SCI 발표논문

2022년 265편

2352022

제1저자 김진영, 정지윤 · 교신저자 박완범, 이경훈

, , , , , , , , , , ,
Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer.
Front Immunol. 2022;13:1028102.

Abstract
INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC).
METHODS In this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group.
RESULTS All participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC.
CONCLUSION In the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.
PubMed IF 7 감염내과
2342022

제1저자 배난영, 이소령 · 교신저자 최의근

, , , , , , , , ,
Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study.
Cardiovasc Diabetol. 2022;21(1):251.

Abstract
BACKGROUND It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF.
METHODS Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed.
RESULTS Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17-1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12-1.17], 1.15 [1.13-1.18], and 1.19 [1.67-1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not.
CONCLUSIONS Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.
PubMed IF 15.6 순환기내과
2332022

제1저자 윤동환 · 교신저자 한승석

, , , , , , ,
Robust R-peak detection in an electrocardiogram with stationary wavelet transformation and separable convolution.
Sci Rep. 2022;12(1):19638.

Abstract
R-peak detection is an essential step in analyzing electrocardiograms (ECGs). Previous deep learning models reported their performance primarily in a single database, and some models did not perform at the highest levels when applied to a database different from the testing database. To achieve high performances in cross-database validations, we developed a novel deep learning model for R-peak detection using stationary wavelet transform (SWT) and separable convolution. Three databases (i.e., the MIT-BIH Arrhythmia [MIT-BIH], the Institute of Cardiological Technics [INCART], and the QT) were used in both the training and testing models, and the MIT-BIH ST Change (MIT-BIH-ST), European ST-T, TELE and MIT-BIH Noise Stress Test (MIT-BIH-NST) databases were further used for testing. The detail coefficient of level 4 decomposition by SWT and the first derivative from filtered ECGs were used for model inputs, and the interval of 150 ms centered at marked peaks was used for labels. Separable convolution with atrous spatial pyramidal pooling was selected as the model's architecture, and noise-augmented waveforms of 5.69 s duration (2048 size in 360 Hz) were used in training. The model performance was evaluated using cross-database validation. The F1 scores of the peak detection model were 0.9994, 0.9985, and 0.9999 in the MIT-BIH, INCART, and QT databases, respectively. When the above three databases were pooled, the F1 scores were 0.9993 for fivefold cross-validation and 0.9991 for cross-database validation. The model performance remained high for MIT-BIH-ST, European ST-T, and TELE, with F1 scores of 0.9995, 0.9988, and 0.9790, respectively. The model performance when trained by severe noise augmentation increased for the MIT-BIH-NST database (F1 scores from 0.9504 to 0.9759) and decreased for the MIT-BIH database (F1 scores from 0.9994 to 0.9991). The present SWT and separable convolution-based model for R-peak detection yields a high performance even for cross-database validations.
PubMed IF 4.9 신장내과
2322022

제1저자 강은정, 이욱비, 김보라 · 교신저자 오국환, 조주연

, , , , , , , , , , , ,
Identification of Serum Metabolites for Predicting Chronic Kidney Disease Progression according to Chronic Kidney Disease Cause.
Metabolites. 2022;12(11):metabo12111125.

Abstract
Early detection and proper management of chronic kidney disease (CKD) can delay progression to end-stage kidney disease. We applied metabolomics to discover novel biomarkers to predict the risk of deterioration in patients with different causes of CKD. We enrolled non-dialytic diabetic nephropathy (DMN, n = 124), hypertensive nephropathy (HTN, n = 118), and polycystic kidney disease (PKD, n = 124) patients from the KNOW-CKD cohort. Within each disease subgroup, subjects were categorized as progressors (P) or non-progressors (NP) based on the median eGFR slope. P and NP pairs were randomly selected after matching for age, sex, and baseline eGFR. Targeted metabolomics was performed to quantify 188 metabolites in the baseline serum samples. We selected ten progression-related biomarkers for DMN and nine biomarkers each for HTN and PKD. Clinical parameters showed good ability to predict DMN (AUC 0.734); however, this tendency was not evident for HTN (AUC 0.659) or PKD (AUC 0.560). Models constructed with selected metabolites and clinical parameters had better ability to predict CKD progression than clinical parameters only. When selected metabolites were used in combination with clinical indicators, random forest prediction models for CKD progression were constructed with AUCs of 0.826, 0.872, and 0.834 for DMN, HTN, and PKD, respectively. Select novel metabolites identified in this study can help identify high-risk CKD patients who may benefit from more aggressive medical treatment.
PubMed IF 4.5 신장내과
2312022

제1저자 한민주, 이소령 · 교신저자 최의근

, , , , , , , , ,
The impact of socioeconomic deprivation on the risk of atrial fibrillation in patients with diabetes mellitus: A nationwide population-based study.
Front Cardiovasc Med. 2022;9:1008340.

Abstract
OBJECTIVE To evaluate the relationship between socioeconomic status and the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM).
RESEARCH DESIGN AND METHODS From the National Health Insurance Service (NHIS) database, we identified 2,429,610 diabetic patients who underwent national health check-ups between 2009 and 2012. Tracing back the subjects for 5 years from the date of health check-up, we determined the subjects' income and whether they received medical aid (MA) during the past 5 years. Subjects were divided into six groups according to the number of years of receiving (MA groups 0 through 5) and into four groups according to socioeconomic status change during the past 5 years. We estimated the risk of AF for each group using the Cox proportional-hazards model.
RESULTS During a median follow-up of 7.2 ± 1.7 years, 80,257 were newly identified as AF. The MA groups showed a higher risk of AF than the non-MA group with the hazard ratios (HRs) and 95% confidence interval (CI) 1.32 (1.2-1.44), 1.33 (1.22-1.45), 1.23 (1.13-1.34), 1.28 (1.16-1.4), and 1.50 (1.39-1.63) for MA groups 1 through 5, respectively. Dividing subjects according to socioeconomic condition change, those who experienced worsening socioeconomic status (non-MA to MA) showed higher risk compared to the persistent non-MA group (HR 1.54; 95% CI 1.38-1.73).
CONCLUSION Low socioeconomic status was associated with the risk of AF in patients with diabetes. More attention should be directed at alleviating health inequalities, targeting individuals with socioeconomic deprivation to provide timely management for AF.
PubMed IF 3 순환기내과
2302022

제1저자 김학령, 전원경 · 교신저자 김학령

, , , , , , ,
Brachial-ankle pulse wave velocity as a predictor of long-term cardiovascular events in 2174 subjects with type 2 diabetes mellitus: A retrospective cohort study.
Medicine (Baltimore). 2022;101(45):e31758.

Abstract
The prognostic value of arterial stiffness in patients with diabetes mellitus (DM) remains unclear. The aim of this study was to investigate the association between brachial-ankle pulse wave velocity (baPWV) and the occurrence of cardiovascular events in people with DM. A total of 2714 subjects (mean age, 63.6 years; males, 59.3%) with type 2 DM and without documented cardiovascular disease and stroke were analyzed. The primary end-point of this study was composite cardiovascular events of cardiac death, non-fatal myocardial infarction, coronary revascularization and stroke. There were 118 composite events (4.3%) during a median follow-up period of 3.84 years (interquartile range, 1.60-5.52 years). In multivariable Cox regression analysis, higher baPWV (≥1672 cm/s) was associated with composite events even after controlling for potential confounders (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.31-3.07; P = .001). Compared to the lowest baPWV tertile, both middle (HR, 1.84; 95% CI, 1.03-3.27; P = .037) and the highest (HR, 2.97; 95% CI, 1.69-5.22; P < .001) tertile of baPWV were associated with increased risk of cardiovascular events in the same multivariable model. In conclusion, the baPWV was associated with cardiovascular events in people with type 2 DM. Considering the simplicity and convenience of baPWV measurement, baPWV may be useful for risk stratification of people with type 2 DM.
PubMed IF 2 순환기내과
2292022

제1저자 신동엽, 임규민 · 교신저자 윤성수, 이동순

, , , , ,
The importance of critically short telomere in myelodysplastic syndrome.
Biomark Res. 2022;10(1):79.

Abstract
A few critically short telomeres trigger genomic instability regardless of average telomere length (TL). Recently, the telomere shortest length assay (TeSLA) was developed to detect critically short telomeres and measure absolute telomeres. Using TeSLA with the internally labeled biotin probe, we measured the TL of bone marrow (BM) aspirates from 52 patients with myelodysplastic syndrome (MDS). A percentage of shortest telomeres (< 1.0 kb (ShTL1.0)) were calculated. ShTL1.0 was correlated to IPSS-R risk (spearman's rho = 0.35 and p = 0.0196), and ShTL1.0 and BM blast (2.61% in < 5% blast, 4.15% in 5-10% blast, and 6.80% in 10-20% blast, respectively, p = 0.0332). Interestingly, MDS patients with a shortest TL ≥ 0.787 kb at the time of diagnosis showed better overall survival (OS) and progression-free survival (PFS) than patients with a shortest TL < 0.787 kb in the multivariate analyses (HR = 0.13 and 0.30, p = 0.011 and 0.048 for OS and PFS, respectively). Our results clearly show the presence and abundance of critically short telomeres in MDS patients. These pathologic telomeres are associated with IPSS-R which is a validated prognostic scoring system in MDS. Furthermore, they are independent prognostic factors for OS in MDS patients. Future prospective studies are needed to validate our results.
PubMed IF 14.6 혈액종양내과
2282022

제1저자 김선미 · 교신저자 오국환

, , , , , , , , ,
Associations among body composition parameters and quality of life in peritoneal dialysis patients.
Sci Rep. 2022;12(1):19192.

Abstract
Health-related quality of life (HRQOL) is an important issue among patients undergoing dialysis treatment. Peritoneal dialysis (PD) is associated with a number of adverse body composition changes. However, whether body composition is associated with HRQOL is uncertain. The purpose of this study was to analyze the effects of body composition on HRQOL in PD patients. We performed a cross-sectional observational study on the association between body composition and HRQOL in PD patients at a single center. Body composition was determined by multifrequency bioimpedance spectroscopy. HRQOL is summarized to three composite scores: kidney disease component summary (KDCS), physical component summary (PCS), and mental component summary (MCS). The relationships between HRQOL and the hydration index, lean tissue index (LTI), and fat tissue index (FTI) were analyzed by regression analysis. One hundred and ninety-seven PD patients were included in the present study. Patients with severe fluid overload showed a lower PCS. The hydration index and FTI showed statistically significant negative associations with PCS. In subgroup analysis, the associations between the hydration index and PCS remained robust after stratifying according to sex, age, and residual urine. Our results indicated that both the hydration index and FTI were negatively associated with HRQOL, especially PCS.
PubMed IF 4.9 신장내과
2272022

제1저자 김학령 · 교신저자 신진호, 성기철

, , , , ,
Lack of the association between height and cardiovascular prognosis in hypertensive men and women: analysis of national real-world database.
Sci Rep. 2022;12(1):18953.

Abstract
Data on the association between height and cardiovascular risk are still conflicting. Moreover, no reports are showing this issue in hypertensive patients. This study was performed to investigate whether height affects cardiovascular prognosis in hypertensive patients using nation-wide real-world data. Using the Korean National Health Insurance Service database, we analyzed 461,492 Korean hypertensive patients without any prior history of cardiovascular disease between January 2002 and December 2017. The incidence of a composite of cardiovascular death, myocardial infarction, and stroke was assessed according to height quintiles. In univariable comparisons, the taller the patients, the younger the age and the higher the proportion of men. In multivariable cox regression analyses, height was not associated with the occurrence of cardiovascular events. Although the risk of clinical events increased in some height quintiles compared to the first height quintile, there was no tendency to increase the risk according to the increase in the height quintile. These results were similar even when men and women were analyzed separately. In the same quintile group of height, there were no significant differences in clinical outcomes between sexes. In Korean hypertensive patients, there was no association between height and the occurrence of cardiovascular events. This result did not differ by sex. The clinical use of height for CVD prediction seems to be still tricky in hypertensive patients.
PubMed IF 4.9 순환기내과
2262022

제1저자 장동기, 최진호 · 교신저자 한경도, 이상협

, , , , , ,
Risk of cardiovascular disease and mortality in patients with diabetes and acute pancreatitis history: a nationwide cohort study.
Sci Rep. 2022;12(1):18730.

Abstract
Patients with acute pancreatitis (AP) may have an increased risk of cardiovascular disease (CVD). Few studies have dealt with the association between AP and the risk of CVD in diabetic patients. This study aimed to investigate the risk of CVD and mortality in patients with diabetes and AP history by analyzing a large-scale national claims database in Korea. Data from the Korean National Health Insurance Service database was analyzed. A total of 2,746,988 participants with type 2 diabetes mellitus that underwent a general health examination between 2009 and 2012 were enrolled. The participants were divided into two groups according to AP history (yes or no) prior to the examination date, and follow-up data until 2018 was analyzed. The primary endpoint was the occurrence of stroke, myocardial infarction (MI), or death. The Cox proportional hazards regression analysis was used to evaluate the association between AP history and the risk of stroke, MI, and mortality. After exclusion, the included number of participants with and without AP history were 3,810 and 2,258,910, respectively. The presence of AP history showed a significantly higher incidence of stroke, MI, and mortality. The adjusted hazard ratios (95% confidence interval) for the risk of stroke, MI, and mortality were 1.534 (1.342-1.753), 1.998 (1.733-2.303), and 2.353 (2.200-2.515), respectively. Age < 65, male sex, current smoking, and drinking significantly increased the risk of death in the subgroup analyses. The risk of stroke, MI, and mortality was significantly higher in diabetic participants with AP history than those without AP history at 9-year follow-up. This suggests that active management of cardiovascular risk factors is necessary in diabetic patients with AP history.
PubMed IF 4.9 소화기내과
2252022

제1저자 박진, 강수진 · 교신저자 윤혁

, , , , , , , , , ,
Histologic Evaluation Using the Robarts Histopathology Index in Patients With Ulcerative Colitis in Deep Remission and the Association of Histologic Remission With Risk of Relapse.
Inflamm Bowel Dis. 2022;28(11):1709-1716.

Abstract
BACKGROUND This study prospectively evaluated the risk of relapse according to the status of histologic activity in patients with ulcerative colitis (UC) who achieved deep remission.
METHODS Patients with UC in clinical remission (partial Mayo score ≤1) and endoscopic remission (ulcerative colitis endoscopic index of severity ≤1) were enrolled. Rectal biopsies were performed in patients, and histologic remission was defined as a Robarts histopathology index of ≤3. Receiver-operating characteristic curve analysis was conducted to determine fecal calprotectin cutoff values for histologic remission. The cumulative risk of relapse was evaluated using the Cox proportional hazards model.
RESULTS Among the 187 patients enrolled, 82 (43.9%) achieved histologic remission. The best cutoff value of fecal calprotectin for predicting histologic remission was 80 mg/kg (area under the curve of 0.646, sensitivity of 74%, and specificity of 61%). Among 142 patients who were followed up for >3 months, 56 (39.4%) showed clinical relapse during a median of 42 weeks. The risk of relapse was lower in patients with histologic remission than in those with histologic activity (P = .026). In multivariable analysis, histologic remission (hazard ratio [HR], 0.551; 95% confidence interval [CI], 0.316-0.958; P = .035), elevated C-reactive protein levels (HR, 3.652; 95% CI, 1.400-9.526; P = .008), and history of steroid use (HR, 2.398; 95% CI, 1.196-4.808; P = .014) were significantly associated with clinical relapse.
CONCLUSIONS In patients with UC who achieved clinical and endoscopic remission, histologic remission was independently associated with a lower risk of clinical relapse.
PubMed IF 5.5 소화기내과
2242022

제1저자 장우영, 김봉영 · 교신저자 김홍빈

, , , , , , , , , ,
Differences in strategies for prevention of COVID-19 transmission in hospitals: nationwide survey results from the Republic of Korea.
J Hosp Infect. 2022;129:22-30.

Abstract
BACKGROUND Hospital infection control measures against coronavirus disease 2019 (COVID-19) are often based on expert discretion due to the lack of detailed guidelines.
AIM To survey the current strategies for preventing the transmission of COVID-19 in medical institutions.
METHODS Thirteen key issues related to the prevention of COVID-19 transmission within medical institutions were selected via discussion among infectious diseases specialists, and related critical questions were obtained following a review of national-level guidelines in government databases. Six hospitals had an open survey between 11^th and 25^th August 2020 to provide responses to these topics. An online questionnaire developed from these data was sent to infection control teams at 46 hospitals in South Korea between 31^st January 2021 and 20^th February 2021.
FINDINGS All 46 hospitals responded to the survey. All operated screening clinics, but 89.1% (41/46) allowed symptomatic patients without COVID-19-associated symptoms to visit general outpatient clinics. Most hospitals (87.2%, 34/39) conducted polymerase chain reaction (PCR) tests for all hospitalized patients. Of 35/46 (76.1%) hospitals with pre-emptive isolation policies for hospitalized patients, 31 (88.6%) released patients from isolation after a single negative PCR test, while most (76.9%, 20/26) allowed shared-room accommodation for patients meeting the national criteria for release from isolation despite positive PCR results with above cycle threshold values (34.6%, 9/26), or after a certain period that satisfied the national criteria (26.9%, 7/26).
CONCLUSION Individual hospitals in South Korea are currently relying on experience to frame relevant guidelines, and responded differently to some infection control issues on hospital settings during the COVID-19 pandemic.
PubMed IF 3.4 감염내과
2232022

제1저자 이승미 · 교신저자 김원, 박중식

, , , , , , , , , , , , , , , , ,
Metabolic Dysfunction-Associated Fatty Liver Disease and Subsequent Development of Adverse Pregnancy Outcomes.
Clin Gastroenterol Hepatol. 2022;20(11):2542-2550.e8.

Abstract
BACKGROUND & AIMS Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), rather than nonalcoholic fatty liver disease (NAFLD), was proposed to better describe liver disease associated with metabolic dysfunction (MD). In this study, we attempted to investigate the impact of MAFLD on pregnancy complications.
METHODS The current study is a secondary analysis of a multicenter prospective cohort designed to examine the risk of NAFLD during pregnancy. In the first trimester, enrolled pregnant women were evaluated for hepatic steatosis by liver ultrasonography, and blood samples were collected for biochemical measurements. The study population was divided into 3 groups: no NAFLD, hepatic steatosis but without metabolic dysfunction (non-MD NAFLD), and MAFLD. The primary outcome was the subsequent development of adverse pregnancy outcomes, including gestational diabetes mellitus, pregnancy-associated hypertension, preterm birth, and fetal growth abnormalities.
RESULTS The study population consisted of 1744 pregnant women, including 1523 with no NAFLD, 43 with non-MD NAFLD, and 178 with MAFLD. The risk of subsequent development of adverse pregnancy outcomes was higher in MAFLD than in non-MD NAFLD (adjusted odds ratio, 4.03; 95% CI, 1.68-9.67), whereas the risk was not significantly different between no NAFLD and non-MD NAFLD. Among women with no NAFLD, the presence of MD increased the risk of adverse pregnancy outcomes. However, women with MAFLD were at higher risk for adverse pregnancy outcomes than women with no NAFLD without MD or those with no NAFLD with MD.
CONCLUSIONS In pregnant women, MAFLD may be associated with an increased risk of subsequent adverse pregnancy outcomes.
PubMed IF 16.2 소화기내과
2222022

제1저자 안화영 · 교신저자 조선욱

, , ,
Incidence of Subacute Thyroiditis During the COVID-19 Pandemic in South Korea Using the National Health Insurance Service Database.
Thyroid. 2022;32(11):1299-1306.

Abstract
Background: Subacute thyroiditis (SAT) is a thyroid disease initiated by viral infection. Whether severe acute respiratory syndrome coronavirus 2 infection can cause SAT is unclear. This study investigated changes in the nationwide incidence of SAT during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This is a retrospective, cross-sectional population-based study. Data regarding SAT and related viral diseases, including COVID-19, from 2017 to 2020 were collected from the National Health Insurance Service and Korea Disease Control and Prevention Agency databases. Results: In a total of 15,447 patients, 2484 men and 12,963 women diagnosed with SAT from 2017 to 2020 were included in this study. The incidence of SAT was significantly higher in 2020 than in 2017-2019 (8.30 vs. 7.27 per 100,000 persons, p < 0.001), while the incidence of SAT-related respiratory viral diseases, except for COVID-19, markedly decreased in 2020. The peak age of SAT incidence in 2020 was 50-59 years, and the women-to-men ratio was 5.4 (similar to that in 2017-2019). Corticosteroids were prescribed more often (72% vs. 58%, p < 0.001), and the prescription rate exceeding 1 month was significantly higher (45% vs. 40%, p < 0.01) in 2020 than in 2017-2019. Conclusions: The incidence of SAT increased in 2020 in association with COVID-19. A diagnostic approach to COVID-19 needs to be considered in patients with SAT during the COVID-19 pandemic.
PubMed IF 6.6 내분비대사내과
2212022

제1저자 이은경, 문재훈 · 교신저자 박영주, 김지훈

, , , , , , , , , , , , , , , , , , , , , ,
Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.
Thyroid. 2022;32(11):1328-1336.

Abstract
Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.
PubMed IF 6.6 내분비대사내과
2202022

제1저자 안효정, 이희선 · 교신저자 최수연

, , , , , , , , ,
Changes in metabolic syndrome burden and risk of coronary artery calcification progression in statin-naïve young adults.
Atherosclerosis. 2022;360:27-33.

Abstract
BACKGROUND AND AIMS We aimed to investigate the association between metabolic syndrome (MetS) and coronary artery calcium (CAC) progression in statin-naïve young adults.
METHODS From the KOrea Initiatives on Coronary Artery calcification registry, we included asymptomatic young adults aged 20-45 years who underwent serial CAC scans for routine health check-ups. The primary endpoint was CAC progression. We estimated the risk of CAC progression based on the presence and burden of MetS. Among participants with MetS, the temporal relationship between changes in metabolic burden and CAC progression was evaluated.
RESULTS Of 2151 young adults (mean age 41.3 ± 3.8 years; male 85.4%), 488 (22.7%) had MetS. The mean CAC score was 10.8 and 81.3% of them had a CAC score of zero at baseline. During follow-up (median, 2.1 years), CAC progression was observed in 325 (15.1%) adults. MetS was associated with an approximately 1.8-fold increased risk of CAC progression (adjusted hazard ratio [aHR] 1.83, p < 0.001). The risk of CAC progression was directly proportional to the metabolic burden. Elevated blood pressure and elevated triglyceride levels were independent components related to CAC progression, with the strongest contribution being made by elevated blood pressure (aHR 2.00, p < 0.001). A reduction in at least two metabolic burdens was associated with a halved risk of CAC progression in young adults having MetS (odds ratio 0.41, p = 0.018).
CONCLUSIONS In statin-naïve young adults, the metabolic burden was associated with a risk of CAC progression in a dose-dependent manner. Improvement in metabolic imbalance may have a preventive effect on CAC progression.
PubMed IF 7.1 순환기내과
2192022

제1저자 김창곤, 김미소, 황지언 · 교신저자 신상준, 이지연, 김상겸

, , , , , , , , , , , , , ,
First-line pembrolizumab versus dabrafenib/trametinib treatment for BRAF V600-mutant advanced melanoma.
J Am Acad Dermatol. 2022;87(5):989-996.

Abstract
BACKGROUND Limited data are available to assist the selection between immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors as first-line treatment for patients with BRAF-mutant advanced malignant melanoma.
OBJECTIVE To investigate the outcomes associated with first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation.
METHODS Data of patients with BRAF V600-mutant melanoma who were treated with first-line pembrolizumab (n = 40) or dabrafenib/trametinib (n = 32) were analyzed. Tumor response, progression-free survival, and overall survival were evaluated. Immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase kinase inhibitors was assessed.
RESULTS A longer overall survival was observed after first-line pembrolizumab treatment than after first-line dabrafenib/trametinib treatment (hazard ratio = 2.910, 95% CI: 1.552-5.459), although there were no significant differences in progression-free survival (P = .375) and response rate (P = .123). Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A-specific CD8⁺ T cells.
LIMITATIONS Analysis was conducted in a retrospective manner.
CONCLUSION Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma.
PubMed IF 12.3 혈액종양내과
2182022

제1저자 안효정, 이소령 · 교신저자 최의근

, , , , , ,
Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis.
Br J Clin Pharmacol. 2022;88(11):4676-4687.

Abstract
AIMS The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy.
METHODS A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval.
RESULTS A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases.
CONCLUSION In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.
PubMed IF 3 순환기내과
2172022

제1저자 목정하, 이명선 · 교신저자 임재준

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.
Lancet. 2022;400(10362):1522-1530.

Abstract
BACKGROUND With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis.
METHODS In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994.
FINDINGS Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group.
INTERPRETATION 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis.
FUNDING Korea Disease Control and Prevention Agency, South Korea.
PubMed IF 109 호흡기내과
2162022

제1저자 박찬순 · 교신저자 박준빈, 김인준

, , , , , , , , , , , , , , , , ,
Sox17 Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met Signaling.
Circ Res. 2022;131(10):792-806.

Abstract
BACKGROUND In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggested as a putative causal gene of pulmonary arterial hypertension (PAH); however, its role and molecular mechanisms remain to be elucidated. We investigated the functional impacts and acting mechanisms of impaired Sox17 (SRY-related HMG-box17) pathway in PAH and explored its potential as a therapeutic target.
METHODS In adult mice, Sox17 deletion in pulmonary endothelial cells (ECs) induced PAH under hypoxia with high penetrance and severity, but not under normoxia.
RESULTS Key features of PAH, such as hypermuscularization, EC hyperplasia, and inflammation in lung arterioles, right ventricular hypertrophy, and elevated pulmonary arterial pressure, persisted even after long rest in normoxia. Mechanistically, transcriptomic profiling predicted that the combination of Sox17 deficiency and hypoxia activated c-Met signaling in lung ECs. HGF (hepatocyte grow factor), a ligand of c-Met, was upregulated in Sox17-deficient lung ECs. Pharmacologic inhibition of HGF/c-Met signaling attenuated and reversed the features of PAH in both preventive and therapeutic settings. Similar to findings in animal models, Sox17 levels in lung ECs were repressed in 26.7% of PAH patients (4 of 15), while those were robust in all 14 non-PAH controls. HGF levels in pulmonary arterioles were increased in 86.7% of patients with PAH (13 of 15), but none of the controls showed that pattern.
CONCLUSIONS The downregulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to hypoxia. Our findings suggest the reactive upregulation of HGF/c-Met signaling as a novel druggable target for PAH treatment.
PubMed IF 18 순환기내과
2152022

제1저자 이서영 · 교신저자 박흥우

, ,
Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly.
Eur J Med Res. 2022;27(1):215.

Abstract
BACKGROUND Little is known about the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO). This study examined the molecular phenotypes of ACO in the elderly.
METHODS A genome-wide investigation of gene expression in sputum cells from the elderly with asthma, ACO, or COPD was performed using gene set variation analysis (GSVA) with predefined asthma- or COPD-specific gene signatures. We then performed a subsequent cluster analysis using enrichment scores (ESs) to identify molecular clusters in the elderly with ACO. Finally, a second GSVA was conducted with curated gene signatures to gain insight into the pathogenesis of ACO associated with the identified molecular clusters.
RESULTS Seventy elderly individuals were enrolled (17 with asthma, 41 with ACO, and 12 with COPD). Two distinct molecular clusters of ACO were identified. Clinically, ACO cluster 1 (N = 23) was characterized by male and smoker dominance, more obstructive lung function, and higher proportions of both neutrophil and eosinophil in induced sputum compared to ACO cluster 2 (N = 18). ACO cluster 1 had molecular features similar to both asthma and COPD, with mitochondria and peroxisome dysfunction as important mechanisms in the pathogenesis of these diseases. The molecular features of ACO cluster 2 differed from those of asthma and COPD, with enhanced innate immune reactions to microorganisms identified as being important in the pathogenesis of this form of ACO.
CONCLUSION Recognition of the unique biological pathways associated with the two distinct molecular phenotypes of ACO will deepen our understanding of ACO in the elderly.
PubMed IF 4.8 알레르기내과
2142022

제1저자 이해영 · 교신저자 이해영

Heart Failure and Diabetes Mellitus: Dangerous Liaisons.
Int J Heart Fail. 2022;4(4):163-174.

Abstract
Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40% of HF patients have DM, having poorer outcomes than those without DM. Myocardial ischemia caused by endothelial dysfunction, renal dysfunction, obesity, and impaired myocardial energetics is pathophysiology of DM-induced HF (DM-HF). Also, patients with HF show an increased risk for the onset of DM due to several mechanisms including insulin resistance. This review is focused on the epidemiology, pathogenic mechanism and treatment strategy of DM-HF.
PubMed IF — 순환기내과
2132022

제1저자 변자민 · 교신저자 고영일

, , , , , , ,
Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease.
J Hematol Oncol. 2022;15(1):150.

Abstract
Extramedullary multiple myeloma (EMD) is an aggressive subentity of multiple myeloma (MM) with poor prognosis. As more innovative therapeutic approaches are needed for the treatment of MM with EMD, we conducted this multicenter, non-randomized phase II trial of daratumumab in combination with dexamethasone, cyclophosphamide, etoposide and cisplatin (DARA-DCEP). A total of 32 patients (median age 59, range 35-73) were treated with DARA-DCEP. Based on the best response during the study, the complete remission (CR) rate was 35.5% and overall response rate (ORR) 67.7%. During the median follow-up of 11 months, the median progression-free survival (PFS) was 5 months and median overall survival (OS) 10 months. There were 7 long-term responders whose median PFS was not reached. The most common grade ≥ 3 hematologic AE was thrombocytopenia. The most common non-hematologic AE was nausea (22.6%), followed by dyspepsia, diarrhea and stomatitis (all 12.9%). Grade ≥ 3 daratumumab infusion-related reaction was noted in 9.7% of the patients. Except for the planned 30% dose adjustment in cycle 1, only 2 patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we successfully laid grounds for implementing immunochemotherapy in MM treatment.
PubMed IF 47.8 혈액종양내과
2122022

제1저자 강지현, 김정연 · 교신저자 조주연, 이은영

, , , , ,
Identification of Metabolic Signature Associated with Idiopathic Inflammatory Myopathy Reveals Polyamine Pathway Alteration in Muscle Tissue.
Metabolites. 2022;12(10):metabo12101004.

Abstract
Idiopathic inflammatory myopathy (IIM) is hard to diagnose without a muscle biopsy. We aimed to identify a metabolite panel for IIM detection by metabolomics approach in serum samples and to explore the metabolomic signature in tissue samples from a mouse model. We obtained serum samples from IIM patients, ankylosing spondylitis (AS) patients, healthy volunteers and muscle tissue samples from IIM murine model. All samples were subjected to a targeted metabolomic approach with various statistical analyses on serum and tissue samples to identify metabolic alterations. Three machine learning methods, such as logistic regression (LR), support vector machine (SVM), and random forest (RF), were applied to build prediction models. A set of 7 predictive metabolites was calculated using backward stepwise selection, and the model was evaluated within 5-fold cross-validation by using three machine algorithms. The model produced an area under the receiver operating characteristic curve values of 0.955 (LR), 0.908 (RF) and 0.918 (SVM). A total of 68 metabolites were significantly changed in mouse tissue. Notably, the most influential pathways contributing to the inflammation of muscle were the polyamine pathway and the beta-alanine pathway. Our metabolomic approach offers the potential biomarkers of IIM and reveals pathologically relevant metabolic pathways that are associated with IIM.
PubMed IF 4.5 류
2112022

제1저자 최백규, 강창경, 박성완 · 교신저자 고영일, 정인경

, , , , , , , , , ,
Single-cell transcriptome analyses reveal distinct gene expression signatures of severe COVID-19 in the presence of clonal hematopoiesis.
Exp Mol Med. 2022;54(10):1756-1765.

Abstract
Clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes individuals to various inflammatory responses, has been reported to be associated with COVID-19 severity. However, the immunological signature and the exact gene expression program by which the presence of CHIP exerts its clinical impact on COVID-19 remain to be elucidated. In this study, we generated a single-cell transcriptome landscape of severe COVID-19 according to the presence of CHIP using peripheral blood mononuclear cells. Patients with CHIP exhibited a potent IFN-γ response in exacerbating inflammation, particularly in classical monocytes, compared to patients without CHIP. To dissect the regulatory mechanism of CHIP (+)-specific IFN-γ response gene expression in severe COVID-19, we identified DNMT3A CHIP mutation-dependent differentially methylated regions (DMRs) and annotated their putative target genes based on long-range chromatin interactions. We revealed that CHIP mutant-driven hypo-DMRs at poised cis-regulatory elements appear to facilitate the CHIP (+)-specific IFN-γ-mediated inflammatory immune response. Our results highlight that the presence of CHIP may increase the susceptibility to hyperinflammation through the reorganization of chromatin architecture, establishing a novel subgroup of severe COVID-19 patients.
PubMed IF 17.5 감염내과
2102022

제1저자 김민관 · 교신저자 김학령, 조주희

, , , , , ,
Association between arterial stiffness and left ventricular diastolic function: A large population-based cross-sectional study.
Front Cardiovasc Med. 2022;9:1001248.

Abstract
BACKGROUND The association between arterial stiffness and left ventricular (LV) diastolic function has been demonstrated in several studies, but the samples size in those studies was small. This study aims to verify this issue in a large number of study subjects.
METHODS A total of 7,013 consecutive participants (mean age 60.6 years and 43.3% female) who underwent both baPWV and transthoracic echocardiography were retrospectively analyzed. Subjects with significant cardiac structural abnormalities were excluded.
RESULTS There were significant correlations of baPWV with septal e' velocity (r = - 0.408; P < 0.001), septal E/e' (r = 0.349; P < 0.001), left atrial volume index (LAVI) (r = 0.122; P < 0.001) and maximal velocity of tricuspid valve regurgitation (TR Vmax) (r = 0.322; P < 0.001). The baPWV values increased proportionally with an increase in the number of LV diastolic indices meeting LV diastolic dysfunction criteria (P-for-trend < 0.001). In multivariable analyses with adjustment for confounding effects of various clinical covariates, higher baPWV was independently associated with septal e' < 7 (odds ratio [OR], 1.30; 95% confidence interval [CI] 1.20-1.60; P < 0.001), septal E/e' ≥ 15 (OR, 1.46; 95% CI, 1.21-1.78; P < 0.001), and TR Vmax > 2.8 m/s (OR, 1.60; 95% CI, 1.23-2.09; P < 0.001) but not with LAVI ≥ 34 mL/m² (OR, 0.89; 95% CI, 0.76-1.03; P = 0.123).
CONCLUSIONS Increased arterial stiffness, as measured by baPWV, was associated with abnormal diastolic function parameters in a large number of study participants, providing strong evidence to the existing data about ventricular-vascular coupling.
PubMed IF 3 순환기내과
2092022

제1저자 허은영, 이경희 · 교신저자 유철규

, , , , , , ,
Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation.
Antioxidants (Basel). 2022;11(10):antiox11101980.

Abstract
Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.
PubMed IF 8.2 호흡기내과
2082022

제1저자 김보람, 장한나 · 교신저자 성문우, 김정희

, , , , , , ,
A Novel Missense PRKAR1A Variant Causes Carney Complex.
Endocrinol Metab (Seoul). 2022;37(5):810-815.

Abstract
The Carney complex (CNC) is an autosomal dominant disorder characterized by endocrine and nonendocrine tumors. Loss-of-function variants of protein kinase A regulatory subunit 1 alpha (PRKAR1A) are common causes of CNC. Here, we present the case of a patient with CNC with a novel PRKAR1A missense variant. A 21-year-old woman was diagnosed with CNC secondary to acromegaly and adrenal Cushing syndrome. Genetic analysis revealed a novel missense heterozygous variant of PRKAR1A (c.176A>T). Her relatives, suspected of having CNC, also carried the same variant. RNA analysis revealed that this variant led to nonsense-mediated mRNA decay. In vitro functional analysis of the variant confirmed its role in increasing protein kinase A activity and cyclic adenosine monophosphate levels. This study broadens our understanding of the genetic spectrum of CNC. We suggest that PRKAR1A genetic testing and counseling be recommended for patients with CNC and their families.
PubMed IF 5.1 내분비대사내과
2072022

제1저자 정현애 · 교신저자 김범석

, , , , , , , , , , ,
A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11).
Clin Cancer Res. 2022;28(19):4240-4247.

Abstract
PURPOSE Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy.
PATIENTS AND METHODS This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. To identify potential biomarkers, whole-exome sequencing, whole-transcriptome sequencing, and immune phenotype analysis based on Lunit SCOPE IO, an artificial intelligence-powered spatial tumor-infiltrating lymphocyte analyzer, were performed.
RESULTS Thirty-six patients were enrolled between June 2018 and June 2019. The ORR was 36.1% and disease control rate was 97.2%. With median follow-up of 22.0 months, median PFS was 13.8 months [95% confidence interval (CI), 8.6-16.8 months]. Median OS was not reached, and OS rate at 6 months was 97.0% (95% CI, 80.4%-99.6%). The grade ≥3 treatment-related adverse events were hypertension (2.8%) and anemia (2.8%). In multivariate analysis of mutation of chromatin modifier gene, tumor mutational burden (≥ 2.1 mut/Mb), and somatic copy-number alteration (SCNA) level, the group with high SCNA (> 3 points; HR, 7.0; 95% CI, 1.3-37.9; P = 0.02) had independently associated with poor PFS. Immune phenotype analysis showed that tumors with high proportion of immune-excluded immune phenotype was significantly correlated with poor PFS (HR, 4.4; 95% CI, 1.2-16.2; P = 0.018).
CONCLUSIONS Nivolumab plus gemcitabine showed promising efficacy with favorable toxicity profiles in patients with advanced NPC in whom platinum-based combination chemotherapy failed.
PubMed IF 10.9 혈액종양내과
2062022

제1저자 안경민 · 교신저자 강혜련

, , , , ,
Validation of Practical Pathway in Patients With Anaphylaxis to Low Osmolar Contrast Media: A Retrospective Cohort Study.
J Allergy Clin Immunol Pract. 2022;10(10):2685-2692.e2.

Abstract
BACKGROUND An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis.
OBJECTIVES To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM.
METHODS A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone.
RESULTS Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group.
CONCLUSIONS We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.
PubMed IF 6.6 알레르기내과

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