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Mesenchymal stem cells (MSCs) are recognized as potential treatments for multiple degenerative and inflammatory disorders as a number of animal and human studies have indicated their therapeutic effects. There are also several clinically approved medicinal products that are manufactured using these cells. For such large-scale manufacturing requirements, the in vitro expansion of harvested MSCs is essential. Multiple subculturing of MSCs, however, provokes cellular senescence processes which is known to deteriorate the therapeutic efficacy of the cells. Strategies to rejuvenate or selectively remove senescent MSCs are therefore highly desirable for fostering future clinical applications of these cells. In this present study, we investigated gene expression changes related to cellular senescence of MSCs derived from umbilical cord blood and found that CD26, also known as DPP4, is significantly upregulated upon cellular aging. We further observed that the inhibition of CD26 by genetic or pharmacologic means delayed the cellular aging of MSCs with their multiple passaging in culture. Moreover, the sorting and exclusion of CD26-positive MSCs from heterogenous cell population enhanced in vitro cell attachment and reduced senescence-associated cytokine secretion. CD26-negative MSCs also showed superior therapeutic efficacy in mouse lung emphysema model. Our present results collectively suggest CD26 is a potential novel target for the rejuvenation of senescent MSCs for their use in manufacturing MSC-based applications.

Increased vasoactive-inotropic score (VIS) is a reliable predictor of mortality and morbidity after cardiac surgery. Here, we retrospectively evaluated the association between VIS and adverse outcomes in adult patients after off-pump coronary artery bypass grafting (OPCAB). We included 2149 patients who underwent OPCAB. The maximal VIS was calculated for the initial 48 postoperative hours using standard formulae. The primary outcome was 1-year death. The composite adverse outcome was death, resuscitation or mechanical support, myocardial infarction, revascularization, new-onset atrial fibrillation, infection requiring antibacterial therapy, acute kidney injury, and stroke. Path-analysis was conducted using lactate and prognostic nutritional index (PNI). VIS was associated with 1-year death (odds ratio [OR] 1.07 [1.04–1.10], p p = 0.008). In path-analysis, high VIS showed a direct effect on the increased risk of 1-year death and composite outcome. In the pathway using lactate as a mediating variable, VIS showed an indirect effect on the composite outcome but no significant effect on death. Low PNI directly affected the increased risk of 1-year death and composite outcome, and had an indirect effect on both outcomes, even when VIS was used as a mediating variable. In patients undergoing OPCAB, high VIS independently predicted morbidity and 1-year death. Patients with increased lactate levels following high VIS had an increased risk of postoperative complications, although not necessarily resulting in death. However, patients with poor preoperative nutritional status had an increased risk of unfavourable outcomes, including death, implying the importance of preoperative nutritional support.

Myocardial injury after non-cardiac surgery (MINS) is a well-known and relevant indicator of early postoperative mortality, but factors related to increased mortality in MINS patients are as yet unknown. The Charlson Comorbidity Index (CCI) is widely used to classify various comorbid conditions and underlying diseases. Our study aimed to determine the prognostic value of CCI with regard to mortality of patients with MINS. This study comprises 5633 patients who had MINS as diagnosed by a rise of postoperative cardiac troponin I above the normal range (≥ 0.04 ng/mL) from January 2010 to June 2019. Patients were divided into two groups according to median weighted CCI score: low CCI (≤ 2) and high CCI (> 2) groups. The primary outcome was 30-day mortality after surgery, and secondary outcomes were 1-year and overall mortalities. Of the 5633 patients, 3428 (60.9%) were in the low CCI group (1.21 ± 0.84) and 2205 (39.1%) were in the high CCI group (4.17 ± 1.82). After propensity score matching, mortality during the first 30 days after surgery was significantly greater in the high CCI group than the low CCI group (9.4% vs. 6.0%, respectively; hazard ratio 1.56, 95% confidence interval 1.23–1.98, p

Background Reference intervals guiding volumetric assessment of the liver and spleen have yet to be established. Purpose To establish population-based and personalized reference intervals for liver volume, spleen volume, and liver-to-spleen volume ratio (LSVR). Materials and Methods This retrospective study consecutively included healthy adult liver donors from 2001 to 2013 (reference group) and from 2014 to 2016 (healthy validation group) and patients with viral hepatitis from 2007 to 2017. Liver volume, spleen volume, and LSVR were measured with CT by using a deep learning algorithm. In the reference group, the reference intervals for the volume indexes were determined by using the population-based (ranges encompassing the central 95% of donors) and personalized (quantile regression modeling of the 2.5th and 97.5th percentiles as a function of age, sex, height, and weight) approaches. The validity of the reference intervals was evaluated in the healthy validation group and the viral hepatitis group. Results The reference and healthy validation groups had 2989 donors (mean age ± standard deviation, 30 years ± 9; 1828 men) and 472 donors (mean age, 30 years ± 9; 334 men), respectively. The viral hepatitis group had 158 patients (mean age, 48 years ± 12; 95 men). The population-based reference intervals were 824.5-1700.0 cm3 for liver volume, 81.1-322.0 cm3 for spleen volume, and 3.96-13.78 for LSVR. Formulae and a web calculator (https://i-pacs.com/calculators) were presented to calculate the personalized reference intervals. In the healthy validation group, both the population-based and personalized reference intervals were used to classify the volume indexes of 94%-96% of the donors as falling within the reference interval. In the viral hepatitis group, when compared with the population-based reference intervals, the personalized reference intervals helped identify more patients with volume indexes outside the reference interval (liver volume, 21.5% [34 of 158] vs 13.3% [21 of 158], P = .01; spleen volume, 29.1% [46 of 158] vs 22.2% [35 of 158], P = .01; LSVR, 35.4% [56 of 158] vs 26.6% [42 of 158], P < .001). Conclusion Reference intervals derived from a deep learning approach in healthy adults may enable evidence-based assessments of liver and spleen volume in clinical practice. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ringl in this issue.

The possibility of preparing highly (002) oriented Ti films on the Si (100) substrate was studied using RF sputtering. The deposition behavior was compared between floating and grounded substrates at room temperature. Highly (002) oriented Ti films could be successfully prepared on the floating Si (100) substrate, which was revealed by X-ray diffraction and high resolution transmission electron microscope. To understand the different deposition behavior between floating and grounded substrates, the incident energy of ions during RF sputtering was estimated from the substrate temperature measured by the K-type thermocouple. The incident energy on the floating substrate was lower by 20% than that on the grounded substrate. It was suggested that the lower incident energy on the floating substrate would be responsible for the deposition of highly (002) oriented Ti films at room temperature.

High-sensitivity cardiac troponin I (hs-cTnI) is a widely used biomarker to identify ischemic chest pain in the Emergency Department (ED), but the clinical impact on emergency coronary artery bypass grafting (eCABG) remains undetermined. We aimed to evaluate the clinical impact of hs-cTnI measured at the ED by comparing outcomes of eCABG in patients with non–ST-segment–elevation acute coronary syndrome (NSTE-ACS) which comprises unstable angina (UA) and non–ST-segment–elevation myocardial infarction (NSTEMI). From January 2012 to March 2016, 242 patients undergoing eCABG were grouped according to serum hs-cTnI level in the ED. The primary endpoint was major cardiovascular cerebral event (MACCE) defined as a composite of all-cause death, myocardial infarction, repeat revascularization, and stroke. The incidence of each MACCE composite, in addition to postoperative complications such as acute kidney injury, reoperation, atrial fibrillation, and hospital stay duration were also compared. Patients were divided into two groups: UA [p-value = 0.032). In-hospital stay was also longer in the NSTEMI group (9.0 days vs. 15.4 days, p-value = 0.008). ECABG for UA and NSTEMI patients showed comparable outcomes, but hs-cTnI elevation at the ED may be associated with immediate postoperative complications.

FDA approved three RAF inhibitors for the treatment of tumors containing BRAFV600 mutations, but one of the major drawbacks of these type I RAF inhibitors is to activate MAPK signaling pathway, instead of inhibiting signaling, which is referred to as paradoxical activation. Such undesired paradoxical activation not only leads to renewed tumor growth but also spurs additional cancer growth in non-cancerous wild-type BRAF tissue. Plus, these first-generation RAF inhibitors targeting BRAFV600 mutants are unable to inhibit oncogenic RAF dimers. This has led to the development of type II RAF inhibitors such as belvarafenib and day101 to block the activity of multiple forms of RAF while avoiding paradoxical activation. Two lead-like stage compounds 1 and 2 were specifically designed as type II RAF inhibitors to have activity across RAF isoforms including BRAFV600E, BRAF wild-type, and CRAF, showing higher potency than competitors. Compounds 1 and 2 potently inhibited the growth of BRAFV600E melanoma cells and NRAS or KRAS mutant cancer cells. Compounds 1 and 2 promoted the formation of BRAF/CRAF heterodimers by directly binding to the RAF kinase domain like other type II RAF inhibitors and inhibited phosphorylation of downstream effectors MEK and ERK in a dose-dependent manner in RAS mutant cancer cells, suggesting less paradoxical activation liability. Compound 2 showed superior on-target inhibitory activity for BRAFV600E, BRAF wild-type, and CRAF than belvarafenib through RAF immunoprecipitation (IP) kinase assay. Inhibition of the RAF downstream signaling was also confirmed by quantifying the level of phospho-ERK in NRAS or KRAS mutant cancer cells. In HCT116 (KRASG13D) subcutaneous xenograft model, compound 1 showed tumor growth inhibition efficacy, suggesting a potential to address RAS mutant driven- as well as BRAFV600 mutant driven tumors. Also, combination treatment with MEK inhibitor and/or immune checkpoint inhibitor would further improve the therapeutic activity and expand target indication for unmet medical needs. Citation Format: Kwangwoo Hwang, SeoHyun Jo, Jieun Choi, Ga-young Choi, Jiseon Choi, Ji-Hye Kwon, Dong-Guk Shin, Jiyeon Kim, Se-Hyuk Kim, Haelee Kim, Ha Yeon Cho, Jung Beom Son, Nam Doo Kim, Hwan Geun Choi, Daekwon Kim, Sunghwan Kim. Antitumor activity of potent RAF inhibitors in solid tumors with activated RAS-RAF axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB521.

Objective To determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). Background Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. Methods Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74/129 without autotransfusion were matched with 74/220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. Results Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/38.3%/39.7% for non-autotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the two groups in overall recurrence (hazard ratio [HR] = 0.72 [0.43-1.21]), intrahepatic recurrence (HR = 0.70 [0.35-1.40]), and extrahepatic recurrence (HR = 0.82 [0.46-1.47]). Also, there were no significant differences in overall death (HR = 0.57 [0.29-1.12]), HCC-related death (HR = 0.59 [0.29-1.20]), and HCC-unrelated death (HR = 0.48 [0.09-2.65]). Conclusion When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

Background Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30‐day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30‐day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30‐day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18–1.42; P P Conclusions Preoperative hyperglycemia was associated with MINS and 30‐day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long‐term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr ; Unique identifier: KCT0004244.

Background: The clinical efficacy of preoperative 2D-echocardiographic assessment of pulmonary arterial pressure (PAP) has not been evaluated fully in liver transplantation (LT) recipients.Methods: From October 2010 to February 2017, a total of 344 LT recipients who underwent preoperative 2D-echocardiography and intraoperative right heart catheterization (RHC) was enrolled and stratified according to etiology, disease progression, and clinical setting. The correlation of right ventricular systolic pressure (RVSP) on preoperative 2D-echocardiography with mean and systolic PAP on intraoperative RHC was evaluated, and the predictive value of RVSP > 50 mmHg to identify mean PAP > 35 mmHg was estimated.Results: In the overall population, significant but weak correlations were observed (R = 0.27; P < 0.001 for systolic PAP, R = 0.24; P < 0.001 for mean PAP). The positive and negative predictive values of RVSP > 50 mmHg identifying mean PAP > 35 mmHg were 37.5% and 49.9%, respectively. In the subgroup analyses, correlations were not significant in recipients of deceased donor type LT (R = 0.129; P = 0.224 for systolic PAP, R = 0.163; P = 0.126 for mean PAP) or in recipients with poorly controlled ascites (R = 0.215; P = 0.072 for systolic PAP, R = 0.21; P = 0.079 for mean PAP). Conclusion: In LT recipients, the correlation between RVSP on preoperative 2D-echocardiography and PAP on intraoperative RHC was weak; thus, preoperative 2D-echocardiography might not be the optimal tool for predicting intraoperative PAP. In LT candidates at risk of pulmonary hypertension, RHC should be considered.

Non-classical crystallization, in which charged nanoparticles (NPs) are the building blocks of film growth, has been extensively studied in chemical vapor deposition (CVD). Recently, a similar mechanism of film growth has been reported during radio frequency (RF) sputtering with a Ti target and DC magnetron sputtering using an Ag target. In this study, the effect of pressure on the generation of Ti NPs and on the film deposition was studied during RF sputtering with a Ti target. Ti NPs were captured on transmission electron microscopy (TEM) membranes with the electric biases of &minus, 30, 0, and +50 V under 20 and 80 mTorr. The number densities of the Ti NPs were 134, 103, and 21 per 100 &times, 100 nm2, respectively, with the biases of &minus, 30, 0, and +50 V under 20 mTorr and were 196, 98, and 0 per 100 &times, 30, 0, and +50 V under 80 mTorr, which was analyzed by TEM. The growth rate of Ti films deposited on Si substrates was insensitive to the substrate bias under 20 mTorr but was sensitive under 80 mTorr, with the thicknesses of 132, 133, 97, and 29 nm, respectively, after being deposited for 15 min with the substrate biases of &minus, 30, &minus, 10, 0, and +50 V. This sensitive dependence of the film growth rate on the substrate bias under 80 mTorr is in agreement with the sensitive dependence of the number density of Ti NPs on the substrate bias under 80 mTorr.

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

BACKGROUND Despite an association between obesity and increased risks for various diseases, obesity has been paradoxically reported to correlate with improved mortality in patients with established cardiovascular disease. However, its effect has not been evaluated to date in patients with myocardial injury after noncardiac surgery (MINS). METHODS From January 2010 to June 2019, of a total of 35,269 adult patients with postoperative cardiac troponin level data, 5633 (16.0%) patients had MINS as diagnosed by postoperative cardiac troponin I above the 99th-percentile upper reference of 40 ng·L-1 using the TnI-Ultra immunoassay. Patients with MINS were divided into 3 groups according to body mass index (BMI), with 3246 (57.6%) were in the normal (18.5-25 kg·m-2), 425 (7.5%) in the low BMI (

We evaluated whether volatile anesthetics can improve the postoperative outcomes of non-cardiac surgery in patients with preoperative myocardial injury defined by the cardiac troponin elevation. From January 2010 to June 2018, 1254 adult patients with preoperative myocardial injury underwent non-cardiac surgery under general anesthesia and were enrolled in this study. Patients were stratified into following two groups according to anesthetic agents; 115 (9.2%) patients whose anesthesia was induced and maintained with continuous infusion of propofol and remifentanil (TIVA group) and 1139 (90.8%) patients whose anesthesia was maintainted with volatile anesthetics (VOLATILE group). The primary outcome was 30-day mortality. To diminish the remifentanil effect, a further analysis was conducted after excluding the patients who received only volatile anesthetics without remifentanil infusion. In a propensity-score matched analysis, 30-day mortality was higher in the TIVA group than the VOLATILE group (17.0% vs. 9.1%; hazard ratio [HR] 2.60; 95% confidence interval [CI], 1.14-5.93; p = 0.02). In addition, the TIVA group showed higher 30-day mortality than the VOLATILE group, even after eliminating the effect of remifentanil infusion (15.8% vs. 8.3%; HR 4.62; 95% CI, 1.82-11.74; p = 0.001). In our study, the use of volatile anesthetics showed the significant survival improvement after non-cardiac surgery in patients with preoperative myocardial injury, which appears to be irrelevant to the remifentanil use. Further studies are needed to confirm this beneficial effect of volatile anesthetics. Clinical trial number and registry URL: KCT0004349 (www.cris.nih.go.kr).

BackgroundPerioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality according to preoperative blood glucose and hemoglobin A1c (HbA1c) level.methodsThe patients were divided according to blood glucose level within one day before surgery. The poorly-controlled group was defined with fasting glucose > 140 mg/dl or random glucose > 180 mg/dl. Additionally, we compared the outcomes according to HbA1c > 6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared.ResultsA total of 12,304 patients was enrolled and divided into 8,324 (67.7%) in the well-controlled group and 3,980 (32.3%) in the poorly-controlled group. After adjustment with inverse probability of weighting, the poorly-controlled group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% vs. 27.6%; odds ratio [OR], 1.29; 95% confidence interval [CI], 1.18–1.42; P P Trial registration: KCT0004244

Non-classical crystallization suggests that crystals can grow with nanoparticles as a building block. In this case, the crystallization behavior depends on the size and charge of the nanoparticles. If charged nanoparticles (CNPs) are small enough, they become liquid-like and tend to undergo epitaxial recrystallization. Here, the size effect of SiC CNPs on film crystallinity was studied in the hot-wire chemical vapor deposition process. To do this, SiC nanoparticles were captured under different processing conditions&mdash, in this case, wire temperature, precursor concentration and the filament bias. Increasing the temperature of tungsten wires and decreasing the ratio of (SiH4 + CH4)/H2 reduced the size of the SiC nanoparticles. When the nanoparticles were small enough, an epitaxial SiC film approximately 100-nm-thick was grown, whereas larger nanoparticles produced polycrystalline SiC films. These results suggest that the size of the CNPs is an important process variable when growing films by means of non-classical crystallization.

Purpose Perioperative myocardial injury is a predictor of postoperative mortality, but the clinical impact of chronic injury during the perioperative period has not been fully investigated. This study aimed to evaluate chronic myocardial injury during the perioperative period in comparison with normal and acute myocardial injury. Methods Patients with serial cardiac troponin measurements before and within 30 days following noncardiac surgery were divided into three groups: normal, acute injury, and chronic injury groups. Acute and chronic myocardial injuries were stratified according to 2018 recommendations by the International Federation of Clinical Chemistry and Laboratory Medicine’s Task Force on Clinical Applications of Bio-Markers. Thirty-day and one-year mortalities after surgery were compared. Results Of the 22,969 patients reviewed, 17,671 (76.9%) were classified into the normal, 5,179 (22.5%) into the acute injury, and 119 (0.5%) into the chronic injury groups. The acute and chronic injury groups had higher 30-day mortalities compared with the normal group (0.8% vs. 8.0%; hazard ratio [HR], 11.00; 95% confidence interval [CI], 9.05–13.37; P < 0.001 and 0.8% vs. 7.6%; HR, 10.55; 95% CI, 5.37–20.72; P < 0.001, respectively). In a direct comparison between the acute and chronic injury groups using an inverse probability of weighting adjustments, the 30-day and one-year mortalities were not significantly different. Conclusion Chronic myocardial injury during the perioperative period may show similar clinical impacts on postoperative mortality compared with acute injury. Further studies are needed.

This study is based on the film growth by non-classical crystallization, where charged nanoparticles (NPs) are the building block of film deposition. Extensive studies about the generation of charged NPs and their contribution to film deposition have been made in the chemical vapor deposition (CVD) process. However, only a few studies have been made in the physical vapor deposition (PVD) process. Here, the possibility for Ti films to grow by charged Ti NPs was studied during radio frequency (RF) sputtering using Ti target. After the generation of charged Ti NPs was confirmed, their influence on the film quality was investigated. Charged Ti NPs were captured on amorphous carbon membranes with the electric bias of &minus, 70 V, 0 V, +5 V, +15 V and +30 V and examined by transmission electron microscopy (TEM). The number density of the Ti NPs decreased with increasing positive bias, which showed that some of Ti NPs were positively charged and repelled by the positively biased TEM membrane. Ti films were deposited on Si substrates with the bias of &minus, 70 V, 0 V and +30 V and analyzed by TEM, field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and X-ray reflectivity (XRR). The film deposited at &minus, 70 V had the highest thickness of 180 nm, calculated density of 4.974 g/cm3 and crystallinity, whereas the film deposited at +30 V had the lowest thickness of 92 nm, calculated density of 3.499 g/cm3 and crystallinity. This was attributed to the attraction of positively charged Ti NPs to the substrate at &minus, 70 V and to the landing of only small-sized neutral Ti NPs on the substrate at +30 V. These results indicate that the control of charged NPs is necessary to obtain a high quality thin film at room temperature.

Myocardial injury after noncardiac surgery (MINS) is recently accepted as a strong predictor of mortality, regardless of symptoms. However, anticoagulation is the only established treatment. This study aimed to evaluate the association between statin treatment and mortality after MINS. From January 2010 to June 2019, a total of 5,267 adult patients who were discharged after the occurrence of MINS were enrolled. The patients were divided into two groups according to statin prescription at discharge. The outcomes were 1-year and overall mortalities. Of the total 5,109 patients, 1,331 (26.1%) patients were in the statin group and 3,778 (73.9%) patients were in the no statin group. The 1-year and overall mortalities were significantly lower in the statin group compared with the no statin group (6.1% vs. 13.3%; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41–0.74; p

BACKGROUND: Regeneration of soft tissue defects is essential for adipose tissue pathologies and disease, trauma, or injury-induced damage. Here, we show that umbilical cord blood-derived mesenchymal stem cells could potentially be tailored and used for the reconstruction of specific damaged sites. Adipogenesis can be exploited in soft tissue reconstruction. Also, primary cilia play a role in the control of adipogenesis. METHODS: The adipogenic differentiation capacity of mesenchymal stem cells (MSCs) was shown to influence ciliogenesis. MSCs transfected with intraflagellar transport 88 (IFT88) small interfering RNA (siRNA), which blocks the assembly and maintenance of cilia, were examined to confirm the relationship between adipogenesis and ciliogenesis. Also, 1,2-Bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), calcium chelator, inhibited the ciliogenesis of MSCs in adipogenic differentiation. RESULTS: IFT88-knockdown led to decreased cilia formation and limitation of cilia elongation in adipogenesis. Additionally, intracellular calcium triggered cilia formation in MSCs adipogenesis. Interestingly, intracellular calcium cannot overcome the inhibition of adipogenesis caused by low numbers of cilia in MSCs. CONCLUSION: Our data suggested that ciliogenesis was negatively regulated by Wnt5a/β-catenin signaling during adipogenesis. Thus, we suggest that calcium induction triggers adipogenesis and ciliogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13770-019-00237-4) contains supplementary material, which is available to authorized users.

Therapeutic treatment of various inflammation-related diseases using mesenchymal stem cells (MSCs) has increased in recent years because of the paracrine action of these cells but shows several limitations. First, MSC-based therapies exhibit varying efficacies; thus, biomarkers should be determined to identify who may benefit from these candidate therapeutic agents. Second, the mechanism underlying the therapeutic effects is poorly understood. To evaluate the effects of human umbilical cord blood-derived MSCs (UCB-MSCs) on macrophages, the macrophage cell line NR8383 stimulated with lipopolysaccharide (LPS) was cocultured by UCB-MSCs. We found that UCB-MSCs mediated changes in macrophage polarization towards M2 from M1 macrophages. To identify the paracrine action underlying the anti-inflammation effect of UCB-MSCs, the secretion of UCB-MSCs exposed to LPS-stimulated NR8383 cells was tested using a biotin label-based 507 antibody array. Among the secreted proteins, we selected pentraxin-related protein PTX3/tumor necrosis factor-inducible gene 14 protein (PTX3) to investigate its association with UCB-MSCs in macrophage polarization. We found that human PTX3 was secreted from UCB-MSCs under inflammation condition and reinforced the M2 macrophage marker via the Dectin-1 receptor by activating MSK1/2 phosphorylation signaling in NR8383 cells. Accordingly, knockdown of PTX3 in UCB-MSCs significantly attenuated their therapeutic effects in a neonatal hyperoxic lung injury resulting in reduced survival, lung alveolarization, M2 marker expression, Dectin-1 levels, anti-inflammatory cytokines, and improved M1 marker expression and inflammatory cytokines compared to control MSC-injected rats. UCB-MSCs show therapeutic potential by controlling macrophage polarization. Interestingly, higher PTX3 levels in UCB-MSCs induced greater improvement in the therapeutic effects than lower PTX3 levels. Collectively, PTX3 is a potential marker with critical paracrine effects for predicting the therapeutic potential of MSC therapy in inflammatory diseases; quality control assessments using PTX3 may be useful for improving the therapeutic effects of UCB-MSCs.

Interactions between lactic acid bacteria (LAB) and dietary polyphenols are not fully understood. This study determined the prebiotic effects of grape seed flour (GSF, a byproduct of wine making) and their polyphenol extracts (GSE) on the growth of 10 strains of probiotic LAB recently isolated from the kefir and pathogenic Clostridium perfringens. Growth rate of the LAB, Leuconostoc mesenteroides DH 1608, was the highest among 10 strains of LAB when cultivated with GSF. GSE, containing an equivalent amount of polyphenol in GSF, also promoted the growth of L. mesenteroides DH 1608 but at a lower rate compared to GSF. Growth of C. perfringens decreased significantly at 10 mg/mL of GSF, but GSE did not affect the growth. In conclusion, GSF may be a useful prebiotic dietary supplement due to its selective antimicrobial capacity via stimulation of probiotic bacteria and inhibition of pathogenic bacteria. A symbiotic combination of selected lactic acid bacteria and GSF may improve gut health.

BACKGROUND: The characteristics of red blood cell (RBC) products change after 2 weeks of cold storage. It is unclear whether older RBCs affect mortality after liver transplantation. This retrospective cohort study aimed to evaluate the association between the age of transfused RBCs and death after living donor liver transplantation (LDLT). STUDY DESIGN AND METHODS: Of 200 recipients who underwent LDLT, 118 who received RBCs with a mean storage duration of less than 10 days (shorter storage group) were compared with 82 with an RBC mean storage duration of more than 14 days (longer storage group). Key exclusion criteria were transfusion of very fresh RBCs stored for less than 4 days and transfusion of old RBCs in recipients of the shorter storage group. The primary outcome was posttransplant overall death. Survival analysis was performed using the Cox model. RESULTS: Mean RBC storage duration was 7 days in the shorter storage group and 17 days in the longer storage group. Death probability at 1, 2, and 5 years posttransplant was 5.1%, 7.6%, and 13.6% in the shorter storage group, respectively, and 6.1%, 8.5%, and 13.5% in the longer storage group. Death risk was comparable between the two groups in univariable (hazard ratio [HR] 1.00, 95% confidence interval [CI], 0.47-2.16, p = 0.991) and multivariable (HR 1.07, 95% CI, 0.46-2.50, p = 0.882) analyses. Graft failure risk was also comparable (HR 1.04, 95% CI, 0.50-2.18, p = 0.916). Hepatocellular carcinoma recurrence probability at 1, 2, and 5 years was 10.8%, 15.4%, and 23.1%, respectively, in the shorter storage group and 11.4%, 15.9%, and 20.7% in the longer storage group (HR 0.84, 95% CI, 0.37-1.89, p = 0.670). No significant differences were observed regarding graft regeneration/function, vascular/biliary complications, acute kidney injury, surgical site infection, or rejection (p > 0.05). CONCLUSIONS: No evidence was found that transfusion of old RBCs contributes to death after LDLT.

Purpose: It is difficult to develop a good defense system that can prevent nurses from experiencing physical and verbal violence from patients and families in intensive care units, which are closed spaces. This study aimed to identify intensive care nurses' experience of violence from patients and families and investigate their coping methods, if there are any, in a tertiary hospital in South Korea. Methods: This study used a mixed methods design using both a survey for collecting quantitative data and individual interviews for a qualitative one. A total of 200 intensive care nurses participated in the survey, with 30 of them taking part in individual interviews. Survey data were analyzed using SPSS 21.0 program, and qualitative data were analyzed by qualitative content analysis method. Results: In the survey, 99.5% of the nurses reported that they had experienced violence from the patients, and 67.5% of the nurses reported that they had experienced violence from their visitors (families or relatives). Verbal violence were reported more than physical ones. They showed moderate or severe responses to violence, scoring an average of 2.98 ± 0.63 of 5. The qualitative data were analyzed to draw four themes, eight categories, and 17 subcategories. The four themes were perception of violence, coping with violence experience, coping resources, and caring mind after violence experience. Conclusion: While intensive care nurses experience unpredicted violence from patients and their visitors, they fail to cope well with the experience. The safe working environment of intensive care units is expected to contribute to quality care and an improvement of expertise in nursing. Keywords: family, intensive care units, nurses, patients, violence

The purpose of the study was to investigate the imaging and clinical features of xanthogranulomatous pancreatitis (XGP). This retrospective series study included 10 patients with pathology-proven XGP. Two radiologists reviewed the computed tomography (CT) and magnetic resonance imaging (MRI) in consensus to determine the morphological features of XGP. The lesion enhancement pattern on dynamic contrast-enhanced scans and the MR signal intensity were also evaluated. Clinical data including symptoms, underlying pancreatic disease, and laboratory findings were reviewed. Two XGP cases were of a solid type; six were of cystic type, and two were mixed type. XGP usually showed a lobulated contour (90%) and heterogeneous enhancement (100%), with lesion size varying from 2 to 11 cm. Perilesional infiltration was common (90%), but pancreatic duct dilatation was less frequent (30%). Cystic type XGP mostly had an irregular thick wall (83%). On dynamic contrast-enhanced CT/MRI, XGP enhanced progressively from arterial to portal or delayed phases. Lesions appeared hypointense on T1-weighted images (89%) and hyperintense on T2-weighted images (100%). All lesions appeared hyperintense on diffusion-weighted images, with the majority (78%) showing diffusion restriction on apparent diffusion coefficient maps. The patients often had abdominal pain (80%) and underlying pancreatic disease (80%), but mostly had normal or clinically insignificant laboratory findings. XGP typically manifests as a clinically silent lobulated heterogeneous mass, with a progressive enhancement pattern and/or irregular thick wall, and diffusion restriction on CT/MRI. Awareness of the imaging and clinical features of XGP may help differentiate it from pancreatic neoplasms, thereby reducing unnecessary surgery.

Objective The aim of this study is to evaluate the association between fresh red blood cell (RBC) transfusion and recipient survival after liver transplantation. Background Fresh RBC products contain many viable leukocytes. Allogeneic leukocytes are responsible for adverse transfusion reactions in the immunocompromised host. Methods Among 343 liver transplant recipients who underwent perioperative RBC transfusion, 91 of 226 who did not receive fresh RBCs were matched with 91 of 117 who received fresh RBCs with 1:1 matching ratio using the propensity score based on the amount of transfused blood products and others. Survival analysis was performed using the Cox model. Results All transfused 3230 RBCs were leukoreduced and irradiated. Before matching, recipients in fresh RBC group received 3 U (2-6 U) of fresh RBCs. After a median follow-up of 60 months, 60 of 343 recipients (17.5%) died. Survival probability at 1/2/5 years after transplantation was 94.7%/92.0%/85.8% for nonfresh RBC group and 82.9%/76.0%/72.0% for fresh RBC group [death hazard ratio (HR) = 2.37 (1.43-3.94), P = 0.001]. In multivariable analysis, fresh RBC transfusion was significantly associated with increased death risk [HR = 2.33 (1.35-4.01), P = 0.002]. After matching, recipients in fresh RBC group received 3 U (2-5 U) of fresh RBCs. After a median follow-up of 56 months, 35 of 182 recipients (19.2%) died. Survival probability at 1/2/5 years was 95.6%/93.2%/86.0% for nonfresh RBC group and 85.7%/78.0%/73.0% for fresh RBC group [HR = 2.23 (1.43-3.94), P = 0.028]. Multivariable analysis confirmed a significance of fresh RBC transfusion [HR = 3.20 (1.51-6.78), P = 0.002]. Conclusion Our findings suggest a potential negative impact of fresh RBC transfusion on the survival of patients undergoing liver transplantation.

The incidence of hyperkalemia (>5.5 mEq/L) or high blood potassium (5–5.5 mEq/L) during living-donor liver transplantation (LDLT) is reported to be more than 10%. It occurs more frequently in the early post-reperfusion period and is a major cause of post-reperfusion arrhythmia and cardiac arrest. Unlike deceased-donor liver transplantation, the pattern of blood potassium changes immediately after reperfusion has not been described in LDLT. From January 2021 to March 2021, fifteen consecutive patients were enrolled. Baseline blood potassium was measured from blood samples obtained 10-min (T-10) and immediately before (T0) reperfusion. During the first 5 min after reperfusion, blood potassium measurements were conducted every one minute (T1–T5). The blood potassium levels at T-10 and T0 were 3.8 ± 0.4 and 3.9 ± 0.4 mEq/L, respectively. After reperfusion, mean increases (95% CI) in blood potassium from T-10 and T0 were 0.5 (0.4–0.6) and 0.4 (0.3–0.5) mEq/L, respectively. Blood potassium peaked at T1, returned to baseline at T3, and fell below the baseline at T5. Peak blood potassium after reperfusion showed strong correlations with blood potassium measured at T-10 (p < 0.001) and T0 (p < 0.0001). These findings can support the establishment of future research plans and perioperative management of blood potassium in LDLT.

Background: Oxygen demand–supply mismatch is supposed to be one of the major causes of myocardial injuries after noncardiac surgery (MINS). Impaired tissue oxygenation during the surgery can lead to intraoperative hyperlactatemia. Therefore, we aimed to evaluate the relationship between intraoperative lactate level and MINS. Methods: A total of 1905 patients divided into groups according to intraoperative hyperlactatemia: 1444 patients (75.8%) into normal (≤2.2 mmol/L) and 461 patients (24.2%) into hyperlactatemia (&gt, 2.2 mmol/L) groups. The primary outcome was the incidence of MINS, and all-cause mortality within 30 days was compared. Results: In the crude population, the risks for MINS and 30-day mortality were higher for the hyperlactatemia group than the normal group (17.7% vs. 37.7%, odds ratio [OR]: 2.83, 95% confidence interval [CI]: 2.24–3.56, p &lt, 0.001 and 0.8% vs. 4.8%, hazard ratio [HR]: 5.86, 95% CI: 2.9–12.84, p &lt, 0.001, respectively). In 365 propensity score-matched pairs, intraoperative hyperlactatemia was consistently associated with MINS and 30-day mortality (21.6% vs. 31.8%, OR: 1.69, 95% CI: 1.21–1.36, p = 0.002 and 1.1% vs. 3.8%, HR: 3.55, 95% CI: 1.71–10.79, p &lt, 0.03, respectively). Conclusion: Intraoperative lactate elevation was associated with a higher incidence of MINS and 30-day mortality.

Spindle assembly checkpoint (SAC) prevents mis-segregation of chromosome and allows accurate division in mitosis. Mps1 (also known as TTK) is one of the essential kinases for recruitment of SAC proteins after chromosome segregation. Failure of SAC induces chromosome instability, mitotic catastrophe, and ultimately apoptotic cell death and Mps1 is induced or activated in rapidly dividing tumor cells. Therefore, Mps1 has been considered an attractive anti-cancer drug target. VRN081569 is a potent type I kinase inhibitor of Mps1, which stabilizes Mps1 kinase domain in a closed conformation by forming a tight interface with its kinase domain. This structural stabilization appears to increase cellular potency for the induction of aneuploidy and apoptosis (~ 10 nM or less GI50 value). The loss of retinoblastoma tumor suppressor gene (Rb1), which is prevalent in advanced cancers, dysregulates cell cycle and promotes cell division. In particular, the resistance to CDK4/6 inhibitors has been reportedly mediated by loss of the Rb1 gene. We found that Rb1-negative cells express higher level of Mps1 than Rb1-positive cells and VRN081569 efficiently induce apoptosis of Rb1-negative Triple Negative Breast Cancer (TNBC) cell line MDA-MB-468 than Rb1-positive TNBC MDA-MB-231. Especially we confirmed that VRN081569 induces caspase 3/7 activity faster in Rb1-negative cells (~50-fold EC50 of caspase 3/7 activity compared to Rb1-positive cells), and cell cycle analysis has shown that our compound induces a dose-dependent dysregulation of mitosis, resulting in a decrease in the frequency of the G0/G1 phase, and also induces aneuploidy and apoptosis. Finally, we confirmed a combination effects with anti-microtubule agents BCL-2 inhibitor and PARP-1 inhibitor, suggesting that modulation of two different cellular processes may overcome the lack of single agent activity for TNBC. Citation Format: Hong Ryul Jung, Yeonsil Kim, Haelee Kim, Ji-Hye Kwon, Dong-hyuk Seo, Jung Beom Son, Nam Doo Kim, Daekwon Kim, Sunghwan Kim. VRN08, a Selective Mps1 Kinase Inhibitor Induces Mitotic Catastrophe and Apoptosis Efficiently in Advanced Cancers Including Rb1-Deficient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB119.

What is known and objective Ketamine in a subanaesthetic dose has been shown to produce rapid antidepressant effects. Here, we describe a long-term follow-up case of a Korean patient with severe major depression who received repeated ketamine intravenous therapy (KIT). Case description A 49-year-old woman with a 6-year history of treatment-resistant major depression was given KIT once every 1 or 2 weeks over 10 months, for a total of 36 treatments. Her mood stabilized, and she showed a nearly 50% reduction in the severity of her depressive symptom. What is new and conclusion Long-term repeated KIT may be an option for alleviating treatment-resistant and relapsing major depression. Further research and large clinical trials are needed on the optimum KIT protocol, including dose, dosing interval, total number of treatments and when to stop.

Bronchopulmonary dysplasia (BPD), caused by hyperoxia in newborns and infants, results in lung damage and abnormal pulmonary function. However, the current treatments for BPD are steroidal and pharmacological therapies, which cause neurodevelopmental impairment. Treatment with umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is an efficient alternative approach. To prevent pulmonary inflammation in BPD, this study investigated the hypothesis that a key regulator was secreted by MSCs to polarize inflammatory macrophages into anti-inflammatory macrophages at inflammation sites. Lipopolysaccharide-induced macrophages co-cultured with MSCs secreted low levels of the inflammatory cytokines, IL-8 and IL-6, but high levels of the anti-inflammatory cytokine, IL-10. Silencing decorin in MSCs suppressed the expression of CD44, which mediates anti-inflammatory activity in macrophages. The effects of MSCs were examined in a rat model of hyperoxic lung damage. Macrophage polarization differed depending on the levels of decorin secreted by MSCs. Moreover, intratracheal injection of decorin-silenced MSCs or MSCs secreting low levels of decorin confirmed impaired alveolarization of damaged lung tissues by down-regulation of decorin. In tissues, a decrease in the anti-inflammatory macrophage marker, CD163, was observed via CD44. Thus, we identified decorin as a key paracrine factor, inducing macrophage polarization via CD44, a master immunoregulator in mesenchymal stem cells.

Despite technical advancements in the perioperative management of cancer surgery, postoperative pain remains a significant clinical issue. We examined the diagnostic value of the intraoperative perfusion index for predicting acute postoperative pain in patients undergoing laparoscopic colorectal cancer surgery. We retrospectively analyzed data for 105 patients who had undergone laparoscopic colorectal cancer surgery. Patients with pain scores &lt, 7 and &ge, 7 on a 10-point scale upon arrival in the postoperative anesthesia care unit (PACU) were categorized into the N and P groups, respectively. The perfusion index value was extracted prior to intubation, at the start and end of surgery, and after extubation. To minimize individual variance in the absolute value of the perfusion index, we calculated the perfusion index change ratio. A total of 98 patients were examined. Among them, 50 (51.0%) and 48 (49.0%) patients reported pain scores of &lt, 7 upon arrival at the PACU, respectively. Fentanyl consumption during the intraoperative and PACU periods was significantly higher in Group P than in Group N (p &lt, 0.001). The perfusion index change ratios did not significantly differ between the groups. The intraoperative perfusion index change ratios do not correlate with acute postoperative pain following laparoscopic colorectal cancer surgery.

The antibreast cancer activities of the ethyl acetate fraction from Orostachys japonicus (OJEF) were investigated in MDA-MB-231 human breast cancer cells through WST assay, DAPI staining, flow cytometry analysis, and western blotting. OJEF effectively inhibited MDA-MB-231 cells by inducing apoptosis via intrinsic, extrinsic, and endoplasmic reticulum (ER) stress response pathways, cell cycle arrest at the G1/S phase, and antimetastasis including inhibition of tight junction, adherens junction, invasion, and migration. The MAPK family-mediated upstream signal transduction through p-p38 and p-ERK was considered to affect the downstream signal transduction including induction of apoptosis, cell cycle arrest, and antimetastasis. In conclusion, we executed an integrated study on the anticancer activities of OJEF, which extensively induced apoptosis, cell cycle arrest, and antimetastasis in estrogen-independent MDA-MB-231 human breast cancer cells known to be liable to metastasize.

Objective To investigate the effect of ascorbic acid (AA) on hemostatic function during living donor liver transplantation (LDLT). Methods Blood samples from 21 LDLT recipients were taken within 30 minutes after induction and at 120 minutes after reperfusion. Rotational thromboelastography (TEG) and western blot analysis were used to analyze for fibrinolysis and functional changes in c-Cbl and Cbl-b, respectively. TEG test samples were prepared as one of three groups: C group (0.36 mL of blood), N group (0.324 mL of blood + 0.036 mL of 0.9% normal saline), and A group (0.324 mL of blood + 0.036 mL of 200 µmol/L-AA dissolved in 0.9% normal saline). Results AA decreased fibrinolysis and increased clot rigidity at baseline and 120 minutes after reperfusion. Cbl-b expression was significantly increased at baseline and 120 minutes after reperfusion in the A group compared with the C and N groups. However, c-Cbl phosphorylation was most significantly decreased in the A group at baseline and 120 minutes after reperfusion. Conclusion AA can significantly decrease fibrinolysis and improve clot rigidity in LT recipients during LDLT, and functional changes in Cbl-b and c-Cbl might represent the underlying mechanism. AA may be considered for use during LDLT to decrease hyperfibrinolysis.

To compare focal-type autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDA) using contrast-enhanced MR imaging (CE-MRI), and to assess diagnostic performance of the lesion contrast at arterial phase (AP) (ContrastAP) for differentiating between the two diseases. Thirty-six patients with focal-type AIP and 72 patients with PDA were included. All included patients underwent CE-MRI with triple phases. The signal intensity (SI) of the mass and normal pancreas was measured at each phase, and the lesion contrast (SIpancreas/SImass) was compared between AIP and PDA groups. The sensitivity and specificity of ContrastAP using an optimal cutoff point were compared with those of key imaging features specific to AIP and PDA. The lesion contrast differed significantly between AIP and PDA groups at all phases of CE-MRI; the maximum difference was observed at AP. For AIP, the sensitivity (94.4%) and specificity (87.5%) of ContrastAP (cutoff ≤ 1.41) were comparable or significantly higher than those of all key imaging features (sensitivity, 38.9–88.9%; specificity, 48.6–95.8%), except for the halo sign. For PDA, the sensitivity (87.5%) and specificity (94.4%) of ContrastAP (cutoff > 1.41) were comparable or significantly higher than those of all key imaging features (sensitivity, 40.3–68.1%; specificity, 72.2–94.4%), except for the discrete mass. Quantitative analysis of the lesion contrast using CE-MRI, particularly at AP, was helpful to differentiate focal-type AIP from PDA. The diagnostic performance of ContrastAP was mostly comparable or higher than those of the key imaging features. • Diagnosis of focal-type AIP vs. PDA using imaging techniques is extremely challenging. • Lesion contrast in the arterial-phase MRI differs significantly between focal-type AIP and PDA. • Quantitative analysis of lesion contrast using CE-MRI, particularly at the arterial phase, is helpful to differentiate focal-type AIP from PDA.

Background This study aimed to evaluate the association between intraoperative blood loss and myocardial injury after non-cardiac surgery (MINS), which is a severe and common postoperative complication. Methods We compared the incidence of MINS based on significant intraoperative bleeding, defined as an absolute hemoglobin level < 7 g/dL, a relative hemoglobin level less than 50% of the preoperative measurement, or need for packed red cell transfusion. We also estimated a threshold for intraoperative hemoglobin level associated with MINS. Results We stratified a total of 15,926 non-cardiac surgical patients with intraoperative hemoglobin and postoperative cardiac troponin (cTn) measurements according to the occurrence of significant intraoperative bleeding; 13,416 (84.2%) had no significant bleeding while 2,510 (15.8%) did have significant bleeding. After an adjustment with inverse probability weighting, the incidence of MINS was higher in the significant bleeding group (35.2% vs. 16.4%; odds ratio, 1.58; 95% confidence interval, 1.43–1.75; p < 0.001). The threshold of intraoperative hemoglobin associated with MINS was estimated to be 9.9 g/dL with an area under the curve of 0.643. Conclusion Intraoperative blood loss appeared to be associated with MINS. Further studies are needed to confirm these findings. Clinical registration The cohort was registered before patient enrollment at https://cris.nih.go.kr (KCT0004244).

Objective Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and Methods A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007–2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B–C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.

본 연구에서는 기후변화로 인한 강우강도의 변화와 댐 시설물의 노후화에 따른 댐 안전성의 문제를 대비하기 위하여 댐 재개발 평가항목을 개발하였으며, 국내외 사례 및 문헌조사, 그리고 전문가 자문을 통해 각 평가항목에 대한 타당성 및 적합성 검토를 실시하고, 각 세부지표에 대한 정량적 평가기준을 선정하였다. 댐 ...

Objective To investigate the technical and clinical efficacy of the percutaneous insertion of a biliary metallic stent, and to identify the factors associated with biliary stent dysfunction in patients with malignant duodenobiliary obstruction. Materials and Methods The medical records of 70 patients (39 men and 31 women; mean age, 63 years; range, 38−90 years) who were treated for malignant duodenobiliary obstruction at our institution between April 2007 and December 2018, were retrospectively reviewed. Variables found significant by univariate log-rank analysis (p < 0.2) were considered as suitable candidates for a multiple Cox's proportional hazard model. Results The biliary stents were successfully placed in all 70 study patients. Biliary stent insertion with subsequent duodenal stent insertion was performed in 33 patients and duodenal stent insertion with subsequent biliary stent insertion was performed in the other 37 study subjects. The median patient survival and stent patency time were 107 days (95% confidence interval [CI], 78–135 days) and 270 days (95% CI, 95–444 days), respectively. Biliary stent dysfunction was observed in 24 (34.3%) cases. Multiple Cox's proportional hazard analysis revealed that the location of the distal biliary stent was the only independent factor affecting biliary stent patency (hazard ratio, 3.771; 95% CI, 1.157–12.283). The median biliary stent patency was significantly longer in patients in whom the distal end of the biliary stent was beyond the distal end of the duodenal stent (median, 327 days; 95% CI, 249–450 days), rather than within the duodenal stent (median, 170 days; 95% CI, 115–225 days). Conclusion The percutaneous insertion of the biliary metallic stent appears to be a technically feasible, safe, and effective method of treating malignant duodenobiliary obstruction. In addition, a biliary stent system with a distal end located beyond the distal end of the duodenal stent will contribute towards longer stent patency in these patients.

BACKGROUND AND OBJECTIVES In patients with perioperative cardiac troponin (cTn) I below the 99th-percentile upper range of limit (URL), mortality according to cTn I level has not been fully evaluated. This study evaluated the association between postoperative cTn I level above the lowest limit of detection but within the 99th-percentile URL and 30-day mortality after noncardiac surgery. METHODS Patients with cTn I values below the 99th-percentile URL during the perioperative period were divided into a no-elevation group with cTn I at the lowest limit of detection (6 ng/L) and a minor elevation group with cTn I elevation below the 99th percentile URL (6 ng/L < cTn I < 40 ng/L). The primary outcome was 30-day mortality. RESULTS Of the 5,312 study participants, 2,582 (48.6%) were included in the no-elevation group and 2,730 (51.4%) were included in the minor elevation group. After propensity score-matching, the minor elevation group showed significantly increased 30-day mortality (0.5% vs. 2.3%; hazard ratio, 4.30; 95% confidence interval, 2.23-8.29; p

Donor safety and graft results of pure laparoscopic living donor right hepatectomy (LLDRH) have previously been compared with those of open living donor right hepatectomy (OLDRH). However, the clinical outcomes of recipients at 1-year follow-up have never been accurately compared. We aimed to compare 1-year outcomes of recipients of living donor right liver transplantation (LRLT) using pure LLDRH and OLDRH. From May 2013 to May 2017, 197 consecutive recipients underwent LRLT. Donor hepatectomies were performed either by OLDRH (n = 127) or pure LLDRH (n = 70). After propensity score matching, 53 recipients were included in each group for analysis. The clinical outcomes at 1-year follow-up were compared between the 2 groups. The primary outcome was recipient death or graft failure during the 1-year follow-up period. In the propensity-matched analysis, the incidence of death or graft failure during the 1-year follow-up period was not different between the 2 groups (3.8% versus 5.7%; odds ratio [OR], 1.45; 95% confidence interval [CI], 0.24-8.95; P = 0.69). However, the composite of Clavien-Dindo 3b-5 complications was more frequent in the pure LLDRH group (OR, 2.62; 95% CI, 1.15-5.96; P = 0.02). In conclusion, although pure LLDRH affords a comparable incidence of fatal complications in recipients, operative complications may increase at the beginning of the program. The safety of the recipients should be confirmed to accept pure LLDRH as a feasible option.

Scope This study aims to determine the separate and combined effect of a prebiotic (catechin-rich wine grapeseed flour, GSF) and a probiotic (newly isolated kefir lactic acid bacteria, LAB) on hepatic steatosis of obese mice. Methods and results High-fat (HF)-induced obese mice are fed a HF diet containing 6% microcrystalline cellulose (MCC, control), 10% GSF, orally administrated LAB, or a combination of GSF and LAB for 9 weeks. There is a significant reduction of body weight gain and liver weights, plasma insulin concentrations, and HOMA-IR in all experimental groups compared to control. Total lipid content, triglyceride, and low-density lipoprotein (LDL)-cholesterol concentrations of the liver are also significantly lowered. The combination of GSF and LAB further significantly affects cecum propionate content, plasma aspartate aminotransferase (AST/GOT), and zonulin concentrations, which is significantly correlated with hepatic lipid content. Analysis of hepatic microarray data reveals that genes related to lipid synthesis, bile acid and cholesterol synthesis, antioxidant activities, oxidative stress, inflammation, and liver function are significantly modulated following the combination of GSF and LAB. Conclusion These data suggest that amelioration of HF-induced hepatic steatosis after consumption of GSF and LAB is partially mediated via alteration of cecum propionate and intestinal permeability, which modulates hepatic gene expression.

The narrowest portions of the pediatric larynx are the glottis and subglottic region. However, the pliable and paralyzed subglottic region, acting like a curtain, is no resistance when passing an endotracheal tube. Therefore, the ‘functionally’ portion of the pediatric upper airway, which may be the most vulnerable to damage during intubation, is the unyielding portion below the cricoid cartilage. We investigated the functionally-narrowest portion below the cricoid cartilage. Computed tomography (CT) was performed under deep sedation. CT images were used for measurement of dimensions and cross-sectional area (CSA) of the larynx at the level of the cricoid, subcricoid, and trachea. We analyzed the anteriorposterior (AP) diameter, transverse diameter, and CSA below the cricoid cartilage (at the cricoid, subcricoid, and tracheal levels). CT images of 46 children from 8 months to 96 months were reviewed from electric medical record (EMR). The mean ± SD of AP diameter was the shortest at the subcricoid level (cricoid, 105.7 ± 15.8 mm; subcricoid, 94.6 ± 15.3 mm; and trachea, 101.5 ± 15.7 mm; P

Mesenchymal stem cells- (MSCs-) based therapies show different degrees of efficacies for the treatment of various diseases, including lipogenesis. We evaluated the adipogenic differentiation ability of human umbilical cord blood-derived MSCs (hUCB-MSCs) from different donors and examined the contribution of the intracellular calcium (Ca2+) level to this diversity. hUCB-MSCs treated with Ca2+ or the Ca2+ chelator BAPTA-AM increased and decreased adipogenic differentiation, respectively. Canonical Wnt5a/β-catenin expression decreased during adipogenic differentiation of hUCB-MSCs. Treatment with Wnt5a blocked the adipogenic differentiation of hUCB-MSCs and activated the Wnt pathway, with a decrease in the adipogenesis markers PPARγ and leptin, and reduced lipid vacuole-associated Oil red O activity. In contrast, inhibition of the Wnt pathway with dickkopf-1 and β-catenin small interfering RNA transfection promoted the adipogenic potential of hUCB-MSCs. Interestingly, the Ca2+-based system exhibited a synergic effect on adipogenic potential through the Wnt5a/β-catenin pathway. Our data suggest that the variable adipogenic differentiation potential of hUCB-MSCs from different lots is due to variation in the intracellular Ca2+ level, which can be used as a marker to predict hUCB-MSCs selection for lipogenesis therapy. Overall, these results demonstrate that exogenous calcium treatment enhanced the adipogenic differentiation of hUCB-MSCs via negatively regulating the Wnt5a/β-catenin signaling pathway.