Purpose: It is unclear whether performing endosonography first in non–small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC. Materials and Methods: This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into ‘no endosonography’ and ‘endosonography first’ groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis. Results: In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models. Conclusion In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

Background: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. Methods: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. Results: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs.4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54–1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81–2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17–2.92). Conclusion TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Purpose: Guidelines recommend that non–small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1. Materials and Methods: Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed. Results: The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients. Conclusion Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Objective: We compared appendiceal visualization on 2-mSv CT vs. conventional-dose CT (median 7 mSv) in adolescents and young adults and analyzed the undesirable clinical and diagnostic outcomes that followed appendiceal nonvisualization. Materials and Methods: A total of 3074 patients aged 15–44 years (mean ± standard deviation, 28 ± 9 years; 1672 female) from 20 hospitals were randomized to the 2-mSv CT or conventional-dose CT group (1535 vs. 1539) from December 2013 through August 2016. A total of 161 radiologists from 20 institutions prospectively rated appendiceal visualization (grade 0, not identified; grade 1, unsure or partly visualized; and grade 2, clearly and entirely visualized) and the presence of appendicitis in these patients. The final diagnosis was based on CT imaging and surgical, pathologic, and clinical findings. We analyzed undesirable clinical or diagnostic outcomes, such as negative appendectomy, perforated appendicitis, more extensive than simple appendectomy, delay in patient management, or incorrect CT diagnosis, which followed appendiceal nonvisualization (defined as grade 0 or 1) and compared the outcomes between the two groups. Results: In the 2-mSv CT and conventional-dose CT groups, appendiceal visualization was rated as grade 0 in 41 (2.7%) and 18 (1.2%) patients, respectively; grade 1 in 181 (11.8%) and 81 (5.3%) patients, respectively; and grade 2 in 1304 (85.0%) and 1421 (92.3%) patients, respectively (p < 0.001). Overall, undesirable outcomes were rare in both groups. Compared to the conventional-dose CT group, the 2-mSv CT group had slightly higher rates of perforated appendicitis (1.1% [17] vs. 0.5% [7], p = 0.06) and false-negative diagnoses (0.4% [6] vs. 0.0% [0], p = 0.01) following appendiceal nonvisualization. Otherwise, these two groups were comparable. Conclusion The use of 2-mSv CT instead of conventional-dose CT impairs appendiceal visualization in more patients. However, appendiceal nonvisualization on 2-mSv CT rarely leads to undesirable clinical or diagnostic outcomes.

Background: Dual energy X-ray absorptiometry (DXA) has evolved from pencil-beam (PB) to narrow fan-beam (FB) densitometers. We performed a meta-analysis of the available observational studies to determine how different modes of DXA affect bone mineral density (BMD) measurements. Methods: A total of 1,233 patients (808 women) from 14 cohort studies were included. We evaluated the differences in BMD according to the DXA mode: PB and FB. Additionally, we evaluated the differences in BMD between the 2 types of FB mode: FB (Prodigy) and the most recent FB (iDXA). Pairwise meta-analysis was performed, and weighted mean differences (WMD) were calculated for (total lumbar, total hip, and total body). Results: No significant difference was observed in total lumbar (pooled WMD, -0.013; P=0.152) and total hip BMD (pooled WMD, -0.01; P=0.889), between PB and FB. However, total body BMD was significantly lower in the PB compared to the FB group (pooled WMD, -0.014; P=0.024). No significant difference was observed in lumbar BMD (pooled WMD, -0.006; P=0.567), total hip (pooled WMD, -0.002; P=0.821), and total body (pooled WMD, 0.015; P=0.109), between Prodigy and iDXA. Conclusions The results of this study warrant the recommendation that correction equations should not be used when comparing BMD from different modes. Further research is still needed to highlight the ways in which differences between DXA systems can be minimized.

Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Acetylcysteine ; Bilirubin ; Carbon Monoxide* ; Carbon* ; Down-Regulation* ; Endothelial Cells ; Heme ; Humans ; Iron ; RNA, Messenger ; RNA, Small Interfering ; Vascular Diseases

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries

A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic ; Acetabulum ; Adult ; Decompression ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Foraminotomy* ; Humans ; Neurologic Manifestations ; Radiculopathy ; Sacrum ; Toes ; Wounds and Injuries