Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells via PCDH10 in Gestational Diabetes Mellitus.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms through which these complications occur are due to functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), which remain less defined. We confirm that intrauterine hyperglycemia leads to the impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with the hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in the offspring of GDM mothers.

Incidence and characteristics of hypotensive transfusion reaction: 10-year experience in a single center.

BACKGROUND: Hypotensive transfusion reaction (HyTR) is rare. It is characterized by a rapid onset of hypotension during transfusion, which usually resolves quickly upon cessation of transfusion. Information on the incidence and clinical characteristics of HyTR has been reported in only a few studies. STUDY DESIGN AND METHODS: We retrospectively reviewed HyTR cases from 10-year hemovigilance data in a tertiary care hospital in Seoul, Korea. RESULTS: We identified 37 HyTRs in 35 patients, and the overall incidence of HyTR was 0.50 per 10,000 transfused units. Among the blood components, the incidence of HyTR was highest in filtered random donor platelets (0.75 per 10,000 units). About half of the HyTRs occurred within 15 min after the start of transfusion (19/37). Blood pressure returned to the normal range within an hour in 73.0% of the cases (27/37). All HyTR cases recovered without severe complications. Known risk factors for HyTR were not prominent in our cohort of patients, with no patients taking angiotensin-converting enzyme inhibitors and only five patients transfused with bedside filtered platelets. DISCUSSION: HyTR can occur in patients with various conditions and types of blood components. Understanding the clinical characteristics of HyTR facilitates proper management, leading to improved transfusion safety.

Patient Perspectives and Preferences Regarding Gout and Gout Management: Impact on Adherence.

BACKGROUND: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). METHODS: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. RESULTS: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). CONCLUSION: Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes.

BACKGROUND: The in vitro production of mature human red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has been the focus of research to meet the high demand for blood transfusions. However, limitations like high costs and technological requirements restrict the use of RBCs produced by iPSC differentiation to specific circumstances, such as for patients with rare blood types or alloimmunized patients. In this study, we developed a detailed protocol for the generation of iPSC lines derived from peripheral blood of donors with O D-positive blood and rare blood types (D-and Jr(a-)) and subsequent erythroid differentiation. METHODS: Mononuclear cells separated from the peripheral blood of O D-positive and rare blood type donors were cultured to produce and expand erythroid progenitors and reprogrammed into iPSCs. A 31-day serum-free, xeno-free erythroid differentiation protocol was used to generate reticulocytes. The stability of iPSC lines was confirmed with chromosomal analysis and RT-PCR. Morphology and cell counts were determined by microscopy observations and flow cytometry. RESULTS: Cells from all donors were successfully used to generate iPSC lines, which were differentiated into erythroid precursors without any apparent chromosomal mutations. This differentiation protocol resulted in moderate erythrocyte yield per iPSC. CONCLUSIONS: It has previously only been hypothesized that erythroid differentiation from iPSCs could be used to produce RBCs for transfusion to patients with rare blood types or who have been alloimmunized. Our results demonstrate the feasibility of producing autologous iPSC-differentiated RBCs for clinical transfusions in patients without alternative options.

Correction to: T1 mapping for liver function evaluation in gadoxetic acid-enhanced MR imaging: comparison of look-locker inversion recovery and B1 inhomogeneity-corrected variable flip angle method.

The original version of this article, published on 22 March 2019, unfortunately contained a mistake. The following correction has therefore been made in the original: Affiliations 1 and 2 were presented incorrectly.

Quantification of liver extracellular volume using dual-energy CT: utility for prediction of liver-related events in cirrhosis.

OBJECTIVES: To determine whether quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) allows prediction of liver-related events (LREs) in cirrhotic patients. METHODS: This retrospective study included 305 cirrhotic patients who underwent dual-source DECT imaging and had serum markers analyzed within 2 weeks of initial CT imaging. The fECV score was measured using an iodine map of equilibrium-phase images obtained 3 min after contrast injection at 100/140 Sn kVp. The association of the fECV score and serum markers with LREs was investigated. A risk model combining the fECV score (< 27 versus ≥ 27%) and serum albumin level (< 4 versus ≥ 4 g/dL) was constructed for LRE prediction. RESULTS: An increased fECV score (odds ratio, 1.27; 95% confidence interval (CI), 1.15, 1.40) was independently associated with decompensated cirrhosis at baseline (n = 85) along with the Model for End-Stage Liver Disease score (odds ratio, 1.32; 95% CI, 1.07, 1.63). Among patients with compensated cirrhosis, 10.5% (23 of 220) experienced LREs during the median follow-up period of 2.0 years (decompensation, n = 14; hepatocellular carcinoma, n = 9). The fECV score (hazard ratio, 1.40; 95% CI, 1.22, 1.62) and serum albumin level (hazard ratio, 0.26; 95% CI, 0.09, 0.73) were independent predictors of LRE. The mean times to LRE among the high (16.5 months, n = 18)-, intermediate (25.6 months, n = 44)-, and low (30.5 months, n = 158)-risk groups were significantly different (p < 0.001). CONCLUSIONS: The fECV score derived from DECT allows prediction of LREs in cirrhotic patients. KEY POINTS: • The extracellular volume fraction (fECV) score derived from the iodine map of dual-energy CT (DECT) was independently associated with the presence of hepatic decompensation. • The fECV score derived from the iodine map of DECT can predict liver-related events (LREs) in patients with cirrhosis. • Equilibrium-phase scanning in dual-energy mode is recommended as part of liver CT in cirrhotic patients because it can provide a prognostic indicator for LRE development.

Erythrocyte Alloimmunity and Genetic Variance: Results from the Collaborative Study of Alloimmunity to Antigen Diversity in Asian Populations (All ADP).

As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Seasonal Variations and Associated Factors of Gout Attacks: a Prospective Multicenter Study in Korea.

BACKGROUND: We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. METHODS: We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. RESULTS: Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; -0.9%, fall; -1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. CONCLUSION: In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

T1 mapping for liver function evaluation in gadoxetic acid-enhanced MR imaging: comparison of look-locker inversion recovery and B1 inhomogeneity-corrected variable flip angle method.

OBJECTIVES: To compare look-locker inversion recovery (LLIR) and B1 inhomogeneity-corrected variable flip angle T1 mapping methods for estimation of liver function and prediction of hepatic insufficiency and decompensation on gadoxetic acid-enhanced MR imaging. METHODS: In this retrospective study, 248 patients with normal liver function, chronic liver disease, or cirrhosis underwent gadoxetic acid-enhanced liver MR imaging, including T1 mapping at 10-min and 20-min hepatobiliary phase (HBP) by using both methods. T1 relaxation times of the liver (T1Liver-pre, T1Liver-post) and the spleen (T1Spleen) were correlated between two methods. ΔT1Liver ([T1Liver-pre - T1Liver-post]/T1Liver-pre), adjusted T1Liver ([T1Spleen - T1Liver-post]/T1Spleen), and functional liver volume-to-weight ratio (liver volume on volumetric T1 map/[T1Liver-post × patient's weight]) were calculated. The diagnostic performance of T1 parameters and the predictive performance of models (serum marker, serum marker plus T1 parameter) were compared. RESULTS: T1Liver-post showed a strong correlation (r = 0.93, p < 0.001) between two methods but was significantly different. For depicting cirrhosis, LLIR-adjusted T1Liver at 10-min HBP showed the highest performance (p < 0.025). For predicting hepatic insufficiency and decompensation, LLIR-adjusted T1Liver (Akaike information criterion (AIC), 58.37; C-index, 0.867) and LLIR-T1Liver-post (AIC, 48.82; C-index, 0.885) at 10-min HBP showed the best performance, respectively, when added to serum albumin level. CONCLUSIONS: T1Liver-post showed a strong correlation between two methods but with significant differences. T1 mapping using LLIR at 10-min HBP with obtainment of adjusted T1Liver and T1Liver-post may be the best approach for estimation of liver function and prediction of hepatic insufficiency and decompensation. KEY POINTS: • T1 Liver-post showed a strong correlation between LLIR and B 1 inhomogeneity-corrected VFA methods, both at 10-min and 20-min HBP but with significant differences. • T1 Liver-post at 10-min and 20-min HBP using LLIR and B 1 inhomogeneity-corrected VFA methods could not be used interchangeably during the follow-up in patients with chronic liver disease (CLD) or cirrhosis. • T1 mapping using LLIR at 10-min HBP with obtainment of adjusted T1 Liver and T1 Liver-post may be the most suitable method and parameter for estimation of global liver function and prediction of clinical outcomes in patients with CLD or cirrhosis.

Distinct clinical characteristics of anti-Ro/SSA-negative primary Sjögren's syndrome: data from a nationwide cohort for Sjögren's syndrome in Korea.

OBJECTIVES: To investigate clinical characteristics of patients with primary Sjögren's syndrome (SS) who were negative for anti-Ro/SSA antibody but positive for minor salivary gland biopsy (MSGB) compared to patients who presented positivity for anti-Ro/SSA antibody. METHODS: The data of 355 patients from the Korean Initiative of primary Sjögren's Syndrome (KISS), a nationwide prospective cohort for primary SS in Korea, were analysed. All patients fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Of these patients, 326 were positive for anti-Ro/SSA antibody and 29 were antibody-negative, although they had positive findings in MSGB. Various clinical features including all kinds of tests for evaluating secretory function, disease-related clinical indices and serological values available in the cohort were compared between the two groups. RESULTS: The anti-Ro/SSA-negative group showed less rheumatoid factor positivity (p<0.001), leucopenia (p=0.003), hyper-gammaglobulinaemia (p<0.001), lower serum ß2-microglobulin level (p=0.034), more anti-centromere antibody positivity (p<0.001), higher score in dryness domain of EULAR SS patient-reported index (p=0.048) and more positivity for peripheral nervous system domain in EULAR SS disease activity index and loss of teeth in SS disease damage index (p=0.021 and 0.041, respectively) than patients who were positive for anti-Ro/ SSA antibody. CONCLUSIONS: Primary SS patients who are negative for anti-Ro/SSA antibody have different clinical characteristics compared to patients who are positive for such antibody in Korea. Therefore, clinicians should consider MSGB in patients with suspicious symptoms who are anti-Ro/SSA-negative.

Platelet storage induces accelerated desialylation of platelets and increases hepatic thrombopoietin production.

BACKGROUND: Stored platelets undergo deleterious changes, referred to as platelet storage lesions (PSLs), which accelerate the desialylation of platelets and result in their phagocytosis and clearance by hepatic macrophages. Recent studies have reported that Ashwell-Morell receptor binds to desialylated platelets, thereby inducing hepatic thrombopoietin (TPO) production in a mouse model. Therefore, this study aimed to demonstrate these relationships between PSL and hepatic TPO production in human study. METHODS: Platelet concentrates (PCs) were obtained from 5 healthy volunteers and the remaining were discarded samples from the blood bank. PCs were divided into two halves, and stored either at 22 or 4 °C. Experiments were conducted using serial samples. Desialylation was assessed using flow cytometry, and structural changes were visualized using electron microscopy. Following co-culture of HepG2 cells (HB-8065, ATCC) with isolated platelets, hepatic TPO production was determined using real-time quantitative polymerase chain reaction and the supernatant TPO level was measured using a Luminex kit. RESULTS: For 5 days of storage duration, platelet counts were not influenced by the storage conditions, but the degree of desialylation was proportional to the storage duration. Significant changes in the platelet surface and structure according to storage conditions were noted in electron microscopy. HepG2 cells incubated with aged platelets expressed more TPO mRNA, and supernatant TPO levels were proportional to the storage duration. Refrigeration also influenced on the results of this study, but they were not statistically significant. CONCLUSIONS: This is the first study to demonstrate that, in vitro, aging and refrigeration affect the integrity of human platelets, resulting in induction of hepatic TPO mRNA and protein expression.

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis.

Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.

Analysis of red blood cell use in elective surgeries over 12 years in Korea.

BACKGROUND: Red blood cell (RBC) transfusion is a lifesaving process for patients with perioperative bleeding, but transfusion can cause adverse events. Effective utilization and management of blood products as a limited resource is essential when considering cost-efficiency and patient safety. STUDY DESIGN AND METHODS: We analyzed the number of RBC units used during the hospitalization of patients who had undergone surgical procedures from 2002 to 2013 using National Health Insurance Service-National Sample Cohort data, which include a total of 487,238 cases for 206 selected operations. RESULTS: RBC units were used in 39,637 (8.1%) cases. A total of 60,815 RBC units were transfused with a mean of 0.13 units per patient overall and a mean of 1.53 units per case receiving RBC transfusion. In addition, 56.7% of the RBC units were transfused for females, and 60.1% of RBC units were transfused into patients aged 60 or older. RBC units were used most often in orthopedic surgeries (33.8%), followed by general surgeries (12.0%) and vascular surgeries (11.8%). The number of operations performed in the cohort increased from 27,690 in 2002 to 49,473 in 2013, and the mean number of RBC units used per operation also increased from 0.08 units in 2002 to 0.15 units in 2013. CONCLUSION: Continuous management for blood preparation and transfusion is needed for efficient utilization of blood. Periodic investigation on the use of blood products through nationwide studies could suggest data applicable to blood product preparation for various elective surgical operations.

The effect of therapeutic leukapheresis on early complications and outcomes in patients with acute leukemia and hyperleukocytosis: a propensity score-matched study.

BACKGROUND: Hyperleukocytosis in acute leukemia is associated with higher early mortality due to the major complications of leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulopathy (DIC). Leukapheresis remains an important modality for the management of patients with acute leukemia and hyperleukocytosis. However, the role of leukapheresis in early mortality is controversial. This study sought to evaluate the prognostic impact of leukapheresis and its beneficial effects on TLS and DIC. STUDY DESIGN AND METHODS: We conducted a propensity score-matched study of 166 patients with acute leukemia and hyperleukocytosis admitted between 2006 and 2016. The incidence of TLS and DIC was determined using well-defined Cairo-Bishop criteria for TLS and International Society of Thrombosis and Haemostasis criteria for DIC. RESULTS: Before matching, 27 of 91 patients (30%) with acute myeloid leukemia (AML) and 32 of 75 patients (43%) with acute lymphoblastic leukemia (ALL) underwent leukapheresis. Propensity score matching was performed to adjust for clinical disparities between the leukapheresis and without-leukapheresis groups and resulted in 22 matched pairs of patients with AML and 16 matched pairs of patients with ALL. After matching, we observed no significant difference in early mortality rates or in the incidence of TLS or DIC between the two groups of patients with AML and ALL. CONCLUSION: Although leukapheresis may rapidly reduce white blood cell counts and leukemic blasts, any positive influence of leukapheresis could not be demonstrated by an effect on survival outcome and the incidence of early complications, such as TLS and DIC. These results suggest that a routinely performed, prophylactic leukapheresis cannot be recommended.

Performance of the 2016 ACR-EULAR classification criteria for primary Sjogren's syndrome in a Korean cohort.

This study compared the performance of the newly proposed 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria to the 2002 American-European Consensus Group (AECG) and 2012 ACR classification criteria for primary Sjogren's syndrome (pSS) in well-characterized Korean patients. Patients with pSS from 12 university-affiliated hospitals in Korea were enrolled from October 2013 to January 2017. Clinical and laboratory data were reviewed. For the validation set, patients who underwent evaluation tests to rule out pSS at Seoul St. Mary's hospital from November 2016 to December 2017 were analyzed. Baseline registry data were available in 458 patients, and 328 patients had sufficient data to determine the fulfillment of each criteria set. All three sets of criteria were met by 307 patients (93.6%). The newly proposed 2016 ACR/EULAR criteria were met by 325 patients (99.1%). The 2002 AECG and 2012 ACR criteria were met by 325 (99.1%) and 310 patients (94.5%), respectively. In a validation cohort consisting of 161 patients with pSS-related symptoms/signs, the sensitivity and specificity of the 2016 ACR/EULAR criteria were 100% [95% confidence interval (CI), 96.11-100.00] and 81.8% [95% CI, 76.15-94.26], respectively. Agreement between the 2016 criteria and 2012 or 2002 criteria was high (Cohen's kappa 0.736 and 0.769, respectively). The newly proposed 2016 ACR/EULAR criteria were met by most patients diagnosed with pSS according to previous criteria and showed higher sensitivity and lower specificity compared with both previous criteria sets.

O-linked-N-acetylglucosamine transferase is associated with metastatic spread of human papillomavirus E6 and E7 oncoproteins to the lungs of mice.

High-risk human papilloma virus (HPV) 16/18 infections are often found in lung cancer. The cellular mechanisms involved in the metastatic spread of HPV-infected cervical cancer cells remain largely elusive. High O-linked-N-acetylglucosamine (O-GlcNAc) modification has also been observed in lung cancer. In the present study, we assessed the relationship between O-GlcNAc transferase (OGT) and HPV 16/18 E6/E7, or C-X-C chemokine receptor type 4 (CXCR4), in HeLa cells and in lungs of xenografted mice. Depleting OGT with an OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins in HeLa cells and xenograft tumors, and reduced tumor formation in vivo. Western blotting and immunofluorescence analysis showed significantly decreased expression levels of E6, E7, and HCF-1 in the lungs of xenografted mice treated with an OGT-specific shRNA compared to those treated with non-targeting shRNA. Additionally, levels of E7 or OGT co-localized with Ki-67 were significantly decreased in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA. Moreover, levels of CXCR4 were significantly decreased in HeLa cells and in the lungs of xenografted mice treated with OGT-specific shRNA compared to those treated with non-targeting shRNA; this may be related to reduced adhesion or invasion of circulating HPV-positive tumor cells. These findings provide novel evidence that OGT functions in metastatic spread of HPV E6/E7-positive tumor cells to the lungs through E6/E7, HCF-1 and CXCR4, suggesting OGT might be a therapeutic target for HPV-positive lung cancer.

Added value of point shear-wave elastography in the diagnosis of acute cholecystitis.

OBJECTIVE: To evaluate the added value of point shear-wave elastography (pSWE) in the diagnostic performance of conventional US for diagnosis of acute cholecystitis. METHODS: B-mode and colour Doppler US and pSWE were performed prospectively in 216 patients with clinically suspected acute cholecystitis. The morphology and mural vascularity of the gallbladder and median shear wave velocity (SWV) of the right liver were evaluated. Two observers independently reviewed conventional US images and subsequently reviewed combined conventional US and pSWE images. RESULTS: Mean SWVs of the acute cholecystitis group (n = 91) were significantly higher than those of the control group (n = 85) in the right liver within 2 cm lateral to the gallbladder (1.56 versus 1.03 m/s, 1.39 versus 1.04 m/s, P < 0.0001) with a cut-off value of 1.29 or 1.16 m/s. The area under the receiver operating characteristic curve of both observers in the diagnosis of acute cholecystitis improved significantly from 0.790 and 0.777 to 0.963 and 0.962, respectively, after additional review of pSWE images (P < 0.0001). Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values of combined image sets were higher than those of conventional US images alone. CONCLUSION: Adding pSWE to conventional US improves the diagnosis of acute cholecystitis when compared with conventional US alone. KEY POINTS: • In acute cholecystitis, stiffness of the right liver increases adjacent to the gallbladder. • The cut-off value for diagnosing acute cholecystitis was 1.29 or 1.16 m/s. • Adding pSWE to conventional US improves the diagnosis of acute cholecystitis.

Successful launch of an ABO-incompatible kidney transplantation program to overcome the shortage of compatible living donors: experience at a single center
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AIMS: ABO-incompatible (ABOi) kidney transplantation (KT) is being increasingly performed to overcome donor shortages. However, debate persists regarding the post-transplant outcomes of ABOi KT vs. that of ABO-compatible (ABOc) KT. METHODS: A total 454 recipients who underwent living-donor KT (LDKT) between June 2010 and July 2014 at Severance Hospital (Seoul) were retrospectively reviewed. 100 ABOi and 354 ABOc KTs were compared. Recipients with a pretransplant positive crossmatch to their donors, pretransplant donor-specific anti-HLA antibody (DSA), or high panel reactive antibody (PRA ≥ 50%) were excluded from both the ABOi and ABOc KT groups. Finally, the authors compared the transplant outcomes of 95 of these ABOi KTs and 121 ABOc KTs performed over the same period. RESULTS: No significant difference in incidence of biopsy-proven acute rejection was observed between the ABOi and ABOc KT groups (p = 0.230), and group glomerular filtration rate of ABOi KT was comparable to that of ABOc KT (p > 0.05 at all time points). 3-year death-censored graft survival rates were similar (96.8 vs. 96.6%, respectively; p = 0.801). However, the incidences of postoperative bleeding, cytomegalovirus infection, fungal infection, and serious infection rates were significantly higher after ABOi KT. CONCLUSIONS: In this study, graft renal function and survival after ABOi KT were excellent, and the incidence of acute rejection was similar to that of ABOc KT. However, efforts are needed to reduce hemorrhagic and infectious complications after ABOi KT. ABOi KT can be a good strategy to overcome ABO antibody barriers and relieve donor shortage.
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