Background: and Purpose The influence of imaging features of brain frailty on outcomes were investigated in acute ischemic stroke patients with minor symptoms and large-vessel occlusion (LVO). Methods: This was a retrospective analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute (within 24 h) minor (National Institutes of Health Stroke Scale score=0–5) ischemic stroke with anterior circulation LVO (acute minor LVO). Brain frailty was stratified according to the presence of an advanced white-matter hyperintensity (WMH) (Fazekas grade 2 or 3), silent/old brain infarct, or cerebral microbleeds. The primary outcome was a composite of stroke, myocardial infarction, and all-cause mortality within 1 year. Results: In total, 1,067 patients (age=67.2±13.1 years [mean±SD], 61.3% males) were analyzed. The proportions of patients according to the numbers of brain frailty burdens were as follows: no burden in 49.2%, one burden in 30.0%, two burdens in 17.3%, and three burdens in 3.5%. In the Cox proportional-hazards analysis, the presence of more brain frailty burdens was associated with a higher risk of 1-year primary outcomes, but after adjusting for clinically relevant variables there were no significant associations between burdens of brain frailty and 1-year vascular outcomes. For individual components of brain frailty, an advanced WMH was independently associated with an increased risk of 1-year primary outcomes (adjusted hazard ratio [aHR]=1.33, 95% confidence interval [CI]=1.03–1.71) and stroke (aHR=1.32, 95% CI=1.00–1.75). Conclusions The baseline imaging markers of brain frailty were common in acute minor ischemic stroke patients with LVO. An advanced WMH was the only frailty marker associated with an increased risk of vascular events. Further research is needed into the association between brain frailty and prognosis in patients with acute minor LVO.

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Background/Aims: We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). Methods: We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. Results: No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06–5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). Conclusions The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Background/Aims: Germline mutations of the rearranged during transfection (RET) gene cause multiple endocrine neoplasia type 2 (MEN2). About 85% of RET mutations in MEN2 occur in codon Cys634. The RET D631Y mutation has recently been discovered, and we have studied its molecular expression and clinical consequences. Methods: We analyzed the clinical characteristics of a total of 34 D631Y variant MEN2 individuals from seven families. We also constructed wild-type and mutant C630Y, D631Y, and C634R/W expression vectors and investigated their effects on signaling pathways and ability to correct the phenotypes of RET mutant cells. Results: The median ages at diagnosis of pheochromocytoma and medullary thyroid carcinoma (MTC) were higher in patients with RET D631Y variant MEN2 than in those with the C634R/W variant (49:53.5 years vs. 33.5:27 years, respectively), and the penetration of the D631Y mutation with respect to MTC was lower than that of the C634R/W mutation (32.3% vs. 90%). The effects of the mutant vectors on phosphorylation of RET signaling molecules and focus formation were significantly different from those of wild type, but there were no significant differences between the mutants. D631Y scored significantly higher for chemotaxis and wound healing than C630Y, but lower than C634R and C634W. Conclusions We suggest that the tumorigenic potential conferred by the D631Y mutation is lower than that conferred by the C634R/W mutation, but higher than that conferred by C630Y. Thus, the risk level of the RET D631Y variant appears to be higher than that of C630Y and lower than that of C634R/W.

We report an inspiring case of a 55-year-old Korean female diagnosed with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) in Mexico.The patient was assessed for lung transplant as a salvage therapy for treatment-refractory ARDS following no signs of clinical improvement for > 7 weeks, despite best treatment.The patient was transported from Mexico to Korea by air ambulance under venovenous extracorporeal membrane oxygenation (ECMO) support. She was successfully bridged to lung transplant on day 88, 49 days after the initiation of ECMO support. ECMO was successfully weaned at the end of operation, and no bleeding or primary graft dysfunction was observed within the first 72 hours. The patient was liberated from mechanical ventilation on postoperative day 9 and transferred to the general ward 5 days later. Despite the high doses of immunosuppressants, there was no evidence of viral reactivation after transplant.At 3 months post-transplantation, she was discharged to home without complication. Our experience suggests that successful lung transplant for COVID-19-associated ARDS is feasible even in a patient with prolonged pre-transplant ECMO support. Lung transplant may be considered a salvage therapy for COVID-19-associated ARDS that does not respond to conventional treatments.

We report an inspiring case of a 55-year-old Korean female diagnosed with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) in Mexico.The patient was assessed for lung transplant as a salvage therapy for treatment-refractory ARDS following no signs of clinical improvement for > 7 weeks, despite best treatment.The patient was transported from Mexico to Korea by air ambulance under venovenous extracorporeal membrane oxygenation (ECMO) support. She was successfully bridged to lung transplant on day 88, 49 days after the initiation of ECMO support. ECMO was successfully weaned at the end of operation, and no bleeding or primary graft dysfunction was observed within the first 72 hours. The patient was liberated from mechanical ventilation on postoperative day 9 and transferred to the general ward 5 days later. Despite the high doses of immunosuppressants, there was no evidence of viral reactivation after transplant.At 3 months post-transplantation, she was discharged to home without complication. Our experience suggests that successful lung transplant for COVID-19-associated ARDS is feasible even in a patient with prolonged pre-transplant ECMO support. Lung transplant may be considered a salvage therapy for COVID-19-associated ARDS that does not respond to conventional treatments.

Objective: Boost radiation using brachytherapy (BT) is a standard treatment for local disease control in concomitant chemoradiation therapy (CCRT) for advanced cervical cancer.However, it is associated with gastrointestinal and genitourinary complications. Hence, this study investigates the feasibility of helical tomotherapy (HT) as an alternative to BT. Methods: Medical records of patients who underwent CCRT between 2000 and 2017 at a single institution were retrospectively reviewed. Patients with stage IIB–IVA cancers were selected based on the 2009 criteria of The International Federation of Gynaecology and Obstetrics.External beam radiation combined with chemotherapy was followed by either BT or HT. The propensity score matching of both groups was calculated using logistic regression analysis.Disease outcomes and treatment-related adverse events were compared between the 2 groups. Results: The matched population included 70 BT patients and 35 HT patients. The 5-year progression-free survival rates for BT and HT were 72.6% and 72.5%, respectively (p=0.721).There was no difference in the overall survival rate between the two groups (p=0.203). The presence of acute and chronic gastrointestinal complications was also similar between the groups (p=0.460 and p=0.563, respectively). The chronic genitourinary toxicities were also comparable (p=0.105). Conclusions HT boost treatment showed comparable disease outcomes with those observed with conventional BT in patients with advanced cervical cancer. HT could be a complementary boost protocol as a single modality or hybrid with BT in selected patients.Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

BACKGROUND/AIMS: Various alterations of microRNA (miRNA) expression have been reported in myelodysplastic syndrome (MDS). We aimed to investigate the unique patterns and prognostic significance of miRNA expression in Korean patients with MDS. METHODS: Bone marrow mononuclear cells were collected from eight healthy controls and 26 patients with MDS, and miRNAs were isolated and assessed via quantitative real-time polymerase chain reaction for selected miRNAs, including miR-21, miR-124a, miR-126, miR-146b-5p, miR-155, miR-182, miR-200c, miR-342-5p, miR-708, and Let-7a. RESULTS: MiR-124a, miR-155, miR-182, miR-200c, miR-342-5p, and Let-7a were significantly underexpressed in patients with MDS, compared to healthy controls. MiR-21, miR-126, 146b-5p, and miR-155 transcript levels were significantly lower in international prognostic scoring system lower (low and intermediate-1) risk MDS than in higher (intermediate-2 and high) risk MDS. Higher expression levels of miR-126 and miR-155 correlated with significantly shorter overall survival and leukemia-free survival. Higher miR-124a expression also tended to be related to shorter survivals. CONCLUSIONS Although our study was limited by the relatively small number of patients included, we identified several miRNAs associated with pathogenesis, leukemic transformation, and prognosis in MDS.

PURPOSE: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. MATERIALS AND METHODS: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and diseasespecific survival (DSS) rates were calculated by the Kaplan–Meier method. RESULTS: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. CONCLUSION: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.
Chordoma ; Cobalt ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Korea ; Methods ; Proton Therapy ; Protons ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Iodine is an intrinsic element of thyroid hormone, which is essential for childhood growth and development. The Ideal Breast Milk (IBM) cohort study aims to evaluate the effects of maternal iodine status during pregnancy and lactation on maternal thyroid function, offspring growth and development, and offspring thyroid function. METHODS: The IBM cohort study recruited pregnant women from Seoul National University Hospital between June 2016 and August 2017, followed by enrollment of their offspring after delivery. For the maternal participants, iodine status is evaluated by urinary iodine concentration (UIC) and dietary records in the third trimester and at 3 to 4 weeks and 12 to 15 months postpartum. For the child participants, cord blood sampling and UIC measurements are performed at birth. At 3 to 4 weeks of age, UIC and breastmilk iodine concentrations are measured. At 12 to 15 months of age, growth and development are assessed and measurements of UIC, a thyroid function test, and ultrasonography are performed. RESULTS: A total of 198 pregnant women in their third trimester were recruited. Their mean age was 35.1±3.5 years, and 78 (39.4%) of them were pregnant with twins. Thirty-three (16.7%) of them had a previous history of thyroid disease. CONCLUSION: Korea is an iodine-replete area. In particular, lactating women in Korea are commonly exposed to excess iodine due to the traditional practice of consuming brown seaweed soup postpartum. The study of the IBM cohort is expected to contribute to developing guidelines for optimal iodine nutrition in pregnant or lactating women.
Breast* ; Child ; Cohort Studies* ; Cordocentesis ; Diet Records ; Female ; Growth and Development* ; Humans ; Infant ; Iodine* ; Korea ; Lactation* ; Milk, Human* ; Parturition ; Postpartum Period ; Pregnancy Trimester, Third ; Pregnancy* ; Pregnant Women ; Prospective Studies* ; Seaweed ; Seoul ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland* ; Twins ; Ultrasonography