Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety and efficacy of evoked gamma oscillation treatment using Cognito's medical device (CogTx-001) in participants with mild to moderate AD. Methods: The present study was a randomized, double blind, sham-controlled, 6-months clinical trial in participants with mild to moderate AD. The trial enrolled 76 participants, aged 50 or older, who met the clinical criteria for AD with baseline MMSE scores between 14 and 26. Participants were randomly assigned 2:1 to receive self-administered daily, one-hour, therapy, evoking EEG-verified gamma oscillations or sham treatment. The CogTx-001 device was use at home with the help of a care partner, over 6 months. The primary outcome measures were safety, evaluated by physical and neurological exams and monthly assessments of adverse events (AEs) and MRI, and tolerability, measured by device use. Although the trial was not statistically powered to evaluate potential efficacy outcomes, primary and secondary clinical outcome measures included several cognitive and functional endpoints. Results: Total AEs were similar between groups, there were no unexpected serious treatment related AEs, and no serious treatment-emergent AEs that led to study discontinuation. MRI did not show Amyloid-Related Imaging Abnormalities (ARIA) in any study participant. High adherence rates (85-90%) were observed in sham and treatment participants. There was no statistical separation between active and sham arm participants in primary outcome measure of MADCOMS or secondary outcome measure of CDR-SB or ADAS-Cog14. However, some secondary outcome measures including ADCS-ADL, MMSE, and MRI whole brain volume demonstrated reduced progression in active compared to sham treated participants, that achieved nominal significance. Conclusion: Our results demonstrate that 1-h daily treatment with Cognito's Evoked Gamma Therapy System (CogTx-001) was safe and well-tolerated and demonstrated potential clinical benefits in mild to moderate AD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03556280.

EDITOR SPOTLIGHT: Interview with Cholinergic Mechanisms Special Issue Guest Editor Hermona Soreq.

Hermona Soreq holds a Hebrew University Slesinger Chair in Molecular Neuroscience and is among the founding members of the Edmond and Lily Safra Center of Brain Sciences (ELSC). Soreq's research (H-impact: 98) focuses on acetylcholine (ACh)-related pathways and combines RNA-sequencing technologies, transgenic engineering, and molecular biology tests with in-depth analysis approaches. Her work addresses microRNAs (miRs) and transfer RNA fragments (tRFs) which have rapidly acquired wide recognition as global controllers of regulatory processes in healthy and diseased brain and body, including anxiety, inflammation, and cognition. Altogether, Soreq's work leads to molecular neuroscience-driven prevention and/or intervention with diseases involving impaired ACh signaling, including schizophrenia, bipolar disorder, Alzheimer's disease, and stress. Hermona led this Special Issue based on the 17th Symposium on Cholinergic Mechanisms (ISCM2022). We interviewed her on the progress in the field, what she wants to achieve as Senior Editor for the Gene Regulation and Genetics category at the Journal of Neurochemistry, key moments, and future directions.

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

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.

Neoadjuvant Nivolumab Therapy for Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. @*Materials and Methods@#Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). @*Results@#Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). @*Conclusion@#Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. @*Materials and Methods@#In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. @*Results@#The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. @*Conclusion@#The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy

Background@#The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. @*Methods@#Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m2 , n = 538), stage II (eGFR 60–89 mL/min/1.73 m2 , n = 953), and stage III–V (eGFR < 60 mL/min/1.73 m2 , n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. @*Results@#Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III–V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39–5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21’ 95% CI, 1.23–3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23–5.58; P = 0.012) was significantly increased. @*Conclusion@#This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60–89 mL/min/1.73 m2 ) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

EDITOR SPOTLIGHT: Interview with Brain Proteostasis Special Issue Guest Editor Mychael Lourenco.

Mychael Lourenco is an Assistant Professor of Neuroscience at the Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro. Research in his lab focusses on understanding the molecular mechanisms underlying cognitive impairment in neurodegeneration and his research on Alzheimer's disease has been recognized by many awards both in Brazil and internationally. He serves as a Reviews Editor for the Journal of Neurochemistry and led this special issue on Brain Proteostasis as a Guest Editor. Here we interviewed him to hear his thoughts on the future of neuroscience and on career development and training.

Minimal expression of dysferlin prevents development of dysferlinopathy in dysferlin exon 40a knockout mice.

Dysferlin is a Ca2+-activated lipid binding protein implicated in muscle membrane repair. Recessive variants in DYSF result in dysferlinopathy, a progressive muscular dystrophy. We showed previously that calpain cleavage within a motif encoded by alternatively spliced exon 40a releases a 72 kDa C-terminal minidysferlin recruited to injured sarcolemma. Herein we use CRISPR/Cas9 gene editing to knock out murine Dysf exon 40a, to specifically assess its role in membrane repair and development of dysferlinopathy. We created three Dysf exon 40a knockout (40aKO) mouse lines that each express different levels of dysferlin protein ranging from ~ 90%, ~ 50% and ~ 10-20% levels of wild-type. Histopathological analysis of skeletal muscles from all 12-month-old 40aKO lines showed virtual absence of dystrophic features and normal membrane repair capacity for all three 40aKO lines, as compared with dysferlin-null BLAJ mice. Further, lipidomic and proteomic analyses on 18wk old quadriceps show all three 40aKO lines are spared the profound lipidomic/proteomic imbalance that characterises dysferlin-deficient BLAJ muscles. Collective results indicate that membrane repair does not depend upon calpain cleavage within exon 40a and that ~ 10-20% of WT dysferlin protein expression is sufficient to maintain the muscle lipidome, proteome and membrane repair capacity to crucially prevent development of dysferlinopathy.

The Role of Adjuvant Chemotherapy after Neoadjuvant Chemoradiotherapy Followed by Surgery in Patients with Esophageal Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to investigate the efficacy of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CCRTx) followed by surgery in patients with esophageal squamous cell carcinoma (ESCC). @*Materials and Methods@#We retrospectively analyzed the data from 382 patients who received neoadjuvant CCRTx and esophagectomy for ESCC between 2003 and 2018. @*Results@#This study included 357 (93.4%) men, and the years median patient age was 63 (range, 40 to 84 years). Overall, 69 patients (18.1%) received adjuvant chemotherapy, whereas 313 patients (81.9%) did not. The median follow-up period was 28.07 months (interquartile range, 15.50 to 62.59). The 5-year overall survival (OS) and disease-free survival were 47.1% and 42.6%, respectively. Adjuvant chemotherapy did not improve OS in all patients, but subgroup analysis revealed that adjuvant chemotherapy improved the 5-year OS in patients with ypT+N+ (24.8% vs. 29.9%, p=0.048), whereas the survival benefit of adjuvant chemotherapy was not observed in patients with ypT0N0, ypT+N0, or ypT0N+. Multivariable analysis revealed that ypStage and adjuvant chemotherapy (hazard ratio, 0.601; p=0.046) were associated with OS in patients with ypT+N+. Freedom from distant metastasis was marginally different according to the adjuvant chemotherapy (48.3% vs. 41.3%, p=0.141). @*Conclusion@#Adjuvant chemotherapy after neoadjuvant therapy followed by surgery reduces the distant metastasis in ypT+N+ ESCC patients, thereby improving the OS. The consideration could be given to administration of adjuvant chemotherapy to ypT+N+ ESCC patients with tolerable conditions.

Sublobar Resection versus Stereotactic Body Radiation Therapy for Clinical Stage I Non–Small Cell Lung Cancer: A Study Using Data from the Korean Nationwide Lung Cancer Registry / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Stereotactic body radiotherapy (SBRT) had been increasingly recognized as a favorable alternative to surgical resection in patients with high risk for surgery. This study compared survival outcomes between sublobar resection (SLR) and SBRT for clinical stage I non–small cell lung cancer (NSCLC). @*Materials and Methods@#Data were obtained from the Korean Association of Lung Cancer Registry, a sampled nationwide database. This study retrospectively reviewed 382 patients with clinical stage I NSCLC who underwent curative SLR or SBRT from 2014 to 2016. @*Results@#Of the patients, 43 and 339 underwent SBRT and SLR, respectively. Patients in the SBRT group were older and had worse pulmonary function. The 3-year overall survival (OS) rate was significantly better in the SLR group compared with the SBRT group (86.6% vs. 57%, log-rank p < 0.001). However, after adjusting for age, sex, tumor size, pulmonary function, histology, smoking history, and adjuvant therapy, treatment modality was not an independent prognostic factor for survival (hazard ratio, 0.99; 95% confidence interval, 0.43 to 2.77; p=0.974). We performed subgroup analysis in the following high-risk populations: patients who were older than 75 years; patients who were older than 70 years and had diffusing capacity of lung for carbon monoxide ≤ 80%. In each subgroup, there were no differences in OS and recurrence-free survival between patients who underwent SLR and those who received SBRT. @*Conclusion@#In our study, there were no significant differences in terms of survival or recurrence between SBRT and SLR in medically compromised stage I NSCLC patients. Our findings suggest that SBRT could be considered as a potential treatment option for selected patients.

Prognostic and Safety Implications of Renin-Angiotensin-Aldosterone System Inhibitors in Hypertrophic Cardiomyopathy: A Real-World Observation Over 2,000 Patients

Background and Objectives@#The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. @*Methods@#We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). @*Results@#RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. @*Conclusions@#RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. @*Materials and Methods@#The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. @*Results@#We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non–small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). @*Conclusion@#In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. @*Materials and Methods@#The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. @*Results@#The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. @*Conclusion@#Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

Psychometric Validation of the Korean Version of the Cancer Survivors’ Unmet Needs (CaSUN) Scale among Korean Non–Small Cell Lung Cancer Survivors / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of the study was to validate the Korean version of Cancer Survivors’ Unmet Needs (CaSUN) scale among non–small cell lung cancer survivors. @*Materials and Methods@#Participants were recruited from outpatient clinics at the Samsung Medical Center in Seoul, South Korea, from January to October 2020. Participants completed a survey questionnaire that included the CaSUN. Exploratory and confirmatory factor analysis and Pearson’s correlations were used to evaluate the reliability and validity of the Korean version of the CaSUN (CaSUN-K). We also tested known-group validity using an independent t test or ANOVA. @*Results@#In total, 949 provided informed consent and all of which completed the questionnaire. Among the 949 patients, 529 (55.7%) were male; the mean age and median time since the end of active treatment (standard deviation) was 63.4±8.8 years and the median was 18 months. Although the factor loadings were different from those for the original scale, the Cronbach’s alpha coefficients of the six domains in the CaSUN-K ranged from 0.68 to 0.95, indicating satisfactory internal consistency. In the CFA, the goodness-of-fit indices for the CaSUN-K were high. Moderate correlations demonstrated the convergent validity of CaSUN-K with the relevant questionnaire. More than 60% of the participants reported information-related unmet needs, and the CaSUN-K discriminated between the needs reported by the different subgroups that we analyzed. @*Conclusion@#The CaSUN-K is a reliable and valid measure for assessing the unmet needs in a cancer population, thus this tool help population to receive timely, targeted, and relevant care.

MRI-Based Stepwise Approach to Anterior Mediastinal Cystic Lesions for Diagnosis and Further Management

As the majority of incidentally detected lesions in the anterior mediastinum is small nodules with soft tissue appearance, the differential diagnosis has typically included thymic neoplasm and prevascular lymph node, with benign cyst. Overestimation or misinterpretation of these lesions can lead to unnecessary surgery for ultimately benign conditions. Diagnosing mediastinal cysts using MRI serves as a problem-solving modality in distinguishing between surgical and nonsurgical anterior mediastinal lesions. The pitfalls of MRI evaluation for anterior mediastinal cystic lesions are as follows: first, we acknowledge the limitation of T2-weighted images for evaluating benign cystic lesions. Due to variable contents within benign cystic lesions, such as hemorrhage, T2 signal intensity may be variable. Second, owing to extensive necrosis and cystic changes, the T2 shine-through effect may be seen on diffusion-weighted images (DWI), and small solid portions might be missed on enhanced images.Therefore, both enhancement and DWI with apparent diffusion coefficient values should be considered. An algorithm will be suggested for the diagnostic evaluation of anterior mediastinal cystic lesions, and finally, a management strategy based on MRI features will be suggested.

Thalidomide and a Dipeptidyl Peptidase 4 Inhibitor in a Rat Model of Experimental Autoimmune Myocarditis

Background and Objectives@#Myocarditis is a potentially fatal disease, but curative treatments have not yet been established. Myocardial inflammation is an important pathogenesis of this disease, and immunosuppressants such as methylprednisolone and immunoglobulin have been used for treatment; however, the effectiveness needs to be improved. Thalidomide and dipeptidyl peptidase (DPP) 4 inhibitors were recently investigated regarding their immunomodulatory properties. This study aimed to test whether thalidomide or a DPP4 inhibitor (evogliptin) can improve the effectiveness of myocarditis treatment using a rat model of experimental autoimmune myocarditis (EAM). @*Methods@#Rats with or without myocarditis were administered thalidomide at 100 mg/ kg/day and DPP4 inhibitor at 10 mg/kg/day orally. Measurement of echocardiography, serum inflammatory cytokines, myocardial histopathological examination, and immunohistochemical staining for leukocytes, macrophages, CD4+ T cells, and cytoskeleton were performed after 3 weeks, and the fibrosis area was measured after 3 and 6 weeks. @*Results@#Thalidomide and DPP4 inhibitor did not reduce the severity of myocarditis compared with the EAM without treatment rats by comparing the echocardiographic data, myocardial CD4 + , macrophages, neutrophil infiltrations, and the heart weight/body weight ratio in 3 weeks. The levels of inflammatory cytokines were not lower in the thalidomide and DPP4 inhibitor-treated group than in the untreated group in 3 weeks. In 6 weeks, thalidomide and DPP4 inhibitors did not reduce the fibrosis area compared to untreated groups. @*Conclusions@#Although thalidomide and the DPP4 inhibitor had an immunomodulatory effect and are used against inflammatory diseases, they did not ameliorate myocardial inflammation and fibrosis in this rat model of EAM.

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score

Background@#This study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer. @*Methods@#This retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting longterm outcomes. @*Results@#Of the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001). @*Conclusion@#Stratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.

Major Clinical Issues in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is one of the most common inheritable cardiomyopathies. Contemporary management strategies, including the advent of implantable cardioverter-defibrillators and effective anticoagulation, have substantially improved the clinical course of HCM patients; however, the disease burden of HCM is still high in Korea. Sudden cardiac death (SCD), atrial fibrillation and thromboembolic risk, dynamic left ventricular outflow tract (LVOT) obstruction, and heart failure (HF) progression remain important issues in HCM. SCD in HCM can be effectively prevented with implantable cardioverter-defibrillators. However, appropriate patient selection is important for primary prevention, and the 5-year SCD risk score and the presence of major SCD risk factors should be considered. Anticoagulation should be initiated in all HCM patients with atrial fibrillation regardless of the CHA 2 DS 2 -VASc score, and non-vitamin K antagonist oral anticoagulants are the first option. Symptomatic dynamic LVOT obstruction is first treated medically with negative inotropes, and if symptoms persist, septal reduction therapy is considered. The recently approved myosin inhibitor mavacamten is promising. HF in HCM is usually related to diastolic dysfunction, while about 5% of HCM patients show reduced left ventricular ejection fraction <50%, also referred to as “end-stage” HCM. Myocardial fibrosis plays an important role in the progression to advanced HF in patients with HCM. Patients who do not respond to guideline-directed medical therapy can be considered for heart transplantation. The development of imaging techniques, such as myocardial deformation on echocardiography and late gadolinium enhancement on cardiac magnetic resonance, can provide better risk evaluation and decision-making for management strategies in HCM.

Prognosis for Pneumonic-Type Invasive Mucinous Adenocarcinoma in a Single Lobe on CT: Is It Reasonable to Designate It as Clinical T3?

Objective@#To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA. @*Materials and Methods@#From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan–Meier method.Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA. @*Results@#The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (p = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (p = 0.11 and p = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95–11.11), p < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59–12.89), p = 0.005 for OS}. @*Conclusion@#The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.