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Growing evidence has suggested that the gut-brain axis plays an important role in the pathogenesis of Parkinson’s disease (PD), and that this role is mediated by the interactions between bile acids (BAs) and intestinal microbiota. Given that cholecystectomy can lead to alterations in BAs and gut microbiota, we investigated whether cholecystectomy is linked to a higher risk of PD. We constructed a cohort of patients with an operation code of cholecystectomy from 2010 to 2015 (n = 161,838) and age- and sex-matched control subjects without cholecystectomy (n = 286,135) using the National Health Insurance Service database. Incident PD was traced over a maximum observation period of 7 years. We identified 1404 incident PD cases during 1,631,265 person-years of follow-up. The cholecystectomy group showed an elevated risk of PD compared to the control group, even after adjusting for potential confounding factors (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.02–1.27). When the data were split by sex, the risk elevation was significant in men (adjusted HR 1.22, 95% CI 1.06–1.41), but not in women (adjusted HR 1.03, 95% CI 0.88–1.22). Our results provide evidence that cholecystectomy is associated with an increased risk of developing PD. This association differed between men and women, suggesting sex-specific effects of cholecystectomy on the risk of PD.

This study aimed to determine the equivalence between definitive chemoradiotherapy (DCRT) and radical esophagectomy in clinical T1bN0M0 esophageal squamous cell carcinoma (ESCC).Among 282 patients with cT1bN0M0 ESCC, 238 underwent radical esophagectomy and 44 underwent DCRT. Both treatments were retrospectively compared overall survival (OS), progression-free survival (PFS), and complications.The DCRT group exhibited poorer patient characteristics than the surgery group, especially with mean age (73 vs. 63 years), Eastern Cooperative Oncology Group (ECOG) status, and Charlson Comorbidity Index (p 0.001, each). The median follow-up duration was 49.5 (range, 0.4-97.0) and 45.5 months (range, 5.0-112.0) in the surgery and DCRT groups, respectively. In the DCRT group, clinical complete response was achieved in 43 patients (97.7%) at 1 month after treatment. The 5-year OS rates were 75.8% and 68.8% (p = 0.135) and the 5-year PFS were 63.8% and 57.8% (p = 0.637) for the surgery and DCRT groups, respectively. Local recurrence rates were identical between the two groups (11.4% and 11.4%), but the distant metastasis rate was lower in the DCRT group (n = 1, 2.27% vs. n = 29, 12.15%). Grade 3-4 hematologic toxicities were observed in 11 patients (25%) of the DCRT group, and 56 patients (23.5%) in the surgery group showed grade 3-5 surgical complications, including mortality (n = 5).Based on the non-inferior survival rates, recurrence patterns, and complication rates without critical surgical mortality, DCRT was comparable to esophagectomy for cT1bN0 esophageal squamous cell carcinoma.

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p

KMRC011 is a novel Toll‐like receptor 5 agonist under development as a treatment for acute radiation syndrome (ARS). The aim of this first‐in‐human study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of a single intramuscular dose of KMRC011 in healthy subjects. A randomized, single‐blind, placebo‐controlled, single dose‐escalation study was conducted with the starting dose of 5 μg. Eight (4 only for 5 μg cohort) subjects per cohort were randomly assigned to KMRC011 or placebo in a 3:1 ratio. Dose‐limiting toxicity (DLT) was assessed throughout the study. Serum concentrations of KMRC011, granulocyte colony‐stimulating factor (G‐CSF), and interleukin‐6 (IL‐6) were measured up to 48 h postdose. Based on safety review, the dose of KMRC011 escalated up to 20 μg, and consequently, a total of 4 dose levels (5, 10, 15, and 20 μg) were explored. The most common adverse event was injection site reaction, showing no dose‐related trend. Three DLTs (2 cases of hepatic enzyme increased and 1 of pyrexia) were observed; 1 in the 15 μg cohort and 2 in the 20 μg cohort. A developed method could not detect any KMRC011 in serum. KMRC011 15 μg and 20 μg showed significant increases of G‐CSF, IL‐6, and absolute neutrophil counts, compared with the placebo. A single intramuscular administration of KMRC011 ranging from 5 to 15 μg was tolerated in healthy subjects. Doses of KMRC011 equal to or greater than 15 μg exerted TLR5 agonist‐like activities by increasing serum G‐CSF and IL‐6. It suggests that KMRC011 has the potential for a treatment for ARS.

Objectives The benefit of adjuvant therapy for heterogenous group of pathological N2 (pN2) non-small cell lung cancer (NSCLC) remains unclear. We evaluated the prognostic effect of adjuvant therapy after stratifying patients with pN2 according to subdivided N2 descriptors. Materials and Methods We performed a retrospective analysis of clinical outcomes in patients with pN2 NSCLC who underwent upfront surgery. N2 descriptors were subdivided as single N2 metastasis without N1 involvement (pN2a1), single N2 with metastasis with N1 involvement (pN2a2), and multiple N2 metastasis (pN2b). Results From 2005–2017, 838 patients with pN2 NSCLC underwent complete resection. There were 173 (21.0 %), 338 (40.3 %), and 324 (38.7 %) in the pN2a1, pN2a2, and pN2b groups. Patients who received chemoradiotherapy (CRTx; n = 389, 46.4 %) or chemotherapy (CTx; n = 204, 24.3 %) had similar prognoses, which were better than prognoses in patients who received with radiotherapy (RTx; n = 116, 13.8 %) or those who did not receive adjuvant therapy (n = 129, 15.4 %). According to the stratified multivariable Cox analysis, patients with pN2b stage in the CTx group had a significantly poor prognosis than those in the CRTx group (hazard ratio, 1.38; 95 % confidence interval, 1.03–1.98; p = 0.046). The difference in survival outcomes between the CRTx and CTx groups was significant in patients with extranodal invasion (ENI) (p = 0.011), but not in those without ENI (p = 0.527) Conclusions Adjuvant CTx improves the overall and recurrence-free survival in patients with pN2 NSCLC undergoing upfront surgery with complete resection. RTx with adjuvant chemotherapy has a combinatorial effect on pN2 NSCLC only with ENI or multiple N2 metastasis.

Objective To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. Methods A YouTube search was performed on April 1, 2020 using the term "restless legs syndrome" in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. Results Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. Conclusion Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Background/Objective: To compare the longitudinal trajectories of cognition according to the presence of the apolipoprotein E (APOE) ɛ4 allele in male and female Parkinson’s disease (PD) patients. Methods: This study included a total of 361 patients with recently diagnosed de novo PD (mean age [standard deviation], 61.4 [9.8] years). The patients were classified into the following groups: APOE ɛ4 + /M (n = 65), APOE ɛ4-/M (n = 173), APOE ɛ4 + /F (n = 25), and APOE ɛ4-/F (n = 98). Cognitive decline was assessed annually over 5 years of follow-up using the Montreal Cognitive Assessment (MoCA). To assess the sex-specific impacts of the APOE ɛ4 status on cognitive decline, we used generalized linear mixed effects (GLME) models separately for men, women, and the two sexes combined. Results: In the sex-stratified GLME models adjusted for covariates, the interaction results showed that the males with APOE ɛ4 had a steeper rate of cognitive decline than those without APOE ɛ4. In contrast, there was no significant interaction between APOE ɛ4 and time on longitudinal MoCA performance in the females. The main effect of APOE ɛ4 on the change in the MoCA score was not significant for either men or women. When the data from both men and women were used, the APOE ɛ4 + /M group exhibited a steeper rate of cognitive decline than did the APOE ɛ4 + /F and APOE ɛ4-/F groups. These results were consistent with those of sensitivity analyses. Conclusion: Sex may be considered when APOE ɛ4-related vulnerability to early cognitive decline is evaluated in PD patients.

Background Complementary and alternative medicine (CAM) has been frequently used and its use continues to increase in lung cancer patients, despite insufficient scientific evidence. We analyzed the current status of the awareness and use of CAM in Korean lung cancer patients. Methods This study was a prospective survey-based study performed at seven medical centers in South Korea between August 2019 and October 2019. The survey included general patient characteristics, and the awareness and use of CAM. We analyzed the differences in the clinical parameters between patients aware and not aware of CAM and between CAM non-users and users. Results A total of 434 patients were included in this study. Among them, 68.8% of the patients responded that they were aware of CAM, and 30.9% of the patients said they experienced CAM. In univariate analysis, patients aware of CAM were younger with poor performance status, patients with advanced-stage lung cancer, those who received more systemic therapy, and those who received CCRT. By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters between CAM non-users and users. Conclusions More lung cancer patients with younger age, poor performance status, advanced stage, and prior CCRT were aware of CAM. There were no significantly different characteristics between CAM users and non-users.

ObjectiveTo determine whether greater physical activity could modify the negative association of APOE ε4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity.MethodsWe used data from the Parkinson's Progression Markers Initiative cohort. Because self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated at 2 years after enrollment, this longitudinal analysis was based on assessments performed at years 2, 3, and 4. Cognitive function was measured annually with the Montreal Cognitive Assessment (MoCA). Dopamine transporter (DAT) imaging was performed at years 2 and 4. We assessed the interactive associations between physical activity and the APOE ε4 allele on the longitudinal changes in MoCA scores and striatal DAT activities.ResultsA total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE ε4 carriers) were included. The APOE ε4 allele showed a steeper rate of cognitive decline than the non–APOE ε4 allele (estimate −1.33, 95% confidence interval [CI] −2.12 to −0.47, p = 0.002). However, there was a significant interaction between physical activity and APOE ε4 such that higher physical activity was related to slower APOE ε4-related cognitive decline (estimate 0.007, 95% CI 0.003–0.011, p = 0.001). No significant interaction was found between physical activity and the APOE ε4 allele regarding the change in striatal DAT activities.ConclusionIncreased physical activity attenuated APOE ε4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function.Trial Registration InformationClinicalTrials.gov Identifier: NCT01141023.Classification of EvidenceThis study provides Class II evidence that increased physical activity was associated with decreased APOE ε4-related early cognitive decline in patients with PD.

As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p, Patients with oesophageal squamous cell carcinoma treated with definitive chemoradiotherapy show highly different prognoses after treatment, especially according to the clinical response to chemoradiotherapy.

Introduction: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy. Methods: A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29). Results: During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ. Conclusions: The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.

Objective To investigate the association between Apolipoprotein E (APOE) genotype and freezing of gait (FOG) in Parkinson's disease (PD). Methods This cohort study included 339 early PD patients who were divided into APOE e4-positive (n = 88) and e4-negative (n = 251) groups. They were followed-up for up to 6 years to identify the development of FOG. To investigate the influence of CSF β-amyloid 1–42 (Aβ42) on the association between APOE e4 and FOG, the patients were additionally dichotomized into “high-level” and “low-level” groups using three different cutoff values for the CSF Aβ42 levels. Results At baseline, the APOE e4-positive group had lower CSF Aβ42 levels than the APOE e4-negative group. During a median follow-up of 5.0 years, the APOE e4-positive group had a higher incidence of FOG than the APOE e4-negative group. In the multivariable Cox model excluding CSF Aβ42, APOE e4 was a significant predictor of FOG. However, after adding CSF Aβ42 in the model, APOE e4 did not survive, whereas lower CSF Aβ42 levels were associated with FOG. In the subgroup analyses, the effect of the APOE e4 allele was not found in the “low-level” group. However, in the “high-level” group, the APOE e4 allele independently increased the risk of FOG, and this association was stronger than the association with CSF Aβ42. Conclusion The APOE e4 allele may be a novel genetic risk factor for FOG in PD. This association seemed to be mainly mediated by Aβ-dependent pathways, but its Aβ-independent effects might also contribute to the development of FOG.

Objective To investigate serum inflammatory cytokine profiles in patients with isolated REM sleep behavior disorder (iRBD) and to explore whether these markers are associated with phenoconversion risk to α-synucleinopathies. Methods In this prospective cohort study, we analyzed serum samples from patients with polysomnography-confirmed iRBD (n = 30) and healthy controls (n = 12). We measured the following cytokines: interleukin (IL)-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-α (TNF-α). All patients underwent motor and non-motor evaluations and dopamine transporter imaging at baseline for predicting the phenoconversion risk. We followed the patients quarterly over up to 6 years to identify disease conversion. We also assessed longitudinal changes in cytokine levels from baseline at the 2- and 4-year follow-up visits. Results The baseline cytokine levels did not differ between the patients and controls. However, the TNF-α levels were significantly increased in a subgroup of the patients with multiple markers (≥3) for phenoconversion risk compared to those without (p = 0.008) and controls (p = 0.003). At longitudinal analyses, patients with TNF-α levels above the median showed a higher incidence of phenoconversion than those with lower TNF-α levels (47% vs. 7%; p = 0.008), and this significant association persisted after adjusting for covariates (p = 0.026). The cytokine levels over 4 years of follow-up period did not change significantly. Conclusions Our data suggest a possible link between serum TNF-α and phenoconversion risk in iRBD. Further studies are warranted to confirm the role of peripheral TNF-α in the pathogenesis of neurodegeneration in this disorder.

The American Joint Committee on Cancer 8th edition staging system presents separate classifications for pTNM and post-neoadjuvant ypTNM (ypTNM-8th) to enhance prognostic prediction after neoadjuvant therapy and surgery. We aimed to validate the ypTNM-8th staging system and to compare the prognostication performance of ypTNM-8th with that of pTNM-7th and pTNM-8th in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT).We reviewed 207 ESCC patients treated with nCRT between January 2007 and December 2014 and compared the Akaike information criterion (AIC) and Harrell's C-index to determine the prognostic performance of each TNM system.Survival curve analysis of pTNM-7th and -8th showed a stepwise drop in survival from ypT0N0 to advanced stages, whereas the survival outcome of ypStage III showed a better prognosis than that of ypStage II according to ypTNM-8th. Lymphovascular invasion, perineural invasion, and tumor regression grade were significantly associated with overall survival on univariate analysis. Each TNM system showed significant p-values for trend (p 0.0001 each), but after adjusting for prognostic factors, ypTNM-8th did not significantly predict survival (p = 0.15), whereas pTNM-7th remained significant (p 0.001). pTNM-7th incorporating ypT0N0M0 and ypT0 (is)N + M0 as separate groups was superior in prognostication as its AIC was smaller and its C-index was higher than those of pTNM-8th and ypTNM-8th, respectively.Because ypTNM-8th did not provide sufficient prognostication for patients with ESCC treated with nCRT followed by esophagectomy, more sophisticated prognostic classification should be developed for the ypTNM staging system in these patients.

Background Quantitative measurement of parkinsonian motor symptoms is crucial in clinical practice and in research. However, the widely used Unified PD Rating Scale (UPDRS) part III is based on a semi-quantitative evaluation with high inter- and intra-rater variability. Sensor-based measurements have been widely studied but are limited for their accessibility. Methods We analyzed 2D-RGB videos recording finger tapping and leg agility tests in 29 PD patients with a marker-less deep-learning based tracking algorithm. The tracking performance was validated with an accelerometer. Four parameters (mean amplitude, mean interpeak interval, amplitude variability and interpeak interval variability) were calculated from the position tracking. Results The performance of the video-tracking was in good agreement with the accelerometer-based tracking (Intra-class correlation coefficient > 0.9 for the peak amplitude, and >0.6 for the interpeak interval). The video-tracking successfully captured variable aspects of limb bradykinesia that have a distinct correlation with the general parkinsonian motor symptoms and gait. In the finger-tapping task, the mean amplitude (R = −0.6, p = 2.4 × 10−6), amplitude variability (R = 0.36, p = 0.0092), mean interpeak interval (R = 0.34, p = 0.014), and interpeak interval variability (R = 0.66, p = 1.4 × 10−7) was significantly correlated with the UPDRS scores. In leg agility test, the mean amplitude (R = −0.58, p = 1.7 × 10−5), mean interpeak interval (R = 0.37, p = 0.0088) and interpeak interval variability (R = 0.7, p = 6.2 × 10−8) were significantly correlated with the UPDRS scores, but not with amplitude variability (R = 0.17, p = 0.26). Limb rigidity was significantly correlated with the interpeak interval (R = 0.40, p = 0.0036) and its variability (R = 0.59, p = 4.2 × 10−6) in the leg agility test. Conclusion The video-based tracking could objectively measure limb bradykinesia in PD patients.

OBJECTIVES To investigate lymph node (LN) metastasis according to tumour location and assess the impact of lobe-specific LN dissection on survival in stage IA non-small-cell lung cancer (NSCLC). METHODS We retrospectively analysed the data of patients with clinical stage IA NSCLC treated with lobectomy and systematic LN dissection at Asan Medical Center (Seoul, Korea) between June 2005 and April 2017. Patients who received neoadjuvant therapy had multiple primary tumours or missed the follow-up during the first postoperative year were excluded. The patients were divided into five groups according to involved lung lobes: right upper lobe (RUL), right middle lobe (RML), right lower lobe (RLL), left upper lobe (LUL) and left lower lobe (LLL), which were further divided into subgroups according to LN station metastasis. Overall survival (OS) and the incidence of metastasis were calculated for each subgroup. Efficacy indices (EIs) were calculated to determine the correlation between each lung lobe and LN station, and the impact of the dissection of these stations on survival. RESULTS A total of 1202 patients were analysed. The 5-year OS in the RUL, RML, RLL, LUL and LLL groups was 74%, 88%, 78%, 80% and 75%, respectively. The incidence of single LN station metastasis was 11%, 10%, 10%, 16% and 14%, respectively. The lobe-specific LNs for RUL, RML, RLL, LUL and LLL were stations 2/3/4, 4/7, 2/4/7, 4/5/6 and 6/7/9, respectively. Moreover, the LN stations with high EIs for RUL, RML, RLL, LUL and LLL were 4, 7, 7, 5 and 7, respectively. In the RUL group, the incidence of metastasis to stations 2, 3 and 4 was 2.3%, 0.5% and 7.6%, and the EI was 0.8, 0.3 and 4.3, respectively. In RML, the incidence of metastasis to stations 4 and 7 was 4% and 6%, and the EI was 1.3 and 2.4, respectively. In RLL, the incidence of metastasis to stations 2, 4 and 7 was 4.4%, 5.6% and 8.3%, and the EI was 1.3, 1.4 and 3.3, respectively. In LUL, the incidence of metastasis to stations 4, 5 and 6 was 1.4%, 11.8% and 2.5%, and the EI was 0.4, 7.1 and 0.5, respectively. In LLL, the incidence of metastasis to stations 6, 7 and 9 was 1.1%, 5.7% and 1.7%, and the EI was 0.6, 2.3 and 0.5, respectively. Furthermore, the OS of patients with lobe-specific LN metastasis was statistically significantly different from that of the non-lobe-specific LN metastasis group with P-values of CONCLUSIONS Our findings support the use of lobe-specific LN dissection in stage IA NSCLC. When LN stations with high EI were negative, LN metastasis in other stations was unlikely. The incidence of LN metastasis beyond lobe-specific LN stations was ∼1% in all subgroups. Dissection of non-lobe-specific LNs may not improve the OS; however, prospective randomized controlled trials are needed to modify the standard approach.

Background The timeline of infections after lung transplantation has been changed with the introduction of new immunosuppressants and prophylaxis strategies. The study aimed to investigate the epidemiological characteristics of infectious diseases after lung transplantation in the current era. Materials and methods All patients who underwent lung or heart-lung transplantation at our institution between October 29, 2008 and April 3, 2019 were enrolled. We retrospectively reviewed the patients' medical records till April 2, 2020. Results In total, 100 consecutive lung transplant recipients were enrolled. The median follow-up period was 28 months after lung transplantation. A total of 127 post-lung transplantation bacterial infections occurred. Catheter-related bloodstream infection (25/84, 29.8%) was the most common within 6 months and pneumonia (23/43, 53.5%) was the most common after 6 months. Most episodes (35/40, 87.5%) of respiratory viral infections occurred after 6 months, mainly as upper respiratory infections. The remaining episodes (5/40, 12.5%) mostly manifested as lower respiratory tract infections. Seventy cytomegalovirus infections observed in 43 patients were divided into 23 episodes occurring before and 47 episodes occurring after discontinuing prophylaxis. Of 10 episodes of cytomegalovirus disease, four occurred during prophylaxis and six occurred after prophylaxis. Of 23 episodes of post-lung transplantation fungal infection, 7 were aspergillosis and all occurred after the discontinuation of prophylaxis. Conclusion Lung transplant recipients experienced a high burden of infection even after 6 months, especially after the end of the prophylaxis period. Therefore, these patients should be continued to be monitored long-term for infectious disease.

Background Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients. Methods Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected. Results Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% vs. 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% vs. 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% vs. 50.1%, P=0.040) and 5-year OS (86.5% vs. 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively). Conclusions PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer., Ku, Kim et al develop a method to analyse the ratio of the alternatively spliced variant of AIMP2 to full length AIMP via single-molecule RNA-FISH. They can subclassify hematologic cancer based on AIMP2-DX2/AIMP2 ratio and find that cells with high AIMP2-DX2 ratio can be sensitized to chemotherapy drugs by depleting AIMP2-DX2.

We evaluated the tolerability, pharmacokinetics (PK) and preliminary efficacy of KML001, an oral trivalent arsenical, as a monotherapy in patients with advanced solid tumors.With a standard 3 + 3 design for dose-escalation stage, the planned dose levels of KML001 were 5, 7.5, 10, 12.5, and 15 mg/day for 28 days. Once the maximum tolerated dose was determined, 22 subjects were additionally enrolled for dose-expansion stage. PK analysis was performed in the 5, 10, and 15 mg/day cohort at the dose-escalation stage and also at the dose-expansion stage. Moreover, response was assessed using the standard RECIST 1.1.A total of 45 Korean subjects were enrolled. No DLT was reported at the dose-escalation stage. Three DLTs, two cases of prolonged QTc interval and one of neutropenia, were reported in the 12.5 mg/day cohort at the dose-expansion stage. Higher total daily doses up to 12.5 mg/day of KML001 resulted in higher trough plasma concentrations. Among the 18 subjects who completed 2 cycles of therapy, 15 had progressive disease and 3 had stable disease.Doses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets.

Background This study aimed to evaluate the relationship between the history of late-life falling and the development of Parkinson’s disease (PD) and investigate whether depressive symptoms interact with falling to increase PD risk. Methods We identified 1,223,726 subjects without PD who underwent the National Screening Program for Transitional Age at 66 years between 2009 and 2013 using the National Health Cohort database. In this program, every participant was assessed whether they experienced falling for the past six months. Depressive symptoms were evaluated with a three-item questionnaire extracted from the Geriatric Depression Scale. Incident PD was traced for a mean 4.23 ± 1.50 years. Cox proportional hazard regression models were used to assess the risk of PD by falling history with and without depressive symptoms after adjusting for other confounding variables. Results In this cohort, the PD incidence rate was 1.30 and 1.03 cases per 1000 person-years in groups with and without falling and 1.34 and 1.00 cases per 1000 person-years in groups with and without depressive symptoms. The predictive risk of PD was increased by either a history of falling (HR = 1.24; 95% CI 1.11–1.40) or the presence of depressive symptoms (HR = 1.31; 95% CI 1.21–1.42) after adjusting for possible confounding variables. For individuals with both falling and depressive symptoms, PD risk increased further (HR = 1.66; 95% CI 1.40–1.97), but with sex-differences. The two factors increased PD risk in a sub-additive manner in men, whereas synergistically in women. Conclusions This national cohort database shows that late-life depressive symptoms accompanied by a falling event pose an increase in the risk of PD in older adults.

Owing to varying clinical definitions of anastomotic stricture following esophageal recon-struction, its reported incidence rate varies from 10% to 56%. Strictures adversely impact patients’ quality of life. Risk factors, such as the anastomosis method, leakage, ischemia, neoadjuvant chemoradiotherapy, and underlying disease have been mentioned, but con-flicting information has been reported. Balloon dilation is regarded as a safe and effective treatment method for patients with benign anastomotic strictures. Reoperations are sel-dom required. The etiology and management of anastomotic strictures are reviewed in this article.

Lymphovascular invasion (LVI) is a well-known poor prognostic factor after lobectomy for non-small cell lung cancer. However, the prognostic effect of LVI in patients who undergo sublobar resection has not been fully evaluated. Thus, we compared the prognostic impact of LVI in stage IA patients who underwent lobectomy or sublobar resection.We retrospectively reviewed the data from patients with stage IA NSCLC who underwent surgical resection between 2007 and 2016. The prognostic impact of LVI was calculated by the Cox proportional hazard regression model. To adjust for the differences in confounding variables between LVI-positive and LVI-negative patients, propensity score matching (PSM) was carried out in patients who underwent lobectomy or sublobar resection.Among the stage IA NSCLC patients (n = 2134), 184 (8.6%) had been diagnosed with LVI, of whom 144 (8.9%) were in the lobectomy group (n = 1614) and 40 (7.7%) were in the sublobar resection group (n = 520). In multivariable analysis, LVI was a significant risk factor for both overall survival (OS) (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.39-2.96; p0.001) and recurrence-free survival (RFS) (HR, 2.31; 95% CI, 1.68-3.17; p0.001). After PSM, the prognostic impact of LVI was greater in the sublobar resection group (HR = 4.93 and 4.25 for OS and RFS, respectively) than in the lobectomy group (HR = 1.77 and 2.51 for OS and RFS, respectively).The presence of LVI was significantly associated with worse OS and RFS in stage IA NSCLC patients. The prognostic impact of LVI was more pronounced in the sublobar resection group than in the lobectomy group.

Background The purpose of this study was to evaluate clinical and radiological outcomes at skeletal maturity after a calcaneo-cuboid-cuneiform osteotomy (triple C osteotomy) for symptomatic flatfoot deformity compared with healthy young adult controls. Methods Nineteen patients (30 feet) who undergone a triple C osteotomy for idiopathic symptomatic flatfeet from July 2006 to April 2013 were compared with 19 controls (38 feet). Radiographic measurements at preoperative examination, 1-year postoperative follow-up, and follow-up at skeletal maturity were evaluated. Functional outcomes were assessed by using the validated visual analog scale foot and ankle (VAS-FA) and the modified American Orthopaedic Foot and Ankle Surgery (AOFAS) score. Results In the triple C osteotomy group, 11 of 12 radiographic measurements were significantly improved at 1 year postoperatively and the last follow-up (p < 0.001). There was no recurrence at skeletal maturity (p > 0.05). There were no significant differences in nine of 12 radiographic measurements between the triple C osteotomy group at maturity and the control group (p > 0.05). Average VAS-FA and AOFAS scores were significantly improved at the time of skeletal maturity (p < 0.001). Conclusions Surgical correction of symptomatic flatfoot deformity in childhood resulted in favorable outcomes after the triple C osteotomy. Deformity correction was also maintained during follow-up at skeletal maturity.

In this study, we aimed to identify a candidate drug that can activate endogenous Angiopoietin 1 (Ang1) expression via drug repositioning as a pharmacological treatment for avascular osteonecrosis. After incubation with 821 drugs from the Food and Drug Administration (FDA)-approved drug library, Ang1 expression in U2OS cell culture media was examined by ELISA. Metformin, the first-line medication for treatment of type 2 diabetes, was selected as a candidate for in vitro and in vivo experimental evaluation. Ang1 was induced, and alkaline phosphatase activity was increased by metformin treatment in U2OS and MG63 cells. Wound healing and migration assay showed increased osteoblastic cell mobility by metformin treatment in U2OS and MG63 cells. Metformin upregulated expression of protein markers for osteoblastic differentiation in U2OS and MG63 cells but inhibited osteoclastic differentiation in Raw264.7 cells. Metformin (25 mg/kg) protected against ischemic necrosis in the epiphysis of the rat femoral head by maintaining osteoblast/osteocyte function and vascular density but inhibiting osteoclast activity in the necrotic femoral head. These findings provide novel insight into the specific biomarkers that are targeted and regulated by metformin in osteoblast differentiation and contribute to understanding the effects of these FDA-approved small-molecule drugs as novel therapeutics for ischemic osteonecrosis.

We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD).This population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years' observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI).3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P 0.0001 for interaction) and duration (P 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014).Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.

Silicon carbide (SiC) is well known as an excellent material for high performance optical applications because it offers many advantages over other commonly used glasses and metals. The excellent attributes of SiC include high strength, high hardness, low density, high thermal resistance, and low coefficient of thermal expansion. The effect of CO2 laser and its tool path on SiCwere investigated. The process started by creating laser pre-cracks on the desired pattern. Subsequently, laser assisted polishing was conducted on the same tool path. The surface showed a sharp increase in material removal in the areas with laser pre-cracks. This high difference in material removal was used not only to fabricate a ⌀ 1100 mm concave mirror with 127 μm in depth but also to generate macro and micro patterns. Grooves from 2 mm to 200 μm in width and 5 μm to 20 μm depth were successfully generated.

We evaluated serum gamma-glutamyltransferase (GGT) and the risk of Parkinson’s disease (PD). Using data from the National Health Insurance Service (NHIS) database, we constructed a cohort consisting of individuals aged above 40 years who underwent a health check-up in 2009. After excluding individuals with heavy alcohol consumption, hepatobiliary and pancreatic disorders, and a previous history of PD, each quartile group of baseline serum GGT levels was monitored for the development of PD for 7 years. Adjusted hazard ratios (HRs) for PD were estimated by Cox proportional hazard models adjusting for potential confounding variables. We additionally analyzed the possible interaction between GGT and obesity or metabolic syndrome. Among the 6,098,405 individuals who were included, PD developed in 20,895 individuals during the follow-up (0.34%, 9,512 men and 11,383 women). The top quartile of serum GGT (geometric means, 90.44 IU/L in men and 41.86 IU/L in women) was associated with a lower risk in men (adjusted HR = 0.72 (95% CI: 0.67–0.76)) and a higher risk in women (adjusted HR = 1.30 (95% CI: 1.23–1.37)) using the lower GGT quartiles as a reference. Obesity and metabolic syndrome increased PD risk in both sexes, and there was only a subadditive interaction between serum GGT and obesity in women.

All-dielectric binary gratings, with and without slab waveguides, are designed to generate polarization-independent guided-mode resonance filters (GMRFs) operating in the THz frequency region using the rigorous coupled-wave analysis (RCWA) method. The filling factor and thickness of the grating were adjusted to have equal resonance frequencies of transverse electric (TE)- and transverse magnetic (TM)-polarized THz beams. The single polarization-independent resonance for a binary grating without a slab waveguide was obtained at 0.459 THz with full width at half maximum (FWHM) values of 8.3 and 8.5 GHz for the TE and TM modes, respectively. Moreover, double-layered polarization-independent resonances for binary gratings with slab waveguides were obtained at 0.369 and 0.442 THz with very high Q-factors of up to 284. This is the first study to propose a polarization-independent GMRF with two resonant frequencies.

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular-level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular-level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2-3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte-vessel coverage and extravascular leakage indicating blood-brain barrier (BBB) dysfunction. At day 5, edema disappeared with recovery of pericyte-vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen-rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes appeared at the peri-infarct area early at day 2 and thereafter accumulated in the peri-infarct. Oral administration of a reversible monoamine oxidase B inhibitor significantly decreased the astrocyte reactivity and fibrous scar formation. Our result suggests that astrocyte reactivity may be a key target to alleviate the impact of microinfarction.

Despite the many comorbidities and the high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors have been based on small sample populations. The goal was to compare the accuracy of artificial intelligence (AI) analysis with that of conventional analysis for identifying the risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants.This nationwide prospective cohort study included 8,369 infants. The participants were divided into an sPDA group and a nonPDA group, and The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression as a standard analytic tool, five AI algorithms were used to identify the factors associated with sPDA. The combination of a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance on the PDA prediction tasks, and the ensemble methods showed the best performances.

We herein report a simultaneous frequency stabilization of two 780-nm external cavity diode lasers using a precision wavelength meter (WLM). The laser lock performance is characterized by the Allan deviation measurement in which we find $\sigma_{y}=10^{-12}$ at an averaging time of 1000 s. We also obtain spectral profiles through a heterodyne spectroscopy, identifying the contribution of white and flicker noises to the laser linewidth. The frequency drift of the WLM is measured to be about 2.0(4) MHz over 36 hours. Utilizing the two lasers as a cooling and repumping field, we demonstrate a magneto-optical trap of $^{87}$Rb atoms near a high-finesse optical cavity. Our laser stabilization technique operates at broad wavelength range without a radio frequency element., Comment: 6 pages, 5 figures

Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Purpose This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).Materials and Methods We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).Results We identified frequent molecular dysregulations in chromatin regulatory genes (KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1–positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1–negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1–positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1–positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.Conclusion Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.

OBJECTIVESubthalamic nucleus deep brain stimulation (STN DBS) is effective against freezing of gait (FOG) in Parkinson’s disease (PD); however, whether this effect persists over the long term is debated. The aim of the current study was to investigate the long-term effect of STN DBS on FOG in patients with PD.METHODSData on 52 cases in which PD patients received bilateral STN DBS were obtained from a prospective registry. The authors blindly analyzed FOG incidence and its severity from the videotapes of a 5-m walking task at the baseline and at the 1-, 2-, and 5- or 7-year follow-up visits. They also compared the axial score from the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, UPDRS part II (UPDRS-II) item 14, and the FOG questionnaire (FOG-Q). Postoperatively, video-based FOG analysis and the axial score were evaluated under 4 conditions (off-medication/off-stimulation, off-medication/on-stimulation, on-medication/off-stimulation, and on-medication/on-stimulation), and UPDRS-II item 14 and the FOG-Q score were evaluated under 2 conditions (off-medication/on-stimulation and on-medication/on-stimulation).RESULTSDuring the off-medication state, the on-stimulation condition improved FOG outcomes, except for video-based FOG severity, up to the last follow-up compared with the baseline. Video-based FOG outcomes and the axial score during the off-medication state were improved with the on-stimulation condition up to the last follow-up compared with the off-stimulation condition. During the on-medication state, the on-stimulation condition did not improve any FOG outcome compared with the baseline; however, it improved video-based FOG outcomes up to the 2-year follow-up and the axial score up to the last follow-up compared with the off-stimulation condition.CONCLUSIONSOur findings suggest that STN DBS has a long-term effect on FOG in the off-medication state. However, STN DBS did not show a long-term effect on FOG in the on-medication state, although it had a short-term effect until the 2-year follow-up.

Celecoxib is a selective cyclooxygenase-2 inhibitor widely used in patients with osteoarthritis and rheumatoid arthritis. Recently, nonclinical data on the inhibition of human ether-à-go-go-related gene potassium channels by celecoxib were reported, but there is no compelling evidence for this finding in humans. The aim of this study was to assess the potential effects of celecoxib on cardiac repolarization by conducting a thorough QT study, which was designed in compliance with the related guidelines.This randomized, open-label, positive- and negative-controlled, crossover clinical study was conducted in healthy male and female subjects. Each subject received, in 1 of 4 randomly assigned sequences, all of the following 3 interventions: celecoxib 400 mg once daily for 6 days; a single dose of moxifloxacin 400 mg, which served as a positive control to assess the assay sensitivity; and water without any drug, which served as a negative control. Serial 12-lead ECG and blood samples for pharmacokinetic analysis were collected periodically over 24 h. Individually RR-corrected QT intervals (QTcI) and Fridericia method-corrected QT intervals (QTcF) were calculated and evaluated.Twenty-eight subjects were allocated to 1 of the 4 intervention sequences. The largest time-matched mean effects of celecoxib on the QTcI and QTcF were5 ms, and the upper bounds of the 1-sided 95% CIs of those values did not exceed 10 ms. Moreover, none of the subjects had an absolute QTcI value of450 ms or a change from baseline in QTcI of60 ms after multiple administrations of celecoxib. The QTcI did not show a positive correlation with celecoxib concentrations in the range up to ~2700 μg/L. The overall effects of moxifloxacin on the QTcI and QTcF were enough to establish assay sensitivity. No serious adverse events were reported, with a total of 11 AEs reported in 8 subjects.Celecoxib caused no clinically relevant increase in the QT/QTc interval at the maximum dose level used in current practice settings. ClinicalTrials.gov identifier: NCT03822520.

Artificial muscle is one of the more prominent topics in modern robotics as it can be applied to robotic arms, electric vehicles and wearable robots (Shahinpoor et al. in Smart Mater Struct 7:15–30, 1998; Jani et al. in Mater Des 56:1078–1113, 2014). The advantages of Shape Memory Alloy (SMA) artificial muscle are lightness and high energy density. The high energy density allows the actuator to make powerful motions. Meanwhile, SMA wire contracts 6% of its length, which means that the required displacement cannot be achieved by a simple connection. To resolve these disadvantages, the SMA wires are coiled in a diamond-shaped structure. If the electric current is given by contracting wires in the longitudinal direction, the actuator can exert force and displacement in the diagonal direction. As the crossed tendon finds its minimal length when actuated, the rotation angle converges to 90°. Parameters related with the rotating motion were selected, such as SMA wires’ diameter and length, distance between the crossed part and elbow part, size of the diamond-shaped structure, friction, etc. To determine the maximum force of the actuator, a graphical method was used, which is similar to the yield strength determination (0.2% offset). Because the robotic elbow joint is connected by the tendon, the connections between links are flexible, and without motor it does not generate any sound or noise during operation. The robotic elbow joint using the SMA actuator is designed and analyzed, which can rotate 86.7° and generates maximum 56.3 N force.

Response spectrum analysis is widely employed in the seismic design of pile-supported wharves, as it can easily determine the maximum response of a structure. The analysis typically uses virtual fixed points to model the structure, without modelling the ground, as the structure is assumed to be a frame. Virtual fixed points can adequately simulate pile responses under horizontal static loads; however, pile responses under seismic loads have not been well studied. Therefore, the dynamic centrifuge tests evaluate the applicability of response spectrum analysis, using virtual fixed points, to the seismic design of a pile-supported wharf. Comparison of results from scale models (3 × 3 groups of piles from sections of Pohang New Port, Korea) with those from the analysis showed that the response spectrum analysis using virtual fixed points does not adequately simulate the natural period or pile bending moment of a pile-supported wharf system.

Arthroscopic fixation of a greater tuberosity (GT) avulsion fracture by suture bridge repair has been described in several articles. However, all of them have used arthroscopic fixation of a small sized GT fracture fragment or have not used purely arthroscopic techniques. In this Technical Note, the authors describe another technique for large displaced GT fracture fixation by arthroscopy only, without any metal fixation. Standard anterior, posterior, lateral, and posterolateral viewing portals are established with an accessory portal for suture anchor insertion. During intra-articular examination, an anteroinferior capsulolabral tear, upper one-third subscapularis tendon tear, and posterosuperior displaced bony fragment are detected. A subscapularis tendon was repaired by a single-row technique. After repair, medial row anchors are inserted into the bare area of infraspinatus tendon and the posterior edge of supraspinatus tendon. A 1-PDS suture is used to pass strands of fiberwire. As with the remplissage procedure, the fiberwire was passed with an 18-gauge needle. Following the acromioplasty, the medial row tightening was done by reducing the fracture fragment. After that, the lateral row anchor was inserted into the bicipital groove, completing the suture bridge technique. This technique can effectively treat other pathologies, has less radiation hazard, and results in fewer soft tissue injuries.

The objective of study was to compare the pharmacokinetic and safety profiles of a fixed‐dose combination (FDC) formulation of 5/160/20 mg amlodipine/valsartan/atorvastatin with those of separate formulations of a 5/160‐mg amlodipine/valsartan tablet and a 20‐mg atorvastatin tablet. This was a randomized, open‐label, single‐dose, 3‐sequence, 3‐period replicate crossover study with 42 subjects. Serial blood samples for pharmacokinetic assessment were collected up to 72 hours postdose. For establishing bioequivalence (BE) for amlodipine, valsartan, and atorvastatin, a reference‐scaled average BE approach was used if applicable, as well as the conventional limit of 0.80‐1.25. The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) for the maximum plasma concentration (Cmax) and the area under the curve to the last measurable concentration (AUCt) between the FDC and separate formulations were within the 0.80‐1.25 limit for all analytes but atorvastatin. The estimated within‐subject standard deviation of the log‐transformed values of the separate formulations, the reference intervention, was 0.3804 for the Cmax of atorvastatin, being set at 0.7489‐1.3352 for the BE acceptance limit. For both the Cmax and AUCt for atorvastatin, the GMRs lay within 0.80‐1.25, and the 90%CIs for the GMRs were within the BE acceptance limit. This 3‐period replicate crossover study demonstrated the BE of the FDC formulation of amlodipine, valsartan, and atorvastatin and the separate formulations of an amlodipine/valsartan tablet and an atorvastatin tablet. A similar incidence of treatment‐emergent adverse events (TEAEs) was observed in both interventions, and headache was the most common TEAE.

We have investigated designs for a superconducting single spoke resonator with a resonant frequency of 325 MHz and an optimum beta of 0.51. In this paper, we suggest a balloon variant of a spoke cavity having an end-wall structure, which has a distinct advantage from the viewpoint of multipacting suppression. We determined the geometric parameters of the balloon-shaped single spoke resonator through electromagnetic, multipacting, and mechanical simulations. In addition, we discuss the resonant frequency shifts caused by the cavity processing, the power coupling, and the cavity tuning.

Background/Aims The role of [18F]-f luorodeoxyglucose positron emission tomography-computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) in first remission is unclear. Methods Medical costs within the first 3 years of treatment completion and clinical outcomes of 118 patients with DLBCL in first remission with and without surveillance PET/CT (PET/CT [+] group [n = 76] and PET/CT [–] group [n = 42], respectively) were retrospectively analyzed. Results In a propensity matched cohort with adjustment for International Prognostic Index risk and relapse, the PET/CT (+) group was shown to have similar medical costs as the PET/CT (–) group. Relapse-free survival (RFS) and overall survival (OS) were comparable between the two groups (median RFS not reached [NR] for both groups, p = 0.133; median OS NR, p = 0.542). Among 76 patients with surveillance PET/CT, 31 (40.8%) had findings suggestive of recurrence and 16 of these (51.6%) were later confirmed to have recurrent disease. Fifteen patients (48.4%) were confirmed to not have recurrence after follow-up CT or PET/CT evaluation (n = 10) and biopsy (n = 4). None of the patients with negative PET/CT findings had disease recurrence. Sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT for detection of recurrence were 1, 0.75, 0.52, and 1, respectively. Conclusions Surveillance PET/CT resulted in similar clinical outcomes and medical costs compared to no surveillance PET/CT. Approximately half of patients with PET/CT findings of recurrence had no recurrence after follow-up imaging and biopsy, which would not have been carried out if PET/CT had not been performed in the first place.

Purpose Respiratory syncytial virus (RSV) infection can cause various neurological complications. This study aimed to investigate the RSV-associated neurologic manifestations that present with seizures. Methods We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea. Results During this period, 1,193 patients with laboratory-confirmed RSV infection were identified. Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizures. Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizures in 13 patients (13 of 27, 48.1%) and complex febrile seizures in 14 (14 of 27, 51.9%). Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient. Lower respiratory symptoms were not observed in 8 patients. In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy. Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient. Conclusion Although febrile seizure are the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizures was higher than that of those with general febrile seizures. Transient cytotoxic edema may be a pathogenic mechanism in RSV-related encephalopathy with seizures.

Objectives This study aimed to compare the predictive ability between the Masaoka-Koga (M-K) staging system and the 8th TNM staging system for the recurrence of thymic epithelial tumors (TETs). In addition, a nomogram was developed on the basis of the proposed TNM classification to predict individual recurrence rate. Methods A retrospective study was performed on 445 patients who underwent complete resection (R0) of TETs between January 2000 and February 2013. Concordance index (C-index) was used as a statistical indicator to quantify the prediction power of the prediction models. Results In multivariate analysis, tumor stage and WHO classification were independent recurrence factors in a predictive model on the basis of M-K and TNM stage. The TNM model showed higher C-index than the M-K model (0.837 vs 0.817). The nomogram, on the basis of the TNM model, revealed a highly predictive performance, with a bootstrap-corrected C-index of 0.85 (95% CI, 0.76 to 0.93). Conclusions A predictive model based on the 8th TNM stage was slightly better than that based on M-K stage with respect to recurrence after R0 of TETs. The proposed nomogram could be applied to estimate the individual recurrence rate and make decisions for proper surveillance.