Altering Cell Junctional Tension in Spheroids through E-Cadherin Engagement Modulation.

Cadherin-mediated tension at adherens junctions (AJs) is fundamental for cell-cell adhesion and maintaining epithelial integrity. Despite the importance of manipulating AJs to dissect cell-cell interactions, existing three-dimensional (3D) multicellular models have not adequately addressed the precise manipulation of these junctions. To fill this gap, we introduce E-cadherin-modified tension gauge tethers (TGTs) at the junctions within spheroids. The system enables both quantification and modulation of junctional tension with specific DNA triggers. Using rupture-induced fluorescence, we successfully measure mechanical forces in 3D spheroids. Furthermore, mechanically strong TGTs can maintain normal E-cadherin-mediated adhesion. Employing toehold-mediated strand displacement allowed us to disrupt E-cadherin-specific cell-cell adhesion, consequently altering intracellular tension within the spheroids. Our methodology offers a robust and precise way to manipulate cell-cell adhesion and intracellular mechanics in spheroid models.

Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction.

Background/Aims: The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. Methods: Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors who tested negative for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV). The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. Results: We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. Conclusions: Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

Influence of Smoking and Controlled Medical Conditions on the Risks of Branch Retinal Vein Occlusion in South Korea: A Population-Based Study.

PURPOSE: To evaluate the effect of controlled medical conditions and risk of lifetime smoking history on the prevalence of branch retinal vein occlusion (BRVO) based on the Korea National Health and Nutrition Survey (KNHANES) database from 2017-2021. METHODS: The study population consisted of individuals aged ≥ 40 years who had completed ophthalmological questionnaires, underwent comprehensive ophthalmological examinations, and had at least one good-quality readable fundus photograph. Age, sex, hypertension status, diabetes status, dyslipidemia status, body mass index status, a history of chronic kidney disease (CKD), a lifetime smoking history of ≥ 100 cigarettes, and glaucoma were subjected to univariate and multivariate logistic regression analyses. RESULTS: The estimated prevalence (± standard error) of RVO was 0.5% (±0.1%). Significant risk factors were one-year increase in age, female sex, hypertension (stage 1, controlled, uncontrolled, and undiagnosed hypertension), underweight, pre-obesity, history of CKD, lifetime smoking history of ≥ 100 cigarettes, and glaucoma. Controlled diabetes decreased the risk of BRVO by 55% (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.22-0.89, p = 0.022) and controlled hyper-high-density-lipoprotein (HDL)-cholesterolemia decreased the risk by 69% (OR = 0.31, 95% CI = 0.13-0.76, p = 0.010). CONCLUSION: This study, for the first time, reported the association between lifetime smoking history of ≥ 100 cigarettes and BRVO in Korea. The risk of BRVO was lower in participants with controlled diabetes and hypo-HDL-cholesterolemia.

The adaptability of the Pulsta valve to the diverse main pulmonary artery shape of native right ventricular outflow tract disease.

BACKGROUND: Pulsta valve is increasingly used for percutaneous pulmonary valve implantation (PPVI) in patients with a large native right ventricular outflow tract (RVOT). This study aims to elucidate the outcomes of Pulsta valve implantation within the native RVOT and assess its adaptability to various native main pulmonary artery (PA) anatomies. METHODS: A multicenter retrospective study included 182 patients with moderate to severe pulmonary regurgitation in the native RVOT who underwent PPVI with Pulsta valves® between February 2016 and August 2023 at five Korean and Taiwanese tertiary referral centers. RESULTS: Pulsta valve implantation was successful in 179 out of 182 patients (98.4%) with an average age of 26.7 ± 11.0 years. The median follow-up duration was 29 months. Baseline assessments revealed enlarged right ventricle (RV) volume (mean indexed RV end-diastolic volume: 163.1 (interquartile range, IQR: 152.0-180.3 mL/m²), which significantly decreased to 123.6(IQR: 106.6-137.5 mL/m2  after 1 year. The main PA types were classified as pyramidal (3.8%), straight (38.5%), reverse pyramidal (13.2%), convex (26.4%), and concave (18.1%) shapes. Pulsta valve placement was adapted, with distal main PA for pyramidal shapes and proximal or mid-PA for reverse pyramidal shapes. Two patients experienced Pulsta valve embolization to RV, requiring surgical removal, and one patient encountered valve migration to the distal main PA, necessitating surgical fixation. CONCLUSIONS: Customized valve insertion sites are pivotal in self-expandable PPVI considering diverse native RVOT shape. The rather soft and compact structure of the Pulsta valve has characteristics to are adaptable to diverse native RVOT geometries.

The impact of physical activity changes on exercise capacity and health-related quality of life in young patients with CHD: a 3-year follow-up study.

OBJECTIVE: This study examined the relationship between changes in physical activity and their impact on exercise capacity and health-related quality of life over a 3-year span in patients with CHD. METHODS: We evaluated 99 young patients with CHD, aged 13-18 years at the outset. Physical activity, health-related quality of life, and exercise capacity were assessed via questionnaires and peak oxygen uptake measurements at baseline and after 3 years; changes in measures were estimated between the two time points and categorised into quartiles. Participants were stratified according to achieved (active) or not-achieved (inactive) recommended levels of physical activity (≥150 minutes/week) at both time points. RESULTS: Despite increases in physical activity, exercise capacity, and health-related quality of life over 3 years, the changes were not statistically significant (all p > 0.05). However, a positive association was found between physical activity changes and exercise capacity (ß = 0.250, p = 0.040) and health-related quality of life improvements (ß = 0.380, p < 0.001). Those with the most pronounced physical activity increase showed notable exercise capacity (p < 0.001) and health-related quality of life increases (p < 0.001) compared with patients with the largest decline in physical activity. The active-inactive category demonstrated a notable decline in exercise capacity compared to the active-active group, while the inactive-active group showed health-related quality of life improvements. CONCLUSIONS: Over 3 years, increased physical activity was consistently linked to increases in exercise capacity and health-related quality of life in patients with CHD, highlighting the potential of physical activity augmentation as an intervention strategy.

Association between knee osteoarthritis and mortality: a serial propensity score-matched cohort study.

BACKGROUND/AIMS: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. METHODS: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010-2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren-Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. RESULTS: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77-1.65), knee pain (HR 0.61; 95% CI 0.27-1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89-2.17). No association was found between the all-cause/cancer mortality and other groups. CONCLUSION: When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

Preoperative Balloon-Occluded Transcatheter Arterial Chemoembolization Followed by Surgical Resection: Pathological Evaluation of Necrosis.

This study investigates the clinical and pathological outcomes of preoperative balloon-occluded transcatheter arterial chemoembolization (B-TACE) in patients with single hepatocellular carcinoma (HCC). The data are from 25 consecutive patients who underwent sequential treatment of subsegmental B-TACE and hepatic surgery for single HCC. Radiological and pathological evaluation of oily subsegmentectomy, defined as the iodized oil-laden necrotic area that includes the entire HCC and surrounding liver parenchyma, were performed. Subsegmental B-TACE was technically successful in all patients. The major and minor complication rates were 8% and 24%, respectively. On the first follow-up computed tomography (CT), oily subsegmentectomy was observed in 18 (72%) out of 25 patients. Apart from one patient showing a partial response, the remaining 24 (96%) patients showed a complete response. Pathological complete necrosis of the HCC was observed in 18 (72%) out of 25 patients with complete or extensive necrosis of the peritumoral liver parenchyma. The remaining seven patients without peritumoral parenchymal necrosis had extensive necrosis of the HCCs. In conclusion, preoperative B-TACE can be a safe and effective method for the treatment of single HCC and a good bridge treatment for subsequent surgical resection. In addition, oily subsegmentectomy itself on the CT can be a good predictor of pathological complete necrosis of the HCC. The findings obtained from this study would provide a potential role of B-TACE in the treatment strategy for single HCC.

Cell-permeable peptide nucleic acid antisense oligonucleotide platform targeting human betacoronaviruses.

Introduction: Antisense oligonucleotides (ASOs) with therapeutic potential have recently been reported to target the SARS-CoV-2 genome. Peptide nucleic acids (PNAs)-based ASOs have been regarded as promising drug candidates, but intracellular delivery has been a significant obstacle. Here, we present novel modified PNAs, termed OPNAs, with excellent cell permeability that disrupt the RNA genome of SARS-CoV-2 and HCoV-OC43 by introducing cationic lipid moiety onto the nucleobase of PNA oligomer backbone. Methods: HCT-8 cells and Caco-2 cells were treated with 1 µM antisense OPNAs at the time of viral challenge and the Viral RNA levels were measured by RT-qPCR three days post infection. Results: NSP 14 targeting OPNA 5 and 11, reduced the viral titer to a half and OPNA 530, 531 and 533 lowered viral gene expression levels to less than 50% of control by targeting the 5' UTR region. Several modifications (oligo size and position, etc.) were introduced to enhance the efficacy of selected OPNAs. Improved OPNAs exhibited a dose-dependent reduction in viral replication and nucleoprotein (NP) protein. When a mixture of oligomers was applied to infected cells, viral titer and NP levels decreased by more than eightfold. Discussion: In this study, we have developed a modified PNA ASO platform with exceptional chemical stability, high binding affinity, and cellular permeability. These findings indicate that OPNAs are a promising platform for the development of antivirals to combat future pandemic viral infections that do not require a carrier.

Discriminative-Region Multi-Label Classification of Ultra-Widefield Fundus Images.

Ultra-widefield fundus image (UFI) has become a crucial tool for ophthalmologists in diagnosing ocular diseases because of its ability to capture a wide field of the retina. Nevertheless, detecting and classifying multiple diseases within this imaging modality continues to pose a significant challenge for ophthalmologists. An automated disease classification system for UFI can support ophthalmologists in making faster and more precise diagnoses. However, existing works for UFI classification often focus on a single disease or assume each image only contains one disease when tackling multi-disease issues. Furthermore, the distinctive characteristics of each disease are typically not utilized to improve the performance of the classification systems. To address these limitations, we propose a novel approach that leverages disease-specific regions of interest for the multi-label classification of UFI. Our method uses three regions, including the optic disc area, the macula area, and the entire UFI, which serve as the most informative regions for diagnosing one or multiple ocular diseases. Experimental results on a dataset comprising 5930 UFIs with six common ocular diseases showcase that our proposed approach attains exceptional performance, with the area under the receiver operating characteristic curve scores for each class spanning from 95.07% to 99.14%. These results not only surpass existing state-of-the-art methods but also exhibit significant enhancements, with improvements of up to 5.29%. These results demonstrate the potential of our method to provide ophthalmologists with valuable information for early and accurate diagnosis of ocular diseases, ultimately leading to improved patient outcomes.

Intermediate-stage (BCLC stage B) infiltrative hepatocellular carcinoma: safety and efficacy of chemoembolization.

OBJECTIVES: To evaluate the safety and efficacy of chemoembolization in patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study evaluated outcomes in treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage infiltrative HCC between 2002 and 2022. Of the 2029 treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage HCC, 244 (12%) were identified as having the infiltrative type. After excluding two patients lost to follow-up, 242 patients were evaluated. RESULTS: Median post-chemoembolization overall survival (OS) was 16 months. Multivariable Cox analysis identified four factors predictive of OS: Child-Pugh class B (hazard ratio [HR], 1.84; p = 0.001), maximal tumor size ≥ 10 cm (HR, 1.67; p < 0.001), tumor number ≥ 4 (HR, 1.42; p = 0.037), and bilobar tumor involvement (HR, 1.64; p = 0.003). These four factors were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. Median OS times in these three groups were 34, 18, and 8 months, respectively (p < 0.001). The objective tumor response rate following chemoembolization was 53%. The major complication rate was 9% overall and was significantly higher in the high-risk group (22%) than in the low (2%) and intermediate (3%) risk groups (p < 0.001). CONCLUSION: Chemoembolization is safe and effective in selected patients with intermediate-stage infiltrative HCC. Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative HCC because of poor OS and high rates of major complications. CLINICAL RELEVANCE STATEMENT: A pretreatment prediction model was developed using four risk factors associated with overall survival following chemoembolization for intermediate-stage infiltrative hepatocellular carcinoma. This model may provide valuable information for clinical decision-making. KEY POINTS: • Four risk factors (Child-Pugh score B, maximal tumor size ≥ 10 cm, tumor number ≥ 4, and bilobar tumor involvement) were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. • Median overall survival (OS) times and major complication rate in these three groups were 34, 18, and 8 months, and 2%, 3%, and 22%, respectively (p < 0.001). Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC) because of poor OS and high rates of major complications.

Impact of Pulmonary Arterial Elastance on Right Ventricular Mechanics and Exercise Capacity in Repaired Tetralogy of Fallot.

BACKGROUND AND OBJECTIVES: Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. METHODS: In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. RESULTS: Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO2] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO2 was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. CONCLUSIONS: We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.

Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes.

Objectives: To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS). Methods: This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021. Results: Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10 cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10 cm (4% [5/138] vs 21% [21/98], p = 0.001). Conclusion: TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10 cm) because of its high rate of major complications (21%).

Relationship between the Consciousness State and the Default Mode Network in Traumatic Brain Injury.

INTRODUCTION: This study investigated the relationship between Coma Recovery Scale-Revised (CRS-R) and the neural networks between the medial prefrontal cortex (mPFC) and precuneus (PCun)/posterior cingulate cortex (PCC) in disorders of consciousness (DOC) patients with a traumatic brain injury (TBI) using diffusion tensor tractography (DTT). MEASURES: Twenty-five consecutive patients with TBI admitted to the rehabilitation department of a university hospital were enrolled in this study. The Coma Recovery Scale-Revised (CRS-R) was used to evaluate the consciousness state. The pathway of the neural networks between the mPFC and the PCun (mPFC-PCun DMN)/PCC (mPFC-PCC DMN) were reconstructed using DTT. Fractional anisotropy (FA) and the tract volume (TV) were obtained to assess the diffusion tensor imaging parameters. RESULTS: The CRS-R score had strong positive correlations with the FA value and TV of the mPFC-PCun DMN (p < 0.05), while it showed a moderate positive correlation with the TV of the mPFC-PCC DMN (p < 0.05). In addition, the FA value of the mPFC-Pcun DMN showed that it could explain the variability in the CRS-R score. CONCLUSIONS: The close correlation was noted between the consciousness state and the mPFC-PCun DMN and mPFC-PCC DMN in DOC patients with TBI. On the other hand, the mPFC-PCun DMN appeared to be more closely correlated with the consciousness state than the mPFC-PCC DMN.

Repeat uterine artery embolization (UAE) for recurrent postpartum hemorrhage in patients who underwent UAE after a previous delivery: a multicenter study.

OBJECTIVE: To evaluate angiographic findings and outcomes of repeat uterine artery embolization (UAE) for recurrent postpartum hemorrhage (PPH) in patients who previously underwent UAE for PPH after a previous delivery. MATERIALS AND METHODS: Among 1805 patients who underwent UAE for PPH from 2007 to 2020 at four participating hospitals, the data of 21 (1.16%) patients who underwent UAE for PPH after subsequent delivery were collected and analyzed retrospectively. The rate of placental abnormalities, causes of PPH, angiographic findings, and clinical success rate were evaluated. RESULTS: The technical success rates were 100% and 95.2%, and clinical success rates were 85.7% and 95.2% in association with first and second UAEs, respectively. The time intervals between first and second UAEs ranged from 15.6 to 103.3 months (46.5 ± 25.0 months). The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). The causes of PPH were different between first and second UAEs with borderline significance (p = 0.049); uterine atony (81.0%) and placenta accreta spectrum (57.1%) were most common in association with first and second UAEs, respectively. During second UAEs, obliterated arteries were observed in 27 uterine arteries (27/42, 64.3%) of 16 patients (16/21, 76.2%), with partial obliteration predominating over total obliteration. Collateral arteries were observed in 15 patients during second UAEs. CONCLUSION: Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE. Obliteration of UAs and formation of collateral arteries are common at the second UAEs. KEY POINTS: • The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). • Obliteration of UAs and formation of collateral arteries are common at the second UAEs. • Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE.

The clinical efficacy of a mixture of ivy leaf extract and coptidis rhizome in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis and cough is the one of most common and major symptoms in IPF. The aim of this study was to evaluate the clinical efficacy of a Mixture of Ivy Leaf Extract and Coptidis rhizome (Synatura®) in patients with IPF. This was a prospective, open-label, single-center, and single-arm study in Korea from October 2019 to September 2020. IPF patients with chronic bronchitis were enrolled. Between baseline and eight weeks after use of Synatura®, clinical measures regarding cough and health-related quality of life, and the systemic inflammatory markers was prospectively collected. Thirty patients were enrolled. Median age was 73 years and 86.7% were men. The median gender-age-pulmonary function stage of IPF was 3. Baseline total score of Leicester cough questionnaire (LCQ) and St. George respiratory questionnaire (SGRQ) were 104.5 and 30.59 respectively. After eight weeks, there was no significant improvement in LCQ (16.8 [15.6-19.1] vs 17.5 [15.2-18.9], P = .772) and SGRQ (30.6 [19.4-37.8] vs 29.9 [19.6-41.8], P = .194) scores. Also, there was no significant difference of systemic inflammatory markers. In analysis of minimal clinically important differences (MCID), one third (33.3%) patients fulfilled the criteria of MCID (1.3) in LCQ scores and median differences was 14 (range: 10-18). In terms of SGRQ, 6 patients (20%) reached MCID (4.0) without significant predictive factors. In our study, use of Synatura® during 8 weeks improved cough-specific life quality in one third patients with IPF. Large-scale, randomized, double-blind, and placebo-controlled clinical trials are needed.

Intranodal Lymphangiography and Embolization for the Treatment of Early Postoperative Lymphatic Leaks after Pelvic Surgery.

PURPOSE: To assess outcome and predictors of outcome after lymphatic embolization (LE) for early postoperative lymphatic leak after pelvic surgery. MATERIAL AND METHODS: Lymphangiography (LG) procedures performed between May 2015 and February 2020 for postoperative intraperitoneal lymphatic leaks after pelvic surgery were reviewed. Treatment indication was lymphatic drainage of >500 mL/d persisting for >1 week. LE was performed by injecting glue into the iliac lymph node. Fisher exact and Wilcoxon rank-sum tests were used for comparative analysis, and logistic regression was used to assess predictors of outcome. RESULTS: LG was performed in 71 patients. A leak was demonstrated in 69 patients who underwent LE. The mean drainage was 1,329 mL/d ± 773. Catheters were removed in 49 (69.0%) patients after 1 procedure and in 69 (97.2%) patients after a mean of 1.3 procedures. The mean drainage at the time of catheter removal was 157 mL/d ± 100. Failure occurred in 12 (16.9%) cases, including 2 (2.8%) cases of unsuccessful catheter removal and 10 (14.1%) cases of catheter reinsertion owing to recurrent ascites (n = 3) and lymphoceles (n = 7). Older age and drainage of >1,500 mL/d were associated with failure (P = .004). Drainage of >1,500 mL/d was associated with a post-LE catheter dwell time of longer than 1 week (P = .024). Minor adverse events were noted in 4 (5.6%) patients who presented with transient leg swelling. CONCLUSIONS: LE was effective for treating pelvic surgery-related lymphatic leaks. Reintervention may be required. Drainage of >1,500 mL/d was associated with clinical failure and a post-LE catheter dwell time of longer than 1 week.

Super-Resolution Tension PAINT Imaging with a Molecular Beacon.

DNA-PAINT enabled super-resolution imaging through the transient binding of fluorescently-labelled single-stranded DNA (ssDNA) imagers to target ssDNA. However, its performance is constrained by imager background fluorescence, resulting in relatively long image acquisition and potential artifacts. We designed a molecular beacon (MB) as the PAINT imager. Unbound MB in solution reduces the background fluorescence due to its natively quenched state. They are fluorogenic upon binding to target DNA to create individual fluorescence events. We demonstrate that MB-PAINT provides localization precision similar to traditional linear imager DNA-PAINT. We also show that MB-PAINT is ideally suited for fast super-resolution imaging of molecular tension probes in living cells, eliminating the potential of artifacts from free-diffusing imagers in traditional DNA-PAINT at the cell-substrate interface.

Ideal Size Range for Embolic Agents in Interventional Oncology Experiments Involving Rat Models of Hepatocellular Carcinoma.

PURPOSE: To optimize future translational research, this study aimed to determine the ideal range of sizes for embolic agents in interventional oncology experiments utilizing rat models of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five male Sprague-Dawley rats were divided into 2 groups to evaluate the distribution of microparticles and tumor response rates. After implanting hepatoma cells into the rodent liver, fluorescent microparticles of sizes ranging from 5 to 35 µm were administered via the hepatic artery. In the first group, the distribution of microparticles was evaluated in hepatoma-free rats, and the tumor necrosis rates following administration of a predetermined aliquot of microparticles (0.4 mL) were measured in tumor-bearing rats. Thereafter, the 3 microparticle sizes associated with the best tumor response rates were chosen for analysis of the tumor necrosis rates following hepatic artery embolization until angiographic stasis is achieved in the second group. RESULTS: The tendency for microparticles to distribute in nontarget organs increased as the microparticle size decreased below 15 µm. Tumor necrosis rates tended to be higher in rats treated with 15-19-µm microparticles than in those treated with 19-24-µm or 19-24-µm microparticles. The in-group deviation of the tumor necrosis rates was highest for microparticle sizes of 19-24 and 25-35 µm, which implies the proximal embolization of the hepatic artery for larger microparticle sizes. However, there was no statistical significance among the 3 groups (P = .095). CONCLUSIONS: The 15-19-µm embolic agents were the most favorable for causing tumor necrosis without nontarget toxicity in the transarterial treatments of rat HCC models.

Clinical usefulness of biomarkers for diagnosis and prediction of prognosis in sepsis and septic shock.

Sepsis is a life-threatening condition and remains a major cause of mortality. The aim of this study was to evaluate the role of biomarkers in the diagnosis of sepsis and septic shock in patients admitted to the emergency department (ED). Medical records of patients who underwent measurement of serum biomarkers including lactic acid, C-reactive protein, procalcitonin (PCT), and presepsin in the ED between May 2019 and May 2020 were retrospectively reviewed. Patients were subdivided into 3 groups; non-sepsis, sepsis, and septic shock according to the new definition using the sequential organ failure assessment score. The mean age was 69.3 years, and 55.8% of the study population was female. Of 249 subjects, 98 patients confined to sepsis group, and 35.7% of them were septic shock. In the multivariable analysis, a high level of PCT was an independent predictor of sepsis (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.006-1.051; P = .011) along with a simplified acute physiology score III (SAPS III) (OR, 1.082; 95% CI, 1.062-1.103, P < .001). PCT was also an independent risk factor for septic shock (OR, 1.043; 95% CI, 1.016-1.071, P = .02). In the receiver operating characteristic curve analysis, the area under the curve of PCT to predict sepsis and septic shock were 0.691 (P < .001) and 0.734 (P < .001), respectively. The overall 30-days mortality rate was 8.8%, and the mortality rate was significantly higher in the sepsis group (sepsis vs non-sepsis, 15.3% vs 4.6%; P = .004). In the multivariate Cox analysis, a higher level of lactic acid (hazard ratio [HR], 1.328; 95% CI, 1.061-1.663, P = .013), predisposing chronic pulmonary diseases (HR, 7.035; 95% CI, 1.687-29.341, P = .007), and a high SAPSIII value (HR, 1.046; 95% CI, 1.015-1.078, P = .003) were independent risk factors for mortality in sepsis patients. PCT was a useful biomarker for predicting sepsis and septic shock in the ED. A higher level of lactic acid, predisposing chronic pulmonary diseases, and a high SAPS III score were associated with a greater mortality risk in patients with sepsis.

Early glycaemic variability increases 28-day mortality and prolongs intensive care unit stay in critically ill patients with pneumonia.

OBJECTIVE: This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia. PATIENTS AND METHODS: This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (>14 days) were also assessed. RESULTS: The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (n = 89) and was not different according to the presence of diabetes (DM vs. non-DM) or HbA1c levels (≥7.5 vs. <7.5%; both p > .05). However, the mortality rate was significantly higher in patients with high GV (CV ≥ 36%) than in those with low GV (CV < 36%; 37.5 vs. 25.4%, p = .028). The risk of mortality in patients with high GV was prominent in the subgroups with DM or low HbA1c levels. Among the surviving patients (n = 193), 44 remained in the ICU for more than 14 days. Compared to low GV, high GV was associated with a higher rate of prolonged ICU stay, although not statistically significant (27.8 vs. 18.5%, p = .171). After adjusting for the severity of illness and treatment strategy, CV was an independent risk factor for 28-day mortality (hazard ratio [HR], 1.01, p = .04) and prolonged ICU stay (odds ratio, 1.02; p = .04). CONCLUSIONS: High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (<7.5%) should be more carefully treated to reduce mortality.