Background: The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. Methods: The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. Results: The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. Conclusions Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS: In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.
Anticoagulants ; Blood Platelets ; Colonoscopy ; Female ; Gastrointestinal Tract ; Glomerular Filtration Rate ; Hemorrhage ; Hemorrhoids ; Humans ; Incidence ; Logistic Models ; Lower Gastrointestinal Tract ; Renal Dialysis ; Renal Insufficiency, Chronic ; Retrospective Studies ; Ulcer ; Uremia

PURPOSE: Characteristic signs – the susceptibility vessel sign (SVS) and the prominent hypointense vessel sign (PHVS) – on T2*-based magnetic resonance imaging (T2*MRI) can be seen for acute ischemic stroke with large artery occlusion. In this study, we investigated the evidence to support our hypothesis that these findings may help to predict outcomes after reperfusion therapy. MATERIALS AND METHODS: We searched for papers describing SVS and PHVS in patients treated with reperfusion therapy for acute ischemic stroke, and their functional/radiologic outcomes were systematically reviewed. RESULTS: Nine studies on the SVS and six studies on the PHVS were included. The pooled odds ratio (OR) of recanalization after intravenous thrombolysis or mechanical thrombectomy was not significantly different with the presence of SVS (OR, 0.615; 95% confidence interval [CI], 0.335–1.131 and OR, 0.993; 95% CI, 0.629–1.567). The OR of favorable functional outcome after reperfusion therapy in terms of the presence of PHVS varied (0.083 to 1.831) by study. CONCLUSION: Our meta-analysis of the published data showed that a SVS was not a predictive factor for recanalization after reperfusion therapy for acute ischemic stroke. Currently, the data available on T2*MRI are too limited to warrant reperfusion therapy in routine practice. More data are needed from studies with randomized treatment allocation to determine the role of T2*MRI.
Arteries ; Humans ; Magnetic Resonance Imaging ; Odds Ratio ; Reperfusion* ; Stroke* ; Thrombectomy

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy, Segmental* ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Time-to-Treatment

BACKGROUND AND PURPOSE: The benefit of carotid endarterectomy (CEA) is directly influenced by the risk of perioperative adverse outcomes. However, patient-level risks and predictors including coronary stenosis are rarely evaluated, especially in Asian patients. The aim of this study was to determine the relationship between the vascular risk factors underlying CEA, including coronary stenosis, and postoperative outcome. METHODS: One hundred and fifty-three consecutive CEAs from our hospital records were included in this analysis. All patients underwent coronary computed tomography angiography before CEA. Data were analyzed to determine the vascular outcomes in patients with mild-to-moderate vs. severe coronary stenosis and high vs. standard operative risk, based on the criteria for high operative risk defined in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial. The vascular outcome was defined as the occurrence of postoperative (< or =30 days) stroke, myocardial infarction (MI), or death. RESULTS: An adverse vascular outcome occurred in 8 of the 153 CEAs, with 6 strokes, 2 MIs, and 3 deaths. The vascular outcome differed significantly between the groups with mild-to-moderate and severe coronary stenosis (p=0.024), but not between the high- and standard-operative-risk groups (stratified according to operative risk as defined in the SAPPHIRE trial). Multivariable analysis adjusting for potent predictors revealed that severe coronary stenosis (odds ratio, 6.87; 95% confidence interval, 1.20-39.22) was a significant predictor of the early vascular outcome. CONCLUSIONS: Severe coronary stenosis was identified herein as an independent predictor of an adverse early vascular outcome.
Aluminum Oxide ; Angiography ; Angioplasty ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis* ; Endarterectomy ; Endarterectomy, Carotid* ; Hospital Records ; Humans ; Myocardial Infarction ; Risk Assessment ; Risk Factors ; Stents ; Stroke

PURPOSE: A significant proportion of patients with cough variant asthma (CVA) eventually develops asthma. The aim of this study was to investigate the relationship between bronchial hyperresponsiveness (BHR) and development of asthma in preschool children with CVA. METHODS: We reviewed the medical records of children aged 5 to 7 years who presented with chronic cough and had regular check-up by the school age. All children had methacholine bronchial challenge test (MBCT) at preschool age with a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Positive BHR was defined as end-point concentration (EPC)< or =8 mg/mL. MBCT was performed at the school age with spirometric method. Positive BHR was defined as PC20< or =8 mg/mL. We collected information on the development of wheezing or dyspnoea from the medical records. RESULTS: Thirty-six children with CVA were analyzed. During follow-up (2.1+/-0.9 years), 9/36 children developed wheezing or dyspnoea (group A), and 27/36 children did not (group B). EPC (geometric mean, 95% confidence interval) was significantly lower in group A than group B (1.59 mg/mL, 0.93 to 2.70 mg/mL vs. 3.43 mg/mL, 2.34 to 5.03 mg/mL; P=0.02, respectively). The prevalence of positive BHR at school age was significantly higher in group A than group B (77.8% vs. 22.2%, P<0.01). CONCLUSION: These results suggest that the increase and the persistence of BHR may have an important role in the development of asthma during the course of CVA in preschool children.
Aged ; Asthma ; Auscultation ; Bronchial Provocation Tests ; Child ; Child, Preschool ; Cough ; Follow-Up Studies ; Humans ; Medical Records ; Methacholine Chloride ; Oxygen ; Phosphorylcholine ; Prevalence ; Respiratory Sounds

PURPOSE: It is important to assess the level of control in asthmatic children who were well-controlled and thus discontinued controller medications. Office spirometry has been regarded to provide objective measures. We aimed to see time changes in lung function indices measured by the office spirometry and their relationship to clues for asthma exacerbation after discontinuation of controller medications. METHODS: As a pilot study, a total of 20 well-controlled children with persistent asthma were included. After discontinuing controller medications, each made follow-up visits at the 2nd, 6th, and 12th week. At each visit, spirometric values before and after bronchodilators were evaluated by the office-based spirometer. Time changes and their relationship to clues for asthma exacerbation were assessed. RESULTS: Among 20 children, 13 (65%) were successfully followed-up for 12 weeks with asthma kept stable. They presented similar spirometric values (forced expiratory volume in 1 second [FEV1], peak expiratory flow rate [PEFR], bronchodilator responses [BDRs] based on the FEV1 and PEFR) across all time-points. No differences in spirometric values were found between those who were stable and those who exhibited clues for asthma exacerbation. BDRs calculated from FEV1 values (BDRFEV1) correlated well with those calculated from PEFR values (BDRPEFR). CONCLUSION: When controller medications were discontinued in children with well-controlled asthma, many of them were able to maintain the stable condition. Since the spirometric measures including BDR failed to differentiate clues for asthma exacerbation, the usefulness of office spirometry needs to be reevaluated by the larger population of children with controlled asthma after discontinuing medications.
Asthma ; Bronchodilator Agents ; Child ; Follow-Up Studies ; Humans ; Lung ; Peak Expiratory Flow Rate ; Pilot Projects ; Spirometry