Search

Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations., Materials and Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2)., Results: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups., Conclusion: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This phenomenological analysis was conducted to explore the experiences of college student volunteers in the field of pediatric palliative care., Methods: In-depth interviews were conducted with nine study participants who had experience volunteering with children receiving pediatric palliative care. The study analysis was conducted using the Colaizzi method, a rigorous qualitative research method, to develop "intra-group" comparisons among the study participants., Results: Through an analysis of the data, 51 themes, 18 theme clusters, and five main categories were derived. The results confirmed that the experience of university student volunteers in pediatric palliative care can be summarized as "awareness of the role of a volunteer," "difficulties encountered while volunteering," "efforts to overcome the difficulties of volunteer work," "personal reflection," and "awareness of life and death.", Conclusion: The results of this study can be used as a practical guide for the effective management of volunteers in the pediatric palliative care setting., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by Korean Society for Hospice and Palliative Care.)

Recent studies have reported that sarcopenia influences morbidity and mortality in surgical patients. However, few studies have investigated the associations of sarcopenia with short-term and long-term graft failure in recipients after living donor liver transplantation (LDLT). In this study, we investigated the associations between sarcopenia and graft failure/mortality in patients undergoing LDLT. We retrospectively examined 2816 recipients who underwent LDLT between January 2008 and January 2018. Cox regression analysis was performed to evaluate the associations between sarcopenia and graft failure/mortality in recipients at 60 days, 180 days, and 1 year and overall. Sarcopenia in the recipient was significantly associated with 60-day graft failure (adjusted hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.09-3.61; p = 0.03), 180-day graft failure (HR, 1.85; 95% CI, 1.19-2.88; p = 0.01), 1-year graft failure (HR, 1.45; 95% CI, 1.01-2.17; p = 0.05), and overall graft failure (HR, 1.42; 95% CI, 1.08-1.87; p = 0.01). In addition, recipient sarcopenia was associated with 180-day mortality (HR, 1.88; 95% CI, 1.17-3.01; p = 0.01), 1-year mortality (HR, 1.53; 95% CI, 1.01-2.29; p = 0.04), and overall mortality (HR, 1.43; 95% CI, 1.08-1.90; p = 0.01). Preoperative sarcopenia was associated with high rates of graft failure and mortality in LDLT recipients. Therefore, preoperative sarcopenia may be a strong predictor of the surgical prognosis in LDLT recipients., (© 2022 American Association for the Study of Liver Diseases.)

Purpose: This study presents our initial experience with endoscopic combined intrarenal surgery (ECIRS) for large renal stones and compares the results of a propensity score-matched cohort of patients undergoing shock-wave lithotripsy (SWL)., Materials and Methods: A total of 100 adults underwent ECIRS for renal stones between August 2017 and January 2019. For comparison, 2172 patients who underwent a first session of SWL between January 2005 and May 2018 were included in the SWL cohort. Propensity score matching was performed using maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) scores. Stone-free rate (SFR) and success rate were compared between ECIRS and SWL., Results: In the ECIRS group, the mean MSL, mean MSD, and mean SHI were 28.7±15.2 mm, 1013.9±360.0 Hounsfield units (HU), 209.4±104.0 HU, respectively. The SFR was 70%, and the success rate was 82.0% in this group. Although the ECIRS group had larger, harder, and more homogeneous stones than the SWL group, ECIRS showed a higher SFR and success rate than SWL. After propensity-score matching, SFR and success rate remained higher with ECIRS than with SWL (both, p <0.001). In multivariate logistic regression, smaller stone size [odds ratio (OR): 0.947, 95% confidence interval (CI): 0.913-0.979, p =0.002] and lower Seoul National University Renal Stone Complexity score (OR: 0.759, 95% CI: 0.610-0.935, p =0.011) were independent predictors of successful ECIRS., Conclusion: ECIRS showed a higher SFR and success rate than SWL for large renal stones. Smaller stone size and lower complexity of stones were associated with a higher likelihood of successful ECIRS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Purpose: In the context of the COVID-19 outbreak, the European Association of Urology (EAU) guidelines Rapid Reaction Group provided recommendations to manage muscle invasive bladder cancer (MIBC) based on priority levels: neoadjuvant chemotherapy (NAC) should be avoided for patients with T2-3N0M0 MIBC. This meta-analysis aims to evaluate the efficacy of NAC compared with radical cystectomy (RC) alone in improving the overall survival (OS) of patients with T2-4aN0M0 MIBC., Materials and Methods: A systematic review was performed according to the PRISMA guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was OS of patients with T2-4aN0M0 MIBC, and the secondary outcome was OS of patients with only T2N0M0 MIBC., Results: Eight studies were included in this meta-analysis. Overall, the quality of all studies was relatively high, and little publication bias was demonstrated. The OS was significantly better in the NAC with RC group than in RC alone (HR, 0.79; 95% CI, 0.68-0.92; p = 0.002). A subgroup analysis was performed on only patients with T2N0M0 MIBC, and five studies were included. There was no difference in the OS between the NAC with RC and the RC alone groups (HR, 0.83; 95% CI, 0.69-1.01 p = 0.06)., Conclusions: As recommended by the EAU guidelines Rapid Reaction Group, patients with T2N0M0 MIBC should strongly consider omitting NAC until the end of the COVID-19 pandemic. Whether to omit NAC in T3-4aN0M0 MIBC needs further discussion, and studies targeting only T2-3N0M0 MIBC are expected to proceed further., Competing Interests: The authors have declared that no competing interests exist.

Introduction: A single dose of preventive antibiotics is known to be sufficient to reduce the rate of infection-related complications in percutaneous nephrolithotomy (PCNL). However, some studies reported that the extended dose showed lower complications for high-risk groups. Therefore, we performed a systematic review and meta-analysis comparing single- and extended-dose antibiotic prophylaxis for PCNL., Materials and Methods: Relevant studies that compared single- and extended-dose antibiotic prophylactic therapies were identified. Articles were selected from PubMed, EMBASE, KoreaMed, and Google Scholar up to September 2021. Fever and systemic inflammatory response syndrome (SIRS) were compared by meta-analysis. A subgroup analysis was performed according to the degree of risk to the patient., Results: A total of 10 articles were included in this study. There were no significant differences between single dose and extended dose in the rate of fever [p = 0.93, OR = 0.96, 95% confidence interval (CI) 0.44-2.13, I2 = 64%]. Extended dose showed lower rate of SIRS compared to single dose (p = 0.0005, OR = 1.81, 95% CI 1.30-2.53, I2 = 53%); in the subgroup analysis, extended dose also showed lower rates of SIRS compared to single dose in high-risk patients (p <0.0001, OR = 3.53, 95% CI 1.91-6.54, I2 = 36%)., Conclusions: The results of our meta-analysis showed that single-dose antibiotic prophylaxis can be effective for PCNL, but extended-dose antibiotics can be required in high-risk patients to reduce post-PCNL infection-related complications., Competing Interests: The authors have declared that no competing interests exist.

Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans, and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance., (© 2022. The Author(s).)

Context: Since pediatric palliative care (PPC) aims to improve the health-related quality of life (HRQoL) of children with life-limiting conditions (LLC), assessment of their HRQoL and identification of its determinants is crucial., Objectives: To examine the clinical and family factors associated with HRQoL of children with LLC METHODS: This was a cross-sectional study of 136 pediatric patients with LLC who were enrolled in the PPC services at Seoul National University Hospital in South Korea. Patients' HRQoL was measured using the Pediatric Quality of Life 4.0. Clinical and family characteristics were gathered from the medical records and PPC registry database., Results: Most children with LLC have a poor HRQoL at their enrollment for PPC services with significant variation in their total HRQoL scores according to the diagnostic categories. Patients with nonmalignant conditions showed significantly lower HRQoL scores than patients with malignancy. Lower HRQoL scores were associated with more caregiver depressive symptoms. In a multivariable regression model, total HRQoL scores of patients were significantly associated with diagnostic categories and caregiver's depressive symptoms after controlling for other clinical and family variables. Physical health summary scores were significantly associated with diagnostic categories and caregiver depressive symptoms. Psychosocial health summary scores were significantly associated with diagnostic categories, patient location, and caregiver's depressive symptoms., Conclusion: The HRQoL of children with LLC receiving PPC differed among underlying disease categories. Lower HRQoL was associated with more caregiver depressive symptoms. These findings suggest the needs for optimized intervention in palliative care for children with nonmalignant conditions and family-centered intervention to address caregivers' psychosocial problems., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The filter concentration method facilitates the rapid detection of foodborne pathogens. The filter concentration method lowered the limit of detection (LOD) of artificially inoculated cabbage with Salmonella Typhimurium; however, the procedure injured foodborne pathogens during filtering procedure. Thus, to detect injured pathogens under the detection limit, an enrichment broth promoting pathogen resuscitation and growth is required. To rapidly recover, cultivate and lower the time to result (TTR) of S. Typhimurium detection after filter concentration method, a brain heart infusion (BHI) broth-based modified enrichment broth (MEB) was developed. The MEB was developed by fitting growth curves to a modified Gompertz model; 1.00 g/L of sodium pyruvate, 0.20 g/L proline and 2.0 g/L magnesium sulphate additives were optimized as additional components to rapidly grow filter-injured S. Typhimurium. As a result, the rate of filter-injured S. Typhimurium went from 100% to 0.0% using MEB within 3.5 h. In contrast, BHI required 4 h and buffered peptone water (BPW) required more than 4 h to decrease the injury rate to 0.0%. Using MEB, BHI and BPW, filter-injured S. Typhimurium in cabbages were enriched to 4.056 ± 0.026 Log CFU/25 g, 3.571 ± 0.187 Log CFU/25 g and 3.708 ± 0.156 Log CFU/25 g, respectively. Additionally, 1-9 CFU/mL S. Typhimurium in cabbage was detected within 3.0 h, including 1 h enrichment with MEB, whereas 5.0 h was required for BHI and BPW. Thus, the MEB developed in this study showed great potential as a short enrichment broth for the rapid detection of filter-injured S. Typhimurium., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Although living donor liver transplantation (LDLT) is the standard treatment option for patients with end-stage liver disease, it always entails ethical concerns about the risk of living donors. Recent studies have reported a correlation between sarcopenia and surgical prognosis in recipients. However, there are few studies of donor sarcopenia and the surgical prognosis of donors. This study investigated the association between sarcopenia and postoperative acute kidney injury in liver donors., Methods: This retrospective study analysed 2892 donors who underwent donor hepatectomy for LDLT between January 2008 and January 2018. Sarcopenia was classified into pre-sarcopenia and severe sarcopenia, which were determined to be -1 standard deviation (SD), and -2 SD from the mean baseline of the skeletal muscle index, respectively. Multivariate regression analysis was performed to evaluate the association between donor sarcopenia and postoperative AKI. Additionally, we assessed the association between donor sarcopenia and delayed recovery of liver function (DRHF)., Results: In the multivariate analysis, donor sarcopenia was significantly associated a higher incidence of postoperative AKI (adjusted odds ratio [OR]: 2.65, 95% confidence interval [CI]: 1.15-6.11, P = .022 in pre-sarcopenia, OR: 5.59, 95% CI: 1.11-28.15, P = .037 in severe sarcopenia, respectively). Additionally, hypertension and synthetic colloid use were significantly associated with postoperative AKI. In the multivariate analysis, risk factors of DRHF were male gender, indocyanine green retention rate at 15 minutes, and graft type, however, donor sarcopenia was not a risk factor., Conclusions: Donor sarcopenia is associated with postoperative AKI following donor hepatectomy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The isothermal amplification method, a molecular-based diagnostic technology, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), is widely used as an alternative to the time-consuming and labor-intensive culture-based detection method. However, food matrices or other compounds can inhibit molecular-based diagnostic technologies, causing reduced detection efficiencies, and false-negative results. These inhibitors originating from food are polysaccharides and polyphenolic compounds in berries, seafood, and vegetables. Additionally, magnesium ions needed for amplification reactions can also inhibit molecular-based diagnostics. The successful removal of inhibitors originating from food and molecular amplification reaction is therefore proposed to enhance the efficiency of molecular-based diagnostics and allow accurate detection of food-borne pathogens. Among molecular-based diagnostics, PCR inhibitors have been reported. Nevertheless, reports on the mechanism and removal of isothermal amplification method inhibitors are insufficient. Therefore, this review describes inhibitors originating from food and some compounds inhibiting the detection of food-borne pathogens during isothermal amplification.

Background: Olfactory Sensory Neuron (OSN) axons project from the zebrafish olfactory epithelium to reproducible intermediate target locations in the olfactory bulb called protoglomeruli at early stages in development. Two classes of OSNs expressing either OMP or TRPC2 exclusively target distinct, complementary protoglomeruli. Using RNAseq, we identified axon guidance receptors nrp2a and nrp2b, and their ligand sema3fa, as potential guidance factors that are differentially expressed between these two classes of OSNs., Methods: To investigate their role in OSN axon guidance, we assessed the protoglomerular targeting fidelity of OSNs labeled by OMP:RFP and TRPC2:Venus transgenes in nrp2a, nrp2b, or sema3fa mutants. We used double mutant and genetic interaction experiments to interrogate the relationship between the three genes. We used live time-lapse imaging to compare the dynamic behaviors of OSN growth cones during protoglomerular targeting in heterozygous and mutant larvae., Results: The fidelity of protoglomerular targeting of TRPC2-class OSNs is degraded in nrp2a, nrp2b, or sema3fa mutants, as axons misproject into OMP-specific protoglomeruli and other ectopic locations in the bulb. These misprojections are further enhanced in nrp2a;nrp2b double mutants suggesting that nrp2s work at least partially in parallel in the same guidance process. Results from genetic interaction experiments are consistent with sema3fa acting in the same biological pathway as both nrp2a and nrp2b. Live time-lapse imaging was used to examine the dynamic behavior of TRPC2-class growth cones in nrp2a mutants compared to heterozygous siblings. Some TRPC2-class growth cones ectopically enter the dorsal-medial region of the bulb in both groups, but in fully mutant embryos, they are less likely to correct the error through retraction. The same result was observed when TRPC2-class growth cone behavior was compared between sema3fa heterozygous and sema3fa mutant larvae., Conclusions: Our results suggest that nrp2a and nrp2b expressed in TRPC2-class OSNs help prevent their mixing with axon projections in OMP-specific protoglomeruli, and further, that sema3fa helps to exclude TRPC2-class axons by repulsion from the dorsal-medial bulb., (© 2021. The Author(s).)

Background and Objectives: Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation., Materials and Methods: To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting., Results: We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy., Conclusion: We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents., (© 2021. The Author(s).)

Background: Malrotation after nailing of femoral shaft fractures occurs in about 25% of cases. It can cause substantial functional problems. The lesser trochanter (LT) profile has been used to assess rotational alignment. However, the extent to which the LT profile is symmetrical between limbs, whether the LT profile varies as a function of age or sex, and the efficacy of the LT profile technique remain unknown. The purpose of this study was to determine if there was a significant side-to-side length difference in the LT profile (LTD) according to age and sex., Methods: We attempted to determine the amount of medial prominence of the lesser trochanter relative to the medial cortex of the femoral shaft (the LT profile) using 3-dimensional computed tomography (3D-CT) images of normal femora obtained bilaterally (366 subjects) in anatomic positions. We also compared the left and right sides to determine the amount of natural asymmetry by age and sex. In addition, we compared the side-to-side difference in the LT version with the LTD to determine whether the LTD represented the difference in femoral rotation., Results: The LTD was <4 mm (meaning an LT version difference of <10°) in 83% of the subjects, but was ≥4 mm (an LT version difference of ≥10°) in 17%. Subset analysis demonstrated that the differences were greatest in women >70 years of age. The largest LTD (both sexes) was observed in individuals over 70 years of age (2.62 ± 1.37 mm, compared with <55 years: 1.55 ± 1.36 mm and 55 to 70 years: 2.27 ± 1.70 mm). There was no significant difference between sexes in the under-70 age groups. However, the LTD was significantly greater in women over 70 years than in men over 70 years (3.10 ± 1.42 versus 2.41 ± 1.30 mm)., Conclusions: Since the LTD demonstrated side-to-side symmetry within 4 mm, or 10° of rotation, in 83% of all subjects, we consider the LT profile to be useful as a guide to assess rotational reduction clinically. However, surgeons should recognize that, in 17% of cases, using this technique could result in malrotation of ≥10°. The rate of malrotation may be even higher in women over 70, for whom supplemental techniques to ensure correct rotation may be appropriate., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G679)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Stroke is the second leading cause of death and disability worldwide. Stroke centers have become a central component of modern stroke services in many high-income countries, but their feasibility and efficacy in low, middle, and emerging high-income countries are less clear. Also, despite the availability of international guidelines, many hospitals worldwide do not have organized clinical stroke care. We present a methodology to help hospitals develop stroke centers and review quality data after implementation. Objectives: To describe and compare demographics, performance, and clinical outcomes of the Pacífica Salud, Hospital Punta Pacífica (PSHPP) stroke center during its first 3 years 2017-2019. Methods: Pacífica Salud, Hospital Punta Pacífica was organized to implement protocols of care based on the best practices by international guidelines and a quality improvement process. The methodology for implementation adapts a model for translating evidence into practice for implementation of evidence-based practices in medicine. This is a retrospective study of prospectively collected quality data between March of 2017 to December of 2019 for patients admitted to PSHPP with primary diagnosis stroke. Data collected include demographics, clinical data organized per the Joint Commission's STK Performance Measures, door to needle, door to groin puncture, 90 day modified Rankin Score, and hemorrhagic complications from IV thrombolysis and mechanical thrombectomy (MT). Primary outcome: year over year proficiency in documenting performance measures. Secondary outcome: year over year improvement. Results: A total of 143 patients were admitted for acute ischemic stroke, TIA, or hemorrhagic stroke. Of these, 36 were admitted in 2017, 50 in 2018, and 57 in 2019. Performance measure proficiency increased in the year-over-year analysis as did the total number of patients and the number of patients treated with IV thrombolysis and MT. Conclusions: We present the methodology and results of a stroke program implementation in Panamá. This program is the first in the country and in Central America to achieve Joint Commission International (JCI) certification as a Primary Stroke Center (PSC). We postulate that the dissemination of management guidelines is not sufficient to encourage the development of stroke centers. The application of a methodology for translation of evidence into practice with mentorship facilitated the success of this program., Competing Interests: VU—Site PI for TIMELESS (Genentech Inc), Grant for investigator sponsored trial OPTIMISTmain (Genentech, Inc.). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Novarro-Escudero, Moon, Olmedo, Ferguson, Caballero, Onodera, Effio, Klein, Zink, Johnson and Urrutia.)

Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.005) and PHN (HR, 1.08; 95% CI, 1.03-1.13; p = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN ( p = 0.020 and p = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, p < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81-0.92; p < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.

CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in resistance to conventional anti-cancer therapies. We evaluated the expression of CSNK2A1 and phosphorylated SIRT6 in the 37 osteosarcoma patients and investigated the effects of CSNK2A1 and the phosphorylation of SIRT6 on Ser338 on resistance to the anti-cancer effects of doxorubicin. Higher expression of CSNK2A1 and phosphorylated SIRT6 was associated with shorter survival in osteosarcoma patients. U2OS and KHOS/NP osteosarcoma cells with induced overexpression of CSNK2A1 were resistant to the cytotoxic effects of doxorubicin, and the knock-down of CSNK2A1 potentiated the cytotoxic effects of doxorubicin. CSNK2A1 overexpression-mediated resistance to doxorubicin was associated with SIRT6 phosphorylation and the induction of the DNA damage repair pathway molecules. CSNK2A1- and SIRT6-mediated resistance to doxorubicin in vivo was attenuated via mutation of SIRT6 at the Ser338 phosphorylation site. Emodin, a CSNK2A1 inhibitor, potentiated the cytotoxic effects of doxorubicin in osteosarcoma cells. This study suggests that blocking the CSNK2A1-SIRT6-DNA damage repair pathway might be a new therapeutic stratagem for osteosarcomas.

Background and Aims: Despite frequent cirrhotic cardiomyopathy or subclinical heart failure (HF), the prognostic value of peri-liver transplant (LT) B-type natriuretic peptide (BNP) has been poorly studied in advanced liver disease. We examined the association between BNP and mortality in a large cohort of LT patients and identified risk factors for peri-LT BNP increase., Approach and Results: Using prospectively collected data from the Asan LT Registry between 2008 and 2019, 3,811 patients who measured serial pretransplant BNP (preBNP) and peak BNP levels within the first 3 posttransplant days (postBNP POD3 ) were analyzed. Thirty-day all-cause mortality predicted by adding preBNP and/or postBNP POD3 to the traditional Revised Cardiac Risk Index (RCRI) was evaluated. PreBNP > 400 pg/mL (known cutoff of acute HF) was found in 298 (7.8%); however, postBNP POD3  > 400 pg/mL was identified in 961 (25.2%) patients, specifically in 40.4% (531/1,315) of those with a Model for End-Liver Disease score (MELDs) > 20. Strong predictors of postBNP POD3  > 400 pg/mL were preBNP, hyponatremia, and MELDs, whereas those of preBNP > 400 pg/mL were MELDs, kidney failure, and respiratory failure. Among 100 (2.6%) post-LT patients who died within 30 days, patients with postBNP POD3  ≤ 150 pg/mL (43.1%, reference group), 150-400 pg/mL (31.7%), 400-1,000 pg/mL (18.5%), 1,000-2,000 pg/mL (4.7%), and >2,000 pg/mL (2.0%) had 30-day mortalities of 0.9%, 2.2%, 4.0%, 7.7%, and 22.4%, respectively. Adding preBNP, postBNP POD3 , and both BNP to RCRI improved net reclassification index to 22.5%, 29.5%, and 33.1% of 30-day mortality, respectively., Conclusions: PostBNP POD3  > 400 pg/mL after LT was markedly prevalent in advanced liver disease and mainly linked to elevated preBNP. Routine monitoring of peri-LT BNP provides incremental prognostic information; therefore, it could help risk stratification for mortality as a practical and useful biomarker in LT., (© 2020 by the American Association for the Study of Liver Diseases.)

This study sought to identify the short- and long-term changes in left ventricular ejection fraction (LVEF) after mitral valve repair (MVr) in patients with chronic primary mitral regurgitation according to preoperative LVEF (pre-LVEF) and preoperative left ventricular end-systolic diameter (pre-LVESD). This study evaluated 461 patients. Restricted cubic spline regression models were constructed to demonstrate the long-term changes in postoperative LVEF (post-LVEF). The patients were divided into four groups according to pre-LVEF (<50%, 50-60%, 60-70%, and ≥70%). The higher the pre-LVEF was, the greater was the decrease in LVEF immediately after MVr. In the same pre-LVEF range, immediate post-LVEF was lower in patients with pre-LVESD ≥ 40 mm than in those with pre-LVESD < 40 mm. The patterns of long-term changes in post-LVEF differed according to pre-LVEF ( p for interaction < 0.001). The long-term post-LVEF reached a plateau of approximately 60% when the pre-LVEF was ≥50%, but it seemed to show a downward trend after reaching a peak at approximately 3-4 years after MVr when the pre-LVEF was ≥70%. The patterns of short- and long-term changes in post-LVEF differed according to pre-LVEF and pre-LVESD values in patients with chronic primary mitral regurgitation after MVr.

Background: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality., Methods: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis., Results: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001)., Conclusions: Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

Various biological indicators are reportedly associated with postoperative acute kidney injury (AKI) in the surgical treatment of hepatocellular carcinoma (HCC). However, only a few studies have evaluated the association between the preoperative prognostic nutritional index (PNI) and postoperative AKI. This study evaluated the association of the preoperative PNI and postoperative AKI in HCC patients. We retrospectively analyzed 817 patients who underwent open hepatectomy between December 2007 and December 2015. Multivariate regression analysis was performed to evaluate the association between the PNI and postoperative AKI. Additionally, we evaluated the association between the PNI and outcomes such as postoperative renal replacement therapy (RRT) and mortality. Cox regression analysis was performed to assess the risk factors for one-year and five-year mortality. In the multivariate analysis, high preoperative PNI was significantly associated with a lower incidence of postoperative AKI (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.85 to 0.99, p = 0.021). Additionally, diabetes mellitus and the use of synthetic colloids were significantly associated with postoperative AKI. PNI was associated with postoperative RRT (OR: 0.76, 95% CI: 0.60 to 0.98, p = 0.032) even after adjusting for other potential confounding variables. In the Cox regression analysis, high PNI was significantly associated with low one-year mortality (Hazard ratio (HR): 0.87, 95% CI: 0.81 to 0.94, p < 0.001), and five-year mortality (HR: 0.93, 95% CI: 0.90-0.97, p < 0.001). High preoperative PNI was significantly associated with a lower incidence of postoperative AKI and low mortality. These results suggest that the preoperative PNI might be a predictor of postoperative AKI and surgical prognosis in HCC patients undergoing open hepatectomy.

We report highly emissive and radiatively cooled metallic surfaces that sustain multiple and high-amplitude gap plasmon cavity modes within the principal thermal radiation spectrum at room temperature (i.e., 8-13 μm). A square-lattice array of Cu/ZnS/Cu gap plasmon cavities with five different widths was designed to avoid the near-field coupling between adjacent cavities and the anticrossing of a cavity mode and the first diffraction mode. The gap plasmon cavities fabricated on a Si substrate exhibited an effective emissivity of >0.62, up to an incidence of 60°. Outdoor solar heating experiments showed that the Cu/ZnS/Cu multicavity array lowered the Si substrate temperature by 4 °C at a maximum solar irradiance of 800 W/m 2 , which is equivalent to a near-one-sun intensity, relative to a planar Cu/ZnS/Cu multilayer. Such mid-infrared spectrum management of metals enables heat dissipation via radiation, which will be further utilized for designing electrodes that cool optoelectronic devices with the same metal/dielectric/metal configuration.

Postoperative hemorrhagic stroke (HS) is a rare yet devastating complication after liver transplantation (LT). Unruptured intracranial aneurysm (UIA) may contribute to HS; however, related data are limited. We investigated UIA prevalence and aneurysmal subarachnoid hemorrhage (SAH) and HS incidence post-LT. We identified risk factors for 1-year HS and constructed a prediction model. This study included 3544 patients who underwent LT from January 2008 to February 2019. Primary outcomes were incidence of SAH, HS, and mortality within 1-year post-LT. Propensity score matching (PSM) analysis and Cox proportional hazard analysis were performed. The prevalence of UIAs was 4.63% ( n = 164; 95% confidence interval (CI), 3.95-5.39%). The 1-year SAH incidence was 0.68% (95% CI, 0.02-3.79%) in patients with UIA. SAH and HS incidence and mortality were not different between those with and without UIA before and after PSM. Cirrhosis severity, thrombocytopenia, inflammation, and history of SAH were identified as risk factors for 1-year HS. UIA presence was not a risk factor for SAH, HS, or mortality in cirrhotic patients post-LT. Given the fatal impact of HS, a simple scoring system was constructed to predict 1-year HS risk. These results enable clinical risk stratification of LT recipients with UIA and help assess perioperative HS risk before LT.

Background and Aim: The proportional increase of corrected QT interval (QTc) along end-stage liver disease (ESLD) severity may lead to inconsistent outcome reporting if based on conventional threshold of prolonged QTc. We investigated the comprehensive QTc distribution among ESLD patients and assessed the association between QTc > 500 ms, a criterion for diagnosing severe long-QT syndrome, and the 30-day major adverse cardiovascular event (MACE) after liver transplantation (LT) and identified the risk factors for developing QTc > 500 ms., Methods: Data were collected prospectively from the Asan LT Registry between 2011 and 2018, and outcomes were retrospectively reviewed. Multivariable analysis and propensity score-weighted adjusted odds ratios (ORs) were calculated. Thirty-day MACEs were defined as the composite of cardiovascular mortality, arrhythmias, myocardial infarction, pulmonary thromboembolism, and/or stroke., Results: Of 2579 patients, 194 (7.5%) had QTc > 500 ms (QTc500&#95;Group), and 1105 (42.8%) had prolonged QTc (QTcP&#95;Group), defined as QTc > 470 ms for women and >450 ms for men. The 30-day MACE occurred in 336 (13%) patients. QTc500&#95;Group showed higher 30-day MACE than did those without (20.1% vs 12.5%, P = 0.003), with corresponding adjusted OR of 1.24 (95% CI: 1.06-1.46, P = 0.007). However, QTcP&#95;Group showed comparable 30-day MACE (13.3% vs 12.8% without prolonged QTc, P = 0.764). Significant risk factors for QTc > 500 ms development were advanced liver disease, female sex, hypokalemia, hypocalcemia, high left ventricular end-diastolic volume, and tachycardia., Conclusion: Our results revealed that, among ESLD patients, a novel threshold of QTc > 500 ms was associated with post-LT 30-day MACE but not with conventional threshold, indicating that a longer QTc threshold should be considered for this unique patient population., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Ischemic osteonecrosis (ION) can produce permanent deformity and osteoarthritis in the femoral head and other joints. No biologic treatment has been established, and the molecular mechanisms involved in the pathogenesis of ION have not been elucidated. In this work, we found that treatment with sirtuin6 (Sirt6) suppressed inflammatory cytokines, bone resorption, progression of osteoarthritis, and reduced bone deformity in an ION mouse model. We used a deacetylase mutant adenovirus to confirm that those effects were caused by the deacetylase function of Sirt6. Among the osteoclastogenic factors of osteoblasts, only the receptor activator of NF-κb ligand (RANKL) level changed in response to Sirt6 knockout in primary osteoblasts. In particular, the vitamin D receptor physically interacted with Sirt6 and induced recruitment of Sirt6 around RANKL promoters. Finally, Tg mice overexpressing Sirt6 resisted osteocyte death, bone resorption, and progression of osteoarthritis after ischemic surgery, whereas osteoblast/osteocyte-specific Sirt6 knockout mice showed aggravated bone loss and severe deformity. Our findings demonstrate that administration of Sirt6 prevents bone loss and osteoarthritis in ischemic conditions. Activation of Sirt6 in osteoblasts/osteocytes could be a new therapeutic approach to treating ION of the femoral head and other bone regions. © 2020 American Society for Bone and Mineral Research (ASBMR)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

Ethnopharmacological Relevance: Myrocarpus frondosus, known as cabreúva, is a tree whose trunk barks are used in folk medicine as tea, syrup, ointments, and tinctures for the treatment of inflammation. However, there is no scientific evidence demonstrating this activity., Aim of the Study: The present investigation was focused on evaluating the antioxidant and anti-inflammatory activities of M. frondosus, using the in vitro model of RAW 264.7 macrophages induced by LPS and the in vivo model of mouse pleurisy induced by carrageenan., Materials and Methods: M. frondosus trunk barks were dried at room temperature for seven days and subjected to exhaustive maceration with ethanol (70%) to obtain its crude extract (CE). CE was subjected to UPLC-HRMS analysis to establish its chemical profile. Its antioxidant activity was evaluated using the DPPH method, reducing power by the iron (III) to iron (II) reduction assay and the β-carotene-linoleic acid bleaching assay. The RAW 264.7 macrophages were pretreated with the CE in a non-cytotoxic concentration and induced by LPS (1 μg/mL). After 24 h, using the supernatant, we evaluated the nitric oxide (NOx) and interleukin-6 (IL-6) levels. The anti-inflammatory effects of CE (at doses of 30, 100 and 300 mg/kg) were evaluated on leukocyte migration (total and differential), exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, NOx, tumor necrosis factor-α (TNF-α), and IL-6 levels, by using a murine model of neutrophilic inflammation., Results: The UPLC-HRMS of CE revealed the presence of isoflavonones, including biochanin A and formononetin. CE exhibited good antioxidant activity by quenching and decreasing free radicals, as well as reducing pro-oxidant metals. CE did not show cytotoxicity at a concentration below 11 μg/mL and reduced the secretion of the pro-inflammatory NOx in the inflamed macrophages. In vivo assay revealed that CE caused a pronounced inhibition on leukocyte migration, and this inhibition was due to its ability to reduce neutrophil migration. Moreover, CE was also able to reduce the release of critical pro-inflammatory mediators such as MPO, NOx, TNF-α, and IL-6., Conclusions: All these findings indicate that M. frondosus exhibited antioxidant activity and anti-inflammatory effect., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Accelerating wound healing with minimized bacterial infection has become a topic of interest in the development of the new generation of tissue bio-adhesives. In this study, we fabricated a hydrogel system (MGC-g-CD-ic-TCS) consisting of triclosan (TCS)-complexed beta-cyclodextrin (β-CD)-conjugated methacrylated glycol chitosan (MGC) as an antibacterial tissue adhesive. Proton nuclear magnetic resonance ( 1 H NMR) and differential scanning calorimetry (DSC) results showed the inclusion complex formation between MGC-g-CD and TCS. The increase of storage modulus (G') of MGC-g-CD-ic-TCS after visible light irradiation for 200 s indicated its hydrogelation. The swollen hydrogel in aqueous solution resulted in two release behaviors of an initial burst and sustained release. Importantly, in vitro and in vivo results indicated that MGC-g-CD-ic-TCS inhibited bacterial infection and improved wound healing, suggesting its high potential application as an antibacterial tissue bio-adhesive.

Background: IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited., Methods: This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test., Results: In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001)., Conclusions: This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.

Background: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures., Methods: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure., Results: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%., Conclusion: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center., (Copyright © 2020. Published by Elsevier Inc.)

The present prospective observational study aimed to analyze the outcomes of inpatients who received integrative Korean medicine treatment in order to provide evidence on its effects on lumbar spinal stenosis (LSS). Patients with LSS who received inpatient treatment at four Korean medicine hospitals from January 2015 to December 2018 were followed up. Outcomes measured included the numeric rating scale (NRS) scores for back and leg pain, and Oswestry Disability Index (ODI). Changes in outcomes at admission, discharge, and follow-up, as well as associated predictors that could account for the improvement in outcomes were analyzed. The NRS score for back pain, NRS score for leg pain, and ODI decreased by 2.20 points (95% confidence interval (CI), -2.41 to -1.99), 2.28 points (95% CI, -2.59 to -1.96), and 17.31 points (95% CI, -19.6 to -15.02), respectively, at long-term follow-up compared with at admission. Patients with LSS who received inpatient integrative Korean medicine treatment exhibited an improvement in pain and functional disability. Further studies are required to determine the effects of integrative Korean medicine treatment.

Background: Cubitus varus is a complex three-dimensional deformity. Various osteotomies have been introduced to correct this complex deformity. The objective of the present study was to evaluate clinical and functional outcomes of adult cubitus varus deformity treated with translation step-cut osteotomy., Methods: Seventeen consecutive patients with a mean age of 25 years (range, 19-50 years) who underwent translation step-cut osteotomy were enrolled in this study. Their average follow-up period was 28.2 months. Radiographic measurements preoperatively, 3-month postoperatively, and at the last follow-up were compared. Functional outcomes were assessed using Disabilities of the Arm, Shoulder and Hand (DASH), Mayo Elbow Performance Score (MEPS), and Oppenheim criteria., Results: The mean humerus-elbow-wrist angle improved from 14.7° ± 6.4° (range, 6°-23°) varus preoperatively to 12.1° ± 6.6° (range, 5°-20°) valgus postoperatively (p <  0.001). The lateral prominence index improved 9.6% from its preoperative value, showing no significant difference from that of a normal elbow. Osseous union was radiographically demonstrated in 16 patients (except one out of 17 patients) within a mean of 12.7 weeks (range, 8-18 weeks). The motion arc of the elbow at the last follow-up was not significantly (p > 0.05) different from that at the initial presentation. Based on Oppenheim criteria, results were excellent for 7, good for 8, and poor for 2 patients. Mean final DASH value and MEPS were 2.5 ± 3.8 points (range, 0-15 points) and 97.0 ± 5.8 points (range, 85-100 points), respectively. With regard to complications, one case had delayed union and one case had transient radial nerve injury., Conclusion: Translation step-cut osteotomy using Y plate is an efficient procedure to correct varus alignment and flexion-extension deformities so that they are within normal limits of adults with post-traumatic cubitus varus deformity., Trial Registration: Institutional Review Board of Jeonbuk National University Hospital (IRB No. 2020-01-020 ).

Introduction: Early allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation., Material and Methods: Of 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed., Results: The prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28-5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1-4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%., Conclusions: Pretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study presents the process of designing workbooks for advance care planning appropriate for the Korean cultural setting and describes actual case studies., Methods: This study focused on single inductive case studies of the utilization of an advance care planning workbook and recruited individual participants., Results: The workbook for adolescents contained six sessions and the workbook for children contained seven sessions. The workbook sessions led to four major discoveries 1) considering the Korean cultural context, discussions on life and death must be held indirectly; 2) the role of the counselor as a supporter is crucial for the workbook to be effective; 3) the workbook must be accessible regardless of the seriousness of the illness; and 4) patients must be able to make their own choice between the workbook versions for children and adolescents. Six facilitating factors improved engagement 1) the role of the counselor as a supporter; 2) building trust with the patient; 3) affirming freedom of expression on topics the patient wished to avoid talking about; 4) having discussions on what private information to keep secret and to whom the information can be disclosed; 5) discovering and regularly discussing relevant topics; and 6) regular communication and information-sharing with the patient's medical service providers., Conclusion: It is necessary to build on actual case studies regarding workbooks for children and adolescents in order to expand the usage of these workbooks to all relevant medical institutions in Korea., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2020 by Korean Society for Hospice and Palliative Care.)

Background: SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy., Methods: We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor., Results: Immunohistochemical expression of SIRT6 was significantly associated with shorter overall survival and relapse-free survival of osteosarcoma patients, especially in patients who received adjuvant chemotherapy. In U2OS and KHOS/NP osteosarcoma cells, knock-down of SIRT6 significantly potentiated apoptotic effects of doxorubicin and SIRT6 overexpression induced resistance to doxorubicin. Moreover, SIRT6 induced the DNA damage repair pathway and SIRT6-mediated resistance to doxorubicin was attenuated by blocking the DNA damage repair pathway with olaparib and ATM inhibitor., Conclusions: This study suggests that suppression of SIRT6 in combination with doxorubicin might be an effective modality in the treatment of osteosarcoma patients, especially for osteosarcomas with shorter survival with high expression of SIRT6.

Here, red phosphorescent platinum(II) complexes based on tetradentate pyridine-containing lig-ands are studied. To investigate their electroluminescent properties, multilayer devices were fabricated in the following sequence; ITO (180 nm)/4,4',4″-Tris[2-naphthyl(phenyl)amino]triphenylamine (2-TNATA) (30 nm)/ N , N '-di(1-naphthyl)- N , N '-diphenyl-1,1'-biphenyl)4,4'-diamine (NPB) (20 nm)/ Tris(4-carbazoyl-9-ylphenyl)amine (TCTA) (10 nm)/4,4'-Bis( N -carbazolyl)-1,1'-biphenyl (CBP) (20 nm)/Platinum(II) complex (20 nm)/1,3,5-Tris(1-Phenyl-1H-benzimidazol-2-yl)benzene) (TPBi) (40 nm)/Liq (2 nm)/Al (100 nm). In particularly, a device using platinum(II) complex based on N -(3,5-di-tert-butylphenyl)-3-(pyridin-2-yl)- N -(3-(pyridin-2-yl)phenyl)benzenamineligand showed the efficient red emission, with a luminous efficiency, power efficiency, and external quantum efficiency of, and the Commission International de LEclairge (CIE) coordinates of 27.26 cd/A, 10.54 lm/W, 8.50% at 20 mA/cm², and (0.65, 0.33) at 11.0 V, respectively.

In this study, we synthesized and characterized two novel deep blue emitting materials based on indenoquinoline-substituted phenylanthracene derivatives. Multilayer organic light-emitting diodes were fabricated with the following sequence: indium-tin-oxide (ITO)/4,4',4″-tris[2-naphthyl(phenyl)amino (2-TNATA)/4,4'-bis( N - N -naphthyl)- N -phenylamino) biphenyl (NPB)/Blue emitting material ( 1 or 2 )/Bathophenanthroline (Bphen)/lithium quinolate (Liq)/Al. A device B using '7,7-dimethyl-9-(10-phenylanthracen-9-yl)-7H-indeno[1,2-f] isoquinoline ( 2 )' as an emitter showed the efficient emission with the luminous efficiency, power efficiency, and external quantum efficiency of 2.30 cd/A, 1.02 lm/W, 2.94% at 20 mA/cm², respectively. This device exhibited deep-blue emission with the Commission Internationale De LÉnclairage (CIE) coordinates of (0.16, 0.08) and λ max = 436 nm at 8.0 V.

Osteoporosis is a degenerative disease characterized by reduced bone mass, in which deregulated bone remodeling by osteoclasts and osteoblasts is a main pathogenesis. Although recently tussilagone, a major active component of flower buds of Tussilago farfara, has been shown to inhibit osteoclastogenesis, its effect on estrogen deficiency-induced osteoporosis remains unknown. This study examined the effect of tussilagone on bone loss in ovariectomized mice and further explored its impact on osteoclast apoptosis and osteoblast formation in addition to osteoclastogenesis. Tussilagone suppression of osteoclastogenesis was confirmed in bone marrow derived macrophages, which was observed with the 1/10 concentration of that of the previous study. As demonstrated by ApoPercentage dye staining and Western blotting, tussilagone enhanced apoptosis in differentiated osteoclasts by increasing estrogen receptor α and Fas ligand expression. On the contrary, either osteoblast differentiation or mineralization was not affected by tussilagone. Lastly, administering tussilagone to mice for 6 weeks prevented trabecular microarchitecture impairment in ovariectomized mice compared to vehicle control groups. These findings suggest that tussilagone or Tussilago farfara prevents osteoporotic bone loss by suppressing osteoclast differentiation and inducing osteoclast apoptosis, and that it may therefore offer a possible remedy against resorptive bone diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The increase in the number of pediatric patients with complex health conditions necessitates the application of advance care planning for children. Earlier, withdrawal of life-sustaining treatment was taboo in the medical society in South Korea due to the history of such practice being punishable by law, and physicians tended to pursue aggressive treatment. With changes in public opinion on end-of-life care, the Korean government enacted a new law that protect human dignity by respecting patients' self-determination and facilitating advance care planning. However, little is known about current state of advance care planning for pediatric patients. The study aimed to assess perceptions regarding advance care planning among South Korean pediatricians and clarify any differences in perception among pediatric subspecialties., Methods: This study was an observational cross-sectional survey that used a web-based self-report questionnaire. Participants comprised of pediatricians currently caring for children with life-limiting conditions in 2018., Results: Of the 96 respondents, 89 were included in the analysis. In a hypothetical patient scenario, more hemato-oncologists and intensivists than neonatologists and neurologists preferred to provide comfort care than aggressive treatment. While 72.2% of hemato-oncologists reported that they usually or always discuss advance care plans with parents during treatment, more than half of other pediatricians reported that they seldom do so. Furthermore, 65% of respondents said that they never discuss advance care planning with adolescent patients. Moreover, there were no notable differences among subspecialties. The most prevalent answers to factors impeding advance care planning were lack of systemic support after performing advance care planning (82.0%) and uncertain legal responsibilities (70.8%)., Conclusions: The pediatricians differed in their experiences and attitudes toward advance care planning based on their subspecialty. Consequently, institutional support and education should be provided to physicians so that they can include children and families in discussions on prognosis.

The accumulation of tracheobronchial secretions may contribute to a deterioration in pulmonary function and its early detection is important. In this study, we analyzed the respiratory sound spectrum in patients with intratracheal secretion, and compared acoustic characteristics before and after therapeutic endotracheal suctioning. After review of anesthetic records of liver transplant recipients, we included recipients with identified intratracheal secretion during surgery. Intraoperative breath sounds recorded through esophageal stethoscope were sampled in 20 s-period before and after suctioning of secretion and analyzed using fast Fourier transform. We also analyzed normal breath sounds from recipients without any respiratory problem as control group. The maximal power (dBm Max ), total power from whole frequency range of 80-500 Hz (P t ), total power of each frequency range (80-200 Hz, P 80-200 ; 200-300 Hz, P 200-300 ; 300-400 Hz, P 300-400 ; 400-500 Hz, P 400-500 ), and their ratio (P 80-200 /P t , P 200-300 /P t , P 300-400 /P t , P 400-500 /P t ) were compared. Breath sounds were obtained from 20 recipients; 9 pairs of breath sound before and after suctioning of secretion and 11 normal breath sounds. Patients with intratracheal secretion showed significantly higher P 80-200 , P 200-300 , P 300-400 , P 400-500 when compared to the those of normal control patients (P = 0.003, P = 0.002, and P = 0.009, respectively), while dBm Max did not differ. Elimination of secretions attenuated P 80-200 , P 200-300 , P 300-400 , and P 400-500 by 22.4%, 25.7%, 48.5%, and 15.3%, respectively (P = 0.002, 0.024, 0.009, and 0.016, respectively). Identifying the presence of intratracheal secretions with power ratio at 80-200 Hz and 300-400 Hz showed the highest area under the curve of 0.955 in receiver operating characteristic curve analysis. We suggest that spectral analysis of breath sounds obtained from the esophageal stethoscope might be a useful non-invasive respiratory monitor for accumulation of intratracheal secretion. Further prospective studies to evaluate the utility of acoustic analysis in surgical patients are warranted.

In this single-center, parallel, randomized controlled trial, we aim to examine the effects and safety of motion style acupuncture treatment (MSAT; a combination of acupuncture and Doin therapy) on pain reduction and functional improvement in patients with whiplash-associated disorders (WADs). Ninety-seven patients with cervical pain admitted to the Bucheon Jaseng Hospital of Korean Medicine, South Korea, due to acute whiplash injury were treated with integrative Korean medicine (IKM) with (MSAT group, 48 patients) or without (control group, 49 patients) an additional 3-day MSAT during hospitalization (5-14 days) and followed-up for 90 days. The mean numeric rating scale (NRS) scores of the MSAT and control groups at baseline were 5.67 (95% confidence interval (CI), 5.33, 6.01) and 5.44 (95% CI, 5.06, 5.82), respectively, and on day 5, 3.55 (95% CI, 3.04, 4.06) and 4.59 (95% CI, 4.10-5.07), respectively. The NRS change difference between the groups was -1.07 (95% CI, -1.76, -0.37). The rate of recovery of neck pain (NRS score change ≥ 2 points) was significantly faster in the MSAT than in the control group (log-rank test p = 0.0055). IKM treatment combined with MSAT may be effective in reducing the pain and improving the range of motion in patients with WADs.

Estrogen, produced mainly in the ovaries, plays a role in sexual development, metabolism, and bone formation. Thus, estrogen deficiency due to menopause can lead to overweight, dyslipidemia, and osteoporosis. In this study, we compared the effects of extracts of Sargassum fusiforme , Pueraria lobata , and their mixtures at various ratios on osteosarcoma SaOS-2 cells and investigated the effect of PS31 ( P. lobata : S. fusiforme  = 3:1, KGC02PS) on postmenopausal symptoms in ovariectomized rats. PS31 supplementation, as little as 100 mg/kg BW, effectively reduced ovariectomy-induced weight gain, and total triglyceride, total cholesterol, and low-density lipoprotein-cholesterol concentrations in serum. In addition, PS31 supplementation prevented bone density loss, inhibited bone resorption, and reduced the expression of catabolic factors in bone. However, PS31 supplementation did not affect uterus weight and expression of c-Jun and c-Fos, which suggests that the mechanism of action of PS31 is distinct from that of estrogen. Taken together, we demonstrated that PS31 supplementation alleviated postmenopausal symptoms, including overweight, dyslipidemia, and osteoporosis. Therefore, PS31 could be potentially used as food supplement to prevent postmenopausal symptoms.

Background: Thin-walled regions (TWRs) of aneurysm surfaces observed in microscopic surgery are thought to be vulnerable areas for growth and rupture of unruptured intracranial aneurysms (UIAs)., Objective: To identify hemodynamic features of TWRs of aneurysms by using computational fluid dynamics (CFD) analyses of unruptured middle cerebral artery bifurcation (MCAB) aneurysms., Methods: Nine patients with 11 MCAB aneurysms were enrolled, and their TWRs were identified. CFD analysis was performed using 3 parameters: pressure, wall shear stress (WSS), and WSS divergence (WSSD). Each parameter was evaluated for its correspondence with TWR., Results: Among 11 aneurysms, 15 TWRs were identified. Corresponding matches with CFD parameters (pressure, WSS, and WSSD) were 73.33, 46.67, and 86.67%, respectively., Conclusion: WSSD, a hemodynamic parameter that accounts for both magnitude and directionality of WSS, showed the highest correspondence. High WSSD might correspond with TWR of intracranial aneurysms, which are likely high-risk areas for rupture., (Copyright © 2019 by the Congress of Neurological Surgeons.)

When a one-dimensional (1D) metal array is coupled to a planar metal mirror with a dielectric gap, localized plasmon resonance is excited inside the gap at a specific polarization of light in free space. Herein, we report on the completely polarized, mid-infrared thermal radiation that is released from gap plasmon resonators with a nanometer-thick dielectric. We fabricated nanogap plasmon resonators with 1D Au or Ni array of various widths (w) using laser interference lithography. An atomic layer deposition process was used to introduce a 10 nm-thick alumina gap between a 1D metal array and a planar metal mirror. It was observed that only for the Au nanogap plasmon resonators, high-amplitude absorption peaks that were attributed to gap plasmon modes with different orders appeared at discrete wavelengths in a polarization-resolved spectrum. In addition, all the pronounced peaks were gradually redshifted with increasing w. At w = 1.2-1.6 µm, the fundamental gap plasmon mode was tuned to the main wavelengths (8-9 µm) of thermal radiation at room temperature (e.g., ∼300 K), which led to polarization-selective camouflage against standard infrared thermal imaging. The results of electromagnetic simulations quantitatively agreed with the measured absorbance spectra in both peak wavelength and amplitude. We believe that these experimental efforts towards achieving radiation/absorption spectra tailored at mid-infrared wavelengths will be further exploited in thermal-radiation harnessed energy devices, spectroscopic sensors, and radiative coolers.

Background and Aims: Enhanced sympathetic nervous activation and peripheral vasodilation in end-stage liver disease (ESLD) may limit the importance of left ventricular ejection fraction (LVEF) as an influential prognosticator. We sought to understand the LVEF and cardiac dimensions in ESLD patients in order to define the LVEF threshold to predict all-cause mortality after liver transplantation (LT)., Approach and Results: Data were collected prospectively from the Asan LT Registry between 2008 and 2016, and outcomes were retrospectively reviewed. LVEF, end-diastolic volume index (EDVI), and end-diastolic elastance (Eed) were measured by preoperative echocardiography. Of 2,799 patients, 452 (16.2%) had LVEF ≤ 60%, with 29 (1.0%) having LVEF < 55% and 269 (9.6%) had LVEF ≥ 70%. Over a median of 5.4-year follow-up, 329 (11.8%) patients died: 104 (3.7%) died within 90 days. LVEF (range, 30%-81%) was directly proportionate to Model for End-stage Liver Disease (MELD) scores, an index of liver disease severity, in survivors but showed a fixed flat-line pattern in nonsurvivors (interaction P = 0.004 between groups), with lower EDVI (P = 0.013) and higher Eed (P = 0.001) in the MELD ≥ 20 group. Patients with LVEF ≤ 60% had higher 90-day (13% vs. 7.4%; log rank, P = 0.03) and median 5.4-year (26.7% vs. 16.2%; log rank, P = 0.003) mortality rates in the MELD ≥ 20 group, respectively, compared to those with LVEF > 60%. Specifically, in the MELD > 35 group, median 5.4-year mortality rate was 53.3% in patients with LVEF ≤ 60% versus 24% in those with LVEF > 60% (log rank P < 0.001). By contrast, mortality rates of LVEF ≤ 60% and > 60% were similar in the MELD < 20 group (log rank P = 0.817)., Conclusions: LVEF ≤ 60% is strongly associated with higher post-LT mortality rates in the MELD ≥ 20 group, indicating the need to appraise both LVEF and liver disease severity simultaneously. Enhanced diastolic elastance with low EDVI provides insights into pathogenesis of low LVEF in nonsurvivors with MELD ≥ 20., (© 2019 by the American Association for the Study of Liver Diseases.)

Several treatment modalities have been proposed for foraminal stenosis, but the treatment options remain unsatisfactory. Previous studies have shown that transforaminal balloon adhesiolysis may be effective in patients with refractory lumbar foraminal stenosis. However, in patients with a high iliac crest, balloon catheter insertion may be difficult via a conventional transforaminal approach (particularly targeting the L5-S1 foramen). It has been reported that an epidural catheter can be placed easily by a contralateral interlaminar retrograde foraminal approach. Therefore, we applied this approach to L5-S1 transforaminal balloon adhesiolysis in patients with a high iliac crest. We retrospectively analyzed data from 22 patients who underwent combined epidural adhesiolysis and balloon decompression (balloon adhesiolysis) using the novel foraminal balloon catheter via a contralateral interlaminar retrograde foraminal approach. The pain intensity significantly decreased over the three-month period after balloon adhesiolysis ( p < 0.001). There were no complications associated with the balloon procedure. The present study suggests that balloon adhesiolysis for L5-S1 foramen via a contralateral interlaminar retrograde foraminal approach may be an effective alternative for patients with a high iliac crest and refractory lumbar radicular pain due to lumbar foraminal stenosis. In addition, detailed procedural aspects are described here., Competing Interests: The authors declare no conflict of interest.

Objective: This study aimed to assess the effects of remote ischemic preconditioning (RIPC) on liver function in donors and recipients after living donor liver transplantation (LDLT)., Background: Ischemia reperfusion injury (IRI) is known to be associated with graft dysfunction after liver transplantation. RIPC is used to lessen the harmful effects of IRI., Methods: A total of 148 donors were randomly assigned to RIPC (n = 75) and control (n = 73) groups. RIPC involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to the upper arm, followed by 5-minute reperfusion with cuff deflation. The primary aim was to assess postoperative liver function in donors and recipients and the incidence of early allograft dysfunction and graft failure in recipients., Results: RIPC was not associated with any differences in postoperative aspartate aminotransferase (AST) and alanine aminotransferase levels after living donor hepatectomy, and it did not decrease the incidence of delayed graft hepatic function (6.7% vs 0.0%, P = 0.074) in donors. AST level on postoperative day 1 [217.0 (158.0, 288.0) vs 259.5 (182.0, 340.0), P = 0.033] and maximal AST level within 7 postoperative days [244.0 (167.0, 334.0) vs 296.0 (206.0, 395.5), P = 0.029) were significantly lower in recipients who received a preconditioned graft. No differences were found in the incidence of early allograft dysfunction (4.1% vs 5.6%, P = 0.955) or graft failure (1.4% vs 5.6%, P = 0.346) among recipients., Conclusions: RIPC did not improve liver function in living donor hepatectomy. However, RIPC performed in liver donors may be beneficial for postoperative liver function in recipients after living donor liver transplantation.