Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Objective: This study aimed to investigate the perception of emergency medical service (EMS) providers and medical directors toward the field skill proficiency of EMS providers. We further examined differences in perception according to the certification and hospital career of individuals. Methods: This survey was conducted enrolling all active EMS providers in Busan, Ulsan, and Gyeongnam, as well as emergency physicians who participated in direct medical direction. Pre-developed questionnaires were sent as text messages to individual EMS providers and emergency physicians using an internet-based survey tool (Google Forms).Questionnaires were composed of 25 items in 7 categories: “airway management”, “ventilatory support”, “circulatory support”, “field assessment and management of trauma patients”, “field assessment and management of patients with chest pain”, “field assessment and management of patients with neurologic symptoms”, and “other items”. The response was based on a five-point Likert scale, where 0 score indicated no experience at all. Results: The questionnaire was distributed to 1,781 EMS providers and 52 medical directors; of these, 1,314 (73.7%) EMS providers and 34 (65.3%) medical directors completed the survey. EMS providers rated themselves as above average (3 points) for most of the questions. However, the majority responded that they had no experience or low proficiency in endotracheal intubation and prehospital delivery (median 2; interquartile range [IQR], 0-3). Conversely, medical directors assessed the EMS provider’s proficiency as above average in use of I-gel, recognition of hypoglycemia, field management of trauma patients, use of oropharyngeal and nasopharyngeal airway, use of laryngeal mask airway, and optimal oxygen supply (median, 4; IQR, 3-4), but responded with low scores for most other questions. Based on the EMS provider certification, nurses scored themselves more proficient than level-1 emergency medical technicians (EMTs) for intravenous access (P<0.001), whereas level-1 EMTs recognized themselves more proficient than nurses for endotracheal intubation (P<0.001), use of Magill forceps (P=0.004), and pediatric cardiopulmonary resuscitation (P<0.001). Conclusion This study recognized the discrepancies in the perception of EMS provider’s field skill proficiency, as perceived by EMS providers and medical directors, and between level-1 EMTs and nurses. We propose that regional EMS authorities need to make persistent efforts to narrow these perception gaps through effective educational programs for EMS providers and medical directors.

The commensal microbiota contributes to the maintenance of immune homeostasis in the human body. Autoimmunity can be aggravated or alleviated by the microbiota, which affects both innate and adaptive immune cells. Many studies have demonstrated the role of gut dysbiosis, the alteration of the gut microbiome, in the development and progression of numerous autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue and is characterized by skin and lung fibrosis, as well as injuries in small arteries. Recent studies have shown variable degrees of dysbiosis in SSc patients and the effect of probiotics on these patients, providing evidence for the potential link between microbiota and SSc. However, further research is needed to elucidate the key microorganisms and the mechanisms through which they affect the pathoimmunological process of SSc. This review summarizes the current knowledge regarding the association between microbiota and SSc, and discusses the changing perspectives and potential therapy strategies based on the microbiota and its products.
Arteries ; Autoimmune Diseases ; Autoimmunity ; Connective Tissue ; Dysbiosis ; Fibrosis ; Gastrointestinal Microbiome ; Homeostasis ; Human Body ; Humans ; Lung ; Microbiota ; Probiotics ; Scleroderma, Systemic ; Skin

BACKGROUND: S: The purpose of this study is to discuss the total joint reconstruction surgery for a patient with recurrent ankylosis in bilateral temporomandibular joints (TMJs) using three-dimensional (3D) virtual surgical planning, computer-aided manufacturing (CAD/CAM)-fabricated surgical guides, and stock TMJ prostheses.CASE PRESENTATION: A 66-year-old female patient, who had a history of multiple TMJ surgeries, complained of severe difficulty in eating and trismus. The 3D virtual surgery was performed with a virtual surgery software (FACEGIDE, MegaGen implant, Daegu, South Korea). After confirmation of the location of the upper margin for resection of the root of the zygoma and the lower margin for resection of the ankylosed condyle, and the position of the fossa and condyle components of stock TMJ prosthesis (Biomet, Jacksonville, FL, USA), the surgical guides were fabricated with CAD/CAM technology. Under general anesthesia, osteotomy and placement of the stock TMJ prosthesis (Biomet) were carried out according to the surgical planning. At 2 months after the operation, the patient was able to open her mouth up to 30 mm without complication. CONCLUSION For a patient who has recurrent ankylosis in bilateral TMJs, total joint reconstruction surgery using 3D virtual surgical planning, CAD/CAM-fabricated surgical guides, and stock TMJ prostheses may be an effective surgical treatment option.

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.
Adenocarcinoma* ; Carcinoma, Endometrioid ; Chemoradiotherapy ; Chemoradiotherapy, Adjuvant ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Risk Factors

PURPOSE: The purpose of this study is to review the indications of ankle lateral complex reconstruction using tendon graft. MATERIALS AND METHODS: We searched PubMed using the index, "ankle, instability, lateral ligament, reconstruction" from 1990 to present (September 30, 2015). We excluded 1) modified Brostrom operation (MBO), 2) conventional tenodesis surgery, 3) review article, 4) technical note, and 5) articles written in another foreign language. We reviewed 24 papers through the publication events, operational method, the indications of surgery, and the specific features of the patient group. RESULTS: There were the indications of 1) previous ligament surgery failure, 2) situation when ligament repair is impossible due to the ligament defect, 3) severe instability (preoperative talar tilt >15degrees, anterior draw >10 mm or the difference of contralateral side talar tilt >5degrees, anterior draw >3 mm), and 4) overweight (body mass index >30 kg/m2). Other considerations included 1) generalized joint laxity and 2) workers, highly-demanded or athlete highly-affected by instability. CONCLUSION: The ankle lateral complex reconstruction using tendon graft could be indicated in patients with the possibility of MBO failure with several considerations.
Ankle* ; Athletes ; Collateral Ligaments ; Humans ; Joint Instability ; Lateral Ligament, Ankle* ; Ligaments ; Overweight ; Publications ; Tendons* ; Tenodesis ; Transplants*

PURPOSE: To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score< or =6, PSA< or =10 ng/mL, and < or =2 positive biopsy cores). MATERIALS AND METHODS: Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. RESULTS: Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL2, obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). CONCLUSIONS: PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.
Aged ; Biopsy, Needle ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm, Residual ; Organ Size ; Predictive Value of Tests ; Prospective Studies ; Prostate/*pathology ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/*blood/*pathology/surgery ; ROC Curve ; Watchful Waiting/*methods

PURPOSE: The aim of this study was to investigate clinicopathologic differences between prostate cancer (PCa) detected at initial and repeat transrectal ultrasound-guided prostate biopsy in a large Korean cohort. MATERIALS AND METHODS: From 2000 through 2012, a total of 7,001 patients underwent transrectal ultrasound-guided prostate biopsy at 6 centers in Daegu and Gyeongbuk provinces. Of these 7,001 patients, the initial biopsy was positive for PCa in 2,118 patients. Repeat biopsy was performed in 374 of the 4,883 patients with an initial negative finding and a persistently elevated prostate-specific antigen (PSA) level, nodules or asymmetry by digital rectal examination (DRE), high-grade prostatic intraepithelial neoplasia, or atypical small acinar proliferation. Numbers of biopsy cores varied from 6 to 12 according to center and biopsy date. RESULTS: Cancer was diagnosed in 2,118 of the 7,001 patients (30.3%) at initial biopsy and in 86 of the 374 patients (23.0%) at repeat biopsy. The repeat biopsy rate was 5.3%. Mean PSA values were 68.7+/-289.5 ng/mL at initial biopsy and 18.0+/-55.4 ng/mL at repeat biopsy (p<0.001). The mean number of cancer-positive cores per biopsy was 5.5+/-3.5 for initial biopsy and 3.0+/-2.9 for repeat biopsy (p<0.001). Mean Gleason score was 7.5+/-1.4 at initial biopsy and 6.6+/-1.3 at repeat biopsy (p<0.001). For detected cancers, the low-stage rate was higher for repeat biopsy than for initial biopsy (p=0.001). CONCLUSIONS: Cancers detected at repeat biopsy tend to have lower Gleason scores and stages than cancers detected at initial biopsy. The present study shows that repeat biopsy is needed in patients with a persistently high PSA or abnormal DRE findings.
Adult ; Aged ; Aged, 80 and over ; Endosonography/*methods ; Follow-Up Studies ; Humans ; Image-Guided Biopsy/*methods ; Incidence ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prostatic Neoplasms/epidemiology/*pathology ; Rectum ; Reproducibility of Results ; Republic of Korea/epidemiology ; Retrospective Studies

Respiratory epithelial adenomatoid hamartoma (REAH) is a rare benign lesion in nasal cavity. We report two cases of REAH of the nasal cavity arising from nasal septum. The etiology of REAH is unknown although inflammation may induce gland proliferation observed in hamartomas. One of our cases was associated with nasal polyposis. REAH is a self-limiting disease, so it is important to differentiate REAH from other pathologic process, including inverted papilloma and low-grade adenocarcinoma. The treatment of choice is complete excision through a conservative approach.
Adenocarcinoma ; Diagnosis, Differential ; Hamartoma ; Inflammation ; Nasal Cavity ; Nasal Septum ; Papilloma, Inverted ; Respiratory System