Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.

INTRODUCTION: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). METHODS: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. RESULTS: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). CONCLUSION: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Role of oxygen reserve index monitoring in patients undergoing robot-assisted radical prostatectomy: a retrospective study.

PURPOSE: Robot-assisted radical prostatectomy (RARP) is a common surgical procedure for the treatment of prostate cancer. Although beneficial, it can lead to intraoperative hypoxia due to high-pressure pneumoperitoneum and Trendelenburg position. This study explored the use of oxygen reserve index (ORi) to monitor and predict hypoxia during RARP. METHODS: A retrospective analysis was conducted on 329 patients who underwent RARP at the Seoul National University Bundang Hospital between July 2021 and March 2023. Various pre- and intraoperative variables were collected, including ORi values. The relationship between ORi values and hypoxia occurrence was assessed using receiver operating characteristic curves and logistic regression analysis. RESULTS: Intraoperative hypoxia occurred in 18.8% of the patients. The receiver operating characteristic curve showed a satisfactory area under the curve of 0.762, with the ideal ORi cut-off value for predicting hypoxia set at 0.16. Sensitivity and specificity were 64.5% and 75.7%, respectively. An ORi value of < 0.16 and a higher body mass index were identified as independent risk factors of hypoxia during RARP. CONCLUSIONS: ORi monitoring provides a non-invasive approach to predict intraoperative hypoxia during RARP, enabling early management. Additionally, the significant relationship between a higher body mass index and hypoxia underscores the importance of individualized patient assessment.

Predictors of sleep quality components in patients undergoing transarterial chemoembolisation: a cross-sectional study.

PURPOSE: Patients undergoing transarterial chemoembolisation experience postembolisation symptoms and interferences affecting sleep quality, which require intervention. The study aimed to identify the predictors of sleep quality components in patients undergoing transarterial chemoembolisation. METHODS: This study included two groups of participants: 50 patients undergoing transarterial chemoembolisation and 45 nurses caring for them. Data were collected from September to November 2022 using a structured questionnaire, and analysed using descriptive statistics, the t-test, analysis of variance, Spearman's rank correlation, and multiple regression analysis using the SPSS 27.0 program (IBM Corp., Armonk, NY, USA). RESULTS: The mean sleep quality score was 40.28±14.10. Heat sensation (t=-2.08, p=.043) and fatigue (t=-4.47, p<.001) predicted sleep fragmentation in 38.6% of the patients. Abdominal pain (t=-2.54, p=.014), vomiting (t=-2.21, p=.032), and the expected fatigue by the nurses (t=2.68, p=.014) predicted sleep length in 41.7% of patients. Abdominal pain (t=-2.05, p=.046) explained 42.9% of sleep depth. CONCLUSION: Based on the predictors of sleep quality components obtained in this study, strategies to improve sleep quality tailored to patients undergoing transarterial chemoembolisation should be developed. This study highlighted the need to bridge the gap between patients' and nurses' expected fatigue and its contribution to sleep fragmentation and sleep length. It also highlighted the importance of noncontact temperature measurement, controlling vomiting, and pain relief for improving sleep length in patients undergoing transarterial chemoembolisation.

Comparison of Volatile Anesthetics Versus Propofol on Postoperative Cognitive Function After Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of volatile anesthetics and propofol on neurocognitive function after cardiac surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. SETTING: A literature search of PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted. PARTICIPANTS: A total of 10 randomized controlled trials comparing volatile anesthetics and propofol in cardiac surgery were included in the study. INTERVENTIONS: The standardized mean difference and risk ratio were calculated to estimate pooled effect sizes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the postoperative neurocognitive function score, and the secondary outcome was the incidence of delirium after cardiac surgery. The analysis did not show significant differences in postoperative neurocognitive function scores (standardized mean difference -0.06, 95% CI -0.81-0.69; p = 0.879). The incidences of delirium (risk ratio 1.10, 95% CI 0.81-1.50) between the volatile anesthetics and propofol groups were not significant (p = 0.533). CONCLUSIONS: Unlike noncardiac surgery, there are no differences between volatile anesthetics and propofol regarding postoperative neurocognitive dysfunction after cardiac surgery.

The Effect of Remimazolam on Seizure Profile, Hemodynamics, and Recovery in Patients With Electroconvulsive Therapy Comparison With Propofol and Etomidate: A Retrospective Study.

OBJECTIVES: To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate. METHODS: A total of 49 patients who underwent 405 ECT treatment sessions under general anesthesia were retrospectively analyzed. Remimazolam, propofol, and etomidate were used for 93, 138, and 174 ECT sessions, respectively. The primary outcome was durations of motor and electroencephalogram (EEG) seizure activity, whereas secondary outcomes included hemodynamics (ie, mean arterial pressure [MAP] and heart rate [HR] at various time points from induction to postanesthesia care unit [PACU] discharge), antihypertensive drugs administration after electrical stimulus, and recovery profiles (ie, length of PACU stay and incidence of postictal confusion). RESULTS: Durations of motor and EEG seizures were shorter for remimazolam than etomidate (motor, P < 0.001; EEG, P = 0.003) but similar compared with propofol (motor, P = 0.191; EEG, P = 0.850). During seizure, remimazolam showed a comparable MAP and HR to etomidate (MAP: P = 0.806; HR: P = 0.116). The antihypertensive drug use was lowest for remimazolam (6.8%), followed by propofol (35.6%) and etomidate (65.6%), and the mean length of PACU stay was comparable for remimazolam (19.7 min), propofol (22.8 min), and etomidate (24.5 min). The occurrence of postictal confusion did not differ among the 3 agents (P > 0.050). CONCLUSIONS: Remimazolam is a promising anesthetic option for ECT because of its comparable seizure profiles, stable hemodynamics, and comparable PACU stay when compared with propofol and etomidate without additional adverse events.

Artificial intelligence model predicting postoperative pain using facial expressions: a pilot study.

PURPOSE: This study aimed to assess whether an artificial intelligence model based on facial expressions can accurately predict significant postoperative pain. METHODS: A total of 155 facial expressions from patients who underwent gastric cancer surgery were analyzed to extract facial action units (AUs), gaze, landmarks, and positions. These features were used to construct various machine learning (ML) models, designed to predict significant postoperative pain intensity (NRS ≥ 7) from less significant pain (NRS < 7). Significant AUs predictive of NRS ≥ 7 were determined and compared to AUs known to be associated with pain in awake patients. The area under the receiver operating characteristic curves (AUROCs) of the ML models was calculated and compared using DeLong's test. RESULTS: AU17 (chin raising) and AU20 (lip stretching) were found to be associated with NRS ≥ 7 (both P ≤ 0.004). AUs known to be associated with pain in awake patients did not show an association with pain in postoperative patients. An ML model based on AU17 and AU20 demonstrated an AUROC of 0.62 for NRS ≥ 7, which was inferior to a model based on all AUs (AUROC = 0.81, P = 0.006). Among facial features, head position and facial landmarks proved to be better predictors of NRS ≥ 7 (AUROC, 0.85-0.96) than AUs. A merged ML model that utilized gaze and eye landmarks, as well as head position and facial landmarks, exhibited the best performance (AUROC, 0.90) in predicting significant postoperative pain. CONCLUSION: ML models using facial expressions can accurately predict the presence of significant postoperative pain and have the potential to screen patients in need of rescue analgesia. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov (NCT05477303; date: June 17, 2022).

Effect of Pethidine Injection on the Duration of Labor and Pregnancy Outcomes: A Retrospective Cohort Study.

Background and Objectives: Long and ineffective labor causes hardships for mothers and doctors and increases the rate of cesarean sections and medical comorbidities. Several factors contribute to effective and less painful labor, including maternal age, parity, fetal characteristics, and the medications or procedures that obstetricians use for labor. We aimed to study the factors that affect labor duration and identify those that make labor more effective. Materials and Methods: This retrospective study included 141 patients who underwent normal vaginal deliveries at the Daegu Catholic University Medical Center between April 2013 and April 2022. Among the 141 patients, 44 received pethidine intravenously, 88 received oxytocin intravenously, and 64 received epidural anesthesia. The duration of the active phase and second stage of labor were recorded according to the findings of a manual examination of the cervix and continuous external electronic monitoring. We analyzed maternal and neonatal medical records and performed binomial logistic regression to identify the factors associated with a shorter active phase of labor. The clinical outcomes in mothers and neonates were also evaluated. Results: Among the various clinical factors, multiparity (odds ratio of parity 0.325) and the use of pethidine (odds ratio 2.906) were significantly associated with shortening the active phase of labor to less than 60 min. The use of epidural anesthesia or oxytocin was not significantly associated with reducing the active phase of labor. When patients were divided into two groups based on whether a pethidine injection had been used during labor, the duration of the active phase was shorter in the pethidine injection group than in the control group for both nulliparas and multiparas. No significant differences in the duration of the second stage of labor were observed between the pethidine injection and control groups. There were no significant differences in pregnancy outcomes, including the need for mechanical ventilation of neonates, Apgar scores, neonatal intensive care unit admissions, number of precipitous deliveries, maternal adverse side effects of drugs, or duration of maternal hospitalization between the two groups. Conclusions: Pethidine can be safely administered to women during labor to help reduce the duration of the active phase by promoting dilatation of the cervix and preventing complications that may result from prolonged labor. Pethidine may be helpful, especially for those who cannot receive epidural anesthesia or who cannot afford it. However, large-scale randomized controlled studies are required to evaluate the efficacy and safety of this drug during labor. Furthermore, it would be helpful if various studies were conducted depending on the timing of administration and indications for delivery.

Cooperative Assembly of Self-Adjusting α-Helical Coiled Coils along the Length of an mRNA Chain to Form a Thermodynamically Stable Nanotube Carrier.

Although mRNA delivery technology is very promising, problems in safety and transport arise due to the intrinsically low thermodynamic stability of the current mRNA carriers. Considering that mRNAs are filamentous and a nanotube is one of the most thermodynamically stable shapes among nanoassemblies, a nanotube is one of the most stable supramolecular structures that can be assembled with mRNA. Here, we develop a nanotube-shaped filamentous mRNA delivery platform that shows exceptionally high thermodynamic stability. The key to the development of the mRNA nanotube is the design of self-adjusting supramolecular building blocks (SABs) that have two disparate properties, i.e., dynamic property and stiffness, in a single molecule. The counterbalance of the dynamic property and stiffness in SABs enables the coating of mRNA by winding its way through the flexible and irregular mRNA chain via cooperative interactions. SAB nanotubes with targeting ligands installed show a high uptake efficiency in mammalian cells and controllable gene expression behavior. Thus, the mRNA nanotube provides an enabling technology toward the development of safe and stable mRNA vaccines and therapeutics.

The Involvement of the Hypothalamus-Pituitary-Adrenal Axis in the Development of Hyperalgesia during the Early Postoperative Period.

INTRODUCTION: Hyperalgesia frequently occurs after surgery and is associated with adverse effects on surgical outcomes. Thus, we aimed to examine whether the hypothalamus-pituitary-adrenal (HPA) axis function after surgery is involved in the development of postoperative hyperalgesia. METHODS: Surgery- and pain-related variables were measured 24 and 48 h after the first and second total knee arthroplasties (TKAs) in postmenopausal patients undergoing 1-week-interval staged bilateral TKA. Two sets of saliva samples were consecutively collected from patients before (pre-T1) and 1 week after (post-T1) the first TKA (n = 69). HPA axis function was analyzed in a subgroup of 20 patients with a typical cortisol awakening response (CAR) in both the sets of saliva samples. RESULTS: Surgery-related variables were comparable between the first and second TKAs. However, pain-related variables (pain ratings and the amount of opioid analgesics consumed) were greater after the second than the first TKA. Cortisol and dehydroepiandrosterone (DHEA) secretion during the post-awakening period (CARauc and Daucawk, respectively) was higher at post-T1 than at pre-T1, but the molar CARauc/Daucawk ratio was comparable between the time points examined. No relationship was observed between the pre-T1 CARauc and pain ratings after the first TKA. However, post-T1 CARauc showed a positive correlation with pain ratings after the second TKA. Postoperative pain ratings were negatively correlated with Daucawk and positively correlated with the molar CARauc/Daucawk ratio at all examined time points. DISCUSSION/CONCLUSION: The results suggest that adrenocortical steroidogenic activity favoring the production of cortisol over DHEA after surgery may contribute to the development of hyperalgesia during the early postoperative period.

Comparison between ketorolac- and fentanyl-based patient-controlled analgesia for acute kidney injury after robot-assisted radical prostatectomy: a retrospective propensity score-matched analysis.

PURPOSE: It is unclear whether ketorolac-based patient-controlled analgesia (PCA) leads to acute kidney injury (AKI) after robot-assisted radical prostatectomy (RARP) in patients susceptible to AKI. We compared the postoperative AKI incidence with ketorolac- and fentanyl-based PCA after RARP. METHODS: After medical record review, eligible patients were divided in ketorolac and fentanyl groups. We conducted propensity score matching of 3239 patients and assigned 641 matched patients to each group, and compared the AKI incidence. We investigated potential risk factors for postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria. We collected preoperative data (age, height, weight, body mass index, American Society of Anesthesiologists physical status, medical history, creatinine level, estimated glomerular filtration rate, and hemoglobin level) and intraoperative data (maintenance anesthetics, surgery duration, anesthesia duration, crystalloid amount, colloid use, total amount of fluid administered, estimated blood loss, norepinephrine use, phenylephrine use, and PCA type). RESULTS: The postoperative AKI incidence was significantly higher in the ketorolac than in the fentanyl group, both before (31.1% vs. 20.4%; p < 0.001) and after (31.5% vs. 22.6%; p < 0.001) matching. In the univariate analysis, ketorolac was significantly associated with postoperative AKI, both before (odds ratio [OR], 1.762; 95% confidence interval [CI], 1.475-2.105; p < 0.001) and after (OR, 1.574; 95% CI, 1.227-2.019; p < 0.001) matching. In the multivariate analysis, ketorolac-based PCA was independently associated with development of postoperative AKI in the matched groups (OR, 1.659; 95% CI, 1.283-2.147; p < 0.001). CONCLUSION: Ketorolac-based PCA may increase postoperative AKI incidence after RARP; thus, renal function should be monitored in these patients.

Effect of the Paravertebral Block on Chronic Postsurgical Pain After Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to identify the benefits of thoracic paravertebral block (PVB) by focusing on its role in reducing chronic postsurgical pain (CPSP) after thoracic surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, were searched to identify studies. PARTICIPANTS: Patients undergoing thoracic surgeries. INTERVENTION: Paravertebral block for postoperative analgesia. MEASUREMENT AND MAIN RESULTS: A total of 1,028 adult patients from 10 RCTs were included in the final analysis. The incidence of CPSP at 3 months after surgery was not reduced in the PVB group compared with the no-block (odds ratio [OR] 0.59, 95% CI 0.34-1.04; p = 0.07; I2 = 6.96%) and other-block (OR 1.39, 95% CI 0.30-6.42; p = 0.67; I2 = 77.75%) groups. The PVB did not significantly reduce the incidence of CPSP after 6 months from surgery when compared with no block (OR 0.44, 95% CI 0.08-2.53; p = 0.36; I2 = 87.53%) and other blocks (OR 1.17, 95% CI 0.71-1.95; p = 0.93; I2 = 45.75%). The PVB significantly decreased postoperative pain at 24 and 48 hours at rest compared with the no- block group. The pain score was higher in the PVB group than in the other block groups 48 hours after surgery at rest. CONCLUSIONS: Thoracic PVB does not prevent CPSP after thoracic surgery. Further large RCTs are required to confirm and validate the authors' results.

Psychometric validation of the Korean Pressure Ulcer Knowledge Assessment Tool.

OBJECTIVE: The purpose of this study was to evaluate the psychometric properties, including content validity, validity of multiple choice items, and the reliability of the Korean version of the Pressure Ulcer Knowledge Assessment Tool (K-PUKAT 2.0), using classical test theory (CTT) and item response theory (IRT). METHOD: Linguistic validation process and factor analysis were conducted among wound care nurses, staff nurses and nursing students. Items were analysed according to the CTT and IRT using a two-parameter logistic model. Intraclass correlation coefficients were used to examine reliability. RESULTS: A total of 378 wound care nurses, staff nurses and nursing students participated in this study. While most items showed moderate difficulty based on the CTT, difficulty index values based on the IRT were more broadly distributed (low: 5 items; moderate: 9 items; high: 1 item). The intraclass correlation coefficient for K-PUKAT 2.0 was 0.72. CONCLUSION: The K-PUKAT 2.0 demonstrated concise and good psychometric properties. Based on the results of this study, repetitive use of K-PUKAT 2.0 will not only help in distinguishing whether an individual has sufficient clinical knowledge, but will also play a key role in supporting learning.

Association between Patients' Self-Judgement, Coagulated Menstrual Blood, and Menorrhagia: Results from a Questionnaire Survey and Blood Test Analysis.

Background and Objectives: Menorrhagia is defined as a blood loss of more than 80 mL, which is significant enough to cause anemia. Previously known methods for evaluating menorrhagia, such as the alkalin-hematin method, pictograms, and measuring the weight of sanitary products, were all impractical, complex, and time-consuming. Therefore, this study aimed to determine which item among menstrual history taking was most associated with menorrhagia and devised a simple evaluating method for menorrhagia through history taking that can be applied clinically. Materials and Methods: The study was conducted from June 2019 to December 2021. A survey was conducted on premenopausal women who underwent outpatient treatment or surgery and those who underwent a gynecologic screening test, and their blood tests were analyzed. The presence of iron deficiency anemia was identified with a Hb level of less than 10 g/dL with microcytic hypochromic anemia on a complete blood count performed within one month of the survey. A questionnaire survey was conducted on six items related to menorrhagia to investigate whether each item was related to "significant menorrhagia". Results: There were 301 participants in the survey during the period. In univariate analysis, the results revealed a statistically significant association between significant menorrhagia and the following items: self-judgement of menorrhagia; menstruation lasting over 7 days; total pad counts in a single menstrual period; Number of sanitary products changed per day; and leakaging of menstrual blood and presence of coagulated menstrual blood. In multivariate analysis, only the "self-judgement of menorrhagia" item showed a statistically significant result (p-value = 0.035; an odds ratio = 2.217). When the "self-judgement of menorrhagia" item was excluded, the "passage of clots larger than one inch in diameter" item showed a statistically significant result (p-value = 0.023; an odds ratio = 2.113). Conclusions: "Patient self-judgement of menorrhagia" is a reliable item for evaluating menorrhagia. Among several symptoms indicating menorrhagia, determining the presence of the "passage of clots larger than one inch in diameter" during the menstrual period is the most useful item for evaluating menorrhagia in clinical history taking. This study suggested using these simple menstrual history taking items to evaluate menorrhagia in real clinical practice.

Pseudo-Isolated α-Helix Platform for the Recognition of Deep and Narrow Targets.

Although interest in stabilized α-helical peptides as next-generation therapeutics for modulating biomolecular interfaces is increasing, peptides have limited functionality and stability due to their small size. In comparison, α-helical ligands based on proteins can make steric clash with targets due to their large size. Here, we report the design of a monomeric pseudo-isolated α-helix (mPIH) system in which proteins behave as if they are peptides. The designed proteins contain α-helix ligands that do not require any covalent chemical modification, do not have frayed ends, and importantly can make sterically favorable interactions similar to isolated peptides. An optimal mPIH showed a more than 100-fold increase in target selectivity, which might be related to the advantages in conformational selection due to the absence of frayed ends. The α-helical ligand in the mPIH displayed high thermal stability well above human body temperature and showed reversible and rapid folding/unfolding transitions. Thus, mPIH can become a promising protein-based platform for developing stabilized α-helix pharmaceuticals.

Direct Observation of Orbital Driven Strong Interlayer Coupling in Puckered Two-Dimensional PdSe2.

Interlayer coupling between individual unit layers is known to be critical in manipulating the layer-dependent properties of two-dimensional (2D) materials. While recent studies have revealed that several 2D materials with significant degrees of interlayer interaction (such as black phosphorus) show strongly layer-dependent properties, the origin based on the electronic structure is drawing intensive attention along with 2D materials exploration. Here, the direct observation of a highly dispersive single electronic band along the interlayer direction in puckered 2D PdSe2 as an experimental hallmark of strong interlayer couplings is reported. Remarkably large band dispersion along the kz -direction near Fermi level, which is even wider than the in-plane one, is observed by the angle-resolved photoemission spectroscopy measurement. Employing X-ray absorption spectroscopy and density functional theory calculations, it is revealed that the strong interlayer coupling in 2D PdSe2 originates from the unique directional bonding of Pd d orbitals associated with unexpected Pd 4d9 configuration, which consequently plays a decisive role for the strong layer-dependency of the band gap.

Incidental Thyroid Nodule on Chest Computed Tomography: Application of Computed Tomography Texture Analysis in Prediction of Ultrasound Classification.

OBJECTIVE: The aim of the study was to evaluate the value of computed tomography (CT) texture analysis (CTTA) in predicting ultrasound (US) classification of incidentally detected thyroid nodule (ITN) on chest CT. METHODS: A total of 117 ITNs (≥1 cm in the longest diameter) on chest CT scan of 107 patients was divided into 4 categories according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification on recent thyroid US within 3 months. Computed tomography texture features were extracted with or without filtration using commercial software. The texture features were compared between the benign (K-TIRADS 2; n = 21) and the suspicious (K-TIRADS 3, 4, 5; n = 96) nodules. Multivariate regression and area under the receiver operating characteristic curve analysis were performed to determine significant prediction factors of the suspicious nodules. RESULTS: The mean value of positive pixels was significantly higher in the suspicious nodules except the unfiltered image (P < 0.05). Entropy of the suspicious nodules was significantly higher with unfiltered and fine filters (P < 0.05), and kurtosis of the suspicious nodules was significantly higher with medium and coarse filters (P < 0.05). A logistic regression model incorporating mean value of positive pixels and kurtosis with a medium filter using volumetric analysis demonstrated the best performance to predict the suspicious nodules with an area under the receiver operating characteristic curve of 0.842 (P < 0.001, sensitivity 82.3%, and specificity 81.0%). CONCLUSIONS: Computed tomography texture analysis for ITN larger than 1 cm showed significant correlation with systematic thyroid US classification and presented excellent performance to predict the suspicious nodules.

Early fluid management affects short-term mortality in patients with end-stage kidney disease undergoing chronic hemodialysis and requiring continuous renal replacement therapy.

BACKGROUND: Early fluid management is considered a key element affecting mortality in critically ill patients requiring continuous renal replacement therapy (CRRT). Most studies have primarily focused on patients with intrinsic acute kidney injury requiring CRRT, although end-stage kidney disease (ESKD) patients generally exhibit greater vulnerability. We investigated the association between fluid balance and short-term mortality outcomes in ESKD patients undergoing chronic hemodialysis and requiring CRRT. METHODS: This retrospective study included 110 chronic hemodialysis patients who received CRRT between 2017 and 2019 at Ewha Womans University Mokdong Hospital. The amounts of daily input and output, and cumulative 3-day and 7-day input and output, were assessed from the initiation of CRRT. The participants were classified into two groups based on 7-day and 14-day mortalities. Cox regression analyses were carried out on the basis of the amounts of daily input and output, cumulative input and output, and cumulative fluid balance. RESULTS: During follow-up, 7-day and 14-day mortalities were observed in 24 (21.8%) and 34 (30.9%) patients. The patients were stratified into two groups (14-day survivors vs. non-survivors), and there were no significant differences in demographic characteristics between the two groups. However, diabetes mellitus was more common among survivors than among non-survivors. Univariate analyses showed that the amounts of daily output at 48, and 72 h, and 3-day cumulative input and output, were significantly associated with 7-day mortality risk regardless of the cumulative fluid balance (HR: 0.28, 95% CI: 0.12-0.70, p = 0.01 for daily output at 48 h; HR: 0.34, 95% CI: 0.13-0.85, p = 0.02 for daily output at 72 h.; HR: 0.72, 95% CI: 0.61-0.86, p = 0.01 for 3-day cumulative input; HR: 0.65, 95% CI: 0.41-0.90, p = 0.01 for 3-day cumulative output). Adjusted multivariate analyses showed that the lower 3-day cumulative output is an independent risk factor for 7-day and 14-day mortality. CONCLUSIONS: In our study, increased cumulative output were significantly associated with reduced short-term mortality risk in chronic hemodialysis patients undergoing CRRT regardless of cumulative fluid balance. Further prospective studies to investigate the association between fluid balance and mortality in ESRD patients requiring CRRT are warranted.

Efficacy of Erector Spinae Plane Block for Analgesia in Thoracic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study was to determine whether erector spinae plane block (ESPB) can provide an effective analgesia for managing pain after thoracic surgery and compare the efficacy of ESPB with that of other regional analgesic techniques. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science were searched. PARTICIPANTS: Patients undergoing thoracic surgeries. INTERVENTION: Erector spinae plane block with local anesthetics for postoperative analgesia. MEASUREMENT AND MAIN RESULTS: Seventeen studies, including 1,092 patients, were included in the final analysis. Erector spinae plane block reduced 24-hour postoperative opioid consumption (mean difference [MD] -17.49, 95% CI -26.87 to -8.12), pain score at rest (MD -0.82, 95% CI -1.31 to -0.33), and pain score at movement (MD -0.77, 95% CI -1.20 to -0.3) compared to no block. Compared with other regional blocks, various results have been observed. Although statistical results showed that ESPB is inferior to thoracic paravertebral block and intercostal nerve block and superior to serratus anterior plan block in postoperative analgesia, clinical differences remain unclear. The incidence of hematoma was lower in the ESPB group than in the other groups (odds ratio 0.19, 95% CI 0.05-0.73). CONCLUSION: Erector spinae plane block may provide effective analgesia after thoracic surgery. Compared with other techniques, it is a safer method, without clinically important differences, for postoperative pain control. Therefore, ESPB may be considered as a valuable option for postoperative pain management after thoracic surgery.

Pigmentation and Flavonoid Metabolite Diversity in Immature 'Fuji' Apple Fruits in Response to Lights and Methyl Jasmonate.

Artificial pigmentation of apple fruits has been intensely evaluated to generate less pigmented red apples, which are profitable because of the changes in fruit quality. In this study, we analyzed the diversity of flavonoids and the patterns of flavonoid metabolic gene expression under light irradiation with or without methyl jasmonate (MeJA) treatment in immature (S1) and color-turning (S2) staged 'Fuji' apples. Further, we assessed the metabolic regulation at the gene level between anthocyanin and flavonol in light-responsive apple skins. UV-B exposure within 3 days was found to significantly stimulate anthocyanin accumulation in apple skin compared to other light exposure. S1 skin was more sensitive to UV-B and MeJA treatment, in the aspect of indaein accumulation. The enhancement of apple pigmentation following treatment with adequate levels of UV-B and MeJA was maximized at approximately 72 h. Red (range from 4.25 to 17.96 µg·g-1 DW), blue (range from 4.59 to 9.17 µg·g-1 DW) and UV-A (range from 3.98 to 19.12 µg·g-1 DW) lights contributed to the induction of idaein content. Most genes related to the flavonoid pathways increased their expression under UV-B exposure, including the gene expression of the transcription factor, MdMYB10, a well-known upstream factor of flavonoid biosynthesis in apples. The boosted upregulation of MdMYB10, MdCHS, MdF3H MdLDOX, and MdUFGT genes due to MeJA in UV-B was found and may contribute the increase of idaein. UV-A and UV-B caused higher quercetin glycoside content in both S1 and S2 apple skins than longer wavelengths, resulting in significant increases in quercetin-3-O-galactoside and quercetin-3-O-glucoside. These results suggest that the application of adequate UV-B with MeJA in less-pigmented postharvest apples will improve apple color quality within a short period.

Targeted Drug Delivery Biopolymers Effectively Inhibit Breast Tumor Growth and Prevent Doxorubicin-Induced Cardiotoxicity.

The anticancer agent doxorubicin(dox) has been widely used in the treatment of a variety of hematological malignancies and solid tumors. Despite doxorubicin's efficiency in killing tumor cells, severe damage to healthy tissues, along with cardiotoxicity, limits its clinical use. To overcome these adverse side effects, improve patient safety, and enhance therapeutic efficacy, we have designed a thermally responsive biopolymer doxorubicin carrier that can be specifically targeted to tumor tissue by locally applying mild hyperthermia (41 °C). The developed drug vehicle is composed of the following: a cell penetrating peptide (SynB1) to promote tumor and cellular uptake; thermally responsive Elastin-like polypeptide (ELP); and the (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH) containing a pH-sensitive hydrazone linker that releases doxorubicin in the acidic tumor environment. We used the in vivo imaging system, IVIS, to determine biodistribution of doxorubicin-delivered ELP in MDA-MB-231 xenografts in nude mice. Tumor bearing mice were treated with a single IV injection of 10 mg/kg doxorubicin equivalent dose with free doxorubicin, thermally responsive SynB1 ELP 1-DOXO, and a thermally nonresponsive control biopolymer, SynB1 ELP 2-DOXO. Following a 2 h treatment with hyperthermia, tumors showed a 2-fold higher uptake when treated with SynB1 ELP 1-DOXO compared to free doxorubicin. Accumulation of the thermally non-responsive control SynB1 ELP2 -DOXO was comparable to free doxorubicin, indicating that an increase in dox accumulation with ELP is due to aggregation in response to thermal targeting. Higher levels of SynB1 ELP1-DOXO and SynB1 ELP2 -DOXO with respect to free doxorubicin were observed in kidneys. Fluorescence intensity from hearts of animals treated with SynB1 ELP1-DOXO show a 5-fold decrease in accumulation of doxorubicin than the same dose of free doxorubicin. SynB1-ELP1-DOXO biopolymers demonstrated a 6-fold increase in tumor/heart ratio in comparison to free doxorubicin, indicating preferential accumulation of the drug in tumors. These results demonstrate that thermally targeted polymers are a promising therapy to enhance tumor targeting and uptake of anticancer drugs and to minimize free drug toxicity in healthy tissues, representing a great potential for clinical application.