Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Rapid investigating of phase I metabolites of SR9009 in vitro horse liver microsomes via feature-based molecular networking approach: Potential applications in doping control.

SR9009, a peroxisome proliferator-activated receptor δ (PPARδ) agonist, is known for its potential benefits in energy homeostasis. It failed to receive the United States Food and Drug Administration (USFDA) approval and its illegal distribution has raised concerns. As a result, it has been classified as a prohibited substance by the World Anti-Doping Agency and the International Federation of Horseracing Authorities (IFHA). This study emphasizes the application of the in-silico molecular networking technology to analyze phase I drug metabolites in horses, distinguishing it from conventional methodologies in forensic science. Feature-based molecular networking (FBMN) analysis identified 15 metabolites, with novel major N-dealkylated metabolite (-C8H7NO4S), indicative of diverse metabolic modifications in horse liver microsomes incubation assay. Additionally, a proposed metabolic pathway of SR9009 in the in vitro assay was outlined, including the previously known dehydroxylated metabolite. Finally, the metabolic pathways included in this study were as follows: hydroxylation, dehydrogenation, N-dealkylation dihydroxylation, and combinations. Molecular networking provided insights into MS spectra connectivity, facilitating rapid interpretation and accurate detection of previously undiscovered metabolites. In conclusion, this study contributes to the understanding of SR9009 metabolism in horses and underscores the importance of advanced analytical techniques, such as molecular networking, in enhancing the accuracy and efficiency of metabolite analysis for forensic and doping control purposes.

Effects of dexmedetomidine on renal function after cardiac surgery for infective endocarditis: An interim analysis of a randomized controlled trial.

BACKGROUND: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE. METHODS: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 µg kg-1 h-1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and ß = 0.2. RESULTS: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups. CONCLUSIONS: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels.

The Barriers to Recognizing and Reporting Child Physical Abuse by Emergency Physicians and Associated Factors.

BACKGROUND: Although the reporting rate of child abuse is increasing every year, the child abuse detection rate is 3.81% as of 2019 in Korea, which is significantly lower than that of developed countries for child rights. OBJECTIVE: We investigated the associated factors with barriers that emergency physicians face in recognizing and reporting cases of child abuse. METHODS: From May to July 2022, 240 emergency physicians working in the 15 emergency department were asked to participate in the survey via email. The questionnaire included the respondent's basic information, treatment experience for child abuse, reasons for reporting or not reporting, and opinions on measures to increase the reporting rate. We conducted a logistic regression analysis to discern the factors contributing to underreporting. RESULTS: Seventy-one individuals were included in the analysis, after excluding those who had never encountered suspected cases of child abuse. A multivariable logistic regression was performed with the above variables, and although it was not statistically significant, there was a tendency for workers to report well when working at a pediatric emergency department (odds ratio [95% confidence interval], 3.97 [0.98-16.09]). The primary reason for reporting suspected abuse was the pattern of damage suspected of abuse. The first reason for not reporting suspected abuse was because they were not sure it was child abuse. Respondents answered that to report better, a quick and appropriate response from the police and confidentiality of the reporter were needed. CONCLUSIONS: Physicians in pediatric emergency departments demonstrated a tendency for more proactive reporting suspected cases of child abuse.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury.

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

The impact of the administration of red ginseng (Panax ginseng) on lipid metabolism and free fatty acid profiles in healthy horses using a molecular networking approach.

This study investigated the potential benefits of the administration of red ginseng (RG) on lipid metabolism and the profiles of individual free fatty acids (FFAs) in healthy horses. Eight healthy horses, raised under similar conditions, were randomly divided into two groups, each comprising four horses. The experimental group received powdered RG (600 mg/kg/day) mixed with a carrier, and the control group received only the carrier. The parameters associated with lipid metabolism and probable adverse effects were evaluated in both groups after 3 weeks. The computational molecular networking (MN) approach was applied to analyze the FFA profiles. The results indicated that RG administration significantly reduced blood triglyceride levels in the experimental group. Analysis of the FFAs using MN revealed significant decreases in specific types of FFAs (C12:0, dodecanoic acid; C14:0, myristric acid; C18:1, oleic acid; C18:2, linoleic acid). RG consumption did not produce significant adverse effects on the renal, hepatic, and immune functions. Thus, RG was found to effectively modulate lipid metabolism and the levels of individual FFAs. The application of the MN for the analysis of FFAs represents a novel approach and can be considered for future research.

Effect of Retrograde Autologous Priming on Coagulation Assessed by Rotation Thromboelastometry in Patients Undergoing Valvular Cardiac Surgery.

OBJECTIVES: To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery. DESIGN: A prospective, randomized, patient- and outcome assessor-blinded study. SETTING: At a single-center university hospital. PARTICIPANTS: Patients aged 20 years or older undergoing valvular cardiac surgery. INTERVENTIONS: A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms. MEASUREMENTS AND MAIN RESULTS: An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups. CONCLUSIONS: Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery.

Ideal chest compression site for cardiopulmonary resuscitation in fontan circulation patients with dextrocardia.

BACKGROUND: We aimed to identify the ideal chest compression site for cardiopulmonary resuscitation (CPR) in patients with a single ventricle with dextrocardia corrected by Fontan surgery. METHODS: The most recent stored chest computed tomography images of all patients with a single ventricle who underwent Fontan surgery were retrospectively analysed. We reported that the ideal chest compression site is the largest part of the compressed single ventricle. To identify the ideal chest compression site, we measured the distance from the midline of the sternum to the point of the maximum sagittal area of the single ventricle as a deviation and calculated the area fraction of the compressed structures. RESULTS: 58 patients (67.2% male) were analysed. The mean right deviation from the midline of the sternum to the ideal compression site was similar to the mean sternum width (32.85 ± 15.61 vs. 31.05 ± 6.75 mm). When chest compression was performed at the ideal site, the area fraction of the single ventricle significantly increased by 7%, which was greater than that of conventional compression (0.15 ± 0.10 vs. 0.22 ± 0.11, P < 0.05). CONCLUSIONS: When performing CPR on a patient with Fontan circulation with dextrocardia, right-sided chest compression may be better than the conventional location.

Comparison of age-adjusted shock indices as predictors of injury severity in paediatric trauma patients immediately after emergency department triage: A report from the Korean multicentre registry.

INTRODUCTION: Shock index paediatric-adjusted (SIPA) was presented for early prediction of mortality and trauma team activation in paediatric trauma patients. However, the derived cut-offs of normal vital signs were based on old references. We established alternative SIPAs based on the other commonly used references and compared their predictive values. METHODS: We performed a retrospective review of all paediatric trauma patients aged 1-15 years in the Emergency Department (ED)-based Injury In-depth Surveillance (EDIIS) database from January 1, 2011 to December 31, 2019. A total of 4 types of SIPA values were obtained based on the references as follows: uSIPA based on the Nelson textbook of paediatrics 21st ed., SIATLS based on the ATLS 10th guideline, SIPALS based on the PALS 2020 guideline, and SIPA. In each SIPA group, the cut-off was established by dividing the group into 4 subgroups: toddler (age 1-3), preschooler (age 4-6), schooler (age 7-12), and teenager (age 13-15). We performed an ROC analysis and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to compare the predicted values of each SIPA in mortality, ICU admission, and emergent surgery or intervention. RESULTS: A total of 332,271 patients were included. The proportion of patients with an elevated shock index was 14.9 % (n = 49,347) in SIPA, 22.8 % (n = 75,850) in uSIPA, 0.3 % (n = 1058) in SIATLS, and 4.3 % (n = 14,168) in SIPALS. For mortality, uSIPA achieved the highest sensitivity (57.0 %; 95 % confidence interval 56.9 %-57.2 %) compared to SIPA (49.4 %, 95 % CI 49.2 %-49.5 %), SIATLS (25.5 %, 95 % CI 25.4 %-25.7 %), and SIPALS (43.8 %, 95 % CI 43.7 %-44.0 %), but there were no significant differences in the negative predictive value (NPV) or area under the curve (AUC). The positive predictive value (PPV) was highest in SIATLS (5.7 %, 95 % CI 5.6 %-5.8 %) compared to SIPA (0.2 %, 95 % CI 0.2 %-0.3 %), uSIPA (0.2 %, 95 % CI 0.2 %-0.2 %), and SIPALS (0.7 %, 95 % CI 0.7 %-0.8 %). The same findings were presented in ICU admission and emergent operation or intervention. CONCLUSION: The ATLS-based shock index achieved the highest PPV and specificity compared to SIPA, uSIPA, and SIPALS for adverse outcomes in paediatric trauma.

Risk stratification model integrating nutritional and inflammatory factors for predicting 1-year mortality after valvular heart surgery: a retrospective cohort study.

INTRODUCTION: Existing risk-scoring systems for cardiac surgery include only standard preoperative factors without considering nutritional and inflammatory status or intraoperative factors. The objective of this study was to develop a comprehensive prediction model for mortality incorporating nutritional, inflammatory, and perioperative factors in patients undergoing valvular heart surgery. MATERIALS AND METHODS: In this retrospective review of 2046 patients who underwent valvular heart surgery, Cox and LASSO regression analyses were performed to identify independent prognostic factors for 1-year postoperative mortality among various perioperative factors known to affect prognosis, including objective nutritional and inflammatory indices. A novel nomogram model incorporating selected prognostic factors was developed, and its discrimination ability was evaluated using the C-index. The model was validated in internal and external cohorts. RESULTS: The 1-year mortality rate after valvular heart surgery was 5.1% (105 of 2046 patients) and was significantly associated with several preoperative objective inflammatory and nutritional indices. Cox and LASSO analyses identified the following five independent prognostic factors for mortality: monocyte-to-lymphocyte ratio (an objective inflammatory index), EuroSCORE II, Controlling Nutritional Status score, cardiopulmonary bypass time, and number of erythrocyte units transfused intraoperatively. The nomogram model incorporating these five factors had a C-index of 0.834 (95% CI: 0.791-0.877), which was higher than that of EuroSCORE II alone (0.744, 95% CI: 0.697-0.791) ( P <0.001). The nomogram achieved good discrimination ability, with C-indices of 0.836 (95% CI: 0.790-0.878) and 0.727 (95% CI: 0.651-0.803) in the internal and external validation cohorts, respectively, and showed well-fitted calibration curves. CONCLUSIONS: A nomogram model incorporating five inflammatory, nutritional, and perioperative factors, as well as EuroSCORE II, was a better predictor of 1-year mortality after valvular heart surgery than EuroSCORE II alone, with good discrimination and calibration power for predicting mortality in both internal and external validation cohorts.

Unpowered scooter injuries in children and risk factors for traumatic brain injuries: An 8-year cross-sectional study using a national registry in South Korea.

INTRODUCTION: Head trauma accounts for a large proportion of unpowered scooter injuries in children. Traumatic brain injury (TBI) is the leading cause of considerable mortality and morbidity in children, who are the main users of unpowered scooters. The aim of this study was to explore the characteristics of unpowered scooter injuries in children and to identify predictors of the occurrence of TBI. METHODS: A multicentre observational retrospective study was conducted using the Emergency Department-based Injury In-depth Surveillance (EDIIS) database in South Korea. Children aged 2 to 18 years old with unpowered scooter injuries between 2011 and 2018 were eligible for inclusion in this study, and the primary outcome was TBI defined based on the International Classification of Diseases, 10th Revision (ICD-10) code. RESULTS: The annual rate of unpowered scooter injuries per 1,000 injured patients increased throughout the study period from 1.4 in 2011 to 16.4 in 2018 (P for trend < 0.001). Of the 3,892 children who had unpowered scooter injuries, 353 (9.2 %) had TBI. Children were at a higher risk of unpowered scooter TBI if they were aged between 2 and 5 years (adjusted odds ratio [aOR]: 1.37; 95 % confidence interval (CI): 1.09-1.73), were male (aOR: 1.45; 95 % CI: 1.14-1.86), were injured either on sidewalks (aOR: 1.80; 95 % CI: 1.20-2.70) or on driveways (aOR: 2.31; 95 % CI: 1.41-3.79), and experienced a fall (aOR: 1.98; 95 % CI: 1.15-3.43). Additionally, children injured after a blunt force were at a lower risk of TBI (aOR: 0.28; 95 % CI: 0.15-0.53). CONCLUSION: Unpowered scooter injuries in children are increasing in South Korea. It is essential for younger children riding unpowered scooters to wear helmets and for caregivers to actively supervise their children to prevent TBI.

Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.

PURPOSE: The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery. METHODS: Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance. RESULTS: The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL-1; 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL-1; 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03). CONCLUSION: Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03699462); first posted 9 October 2018.

RéSUMé: OBJECTIF: L'intégrité du glycocalyx endothélial (GE), un acteur essentiel de l'homéostasie vasculaire, influencerait le devenir des patient·es gravement malades. Nous avons étudié l'effet de l'albumine à 5 %, qui préservait l'intégrité du GE dans les études précliniques, par rapport à une solution cristalloïde équilibrée sur la dégradation du GE chez les patient·es bénéficiant d'une chirurgie coronarienne à cœur battant. MéTHODE: Les patient·es ont été randomisé·es à recevoir soit de l'albumine à 5 % (N = 51) ou de la solution cristalloïde équilibrée (Plasma-Lyte [Baxter Incorporated, Séoul, République de Corée]; N = 53) pour le remplacement du volume intraveineux pendant la chirurgie (en double aveugle). Le critère d'évaluation principal était la concentration plasmatique de syndécan-1, un marqueur de la dégradation du GE, mesurée après l'induction de l'anesthésie (ligne de base), la fin de la greffe et la fermeture du sternum. Les critères d'évaluation secondaires étaient le peptide natriurétique auriculaire (ANP), le facteur de nécrose tumorale (TNF)-α, la thrombomoduline soluble et le bilan hydrique périopératoire. RéSULTATS: Les besoins liquidiens moyens (écart type) étaient de 833 (270) mL et 1323 (492) mL dans les groupes albumine et Plasma-Lyte, respectivement (différence moyenne, −489 mL; intervalle de confiance [IC] à 95 %, −643 à −335; P < 0,001). La concentration plasmatique de syndécan-1 a augmenté après la fin de la greffe (différence médiane, 116 ng·mL−1; IC 95 %, 67 à 184; P < 0,001) et la fermeture du sternum (différence médiane, 57 ng·mL−1; IC 95 %, 36 à 80; P < 0,001) par rapport aux concentrations au départ, sans différences intergroupe. Les concentrations de peptide natriurétique auriculaire, de TNF-α et de thrombomoduline soluble étaient similaires entre les deux groupes. La quantité de drainage du drain thoracique était plus importante dans le groupe albumine que dans le groupe Plasma-Lyte (différence médiane, 190 mL; IC 95 %, 18 à 276; P = 0,03). CONCLUSION: La chirurgie coronarienne à cœur battant a été associée à une dégradation significative du glycocalyx endothélial. Pourtant, la fluidothérapie peropératoire avec 5 % d'albumine n'a pas pu améliorer la dégradation du GE par rapport à une solution cristalloïde équilibrée. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03699462); enregistrée pour la première fois le 9 octobre 2018.

Inhaled iloprost in off-pump coronary artery bypass surgery: a randomized controlled trial.

PURPOSE: Mechanical cardiac constraint during off-pump coronary artery bypass surgery (OPCAB) causes right ventricle (RV) compression and increased pulmonary artery pressure (PAP), which may further compromise RV dysfunction. We aimed to assess the effect of inhaled iloprost, a potent selective pulmonary vasodilator, on the cardiac index (CI) during mechanical constraint. The secondary aim was to determine the resultant changes in the hemodynamic and respiratory parameters. METHODS: A total of 100 adult patients with three-vessel coronary artery disease who had known risk factors for hemodynamic instability (congestive heart failure, mean PAP ≥ 25 mm Hg, RV systolic pressure ≥ 50 mm Hg on preoperative echocardiography, left ventricular ejection fraction < 50%, myocardial infarction within one month of surgery, redo surgery, and left main disease) were enrolled in a randomized controlled trial. The patients were randomly allocated to the control or iloprost groups at a 1:1 ratio, in which saline and iloprost (20 µg) were inhaled for 15 min after internal mammary artery harvesting, respectively. Cardiac index was measured by pulmonary artery catheterization. RESULTS: There were no significant intergroup differences in CI during grafting (P = 0.36). The mean PAP had a significant group-time interaction (P = 0.04) and was significantly lower in the iloprost group at circumflex grafting (mean [standard deviation], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0.01). The remaining hemodynamic parameters were similar between the groups. CONCLUSION: Inhaled iloprost showed a neutral effect on hemodynamic parameters, including the CI and pulmonary vascular resistance index, during OPCAB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04598191); first submitted 12 October 2020.

RéSUMé: OBJECTIF: La contrainte cardiaque mécanique lors d'un pontage aortocoronarien à cœur battant (OPCAB) provoque une compression du ventricule droit (VD) et une augmentation de la pression artérielle pulmonaire (PAP), ce qui peut compromettre davantage le dysfonctionnement du VD. Notre objectif était d'évaluer l'effet de l'iloprost inhalé, un puissant vasodilatateur pulmonaire sélectif, sur l'index cardiaque (IC) au cours de la contrainte mécanique. L'objectif secondaire était de déterminer les modifications résultantes des paramètres hémodynamiques et respiratoires. MéTHODE: Au total, 100 patient·es adultes atteint·es d'une coronaropathie à trois vaisseaux qui présentaient des facteurs de risque connus d'instabilité hémodynamique (insuffisance cardiaque congestive, PAP moyenne ≥ 25 mm  Hg, pression systolique du VD ≥ 50 mm Hg à l'échocardiographie préopératoire, fraction d'éjection ventriculaire gauche < 50 %, infarctus du myocarde dans le mois précédant la chirurgie, chirurgie de reprise et maladie principale gauche) ont été inclus·es dans une étude randomisée contrôlée. Les patient·es ont été réparti·es au hasard dans les groupes témoin ou iloprost dans un rapport de 1:1, dans lequel la solution saline et l'iloprost (20 µg) ont été inhalés pendant 15 minutes après le prélèvement de l'artère mammaire interne, respectivement. L'indice cardiaque a été mesuré par cathétérisme de l'artère pulmonaire. RéSULTATS: Il n'y a eu aucune différence significative entre les groupes en matière d'IC pendant le pontage (P = 0,36). La PAP moyenne présentait une interaction significative groupe-temps (P = 0,04) et était significativement plus faible dans le groupe iloprost au pontage de l'artère circonflexe (moyenne [écart type], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0,01). Les autres paramètres hémodynamiques étaient similaires entre les groupes. CONCLUSION: L'iloprost inhalé a montré un effet neutre sur les paramètres hémodynamiques, y compris sur l'IC et l'indice de résistance vasculaire pulmonaire, pendant un pontage aortocoronarien à cœur battant. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04598191); soumis pour la première fois le 12 octobre 2020.

A pharmacokinetic study on red ginseng with furosemide in equine.

Red ginseng (RG) is a popular ingredient in traditional Korean medicine that has various health benefits. It is commonly taken orally as a dietary supplement; however, its potential interactions with concomitantly administered drugs are unclear. In this study, we examined the pharmacokinetic interaction between furosemide and RG in equine plasma. Liquid chromatography with tandem mass spectrometry analysis was performed to evaluate ginsenosides in the plasma of horses after feeding them RG and furosemide and validate the results. A single bolus of furosemide (0.5 mg/kg) was administered intravenously to female horses that had consumed RG (600 mg/kg/day) every morning for 3 weeks (experimental group), and blood samples were collected from 0 to 24 h, analyzed, and compared with those from female horses that did not consume RG (control group). Four (20s)-protopanaxadiol ginsenosides (Rb1, Rb2, Rc, and Rd) were detected in the plasma. Rb1 and Rc individually showed a high concentration distribution in the plasma. The Cmax, AUC0-t, and AUC0-∞ of furosemide was significantly increased in the experimental group (p < 0.05), while the CL, Vz, and Vss was decreased (p < 0.05, p < 0.01). These changes indicate the potential for pharmacokinetic interactions between furosemide and RG.

Exploring Metabolic Pathways of Anamorelin, a Selective Agonist of the Growth Hormone Secretagogue Receptor, via Molecular Networking.

In this study, we delineated the poorly characterized metabolism of anamorelin, a growth hormone secretagogue receptor agonist, in vitro using human liver microsomes (HLM), based on classical molecular networking (MN) and feature-based molecular networking (FBMN) from the Global Natural Products Social Molecular Networking platform. Following the in vitro HLM reaction, the MN analysis showed 11 neighboring nodes whose information propagated from the node corresponding to anamorelin. The FBMN analysis described the separation of six nodes that the MN analysis could not achieve. In addition, the similarity among neighboring nodes could be discerned via their respective metabolic pathways. Collectively, 18 metabolites (M1-M12) were successfully identified, suggesting that the metabolic pathways involved were demethylation, hydroxylation, dealkylation, desaturation, and N-oxidation, whereas 6 metabolites (M13a*-b*, M14a*-b*, and M15a*-b*) remained unidentified. Furthermore, the major metabolites detected in HLM, M1 and M7, were dissimilar from those observed in the CYP3A4 isozyme assay, which is recognized to be markedly inhibited by anamorelin. Specifically, M7, M8, and M9 were identified as the major metabolites in the CYP3A4 isozyme assay. Therefore, a thorough investigation of metabolism is imperative for future in vivo studies. These findings may offer prospective therapeutic opportunities for anamorelin.

Conversion of CH4 and Hydrogen Storage via Reactions with MgH2-12Ni.

The main key to the future transition to a hydrogen economy society is the development of hydrogen production and storage methods. Hydrogen energy is the energy produced via the reaction of hydrogen with oxygen, producing only water as a by-product. Hydrogen energy is considered one of the potential substitutes to overcome the growing global energy demand and global warming. A new study on CH4 conversion into hydrogen and hydrogen storage was performed using a magnesium-based alloy. MgH2-12Ni (with the composition of 88 wt% MgH2 + 12 wt% Ni) was prepared in a planetary ball mill by milling in a hydrogen atmosphere (reaction-involved milling). X-ray diffraction (XRD) analysis was performed on samples after reaction-involved milling and after reactions with CH4. The variation of adsorbed or desorbed gas over time was measured using a Sieverts'-type high-pressure apparatus. The microstructure of the powders was observed using a scanning transmission microscope (STEM) with energy-dispersive X-ray spectroscopy (EDS). The synthesized samples were also characterized using Fourier transform infrared (FT-IR) spectroscopy. The XRD pattern of MgH2-12Ni after the reaction with CH4 (12 bar pressure) at 773 K and decomposition under 1.0 bar at 773 K exhibited MgH2 and Mg2NiH4 phases. This shows that CH4 conversion took place, the hydrogen produced after CH4 conversion was then adsorbed onto the particles, and hydrides were formed during cooling to room temperature. Ni and Mg2Ni formed during heating to 773 K are believed to cause catalytic effects in CH4 conversion. The remaining CH4 after conversion is pumped out at room temperature.

Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model.

The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1ß and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1ß, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1ß signaling-induced inflammation and enhancing NK cell activity.

Brain natriuretic peptide as a clinical screening tool for the diagnosis of Kawasaki disease.

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been studied as a diagnostic screening tool for Kawasaki disease (KD). However, brain natriuretic peptide (BNP) has been less studied while has less variability among age groups. We aimed to find out if BNP can be used as a diagnostic screening tool for KD in Korea. This was a retrospective cohort study performed in a single pediatric emergency department. Patients younger than 19 years of age who presented with fever and underwent BNP examination for suspected KD was included. The primary outcome was the diagnostic performance of BNP for KD, and the secondary outcome was the diagnostic performance of BNP for coronary artery aneurysm (CAA). We also derived a scoring system for predicting KD and CAA. Of the 778 patients who were finally included, 400 were not diagnosed with KD and 378 were diagnosed with KD. The odds ratio of BNP at the cutoff of 30 pg/mL for KD was 7.80 (95% CI, 5.67-10.73) in the univariate analysis and 3.62 (95% CI, 2.33-5.88) in the multivariable analysis. The odds ratio of BNP at the cutoff of 270 pg/mL for CAA was 3.67 (95% CI, 2.18-6.19) in the univariate analysis and 2.37 (95% CI, 1.16-8.74) in the multivariable analysis. The AUC of KD and CAA were 0.884 and 0.726, respectively, which was the highest AUCs among all variables. Additionally, we proposed a scoring system for KD and CAA. It is important to clinically suspect KD and CAA in children with high BNP levels.

Identification of a metabolite for the detection of the hydrophilic drug diisopropylamine for doping control.

Diisopropylamine (DIPA), a hydrophilic chemical compound, is used as an intravenous antihypertensive agent. DIPA is prohibited for use in the horse racing industry due to its performance enhancing effects. A cyano (CN) hydrophilic interaction liquid chromatography (HILIC) column was used for the separation of DIPA from its metabolite. Ammonium formate was added to the mobile phase to increase the ionization of the basic substance. The metabolite was identified as an N-oxidized metabolite of DIPA, which eluted earlier than the parent drug and was less polar on the HILIC column. The main finding of the study was the identification of a metabolite with a mass shift of 15.9944. The in vitro experiment showed that the metabolite was produced as a result of N-oxidation processes, mainly mediated by flavin-containing monooxygenase (FMO). Methimazole was used to inhibit the FMO enzyme-mediated N-oxidation metabolism and metabolite production in a concentration-dependent manner. The metabolite was confirmed to be present in an actual horse urine sample that tested positive for DIPA. This study demonstrated that the metabolite could be screened using in vitro samples and their presence corresponded to a positive result in actual samples. This metabolite screening could therefore find application as a flexible way to test for new and modified banned substances in the racing industry.

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial.

BACKGROUND: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). METHODS: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. RESULTS: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). CONCLUSIONS: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).