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To compare the diagnostic performance of abbreviated breast MRI (AB-MRI) and digital breast tomosynthesis (DBT) in women with a personal history (PH) of breast cancer as a postoperative screening tool.A total of 471 patients who completed both DBT and AB-MRI examinations were included in this study (median age, 54.5 years). The detected cancer characteristics were analyzed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) were calculated by receiver operating characteristic (ROC) curve analysis.Eleven malignancies were diagnosed, and most of the detected cancers were stage I (7 of 11, 63.6%). Eight were invasive ductal carcinomas (IDC), and 3 were ductal carcinoma in situ (DCIS). Of the 11 recurrences, 6 malignancies were detected by DBT, and 11 were detected by AB-MRI. AB-MRI detected all 8 IDC and 3 DCIS lesions, and DBT detected 6 of 8 IDC lesions. The CDRs for DBT and AB-MRI screenings were 12.7 and 23.4 per 1,000 women, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of DBT versus AB-MRI were 54.6% versus 100%, 97.6% versus 96.5%, 35.3% versus 40.7%, 98.9% versus 100%, and 96.6% versus 96.6%, respectively. AB-MRI showed a higher AUC value (0.983) than DBT (0.761) (p = 0.0049).AB-MRI showed an improved CDR, especially for invasive cancer. The diagnostic performance of AB-MRI was superior to that of DBT with high sensitivity and PPV without sacrificing specificity in women with a PH of breast cancer.

Background Sleep disturbance in pregnant women needs to be accurately assessed in a timely manner during pregnancy, to receive assessment-driven accurate intervention. This study aims to compare the factor structure of the Pittsburgh Sleep Quality Index (PSQI) among women in mid- and late pregnancy and evaluate the psychometric features of the Korean version of the PSQI. Methods The survey questionnaire with the PSQI, Center for Epidemiological Studies Depression scale, and pregnancy stress, was completed by 281 women in mid- or late pregnancy. Exploratory factor analysis determined the best factor structure of the PSQI, and the Pearson correlation coefficient examined a convergent validity with depressive symptoms and pregnancy stress. Internal consistency was examined using Cronbach’s alpha. Results In both mid- and late-pregnancy women, a two-factor structure model was identified. However, each factor’s different components were named differently. For women in mid-pregnancy, it was named “quantitative sleep quality” and “subjective sleep quality,” and for those in later stages of pregnancy, they were named “perceived sleep quality” and “daily disturbance.” The PQSI score showed a significantly positive correlation between depressive symptoms and pregnancy stress in mid- (r = 0.57 and r = 0.39, respectively), and late pregnancy (r = 0.48 and 0.28, respectively). The overall Cronbach’s alpha for the PSQI was 0.63. Conclusions The Korean version of the PSQI demonstrated excellent construct and convergent validity, making it suitable to assess the sleep quality of women in middle to late stages of their pregnancy. The PSQI was found to have a two-factor structure in the mid-and late pregnancy, but the components were different. As sleep quality changes with each gestational stage, factors affecting it during mid- and late pregnancy need to be separately examined. It will make it easier for medical professionals to provide pregnant women sleeping irregularly, with the right kind of intervention.

Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

Metabolic syndrome (MS) is diagnosed using absolute criteria that do not consider age and sex, but most studies have shown that the prevalence of MS increases with age in both sexes. Thus, the evaluation of MS should consider sex and age. We aimed to develop a new index that considers the age and sex for evaluating an individual’s relative overall MS status. Data of 16,518,532 subjects (8,671,838 males and 7,846,694 females) who completed a validated health survey of the National Health Insurance Service of the Republic of Korea (2014‒2015) were analyzed to develop an MS-biological age model. Principal component score analysis using waist circumference, pulse pressure, fasting blood sugar, triglyceride levels, and high-density lipoprotein level, but not age, as independent variables were performed to derive an index of health status and biological age. In both sexes, the age according to the MS-biological age model increased with rising smoking and alcohol consumption habits and decreased with rising physical activity. Particularly, smoking and drinking affected females, whereas physical activity affected males. The MS-biological age model can be a supplementary tool for evaluating and managing MS, quantitatively measuring the effect of lifestyle changes on MS, and motivating patients to maintain a healthy lifestyle.

Purpose Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. Methods Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. Results In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p, Highlights • Radiation dose is associated with the risk of breast reconstruction complications. • We conducted a retrospective multi-center observational study of 314 women in Korea. • Complication-related risk factors were identified using multivariate analysis. • Use of hypofractionated radiation therapy may improve breast reconstruction outcomes. • A prospective multi-center study is under way to further validate our findings.

It has been reported worldwide that the Zika virus (ZIKV) could be transmitted through placentas and sexual contact. ZIKV can also cause Guillain-Barre syndrome, microcephaly and neurological abnormalities. However, there are no approved vaccines available. We constructed six DNA vaccine candidates and tested the immunogenicity. Tandem repeated envelope domain Ⅲ (ED Ⅲ × 3) induced highly total IgG and neutralization antibody, as well as CD8+ T cell responses. Also, stem region-removed envelope (E ΔSTEM) elicited a robust production of IFN-γ in mice. To examine in vivo protection, we used mice treated with an IFNAR1 blocking antibody before and after the challenge. Vaccination with the two candidates led to a decline in the level of viral RNAs in organs. Moreover, the sera from the vaccinated mice did not enhance the infection of Dengue virus in K562 cells. These findings suggest the potential for the development of a novel ZIKV DNA vaccine.

Women traumatized by sexual abuse as children or adults experience psychological disorders, such as post-traumatic stress, depression, anxiety, and social adjustment. The published research includes a broad array of studies on psychological interventions intended to ease their symptoms. This study systematically examined the specific effects of psychological interventions for women traumatized by sexual abuse and statistically evaluated interventions by calculating effect sizes in a meta-analysis. A literature search was conducted of electronic databases of journals, gray literature and Clinical Research Information Service. Medical Subject Heading terminology, text words, and logical operators were applied, and 2,029 articles published in English or Korean were retrieved. Inclusion criteria were full-text articles on randomized controlled trials in which: (1) the subjects were women 18 years or older who had been sexually assaulted or raped; (2) all types of exclusively psychological treatment were used; (3) comparisons were mediated or routinely managed without psychosomatic treatment; (4) interventions did not target patients with chronic mental illnesses or neurocognitive dysfunctions; and (5) the studies were not on animals, empirical research, cohorts, research protocols, or integrated literature reviews. Ten articles fully met the inclusion criteria. The main findings were: (1) interventions had long-term effects on post-traumatic stress reduction, (2) effects on depression were effective only 3 months post-intervention, and (3) there were no follow-up effects on anxiety reduction or social adjustment improvement. The types of therapeutic intervention, delivery mode, number and duration of sessions, and number of weeks varied.

The clinical significance of long-term methicillin-resistant Staphylococcus aureus (MRSA) bacteremia remains unclear. We evaluated the clinical, microbiological characteristics, and clinical outcomes of long-term MRSA bacteremia. A nested case-control study was conducted in a prospective cohort of adult patients with MRSA bacteremia at a tertiary hospital between August 2008 and December 2017. Patients with long-term MRSA bacteremia (≥ 14 days) were compared with control patients, defined as having bacteremia that resolved in less than 3 days. The following variables were documented: heteroresistance phenotype, genotypes, agr dysfunction, and the presence of 41 virulence genes in isolates. Of the total 890 patients studied, 69 patients (7.8%) exhibited long-term MRSA bacteremia and 599 (67.3%) exhibited resolving bacteremia. The most common sources of long-term bacteremia were central venous catheter–related infection (39%) and osteomyelitis (19%). Independent risk factors for long-term MRSA bacteremia included male sex (adjusted odds ratio [aOR] = 2.43), community-acquired bacteremia (aOR = 2.93), the presence of a prosthetic device (aOR = 3.40), and osteomyelitis (aOR = 7.98). Metastatic infections developed more frequently in patients with long-term bacteremia than in those with resolving bacteremia (56.5% vs. 8.0%; P

Background To evaluate the usefulness of surveillance-abbreviated magnetic resonance imaging (AB-MRI) for the detection of ipsilateral local tumor recurrence (LTR) in patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) by comparing its diagnostic performance with that of mammography (MG) and ultrasonography (US). Methods The postoperative MG, US, and AB-MRI findings of the ipsilateral breast and pathological results of 324 patients who underwent oncoplastic BCS using ADM were reviewed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV) for biopsy, accuracy, and area under the curve (AUC) for each imaging modality were calculated. Results A total of 8 ipsilateral LTRs were diagnosed, and most cancers (87.5%) were stage 0 or 1 (median size of invasive cancer, 1.44 cm; range, 0.7–2 cm). The CDRs of MG, US, MG + US, and AB-MRI were 0.009, 0.012, 0.015, and 0.025 per woman, respectively. Three cancers were detectable on only AB-MRI, and the additional CDR of AB-MRI was 0.010. The sensitivity and specificity of MG, US, MG + US, and AB-MRI were 37.5%, 50%, 62.5%, and 100% and 99.7%, 98.4%, 98.1%, and 97.8%, respectively. The PPVs for biopsy were 75%, 44.4%, 45.5%, and 53.3%, respectively. The AUC was significantly higher for AB-MRI (0.989) than for MG alone (0.686, P = 0.0009), US alone (0.742, P = 0.009), and MG + US (0.803, P = 0.04). A total of 66.7% of cancers visible on only AB-MRI were located at the deep posterior portion of the excision cavity, which might have been missed with MG or MG + US due to masking by the ADM filler. Conclusion AB-MRI can improve the detection of ipsilateral LTR despite postoperative changes caused by ADM fillers compared to conventional MG and US. Patients who undergo BCS with ADM can be candidates for AB-MRI surveillance considering improved cancer detection and high sensitivity.

PurposeTo evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomyMaterials and MethodsMedical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p

We investigated the relationship between diabetes family conflict and parental conflict on problem recognition in illness self-management (PRISM) among individuals with type 1 diabetes mellitus (T1DM). We employed a descriptive research design. Participants were 243 individuals with T1DM who completed online questionnaires. Data were analyzed with descriptive statistics, correlations, and multiple regression analyses. Results revealed that barriers were felt in all areas (understanding and organizing care, regimen pain and bother, healthcare team interaction, family interaction, and peer interaction), especially peer interaction. The significant influencing factors in the regression model for the total PRISM score of individuals with T1DM were conflict behavior toward mothers (t = 4.44, p &lt, 0.001), diabetes family conflict (t = 5.77, p &lt, 0.001), conflict behavior toward fathers (t = 2.58, p = 0.011), women (t = 2.67, p = 0.008), non-religious (t = −2.33, p = 0.020), and diabetic complications (t = 2.17, p = 0.031). The explanatory power of the constructed regression model for PRISM was 42.0% (F = 30.12, p &lt, 0.001). To promote self-management among individuals with T1DM, the development of interventions that promote improved peer interactions, a family-centered approach, and a program that can minimize conflicts between families and parents are required.

Background To map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV). Methods Cervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTVRTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTVK was contoured as proposed by Keenan et al. CTVM was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12–L1 interspace. CTVnew was created by modifying CTVRTOG to obtain better coverage. Results We identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTVRTOG, CTVK, and CTVM covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTVnew to cover 96.7% of all PALNs and all nodes in 91.4% of patients. Conclusion CTVRTOG and CTVK encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered.

Lung cancer screening with low-dose computed tomography reduced mortality in selected high risk patients. However, the use of chest radiography for lung cancer screening in Asian populations is still controversial. We investigated the effectiveness of chest radiographic surveillance using a nationwide health service data in South Korea.Data from the Korean National Health Insurance Service examinee cohort of 2004 to 2013 were examined, and 63,228 patients with lung cancer were identified, 38,494 (57%) of whom underwent chest radiography screening. The others did not undergo lung cancer screening and were considered as a control group. Clinical data including age, smoking, screening intervals, lung cancer stages, treatments, and survival were collected. Survival gain from surveillance after adjustment for lead-time bias based on the sojourn time was calculated. Cox-proportional hazard analyses were performed to evaluate the effectiveness of screening and to determine the appropriate screening interval for chest radiography surveillance.Early lung cancer was found in 38% of patients receiving chest radiography versus 26% of those without surveillance. A patient age of more than 65 years (hazard ratio [HR], 1.53; 95% confidence limits [CL], 1.50-1.56), male (HR, 1.66; 95% CL, 1.62-1.70), and high lung cancer stages at the time of diagnosis were independent factors associated with mortality (each, P 0.001). Chest radiography surveillance was a factor for decreasing mortality in female (HR, 0.81; 95% CL, 0.77-0.84, P 0.001), with mortality reduction of 10% at the 3- and 5-year survival time-points. In female patients, chest radiography surveillance at intervals of less than 3 years was an independent predictor of improved survival.Surveillance chest radiography increased survival in a female screened population in South Korea. Chest radiography intervals of less than 3 years may help to detect lung cancer in female patients.

Background Simulation-based learning was developed to enable nursing and medical students to obtain clinical experience in a safe and controlled environment. The extent to which students concentrate in simulation situations can influence their educational outcomes. However, there are no studies yet on the factors that influence flow in simulation practice. Understanding which factors influence flow might help in achieving better simulation-based learning outcomes. Objectives The purpose of this study was to identify the factors related to flow in simulation practice, including stress, self-esteem, and collective efficacy. Design This was a descriptive cross-sectional study. Setting A university in South Korea during the 2015 academic year. Participants This study was conducted with 84 senior nursing students. Their average age was 23 years old and >90% were female. Methods The stress, self-esteem, and collective efficacy of senior nursing students were measured before simulation practice, while flow in simulation practice was measured after simulation. Results Flow during simulation practice was positively correlated with self-esteem and collective efficacy, but negatively correlated with stress. Furthermore, only collective efficacy was a significant predictor of flow during simulation. Conclusions Nursing education must be oriented to help emphasize collective efficacy to improve students' outcomes from simulation-based learning.

Background: The sensitivity of galactomannan (GM) assay is suboptimal for detecting invasive pulmonary aspergillosis (IPA) in serum samples. However, the clinical characteristics, radiologic findings, and outcomes in patients with GM-negative IPA have not been fully elucidated. Methods: Over a 7-year period, adult patients with proven or probable IPA by the EORTC/MSG definition were retrospectively enrolled. Patients with negative GM results and positive Aspergillus spp. cultures from sputum or bronchoalveolar lavage were classified into GM-negative IPA group. GM-positive and culture-negative IPA cases were selected at a 1:2 ratio. Results: Thirty-four patients with GM-negative IPA were compared to 68 randomly selected patients from 158 patients with GM-positive and culture-negative IPA. Patients with diabetes mellitus, chronic kidney disease, and steroid use were more common but those with hematologic malignancy, prior receipt of mold-active antifungal drugs, and neutropenia were less common in GM-negative IPA than in GM-positive IPA. Regarding radiologic findings, angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. The median number of days from diagnosis to appropriate antifungal therapy was higher in GM-negative IPA than in GM-positive IPA. Multivariate analysis indicated that neutropenia (adjusted odds ratio [aOR], 0.10) and prior receipt of mold-active antifungal drugs (aOR, 0.12) were inversely associated with GM-negative IPA. The 30-day and 90-day mortality were similar between the two groups. Conclusion: Neutropenia and prior receipt of mold-active antifungal drugs before GM assay were independently associated with GM positivity among patients with proven/probable IPA. Angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. Keywords: Galactomannan, Invasive pulmonary aspergillosis, Neutropenia

Please see the Editorial Comment by Chi Wan Koo discussing this article. BACKGROUND. Prognostic factors on preoperative CT in stage IA non–small cell lung cancer (NSCLC) may help select patients fo...

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

The purposes of this study were to investigate the trajectory groups of depressive symptoms and anxiety in women during pregnancy and to identify the factors associated with those groups. Participants were recruited from the outpatient clinic of a women’s health hospital in Seoul, Korea. Pregnant women (n = 136) completed a survey questionnaire that included questions on depressive symptoms, anxiety, and pregnancy stress, additionally, their saliva was tested for cortisol hormone levels three times during their pregnancies. The group-based trajectory modeling approach was used to identify latent trajectory groups. Ordinal logistic regressions were used to explore the association of latent trajectory groups with sociodemographic factors and pregnancy stress. Three trajectory groups of depressive symptoms were identified: low-stable (70%), moderate-stable (25%), and increased (5%). Four trajectory groups of anxiety were identified: very low-stable (10%), low-stable (67%), moderate-stable (18%), and high-stable (5%). The only factor associated with both the depressive symptoms and anxiety trajectory groups was pregnancy stress (p &lt, 0.001). Most participants showed stable emotional status, however, some participants experienced higher levels of depressive symptoms and anxiety related to higher pregnancy stress. These pregnant women may need additional care from healthcare providers to promote their wellbeing during pregnancy.

Background Electromagnetic navigation bronchoscopy (ENB) is a useful method to obtain tissue for peripheral lung nodules. We aimed to understand the diagnostic yield and safety profile in high‐risk pulmonary nodules that cannot be accessed by percutaneous transthoracic needle biopsy. Methods In this single‐center retrospective study, we reviewed patients who underwent ENB for high‐risk pulmonary nodules. All procedures were performed under moderate sedation using intravenous midazolam and fentanyl. Results A total of 100 pulmonary nodules in 90 patients were subjected to ENB between October 2018 and May 2020. The median age of the study population was 66 (59–73). The mean diameter of the lung nodules was 27.9 mm. The diagnostic yield of ENB‐guided biopsy was 53.0%. Although the nodule size (odds ratio: 1.055, p = 0.007) and positive bronchus sign (odds ratio: 2.918, p = 0.020) were associated with the diagnostic yield during univariate analysis, nodule size was the only independent variable on the multivariable analysis. Interestingly, the diagnostic yield showed an upward trend after 60 cases, from 45%–65%. Procedure‐related complications were reported in 16 cases; among these, pneumothorax occurred in three cases, and four cases experienced moderate bleeding. No instance of major bleeding or death was linked to ENB‐guided biopsy. Conclusion ENB‐guided biopsy for high‐risk pulmonary nodules demonstrated an acceptable diagnostic yield and good safety profile. Moreover, the diagnostic yield was associated with nodule size and procedure experience., In this single‐center retrospective study, we reviewed a total of 100 pulmonary nodules in 90 patients who underwent ENB for high‐risk pulmonary nodules under moderate sedation. The diagnostic yield of ENB‐guided biopsy was 53.0% and showed an upward trend after 60 cases, from 45%–65%. The diagnostic yield was associated with nodule size and the operator's experience with the procedure. Procedure‐related complications were reported in 16 cases without major bleeding events or death. ENB can be used for high‐risk patients because of an acceptable diagnostic yield and a good safety profile.

While chest CT provides important clue for diagnosis of miliary tuberculosis (TB), patients are occasionally missed on initial CT, which might delay the diagnosis. This study was to evaluate the clinical and radiological characteristics of radiologically missed miliary TB. Total 117 adult patients with microbiologically confirmed miliary TB in an intermediate TB-burden country were included. ‘Missed miliary TB’ were defined as the case in which miliary TB was not mentioned as a differential diagnosis in the initial CT reading. Clinical characteristics and radiologic findings including the predominant nodule size, demarcation of miliary nodules and disease extent on CT were retrospectively evaluated. Findings were compared between the missed and non-missed miliary TB groups. Multivariable analyses were performed to determine independent risk factors of missed miliary TB. Of 117 patients with miliary TB, 13 (11.1%) were classified as missed miliary TB; these patients were significantly older than those with non-missed miliary TB (median age, 71 vs 57 years, P = .024). There was a significant diagnostic delay in the missed miliary TB group (P

Background Afatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy. Methods EGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms. Results Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year. Conclusions No unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations. Trials registration ClinicalTrials.gov NCT01931306; 29/08/2013.

IntroductionWe assessed the applicability of next-generation sequencing (NGS)-basedIGH/IGKclonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time.MethodsFifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted theIGHandIGKgenes was performed usingIGHFR1 andIGKprimer sets.ResultsClonalIGHandIGKrearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonalIGHand/orIGKrearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells.IGHV3-9(11.63%) andIGHV4-31(9.30%) were the most frequently reportedIGHVgenes and were more common in Koreans with MM than in Western counterparts.IGHD3-10andIGHD3-3(13.95% each) were the most frequent IGHD genes;IGHD3-3was more common in Koreans with MM. NoIGKrearrangement was particularly prevalent, but singleIGKV-Jrearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts.IGKV4-1was less frequent in Koreans regardless of light chain type. Otherwise, the usages of theIGHV, D, and J genes and of theIGKgene were like those observed in previous Western studies.ConclusionNGS-basedIGH/IGKclonality testing ought to be applicable to most Koreans with MM. The overrepresentation ofIGHV3-9,IGHV4-31, andIGHD3-3along with the underrepresentation ofIGKV4-1and the differences inIGKgene rearrangement types suggest the existence of ethnicity-specific variations in this disease.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported., Graphical Abstract

In our previous study, we designed and evaluated the efficacy of six DNA vaccine candidates based on the E protein of Zika virus (ZIKV). To optimize the DNA vaccine, we inoculated C57BL/6 and IFNAR1- mice with the vaccine candidate expressing tandem repeated ZIKV envelope domain III (ED III × 3) doses; 50 μg by intramuscular (IM), jet injection (JET), or electroporation (EP) routes. Results showed that vaccination by all routes induced humoral and cellular immunity. Among them, EP induced robust ZIKV E specific-total IgG and neutralizing antibodies, as well as T cell responses. Additionally, EP showed superior protective efficacy against the ZIKV Brazil strain compared to the IM and JET routes. Finally, in the dose optimization test of EP route, cellular immunity of 50 μg was induced a significant level than other dose groups. These results showed that the EP delivery system enhanced the potential immunogenicity and protective efficacy of DNA vaccines.

PURPOSE The purpose of this study was to identify the factors affecting problem drinking among adolescents in Korea. METHODS This survey involved 68,043 adolescents who participated in the Korea Youth Risk Behavior Web-Based Survey conducted in 2015. The data were analyzed using the PASW Statistics 23.0 program. RESULTS The subjects were aged 14.96 ± 1.74 years (mean ± standard deviation), including 52.1% male subjects and 53.0% high school students. Most of the drinkers started drinking during their middle school years (13,906 students, 51.6%). Among the 11,021 adolescent drinkers, 7,391 (67.1%) reported at least one of six behavioral problems related to drinking. Problem drinking behaviors involved (a) drinking alcohol to relieve stress; (b) drinking alcohol alone; (c) receiving advice from family or friends to reduce alcohol consumption; (d) driving a motorcycle or riding a bicycle after drinking alcohol, or riding on a motorcycle or a car with a drunk driver at the steering wheel; (e) memory loss after drinking alcohol; and (f) arguing with others after drinking alcohol. The overall problem-drinking score was 1.36 ± 1.42 (range: 0-6). A regression model that included individual (5.7%), interpersonal (3.6%), social (0.3%), contextual (11.7%), and drinking (6.6%) behaviors as predictors accounted for 27.9% of the variance in problem drinking (Wald F = 70.10, p < .001). CONCLUSION The drinking levels as well as method and ease of alcohol purchase were the most significant variables predicting problem drinking by adolescents in Korea.

The South Korean government effectively contained the coronavirus disease-2019 (COVID-19) outbreak primarily associated with a religious group. We conducted SARS-CoV-2 whole genome sequencing of 66 cases to investigate connections among the initial South Korean cases and the religious group outbreak. We assessed the accuracy of genomic investigation by comparing the whole genome sequences with comprehensive contact tracing records. Five transmission clusters were estimated among the 15 initial cases. The six close-contact cases and two potential exposure pairs identified by contact tracing showed two or fewer nucleotide base differences. Additionally, we identified two transmission clusters from the religious group outbreak that were phylogenetically distinct from the initial clusters, sharing common G11083T, G26144T, and C14805T markers. The strain closest to the two religious group clusters was identified from a pair of identical sequences isolated from individuals who traveled from Wuhan to Italy. Our findings provide insights into the origins of community spread of COVID-19.

WHAT IS KNOWN ON THE SUBJECT?: Pre- and postmenopausal women (PPW) experience changes in physical, psychological and social health. South-East Asia's female suicide rate is the highest compared with other countries, and the suicide rate of PPW in these countries continues to increase. The most influential factor in Asian women's suicidal ideation is family conflict; specifically, if PPW in South Korea cannot express their anger, it results in a culture-bound syndrome called "Hwa-Byung." However, there is a lack of research on Asian PPW. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This study found differences in individual- and community-level factors affecting suicidal ideation between pre- and postmenopausal women. Individual factors that commonly affected suicidal ideation were experiencing violence, stress and depression. Individual factors that affected the suicidal ideation of premenopausal women more than postmenopausal women were religious beliefs, alcohol use and chronic disease. Community level factors affecting suicidal ideation were locational depression and locational counselling for stress in premenopausal women and locational counselling for depression in postmenopausal women. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses could help prevent suicide by developing and applying community-based programmes for PPW, considering the specific socio-economic and cultural context and characteristics of Asian women. Mental health nurses could help PPW participate in programmes by preparing various interventions such as case management, personal counselling, physical activity, home-based mental health services, cognitive behavioural therapy and digital interventions for self-management. Mental health nurses need to prepare various methods such as online, offline, individual and group methods to work effectively in any social situation. ABSTRACT: Introduction Pre- and postmenopausal women (PPW) experience physical and psychological changes with hormonal changes. Among Asian middle-aged women, family and culture affect suicidal ideation, and the suicide rate among this population is increasing. There are few existing research on suicidal ideation among Asian PPW. Aim We examined individual- and community-level factors that predict suicidal ideation among PPW. Method Large-scale panel data from 5,154 South Korean PPW aged 35-64 years were used in a series of multilevel logistic regression analyses to examine factors associated with suicidal ideation at individual and community levels. Results Among premenopausal women, religious beliefs, alcohol use, chronic disease, experience of violence, stress and depression were individual-level factors. Locational depression and locational counselling for stress were community-level factors. Among postmenopausal women, experience of violence, stress, depression and perceived health status were individual level factors, and locational counselling for depression was a community level factor. Discussion Suicidal ideation among PPW is affected by both individual and community level factors. Nurses must comprehensively determine what risk factors affect suicidal ideation through various intervention methods-including online, offline, individual and group methods-while considering socio-economic situations. Implications for Practice Mental health nurses should provide targeted biopsychosocial interventions targeting psychosocial and physical problems and promoting the use of community resources to reduce PPW's suicidal ideation.

Recently, biological markers of maternal prenatal stress, hair cortisol, along with saliva, blood, and urine cortisol, have received attention. However, it is necessary to validate measuring hair cortisol concentrations (HCC) as a biomarker of perceived stress among healthy and high-risk pregnant women. This study aimed to confirm the correlation between HCC and the perceived stress of pregnant women over 18 years of age. In this systematic review, we used various search engines to extract relevant articles using specific keywords related to pregnancy, hair cortisol, and psychological stress. Four out of 3639 studies met the inclusion criteria. We conducted a quality assessment with the help of three independent reviewers using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. The correlation between HCC and perceived stress was confirmed in one study. There was only one study on hair washing, shampoo, conditioner, and hair structure that could affect hair samples. In four studies, hair samples differed in length, methods of storage, and laboratory analysis. The review was limited to confirming the relationship between HCC and perceived stress in pregnant women based on the current evidence. Studies on hair cortisol need regulated and standardized methods for collection, storage, and analysis of hair samples.

Background In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. Methods From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. Results A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. Conclusion The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down., Graphical Abstract

Summary In this study, a strategy based on polymeric immunoglobulin G scaffolds (PIGS) was used to produce a vaccine candidate for Mycobacterium tuberculosis. A genetic fusion construct comprising genes encoding the mycobacterial Ag85B antigen, an immunoglobulin γ‐chain fragment and the tailpiece from immunoglobulin μ chain was engineered. Expression was attempted in Chinese Hamster Ovary (CHO) cells and in Nicotiana benthamiana. The recombinant protein assembled into polymeric structures (TB‐PIGS) in N. benthamiana, similar in size to polymeric IgM. These complexes were subsequently shown to bind to the complement protein C1q and FcγRs with increased affinity. Modification of the N‐glycans linked to TB‐PIGS by removal of xylose and fucose residues that are normally found in plant glycosylated proteins also resulted in increased affinity for low‐affinity FcγRs. Immunization studies in mice indicated that TB‐PIGS are highly immunogenic with and without adjuvant. However, they did not improve protective efficacy in mice against challenge with M. tuberculosis compared to conventional vaccination with BCG, suggesting that additional or alternative antigens may be needed to protect against this disease. Nevertheless, these results establish a novel platform for producing polymeric antigen‐IgG γ‐chain molecules with inherent functional characteristics that are desirable in vaccines.

Background/Aims The annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated. Methods Cirrhotic patients with non-hypervascular HBPI hypointense nodules were retrospectively analyzed if they were diagnosed as HCC and MR followed up longer than 1 year during the period from January 2010 to October 2016 with regular intervals of 3 to 6 months. Risk factors for transformation into hypervascular HCCs were analyzed using the Cox proportional hazard model. Results Among the 103 non-hypervascular HBPI hypointense nodules meeting the inclusion criteria, transformation into hypervascular HCCs occurred in 44 tumors (42.7%). The median follow-up period was 24 months. Multivariate analysis revealed that hyperintensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI) were the two independent predictors of transformation into hypervascular HCCs (p=0.036 and p=0.041, respectively). Most tumors with hyperintensity on T2WI or DWI on the initial or follow-up MR were transformed into hypervascular HCCs within the first year. Among the 22 nodules (21.3%) showing a new change in dynamic phases during follow-up, 14 nodules (13.6%) showed malignant transformations. Conclusions The transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.

Background Non-invasive anatomical and physiological evaluations of coronary artery disease (CAD) may be obtained with static single-scan stress perfusion cardiac computed tomography (SSPCT). Purpose To determine the diagnostic performance of static SSPCT for identifying hemodynamically significant CAD. Material and Methods This prospective study included 29 patients with suspected or known CAD who underwent static SSPCT, cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI), and invasive coronary angiography (ICA). CT was performed as follows: (i) coronary calcium scan; (ii) static SSPCT for both coronary artery (coronary CT angiography [CCTA]) and myocardial perfusion (perfusion CT [PCT]) during adenosine infusion; (iii) late-phase scan. The diagnostic performance of CCTA alone, PCT alone, and SSPCT for the detection of a hemodynamically significant CAD (a perfusion defect in a vascular territory subtended by a coronary vessel with ≥ 50% stenosis) was compared with that of combined ICA/CMR-MPI representing the standard of reference. Results Twenty-three (79%) patients and 47 (54%) vascular territories manifested ischemia-causing coronary stenoses by combined ICA/CMR-MPI. The per-vessel sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curve (AUC) of the SSPCT were 92%, 88%, 90%, 90%, and 0.90, respectively, compared to those of the combined ICA/CMR-MPI. These values for the CCTA alone were 96%, 63%, 75%, 93%, and 0.79, respectively; and the values for the PCT alone were 94%, 83%, 86%, 92%, and 0.88, respectively. The AUC of SSPCT was significantly ( P = 0.013) higher than that of the CCTA alone. Conclusion Static SSPCT may facilitate detection of hemodynamically significant CAD.

We investigated the usefulness of abbreviated breast MRI (AB-MRI), including fat-suppressed T2-weighted imaging, pre- and postcontrast image acquisition, and subtracted maximum-intensity projection imaging, for the screening of women with a history of breast cancer surgery. Between October 2014 and March 2016, a total of 799 AB-MRI examinations were performed for 725 women with a history of breast cancer surgery. The image acquisition time was 8.5 min. Screening mammography, ultrasound, and AB-MRI were generally performed around the same time. The cancer detection rate, positive predictive values for recall and biopsy, sensitivity and specificity of screening MRI, and rate of malignancy belonging to each breast imaging reporting and data system (BI-RADS) category were assessed. AB-MRI detected 12 malignancies in 12 women (15.0 cancers per 1000 cases). Seven of these 12 malignancies were initially invisible on ultrasound and mammography, although subsequent targeted ultrasound revealed lesions corresponding to the MRI-detected lesions. The positive predictive values for recall and biopsy and sensitivity and specificity values for screening MRI were 12.4, 61.5, 100, and 89.2%, respectively. The rates of malignancies belonging to categories 1, 2, 3, and 4 of the BI-RADS were 0, 0, 4.8, and 57.1%, respectively. The diagnostic performance of screening AB-MRI for women with a history of breast cancer surgery is acceptable, with the advantages of short examination and interpretation times and low costs. Thus, it could be used as a main screening modality that may replace conventional imaging in breast cancer survivors.

Mammography detects calcium deposits sensitively, but the specificity for differentiating malignancy from benign calcifications is low. Thus, we investigated whether adjunctive breast-specific gamma imaging (BSGI) has incremental value for detecting cancer in women with suspicious calcifications detected by mammography, and compared BSGI with adjunctive ultrasonography (US). The medical records of women without a personal history of breast cancer who underwent mammography for breast evaluation from 2009 to 2014 were reviewed retrospectively. Patients who had calcifications detected by mammography, with a result of Breast Imaging Reporting and Data System (BI-RADS) categories 3–5, underwent adjunctive US and BSGI and were included in this study. A total of 302 breast lesions in 266 women (mean age ± standard deviation 49 ± 9 years) were selected for this study. For detecting breast cancer using mammography plus BSGI, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve with 95% confidence intervals were 94% (91–96), 90% (86–93), 91% (87–94), 94% (90–96), and 0.92 (0.89–0.95), respectively. For mammography plus US, the respective values were 97% (94–98), 51% (46–57), 68% (63–73), 94% (90–96), and 0.74 (0.70–0.78). Adjunctive BSGI had higher specificity than adjunctive US without loss of sensitivity. This finding suggests that adjunctive BSGI may be a useful complementary initial imaging method to improve the detection of breast cancer in women who have calcifications with suspicious morphology at mammography.

Summary In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a polymeric immunoglobulin G scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen‐presenting cells. These self‐adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII‐PIGS were fractionated by HPLC into low and high molecular weight forms, corresponding to monomers, dimers and polymers. cEDIII‐PIGS were shown to retain important Fc receptor functions associated with immunoglobulins, including binding to C1q component of the complement and the low affinity Fcγ receptor II, as well as to macrophage cells in vitro. These molecules were shown to be immunogenic in mice, with or without an adjuvant, inducing a high level IgG antibody response which showed a neutralizing potential against the dengue virus serotype 2. The cEDIII‐PIGS also induced a significant cellular immune response, IFN‐γ production and polyfunctional T cells in both the CD4+ and CD8+ compartments. This proof‐of‐principle study shows that the potent antibody Fc‐mediated cellular functions can be harnessed to improve vaccine design, underscoring the potential of this technology to induce and modulate a broad‐ranging immune response.

The psychological adaptation of mothers of children with cancer has a significant impact on the management of the disease. As the mothers’ psychological adaptation and positive emotions have an impact on the psychological adaptation of the children, it is important to facilitate the positive growth of the mothers during their adjustment to their children’s illness. Therefore, it is necessary to determine the factors that influence posttraumatic growth (PTG) in these mothers. This research aimed to test the variables of PTG based on an existing theoretical model of PTG in mothers of children with cancer. Data were collected, using self-report questionnaires, from 222 mothers of children with cancer who visited an outpatient clinic between August 9 and September 17, 2013. The variables of optimism, disruption of core beliefs, social support, and deliberate rumination accounted for 41.4% of the variance in the mothers’ PTG. Social support and deliberate rumination are important factors directly affecting PTG in mothers of children with cancer.

Background:In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+).Methods:Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-Time PCR kit.Results:EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P

Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilized. Here, we describe a novel liposome-based subunit vaccine formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B, and ESAT-6. We show that the resulting liposomes (Lipo-AE) are stable upon storage and can be readily taken up by antigen presenting cells and that their antigenic cargo is delivered and processed within endosomal cell compartments. The Lipo-AE vaccine formulation combined with the PolyIC adjuvant induced a mixed Th1/Th17-Th2 immune response to Ag85B but only a weak response to ESAT-6. An immunization regimen based on systemic delivery followed by mucosal boost with Lipo-AE resulted in the accumulation of resident memory T cells in the lungs. Most importantly though, when Lipo-AE vaccine candidate was administered to BCG-immunized mice subsequently challenged with low dose aerosol Mycobacterium tuberculosis, we observed a significant reduction of the bacterial load in the lungs and spleen compared to BCG alone. We therefore conclude that the immunization with mycobacterial antigens delivered by phosphatidylserine based liposomes in combination with Poly:IC adjuvant may represent a novel BCG boosting vaccination strategy.

Background Menkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic “kinky” hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. In this study, we studied the clinical features and outcomes of MD, focusing on urological complications. Methods A total of 14 unrelated Korean pediatric patients (13 boys and 1 girl) with MD were recruited, and their phenotypes and genotypes were analyzed by retrospective review of their medical records. Results All the patients had early-onset neurological deficit, including developmental delay, seizures, and hypotonia. The girl patient showed normal serum copper and ceruloplasmin levels as well as milder symptoms. Mutational analysis of the ATP7A gene revealed 11 different mutations in 12 patients. Bladder diverticula was the most frequent urological complication: 8 (57.1%) in the 14 patients or 8 (72.7%) in the 11 patients who underwent urological evaluation. Urological imaging studies were performed essentially for the evaluation of accompanying urinary tract infections. Four patients had stage II chronic kidney disease at the last follow-up. Conclusion Urologic problems occurred frequently in MD, with bladder diverticula being the most common. Therefore, urological imaging studies and appropriate management of urological complications, which may prevent or reduce the development of urinary tract infections and renal parenchymal damage, are required in all patients with MD., Graphical Abstract

Background Nintedanib targets VEGF receptors 1-3, PDGF receptors alpha and beta, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma. Methods This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged >= 18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100. Findings Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5.3 months (IQR 2.8-7.3) in the nintedanib group and 5.1 months (2.7-7.8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6.8 months [95% CI 6.1-7.0]) and the placebo group (7.0 months [6.7-7.2]; HR 1.01 [95% CI 0.79-1.30], p=0.91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]). Interpretation The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

The purposes of the study were to (1) identify clusters based on patterns of sleep quality and duration and physical activity levels of healthy Korean pregnant women, and (2) subsequently investigate the association of identified clusters with pre-pregnancy healthy behaviors, depressive symptoms, and pregnancy stress. Two hundred eighty-four pregnant women participated in the study while attending a prenatal education program provided by a tertiary hospital in Seoul, Korea. The survey questionnaire consisted of the Pittsburg Sleep Quality Index, the International Physical Activity Questionnaire, and the Center for Epidemiologic Studies Depression scale. We used the Latent GOLD to identify distinct clusters and the chi-square test and ANOVA to compare clusters. We identified three clusters: ‘good sleeper’ (63.4%), ‘poor sleeper’ (24.6%), and ‘low activity’ (12.0%). Women in the good-sleeper cluster were more likely to have higher education and income levels and reported more healthy behaviors before pregnancy. Poor-sleeper and low-activity clusters were more likely to report higher scores in depressive symptoms and pregnancy stress (p &lt, 0.001 and p = 0.005, respectively). Tailored intervention for pregnant women who are physically inactive or sleep poorly may promote their psychological well-being as well as bringing good obstetric outcomes.

Summary: Background: axillary lymph nodes dissection (ALND) has been a standard treatment in breast cancer with positive sentinel LNs. However, various short- and long-term postoperative morbidities have been reported after conventional ALND. To define the concept of targeted axillary sampling (AS) and to assess its oncological feasibility for breast cancer. We compared the oncological outcomes in the axillary area between conventional ALND and targeted AS with or without radiotherapy. Methods: One hundred and twenty-nine female patients with cT1-2N1 breast cancer underwent breast and axillary surgery. We defined the concept of targeted AS in clinical and pathological terms, and the oncological outcomes were compared between ALND and AS, and between AS with and without radiotherapy. Results: There were no significant differences in oncological outcomes in the axilla between conventional ALND and AS, or between AS with radiotherapy and AS alone. Conclusions: The 5-year oncological outcomes of targeted AS were not inferior to those of conventional ALND, regardless of whether radiotherapy was added. Keywords: Breast, Carcinoma, Lymph node, Dissection, Sampling

Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi-Pasteur Denvaxia vaccine does not protect children under the age of nine and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant-expression to produce a humanised and highly immunogenic Poly-Immunoglobulin G Scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralising antibodies and evidence of cell-mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen-specific CD4+ and CD8+ T cell proliferation, IFN-γ and antibody production. The purified polymeric fraction of dengue PIGS (D-PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low affinity Fcγ receptors on antigen-presenting cells. These results show that the plant-expressed D-PIGS have the potential for translation towards a safe and easily scalable single antigen based tetravalent dengue vaccine. This article is protected by copyright. All rights reserved.

Rationale: Poroid hidradenoma (PH) is a rare variant of benign sweat gland neoplasm without connection to the epidermis. This tumor presents clinically as a solitary lesion with a cystic component located in the subcutaneous layer abutting the skin. On ultrasound, it appears as a circumscribed complex cystic and solid mass abutting the dermis. The occurrence of PH in the breast is very rare. Its features overlap with intraductal papilloma and papillary carcinoma. Patient concerns: A 66-year-old woman presented with a palpable lump in her right breast. Diagnoses: Clinical examination revealed dark bluish dome-shaped nodule which presented as circumscribed round isodense mass on mammography and oval complex cystic and solid mass abutting the dermis on ultrasound. Clinically, a papillary neoplasm was suspected. Interventions: The patient underwent En bloc surgical excision including the overlying epidermis and the surrounding adipose tissue to prevent recurrence. Outcomes: A well-demarcated, non-encapsulated grayish white mass composed of a partly solid and partly cystic area was completely removed and histopathologically confirmed as PH. At the 12-month follow-up, no recurrence was evident. Lessons: PH should be considered in the differential diagnosis of a slowly growing breast mass that is bluish, cystic, and solid and abuts the dermis.

Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome.From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8-30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed byThe final diagnoses showed that 41 (75%) of the SPNs were malignant (21 squamous cell carcinomas, 9 adenocarcinomas, 5 small-cell carcinomas, 4 mixed-type carcinomas, 1 large-cell neuroendocrine carcinoma, and 1 sarcoid carcinoma) and 14 (25%) were benign. The determination of malignant SPNs by visual analysis of the PET/CT images had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 98, 86, 95, and 92%, respectively. The semiquantitative analysis using a maximum standardized uptake value of 2.0 as the cut-off had a sensitivity, specificity, PPV, and NPV of 95, 93, 98, and 87%, respectively.

Background Ischemic heart disease (IHD) is associated with cognitive decline and may contribute to an increased risk of dementia. Objective The goal of the present study was to investigate whether cilostazol use is associated with a lower risk of incident dementia in Asian patients with IHD, and whether these effects differed based on sex. Methods This retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service; the duration of the study was from January 1, 2007 to December 31, 2015. The study group comprised 66,225 patients with IHD, aged >65 years, who had received cilostazol. Age- and sex-matched IHD patients without cilostazol exposure were selected as the control group. The risk of dementia was compared between the cilostazol and control groups. Results Compared to the control group, total cilostazol users had a marginally significant lower risk of incident dementia. After stratification by sex, the reducing effect of cilostazol on incident dementia was significant in female participants, but not in male participants. Female patients who had cilostazol for over 2 years showed a clinically meaningful preventive effect (HR, 0.85; 95% CI, 0.82-0.88). Conclusions This study suggested that cilostazol treatment may reduce the risk of incident dementia in Korean patients with IHD. Its beneficial effect was remarkably significant in female patients who received cilostazol for over a 2-year period.

GATA3 is a master regulator that drives mammary epithelial cell differentiation, and the suppression of GATA3 expression is associated with the development of aggressive breast cancer. However, the mechanism through which GATA3 loss drives cancer development is poorly understood. Previously, we reported that ELK3 suppression in MDA-MB-231 (ELK3 KD) resulted in the reprogramming of these cells from a basal to luminal subtype, which was associated with the induction of GATA3 expression, and that the ELK3-GATA3 axis orchestrated the metastatic characteristics of MDA-MB-231. Here, we show that GATA3 suppression in ELK3 knockdown MDA-MB-231 cells (ELK3/GATA3 DKD) restores the metastatic ability comparably to that of control MDA-MB-231 cells, even though the epithelial cell morphology and TGF-β signaling of ELK3 KD are not recovered in ELK3/GATA3 DKD. The expression of E-cadherin and tight junctional proteins, including occludin, claudin and ZO-1, which is activated in ELK3 KD, is suppressed in ELK3/GATA3 DKD. These results reveal the possibility that the ELK3-GATA3 axis determines the metastatic characteristics of MDA-MB-231 by regulating the expression of cell-cell adhesion factors.

The use of a multidisciplinary team approach is essential for increasing the likelihood of recovery among individuals with early psychosis. The aim of the present study was to investigate the effects of community-based mental health services on the symptoms and socio-occupational functioning of subjects with early psychosis. The study included participants who were referred to our Mental Health Promotion Center and who agreed to participate in diverse individual and group programs. During the 1-year follow-up, the medication adherence rate remained high, the recovery rate substantially increased, and the scores on the Positive and Negative Syndrome Scale, Psychotic Symptom Rating Scale-Delusion and Auditory Hallucinations subscales, Global Assessment of Functioning, Interpersonal Sensitivity Measure, and Social Functioning Questionnaire significantly improved over time. The findings suggest that the 1-year outcome of subjects with early psychosis can be improved by diverse community-based psychosocial interventions.

Background Shear-wave elastography (SWE) has the potential to improve diagnostic performance of conventional ultrasound (US) in differentiating benign from malignant breast masses. Purpose To investigate false positive or negative results of SWE in differentiating benign from malignant breast masses and to analyze clinical and imaging characteristics of the masses with false SWE findings. Material and Methods From May to October 2013, 166 breast lesions of 164 consecutive women (mean age, 45.3 ± 10.1 years) who had been scheduled for biopsy were included. Conventional US and SWE were performed in all women before biopsy. Clinical, ultrasonographic morphologic features and SWE parameters (pattern classification and standard deviation [SD]) were recorded and compared with the histopathology results. Patient and lesion factors in the “true” and “false” groups were compared. Results Of the 166 masses, 118 (71.1%) were benign and 48 (28.9%) were malignant. False SWE features were more frequently observed in benign masses. False positive rates of benign masses and false negative rates of malignancy were 53% and 8.2%, respectively, using SWE pattern analysis and were 22.4% and 10.3%, respectively, using SD values. A lesion boundary of the masses on US ( P = 0.039) and younger patient age ( P = 0.047) were significantly associated with false SWE findings. Conclusion These clinical and ultrasonographic features need to be carefully evaluated in performance and interpretation of SWE examinations.

Forrest classification is a valid tool to predict rebleeding rate in peptic ulcer, not in post-endoscopic resection ulcer. We evaluated the delayed bleeding rate in Forrest classification II and III lesions when they were not treated in second-look endoscopy. Between July 2011 and February 2012, 706 lesions in 656 consecutive patients who underwent second-look endoscopy performed on the second day after endoscopic submucosal dissection (ESD) were prospectively investigated. Endoscopic findings were described according to Forrest classification, and late delayed bleeding was defined as bleeding from second-look endoscopy to 1 month. We evaluated the rate of late delayed bleeding in untreated Forrest classification II and III lesions during second-look endoscopy. Among the 706 gastric tumors analyzed, late delayed bleeding after ESD occurred in 29 lesions (4.1 %). At second-look endoscopy, Forrest I lesions (immediately treated by endoscopic hemostasis) were found in 63 cases [Ia, 8 lesions (1.1 %); Ib, 55 lesions (7.8 %)]; there was no further bleeding after discharge. Forrest II and III lesions (not treated in second-look endoscopy) were found in 643 cases [IIa, 62 lesions (8.8 %); IIb, 119 lesions (16.9 %); IIc, 460 lesions (65.2 %); III, 2 lesions (0.3 %)]; and there was no significant difference in the late delayed bleeding rate between these groups [IIa, 2/62 (3.2 %); IIb, 5/119 (4.2 %); IIc and III, 22/462 (4.8 %); P = 1.000]. The rate of late delayed bleeding of post-ESD ulcers with non-bleeding visible vessels was not significantly different from that of ulcers with non-visible vessels ( http://cris.nih.go.kr , identifier KCT0000268).