra- and postoperative complications and reoperations were investigated. RESULTS: There were six female and 12 male patients with a mean age of 47 years (range, 22 to 86 years). At a mean follow-up of 17 ± 10 months (range, 10 to 28 months), the mean ASES score was 88.8 ± 19.9 and the mean UCLA score was 30.9 ± 5.2. Intraoperatively, seven complications developed: breach of lateral cortex of the coracoid process in five patients, medial cortex of the coracoid process in one, and anterior cortex of the clavicle in one. Postoperative complications developed in eight patients: four ossifications of the CC interspace, four tunnel widening of the clavicle, one bony erosion on the clavicle, and one superficial infection. A loss of reduction was found in six patients. Reoperation was performed in three patients for loss of reduction in two and superficial infection in the other. CONCLUSIONS: Arthroscopic CC stabilization resulted in high rates of intraoperative and early postoperative complications. Most of them were related to the surgical technique involving bone tunnel placement in the coracoid process and the clavicle.
California ; Clavicle ; Dislocations ; Elbow ; Female ; Follow-Up Studies ; Humans ; Ligaments ; Male ; Postoperative Complications ; Reoperation ; Retrospective Studies ; Shoulder ; Surgeons

Cephalopods have the most advanced nervous systems and intelligent behavior among all invertebrates. Their brains provide comparative insights for understanding the molecular and functional origins of the human brain. Although brain maps that contain information on the organization of each subregion are necessary for a study on the brain, no whole brain atlas for adult cephalopods has been constructed to date. Here, we obtained sagittal and coronal sections covering the entire brain of adult Octopus minor (Sasaki), which belongs to the genus with the most species in the class Cephalopoda and is commercially available in East Asia throughout the year. Sections were stained using Hematoxylin and Eosin (H&E) to visualize the cellular nuclei and subregions. H&E images of the serial sections were obtained at 30~70-µm intervals for the sagittal plain and at 40~80-µm intervals for the coronal plain. Setting the midline point of the posterior end as the fiducial point, we also established the distance coordinates of each image. We found that the brain had the typical brain structure of the Octopodiformes. A number of subregions were discriminated by a Hematoxylin-positive layer, the thickness and neuronal distribution pattern of which varied markedly depending upon the region. We identified more than 70 sub-regions based on delineations of representative H&E images. This is the first brain atlas, not only for an Octopodiformes species but also among adult cephalopods, and we anticipate that this atlas will provide a valuable resource for comparative neuroscience research.
Adult ; Arm* ; Brain* ; Cephalopoda ; Eosine Yellowish-(YS) ; Far East ; Hematoxylin ; Histology, Comparative ; Humans ; Invertebrates ; Nervous System ; Neurons ; Neurosciences ; Octopodiformes*

Microarray analysis was used to investigate the lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes to overcome cross-talk at non-muscle invasive high-grade (HG)-urothelial carcinoma (UC) of the bladder, gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K, and eIF4E) small interfering RNAs (siRNAs) or rapamycin in 5637 and T24 cell lines. We selected mTOR pathway downstream genes that were suppressed by siRNAs more than 2-fold, or were up-regulated or down-regulated by rapamycin more than 2-fold. We validated mTOR downstream genes with immunohistochemistry using a tissue microarray (TMA) of 125 non-muscle invasive HG-UC patients and knockout study to evaluate the synergistic effect with rapamycin. The microarray analysis selected mTOR pathway downstream genes consisting of 4 rapamycin up-regulated genes (FABP4, H19, ANXA10, and UPK3A) and 4 rapamycin down-regulated genes (FOXD3, ATP7A, plexin D1, and ADAMTS5). In the TMA, FABP4, and ATP7A were more expressed at T1 and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed in tumors ≤ 3 cm in diameter. In a multivariate Cox regression model, ANXA10 was a significant predictor of recurrence and ATP7A was a significant predictor of progression in non-muscle invasive HG-UC of the bladder. In an ATP7A knock-out model, rapamycin treatment synergistically inhibited cell viability, wound healing, and invasion ability compared to rapamycin only. Activity of the ANXA10 and ATP7A mTOR pathway downstream genes might predict recurrence and progression in non-muscle invasive HG-UC of the bladder. ATP7A knockout overcomes rapamycin cross-talk.
Cell Line ; Cell Survival ; Gene Expression ; Gene Ontology ; Humans ; Immunohistochemistry ; Microarray Analysis ; Recurrence* ; RNA, Small Interfering ; Sirolimus ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Wound Healing

PURPOSE: The lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes that overcome cross-talk in nonmuscle invasive low grade (LG)-urothelial carcinoma (UC) of the bladder is a clinical limitation in the use of mTOR inhibitor for the treatment of UC. MATERIALS AND METHODS: Presently, gene expression patterns, gene ontology, and gene clustering by dual (p70S6K and S6K) siRNAs or rapamycin in 253J and TR4 cell lines were investigated by microarray analysis. mTOR/S6K pathway downstream genes suppressed to siRNAs, and rapamycin up-regulated or rapamycin down-regulated genes were identified. The mTOR downstream genes examined using a tissue microarray of 90 nonmuscle invasive LG-UC patients to assess whether any of these genes predicted clinical outcomes. A knockout study evaluated the synergistic effect with rapamycin. RESULTS: In the microarray analysis, mTOR pathway downstream genes selected consisted of 4 rapamycin down-regulated (FOXM1, KIF14, MYBL2, and UHRF1), and 4 rapamycin up-regulated (GPR87, NBR1, VASH1, and PRIMA1). In the tissue microarray, FOXM1, KIF14, and NBR1 were more expressed at T1, and MYBL2, and PRIMA1 were more expressed in tumors exceeding 3 cm. In a multivariate Cox regression model, KIF14 and NBR1 were significant predictors of recurrence in nonmuscle invasive LG-UC of the bladder. In a NBR1 knock out model, rapamycin treatment synergistically inhibited cell viability and colony forming ability compared to rapamycin only. CONCLUSIONS: The results implicate KIF14 and NBR1 as mTOR/S6K pathway downstream genes that predict recurrence in nonmuscle invasive LG-UC of the bladder and demonstrate that NBR1 knockout overcomes rapamycin cross-talk.
Biomarkers ; Cell Line ; Cell Survival ; Gene Expression ; Gene Ontology ; Humans ; Microarray Analysis ; Recurrence* ; RNA, Small Interfering ; Sirolimus* ; Urinary Bladder Neoplasms ; Urinary Bladder*

OBJECTIVE: The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer. METHODS: To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 microL saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls. RESULTS: Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses). CONCLUSION: Metronomic oral chemotherapy with DHP107 showed anti-tumor efficacy in vivo similar to IP paclitaxel in an orthotopic mouse model.
Animals ; Drug Therapy ; Female ; Humans ; Mice* ; Mice, Nude ; Ovarian Neoplasms* ; Paclitaxel* ; Tumor Burden

We describe a 48-year-old man with family history of rheumatoid arthritis (RA) affected by chronic eosinophilic pneumonia (CEP) with severe peripheral eosinophilia. CEP might develop as a complication of longstanding active RA. The patient with 5 months history of seropositive RA and chronic respiratory symptoms, alveolar and blood eosinophilia, peripheral pulmonary infiltrates and pleural effusion on chest imaging. The lung may be involved as an extraarticular manifestation of RA. However, CEP is not recognized as a typical lung manifestation of RA, and the two diseases rarely coexist. The effusion was an eosinophil predominant exudates and was characterized by low pH, and glucose level and high lactic dehydrogenase. The patient responded rapidly to combination of steroids and disease modifying anti-rheumatic drugs.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Eosinophilia ; Eosinophils* ; Exudates and Transudates ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Lung ; Middle Aged ; Oxidoreductases ; Pleural Effusion* ; Pulmonary Eosinophilia* ; Steroids ; Thorax