Prognostic value of CT body composition analysis for 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVES: To investigate the value of body composition indices derived from pre-procedural computed tomography (CT) in predicting 1-year mortality among patients who underwent transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: We assessed consecutive patients who underwent TAVR between June 2016 and December 2021 at a single academic medical center. Skeletal muscle and subcutaneous fat area at the T4, T12, and L3 levels on pre-procedural CT were measured. The association between body composition and 1-year mortality was evaluated using Cox proportional hazard regression analysis. RESULTS: Finally, 408 patients were included (185 men and 223 women; mean age, 81.7 ± 5.1 years; range, 62-98 years). Post-procedural death occurred in 13.2% of patients. The muscle-height index and fat-height index at the L3 level were more strongly correlated with those at the T12 level (r = 0.765, p < 0.001 and r = 0.932, p < 0.001, respectively) than with those at the T4 level (r = 0.535, p < 0.001 and r = 0.895, p < 0.001, respectively). The cumulative 1-year mortality rate was highest for patients with both sarcopenia and adipopenia (26%), followed by those with adipopenia only (17%), those with sarcopenia only (12%), and those with neither sarcopenia nor adipopenia (8%, p = 0.002). Multivariable analysis revealed that body composition at the T12 level was an independent risk factor for 1-year mortality (hazard ratio: 4.09, 95% confidence interval: 2.01-8.35) in patients with both sarcopenia and adipopenia (p < 0.001). CONCLUSION: Sarcopenia or adipopenia assessed with CT at the thoracic level may be valuable for stratifying 1-year all-cause mortality in patients who undergo TAVR. CLINICAL RELEVANCE STATEMENT: Skeletal muscle and subcutaneous fat mass indices at the level of T12, measured on pre-procedural CT, have value for risk stratification of 1-year all-cause mortality in patients who undergo transcatheter aortic valve replacement. KEY POINTS: Sarcopenia and adipopenia are associated with the prognosis of patients undergoing transcatheter aortic valve replacement. Body composition at the T12 level was an independent risk factor for 1-year all-cause mortality. Sarcopenia or adipopenia assessed at T12 with pre-procedural CT is valuable for risk stratification.

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.

An In Silico-Guided Approach for Assessing Herb-Drug Interaction Potential: A Case Study with Cudrania tricuspidata Leaf Extracts.

Cudrania tricuspidata leaf extracts have long been utilized as traditional oriental medicines across Asian countries like Korea, China, and Japan. These extracts are renowned for their therapeutic benefits in addressing inflammation, tumors, obesity, and diabetes, maintaining their status as a pivotal folk remedy. Given the rising trend of combining medicinal herbs with conventional medications, it is imperative to explore the potential herb-drug interactions. However, there is a dearth of research on evaluating the herb-drug interactions of C. tricuspidata leaf extracts. Also, the intricate chemical composition of medicinal herbs presents methodological hurdles in establishing causal relationships between their constituents and herb-drug interactions. To overcome these challenges, a combined in silico and in vitro workflow was developed and effectively applied to evaluate the potential herb-drug interaction of C. tricuspidata leaf extracts along with the associated chemical factors. In in vitro CYP inhibition assays, C. tricuspidata leaf extracts exhibited potent inhibition of CYP1A2 and CYP2C8, with quercetin, kaempferol, and their glycosides identified as the major constituents. In silico analysis based on the prediction tools (ADMETlab 2.0 and pkCSM) identified key contributors to CYP inhibition, quercetin and kaempferol. Additionally, molecular docking analysis validated the binding of ligands (quercetin and kaempferol) to proteins (CYP1A2 and CYP2C8). These findings suggest that C. tricuspidata leaf extracts could inhibit CYP1A2 and CYP2C8, aiding in understanding the herb-drug interaction potential of C. tricuspidata leaf extracts for safe clinical application. Furthermore, this approach can be broadly applied to study herb-drug interactions of various medicinal herbs, enhancing their therapeutic benefits and reducing adverse reactions by considering chemical profiles relevant to herb-drug interaction potential in herbal preparations.

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.

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.

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.

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.

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).

Predictors of Caregiver Satisfaction With Pediatric Laceration Repair in the Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to define the care factors that are important to caregivers' satisfaction with pediatric laceration repair and the overall emergency department (ED) experience. METHODS: This was a cross-sectional observation study performed in an urban tertiary hospital. The caregivers of patients younger than 18 years who presented to the ED for laceration repair completed a survey. Demographic data were analyzed. Univariate and multivariate logistic regressions were used to determine the factors related to satisfaction with the laceration repair and the overall ED experience. RESULTS: Fifty-five caregivers were enrolled. Most of the children had facial lacerations (n = 44, 80%). The median length of ED stay was 181 minutes (interquartile range [IQR], 157-208 minutes). The children's median age was 41.8 months (IQR, 23-91 months); the caregivers' median age was 37 years (IQR, 35-41 years). Most lacerations were repaired by plastic surgeons (81.8%). In the multivariate regression analysis, preparation before the procedure, mid-income family, caring attitude of the nurse, cosmetic outcome, and measures to control the patient's anxiety were significantly related to the caregiver's satisfaction with laceration repair (P < 0.05), whereas preparation before the procedure and ED environment were significantly related to the caregiver's satisfaction with the overall ED experience (P < 0.05). CONCLUSIONS: Preparation before the procedure was significantly related to the caregiver's satisfaction with both pediatric laceration repair and the overall PED experience. The strongest predictors were cosmetic outcome for laceration repair and preparation for the procedure for the overall PED experience. Our findings suggest that improvements in various aspects will increase parent satisfaction.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

External validation and update of the early detection rule for severe hyperkalemia among patients with symptomatic bradycardia.

OBJECTIVE: Chon et al. suggested a high prevalence of severe hyperkalemia (serum potassium ≥ 6.0 mEq/L with electrocardiographic [ECG] changes) among patients with symptomatic or extreme bradycardia. Despite the urgent need to detect and treat severe hyperkalemia, serum potassium result may be available too late and is often spuriously high. Meanwhile, the traditional, descriptive ECG findings of severe hyperkalemia have shown unsatisfactory diagnostic powers. To overcome these diagnostic problems, they outlined the following quantitative rules to facilitate its early detection: Maximum precordial T wave ≥ 8.5 mV (2), atrial fibrillation/junctional bradycardia (1), heart rate (HR) ≤ 42/min (1) with (original rule)/without (ECG-only rule) diltiazem medication (2), and diabetes mellitus (1). Here we report on our external validation of these rules and the resulting updates. METHODS: This retrospective, cross-sectional study included all adults with symptomatic (HR ≤ 50/min with syncope/pre-syncope/dizziness, altered mentality, chest pain, dyspnea, general weakness, oliguria, or shock) or extreme (HR ≤ 40/min) bradycardia who visited a university emergency department from 2014 to 2019. After validating the abovementioned rules externally, we selected risk factors of severe hyperkalemia among the ECG findings and easy-to-assess clinical variables by multiple logistic regression analysis. After modelling the updated 'ECG-only' and 'ECG-plus' indices, we internally validated the better of the two by bootstrapping with 1000 iterations. RESULTS: Among 455 symptomatic/extreme bradycardia cases (70.3 ± 13.1 years; 213 females [46.8%]), 70 (15.4%) had severe hyperkalemia. The previous ECG-only rule showed a c-statistic of 0.765 (95% CI: 0.706-0.825), Hosmer-Lemeshow test of p < 0.001, and a calibration slope of 0.719 (95% CI: 0.401-1.04). On updating, the ECG-plus index summing junctional bradycardia/atrial fibrillation (1), maximum precordial T wave≥8.0 mV (2), general weakness as the chief complaint (2), oxygen demand (1), and dialysis (2) outperformed the ECG-only index (c-statistic, 0.832; 95% CI, 0.785-0.880 vs. 0.764; 95% CI, 0.700-0.828; p = 0.011). On bootstrapping, the c-statistic was 0.832 (95% CI: 0.786-0.878). For scores ≥ 3 (positive likelihood ratio ≥ 5.0), the sensitivity and specificity were 0.514 and 0.901, respectively. For scores ≤ 1, negative likelihood ratio was ≤0.2. CONCLUSIONS: Previous rules showed less satisfactory calibration but fair discrimination to detect severe hyperkalemia in patients with symptomatic or extreme bradycardia. We propose the ECG-plus index as the optimum tool to facilitate its early detection.

Effects of intraoperative dexmedetomidine infusion on renal function in elective living donor kidney transplantation: a randomized controlled trial.

PURPOSE: Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial. METHODS: A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 µg·kg-1·hr-1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1ß, and IL-18 during the perioperative period. RESULTS: The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL-1 vs 1.06 [0.73] mg·dL-1; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03327389); registered 31 October 2017.

RéSUMé: OBJECTIF: Les lésions d'ischémie-reperfusion sont inévitables lors du prélèvement d'organes du donneur et de la reperfusion de l'allogreffe chez le receveur pour une transplantation rénale, et affectent le devenir du greffon. La dexmédétomidine, un agoniste des adrénorécepteurs de type α2, a des effets néphroprotecteurs sur les lésions d'ischémie-reperfusion. Nous avons réalisé une étude randomisée contrôlée afin d'examiner les effets d'une perfusion peropératoire de dexmédétomidine sur la fonction rénale et l'apparition d'un retard de fonctionnement du greffon après une transplantation rénale élective issue de donneurs vivants. MéTHODE: Au total, 104 patients ont été aléatoirement répartis pour recevoir une perfusion peropératoire de 0,4 µg·kg-1·r-1 de dexmédétomidine ou une solution saline à 0,9 %. Le critère d'évaluation principal était la créatininémie au jour postopératoire (JPO) 7. Les critères d'évaluation secondaires étaient la fonction rénale et le degré d'inflammation et comprenaient les variables suivantes : créatininémie et infiltration glomérulaire estimée jusqu'à six mois; incidence de retard de fonctionnement du greffon; et taux sériques de cystatine C, d'interleukine plasmatique (IL)-1ß et d'IL-18 pendant la période périopératoire. RéSULTATS: Le taux moyen (écart type) de créatinine sérique au JPO 7 était comparable entre les groupes (dexmédétomidine vs témoin : 1,11 [0,87] mg·dL-1 vs 1,06 [0,73] mg·dL-1; différence moyenne, 0,05; intervalle de confiance à 95 %, -0,27 à 0,36; P = 0,77). Un patient de chaque groupe a subi un retard de fonctionnement du greffon (rapport de cotes, 1,020; P > 0.99). Aucune différence intergroupe significative n'a été observée en ce qui concerne les critères d'évaluation secondaires. CONCLUSION: La perfusion peropératoire de dexmédétomidine n'a produit aucun effet bénéfique sur la fonction rénale ou le retard de fonctionnement du greffon chez les patients bénéficiant d'une transplantation rénale élective issue de donneur vivant. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03327389); enregistrée le 31 octobre 2017.

Tablet personal computer distraction during intravenous placement for young children in the pediatric emergency department: A pilot study.

BACKGROUND: Intravenous (IV) placement is a common procedure experienced by children visiting the pediatric emergency department (PED). However, uncontrolled anxiety and pain cause children to interfere with the procedure. In this pilot study, we sought to evaluate the effectiveness of tablet personal computers as a distraction method during IV placement. METHODS: This is a single-center pilot study conducted at a tertiary teaching hospital. Children visiting the PED were eligible if they were aged 3-5 years and required IV placement during the PED visit. After written consent was obtained from the guardian, the child was randomly assigned to a control group or an intervention group. For the intervention group, an animated video was played via tablet PC during IV placement. For both groups, children's anxiety, heart rate, and pain scale scores (the Face, Legs, Activity, Cry, Consolability and Evaluation Enfant Douleur) and guardian satisfaction were recorded. RESULTS: 22 children were eligible for the final analysis. There was no significant difference in the pain scale scores between the two groups, with the exception of the degree of pain relief after the procedure measured using Evaluation Enfant Douleur (intervention group: 6.0, interquartile range (IQR): 4.2-6.8, and control group; 3.0, IQR: 2.0-3.8, P = 0.011) and Face, Legs, Activity, Cry, Consolability (intervention group: 4.0, IQR: 4.0-4.2 and control group; 3.0, IQR: 1.5-3.5, P = 0.043). CONCLUSION: In this pilot study, distraction using tablet personal computers may have reduced children's distress during the recovery phase after venipuncture. Further study with a larger sample size and different methods of distraction is essential.

Successful systemic treatment outcomes of lichen planus: A single-center retrospective review.

Lichen planus (LP) affects up to 4% of adults and can cause significant distress and morbidity, especially to those with persistent disease. As many as 20% of patients with LP may exhibit widespread or recalcitrant disease necessitating systemic treatment options. We sought to evaluate the effectiveness of systemic treatments for severe and recalcitrant LP not responsive to topical corticosteroids or calcineurin inhibitors. Over a 10-year period, 374 patients with cutaneous and mucosal LP were evaluated at a major regional tertiary medical center; 94 qualified for inclusion in the study. In all, 26 (28%) patients achieved remission, 52 (55%) experienced stable disease control, and 16 (17%) failed all attempted treatments. Among medications most trialed, intramuscular triamcinolone (IM TAC), hydroxychloroquine, and methotrexate were most successful with 79%, 61%, and 42% respective response rates. In contrast, oral corticosteroids and dapsone were less frequently successful at rates of 24% and 20%. IM TAC represented the highest level of treatment success and was statistically significant compared to other systemic treatments (P < .01). Among adjuvant therapies, intralesional triamcinolone (IL TAC) demonstrated higher success (71%) than oral corticosteroids (29%). Based on this multi-year evaluation, we recommend that clinicians consider IM TAC as a first-line systemic option for severe or refractory LP, with hydroxychloroquine as the steroid-sparing treatment of choice. For patients requiring adjuvant therapy, IL TAC should be considered to hasten response and symptom relief. Patients with severe or widespread disease may benefit from earlier initiation of systemic therapy to prevent significant morbidity and impact on daily function.

The immunomodulatory effect of ketamine in colorectal cancer surgery: a randomized-controlled trial.

PURPOSE: Ketamine's inhibitory action on the N-methyl-D-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery. METHODS: A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg-1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg-1·hr-1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery. RESULTS: The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62). CONCLUSIONS: Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients. TRIAL REGISTRATION: www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.

RéSUMé: OBJECTIF: L'action inhibitrice de la kétamine sur le récepteur du N-méthyle-D-aspartate et ses effets anti-inflammatoires pourraient procurer une immunomodulation bénéfique lors d'une chirurgie oncologique. Nous avons étudié l'effet de la kétamine en dose sous-anesthésique en complément à une anesthésie au desflurane sur l'activité des cellules tueuses naturelles (NK) et l'inflammation chez les patients subissant une chirurgie de cancer colorectal. MéTHODE: Au total, 100 patients ont été randomisés à un groupe témoin ou kétamine. Le groupe kétamine a reçu un bolus de 0,25 mg·kg−1 de kétamine cinq minutes avant le début de la chirurgie, suivi d'une perfusion de 0,05 mg·kg−1·h−1 jusqu'à la fin de la chirurgie; le groupe témoin a reçu une quantité similaire de solution physiologique salée. Nous avons mesuré l'activité des cellules NK et des cytokines pro-inflammatoires (interleukine-6 [IL-6] et facteur de nécrose tumorale α [TNF-α]) avant la chirurgie et une, 24 et 48 heures après la chirurgie. La protéine C réactive (CRP) a été mesurée avant la chirurgie puis un, trois et cinq jours après la chirurgie. L'antigène carcinoembryonnaire et la récurrence du cancer ou les métastases ont été évalués deux ans après la chirurgie. RéSULTATS: L'activité des cellules NK a été significativement réduite après la chirurgie dans les deux groupes, mais le changement ne différait pas entre les groupes dans l'analyse de modèle mixte linéaire (P = 0,47). Les changements dans les taux d'IL-6, de TNF-α, de CRP, et d'antigène carcinoembryonnaire n'étaient pas différents entre les groupes (P = 0,27, 0,69, 0,99 et 0,97, respectivement). La récidive du cancer au cours des deux années suivant la chirurgie était similaire entre les groupes (10 % vs 8 %, P = 0,62). CONCLUSION: L'administration peropératoire de kétamine de faible dose ne s'est pas traduite par un quelconque impact favorable sur l'activité postopératoire g des cellules NK, la réaction inflammatoire, et le pronostic chez les patients de chirurgie de cancer colorectal. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03273231); enregistrée le 6 septembre 2017.

Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors.

Frequent oxidative modification of the neural genome is a by-product of the high oxygen consumption of the nervous system. Rapid correction of oxidative DNA lesions is essential, as genome stability is a paramount determinant of neural homeostasis. Apurinic/apyrimidinic endonuclease 1 (APE1; also known as "APEX1" or "REF1") is a key enzyme for the repair of oxidative DNA damage, although the specific role(s) for this enzyme in the development and maintenance of the nervous system is largely unknown. Here, using conditional inactivation of murine Ape1, we identify critical roles for this protein in the brain selectively after birth, coinciding with tissue oxygenation shifting from a placental supply to respiration. While mice lacking APE1 throughout neurogenesis were viable with little discernible phenotype at birth, rapid and pronounced brain-wide degenerative changes associated with DNA damage were observed immediately after birth leading to early death. Unexpectedly, Ape1Nes-cre mice appeared hypothermic with persistent shivering associated with the loss of thermoregulatory serotonergic neurons. We found that APE1 is critical for the selective regulation of Fos1-induced hippocampal immediate early gene expression. Finally, loss of APE1 in combination with p53 inactivation resulted in a profound susceptibility to brain tumors, including medulloblastoma and glioblastoma, implicating oxidative DNA lesions as an etiologic agent in these diseases. Our study reveals APE1 as a major suppressor of deleterious oxidative DNA damage and uncovers specific and broad pathogenic consequences of respiratory oxygenation in the postnatal nervous system.

Impact of the COVID-19 Outbreak on Trends in Emergency Department Utilization in Children: a Multicenter Retrospective Observational Study in Seoul Metropolitan Area, Korea.

BACKGROUND: Understanding the changes in emergency department (ED) visit patterns during the coronavirus disease 2019 (COVID-19) outbreak is important for effectively operating EDs during the pandemic. We aimed to analyze the changes in pediatric ED visits during the COVID-19 pandemic and examine the relationship between the number of ED visits and the stringency of government social distancing measures. METHODS: This multicenter retrospective study used data of pediatric (age < 18 years) ED visits in Seoul metropolitan area from June 1, 2018, to May 31, 2020. Patient demographics, ED results, and diagnoses were compared during the COVID-19 period and the previous year. To evaluate the effect of the stringency of social distancing measures on the number of ED visits, a Poisson regression model was developed with month, year, and the average monthly Government Response Stringency Index (GRSI) as fixed effects. RESULTS: In total, 190,732 patients were included. The number of pediatric ED visits during the COVID-19 period was 58.1% lower than in the previous year. There were disproportionate decreases in the numbers of ED visits for children in early childhood (66.5%), low-acuity children (55.2-63.8%), those who did not use an ambulance (59.0%), and those visiting the ED for noninjury complaints (64.9%). The proportion of admissions increased from 11.9% to 16.6%. For every 10-point increase in the GRSI, there was a 15.1% decrease in monthly ED visits. CONCLUSION: A striking decrease in pediatric ED visits was observed during the COVID-19 outbreak, the scale which was associated with the stringency of government policies. Changes in the number and characteristics of children visiting the ED should be considered to facilitate the effective operation of EDs during the pandemic.

Effects of Emergency Care-related Health Policies during the COVID-19 Pandemic in Korea: a Quasi-Experimental Study.

BACKGROUND: The purpose of this study was to review the nationwide emergency care-related health policies during the coronavirus disease 2019 (COVID-19) pandemic disaster in Korea and to analyze the effects of the policies on the safety of patients who visit emergency departments (EDs) during this period. METHODS: This study is a quasi-experiment study. The study population was patients who visited all 402 EDs in Korea between December 31, 2019 and May 13, 2020, using the National Emergency Department Information System (NEDIS) database. The study period was classified into 5 phases according to the level of national crisis warning of infectious disease and the implementation of emergency care-related health policies, and all study phases were 27 days. The primary outcome was in-hospital mortality, and the secondary outcome was length of stay (LOS) in the ED during the COVID-19 outbreak. RESULTS: The number of ED visits during the study period was 2,636,341, and the in-hospital mortality rate was 1.4%. The number of ED visits decreased from 803,160 in phase 1 to 496,619 in phase 5 during the study period. For in-hospital mortality, the adjusted odds ratio (OR) (95% confidence interval) was 0.77 (0.74-0.79) in phase 5 compared to phase 3. Additionally, by subgroup, the ORs were 0.69 (0.57-0.83) for the patients with acute myocardial infarction and 0.76 (0.67-0.87) for severe trauma in phase 5 compared to phase 3. The ED LOS increased while the number of ED visits decreased as the COVID-19 pandemic progressed, and the ED LOS declined after policy implementation (beta coefficient: -5.3 [-6.5 to -4.2] minutes in phase 5 compared to phase 3). CONCLUSION: Implementing appropriate emergency care policies in the COVID-19 pandemic would have contributed to improving the safety of all emergency patients and reducing in-hospital mortality by preventing excessive deaths.

Perioperative Nadir Hemoglobin Concentration and Outcome in Off-Pump Coronary Artery Bypass Surgery　- A Retrospective Review.

BACKGROUND: Emerging evidence advocates the use of restrictive transfusion strategies at hemoglobin (Hb) levels of approximately 7-8 g/dL in cardiac surgeries using cardiopulmonary bypass. Yet, it is unclear whether the same thresholds can be applied to off-pump coronary bypass (OPCAB) that accompanies cardiac displacement and warm regional ischemia-reperfusion injury without the aid of a bypass machine. The aim of this study is to investigate the relationship between perioperative nadir Hb level and outcome following OPCAB.Methods and Results:Medical records of 1,360 patients were reviewed. Hb levels were serially assessed during and after surgery. The incidence of composite endpoints was 35%, which included myocardial infarction, stroke, acute kidney injury, sternal infection, reoperation, prolonged mechanical ventilation, and in-hospital mortality. The nadir Hb level was significantly lower in the morbidity group than in the non-morbidity group (8.1 [7.4-9.1] vs. 8.8 [7.9-9.8] g/dL, P<0.001). Multivariable logistic regression analysis revealed nadir Hb as an independent risk factor of adverse outcome (odds ratio: 0.878, 95% confidence intervals: 0.776-0.994, P=0.04), whereas preoperative anemia and perioperative transfusion were not. The critical value of Hb for predicting detrimental outcome was 8.05 g/dL. CONCLUSIONS: A significant association is found between perioperative nadir Hb and adverse outcome after OPCAB. Although preoperative anemia was not associated with poor prognosisper se, it was the only modifiable risk factor that was closely linked to nadir Hb.

Effect of dexmedetomidine on acute kidney injury after aortic surgery: a single-centre, placebo-controlled, randomised controlled trial.

BACKGROUND: Acute kidney injury (AKI) is a frequent and serious complication after aortic surgery requiring cardiopulmonary bypass (CPB). Dexmedetomidine, a selective α-2 adrenoreceptor agonist, may reduce AKI because of its sympatholytic and anti-inflammatory effects against ischaemia-reperfusion injury. We investigated the effect of dexmedetomidine administration on AKI after aortic surgery requiring CPB in a placebo-controlled randomised controlled trial. METHODS: A total of 108 patients were randomly assigned to an infusion of dexmedetomidine or saline at a rate of 0.4 µg kg-1 h-1 for 24 h starting after anaesthetic induction. The primary outcome was the incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes included delirium and major morbidity. Safety outcomes were drug-related adverse events (bradycardia, hypotension). RESULTS: AKI occurred in 7/54 (13%) subjects randomised to dexmedetomidine, compared with 17/54 (31%) subjects randomised to saline infusion (odds ratio=0.32; 95% confidence interval [CI], 0.12-0.86; P=0.026). Secondary outcomes, including stroke, mortality, and delirium, were similar between subjects randomised to dexmedetomidine (16/54 [30%] or saline control (22 [41%]; odds ratio=0.61 [95% CI, 0.28-1.36]). The incidence of bradycardia and hypotension was similar between groups (14/54 (26%) vs. 17/54 (32%) (odds ratio:0.76 (95%CI:0.33-1.76) and 29/54 (54%) vs. 36/54 (67%) (odds ratio:0.58 (95%CI:0.27-1.26), respectively). The length of hospital stay was shorter in the dexmedetomidine group (12 [10-17] days) vs saline control (15 [11-21] days; P=0.039). CONCLUSIONS: Pre-emptive dexmedetomidine administration for 24 h starting after induction of anaesthesia reduced the incidence of AKI after aortic surgery requiring CPB, without any untoward side-effects related to its sedative or sympatholytic effects. CLINICAL TRIAL REGISTRATION: NCT02607163 (www.ClinicalTrials.gov).