Frequency domain analysis of photoplethysmographic and arterial pressure waveforms for assessing hemodynamics in children with congenital heart surgery.

BACKGROUND: Time-domain parameters are less reliable in children due to increased arterial and chest wall compliance. We assessed the ability of indices derived from frequency analysis of photoplethysmography (PPG) and arterial blood pressure (ABP) waveforms to predict the hemodynamic state in children undergoing congenital heart surgery. METHODS: We analyzed waveforms after cardiopulmonary bypass period in 76 children who underwent total repair of congenital heart disease. Amplitude density of baseline and amplitude modulation in PPG and ABP by respiratory frequency were obtained using fast Fourier transform analysis and normalized by cardiac pulse height (representing respiratory modulations in venous blood [PPG-DC%] and in amplitude [PPG-AC%] at respiratory frequency). The ratio of amplitude density of PPG at the cardiac frequency (CF) to ABP-CF was used to assess vascular compliance. We assessed volume replacement (ml/kg) and vasoactive inotropic score (VIS). RESULTS: Children requiring volume replacement > 10 ml/kg (15.8%) showed higher PPG-DC% than those not requiring it (median: 52.4%, 95% CI [24.8, 295.1] vs. 36.7% [10.7, 125.7], P = 0.017). In addition, children with a VIS > 7 (22.4%) showed higher PPG-CF/ABP-CF (3.6 [0.91, 10.8] vs. 1.2 [0.27, 5.5], P = 0.008). On receiver operating characteristic curve analysis, PPG-DC% predicted a higher fluid requirement (area under the curve: 0.71, 95% CI [0.604, 0.816], P = 0.009), while PPG-CF/ABP-CF predicted a higher VIS (0.714, [0.599, 0.812], P = 0.004). CONCLUSIONS: Frequency domain analysis of PPG and ABP may assess hemodynamic status requiring fluid or vasoactive inotropic therapy after congenital heart surgery.

Preoperative low muscle mass and early postoperative outcomes in children undergoing living donor liver transplantation: A retrospective study.

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm 2 /m 2 ). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8-38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm 2 /m 2 ) and high (mean TSMI 2188.1 ± 273.5 mm 2 /m 2 ) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT.

Neutrophilia is more predictive than increased white blood cell counts for short-term mortality after liver transplantation in patients with acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF. METHODS: A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis. RESULTS: The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern. CONCLUSIONS: Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

Suspected Malignant Hyperthermia in a Brain-Dead Donor During Anesthesia for Organ Procurement Surgery: A Case Report.

We report an unusual case of highly suspected malignant hyperthermia after inducing anesthesia in a brain-dead 18-year-old male patient undergoing organ procurement surgery. The patient was administered desflurane (3 vol%) and rocuronium bromide (50 mg) to induce and maintain general anesthesia. He experienced hypercapnia and tachycardia within 5 minutes of anesthesia induction; however, his body temperature rapidly rose only after 15 minutes. The volatile anesthetic was discontinued, and dantrolene was administered at a low dose (1 mg/kg) to avert possible hepatotoxic effects on the donor liver. Fortunately, the clinical course of the brain-dead donor until the organs were harvested and the liver transplantation outcome of the recipient was favorable. A comprehensive understanding of the pathophysiology of brain death, organ transplantation, and malignant hyperthermia is essential to respond promptly and appropriately. Based on our experience, low-dose dantrolene may be clinically used in brain-dead donors while accounting for its potential hepatotoxic effects.

Characterizing Heart Failure With Preserved Ejection Fraction in End-Stage Liver Disease and Liver Transplant Outcomes.

Background: Heart failure with preserved ejection fraction (HFpEF) and its risk factors are increasingly recognized in patients with end-stage liver disease (ESLD). Objectives: The aim of this study was to characterize HFpEF and identify relevant risk factors in patients with ESLD. Additionally, the prognostic impact of high-probability HFpEF on post-liver transplantation (LT) mortality was investigated. Methods: Patients with ESLD prospectively enrolled from the Asan LT Registry between 2008 and 2019 were divided into groups with low (scores of 0 and 1), intermediate (scores of 2-4), and high (scores of 5 and 6) probability using the Heart Failure Association-PEFF diagnostic score for HFpEF. Gradient-boosted modeling in machine learning was further used to appraise the apparent importance of risk factors. Finally, post-LT all-cause mortality was followed for 12.8 years (median 5.3 years); there were 498 deaths after LT. Results: Among the 3,244 patients, 215 belonged to the high-probability group, commonly those with advanced age, female sex, anemia, dyslipidemia, renal dysfunction, and hypertension. The highest risk factors for the high-probability group, according to gradient-boosted modeling, were female sex, anemia, hypertension, dyslipidemia, and age >65 years. Among patients with Model for End-Stage Liver Disease scores of >30, those with high, intermediate, and low probability had cumulative overall survival rates of 71.6%, 82.2%, and 88.9% at 1 year and 54.8%, 72.1%, and 88.9% at 12 years after LT (log-rank P = 0.026), respectively. Conclusions: High-probability HFpEF was found in 6.6% of patients with ESLD with poorer long-term post-LT survival, especially those with advanced stages of liver disease. Therefore, identifying HFpEF using the Heart Failure Association-PEFF score and addressing modifiable risk factors can improve post-LT survival.

Association Between Preoperative Sarcopenia and Early Postoperative Outcomes in Pediatric Patients Undergoing Total Correction of Tetralogy of Fallot: A Retrospective Cohort Study.

OBJECTIVES: To identify the association between preoperative low muscle mass and early postoperative outcomes in pediatric patients undergoing total correction of tetralogy of Fallot (TOF). DESIGN: A retrospective cohort study. SETTING: A single university hospital in Seoul, South Korea. PARTICIPANTS: Pediatric patients (≤3 years) who underwent total correction of TOF between May 2008 and February 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cross-sectional areas of the pectoralis and erector spinae muscles were measured using preoperative chest computed tomography (CT) scans, and adjusted to body surface area to define muscle mass index. The patients were divided into sarcopenia, presarcopenia, and no sarcopenia groups based on cutoff values determined using the mean and SD of the muscle mass index in the third z-weight quintile. Of a total of 330 patients included in the final analysis, 13 were associated with the sarcopenia group, 57 in the presarcopenia group, and 260 in the no sarcopenia group. The sarcopenia group exhibited a higher incidence of major adverse events than the presarcopenia and no sarcopenia groups, respectively (38% v 25% v 18%; p = 0.033). Logistic regression analyses revealed that only younger age at the time of surgery was significantly associated with major adverse events (odds ratio 0.82; 95% CI 0.72-0.94, p = 0.003). CONCLUSIONS: The incidence of sarcopenia, as assessed by preoperative chest CT, was low in pediatric patients undergoing total correction of TOF, and preoperative sarcopenia did not predict early postoperative major adverse events.

Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities.

AIM: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight/obese patients with co-morbidities, with and without type 2 diabetes (T2D). MATERIALS AND METHODS: This was a phase 1, double-blind, randomized, placebo-controlled, two-part trial with a 12-week treatment period of once-weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D. RESULTS: In part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment-emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose-dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part. CONCLUSIONS: This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.

Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: Observational retrospective study.

BACKGROUND: Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated. METHODS: In this observational retrospective cohort study, 3,211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [ß] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI20] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (ß > 6.16) were categorized into 3 groups; leftward-shifted (EDVI20 <51 mL/m2), rightward-shifted (EDVI20 > 69.7 mL/m2), and intermediate (EDVI20 51-69.7 mL/m2). RESULTS: As the model for ESLD score increases, both EDVI20 and ß gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (ß > 6.16, n = 1,090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P = 0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension. CONCLUSIONS: As ESLD advances, diastolic ventricular properties are characterized by increased EDVI20 and ß on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.

A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM® ) test.

There is a paucity of evidence about the coagulation profile regarding the complexity of children undergoing liver transplantation (LT). This study aimed to investigate intraoperative hemostatic changes during pediatric LT according to the etiology for LT and examine the ability of rotational thromboelastometry (ROTEM® , TEM International GmbH, Munich, Germany) as a point-of-care monitoring method. We evaluated 106 patients aged 3 months to 17 years undergoing LT for acute liver failure (ALF) and chronic liver disease, which consists of patients with cholestatic disease, metabolic/genetic disease, and cancer. A total of 731 ROTEM® measurements, including 301 ellagic acid to initiate clotting via the intrinsic pathway, 172 tissue factor to initiate the extrinsic clotting cascade (EXTEM), and 258 cytochalasin D to inhibit platelet activity reflecting fibrinogen (FIBTEM), were analyzed at predetermined time points (the preanhepatic, anhepatic, and postreperfusion phases). We simultaneously conducted conventional coagulation tests. In children with ALF, preanhepatic measurements of conventional coagulation tests and ROTEM® showed a more hypocoagulable state than other diseases. During LT, the coagulation profile was deranged, with a prolonged clotting time and reduced clot firmness, changes that were more profound in the cholestatic disease group. Maximum clot firmness (MCF) on EXTEM and FIBTEM were well correlated with the platelet count and fibrinogen concentration (r = 0.830, p < 0.001 and r = 0.739, p < 0.001, respectively). On the EXTEM, MCF with 30 mm predicted a platelet count <30,000/mm3 (area under the curve, 0.985), and 6 mm predicted a fibrinogen concentration <100 mg/dl on the FIBTEM (area under the curve, 0.876). However, the activated partial thromboplastin time and prothrombin time were significant but only weakly correlated with the clotting time on the ROTEM® . In children undergoing LT, coagulation profiles depend on the etiology for LT. During LT, ROTEM® parameters could help detect thrombocytopenia and hypofibrinogenemia and guide transfusion therapy as a point-of-care monitoring method.

A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects.

AIM: To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue under development, in healthy males and females presenting with no childbearing potential. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, single-ascending dose study was conducted in 56 subjects who randomly received a single subcutaneous dose of HM15136 or its matching placebo at a ratio of 6:2 at 10, 20, 30, 50, 80, 100, and 120 µg/kg. RESULTS: All adverse events were mild and transient. Neither serious adverse events nor discontinuation as a result of adverse events occurred. The most frequent adverse drug reaction was nausea (5.3%, only in the 100- and 120-µg/kg groups). HM15136, particularly at doses of 50 µg/kg or higher, increased fasting blood glucose, with a maximum increase and area under the curve of 1.5 mmol/L at day 10 (P = .006) and 166.3 day·mmol/L (P = .022) at the dose of 80 µg/kg, while suppressing the secretion of endogenous glucagon, which continued until day 17. HM15136 also significantly reduced gluconeogenic and ketogenic amino acids. Compensatory changes in endogenous insulin and incretin hormones by HM15136 were not apparent. HM15136 was slowly but steadily absorbed and reached a peak concentration at 46-68 hours after a single subcutaneous injection. HM15136 was eliminated with a terminal phase half-life of 77.1-101.1 hours. CONCLUSIONS: A single subcutaneous dose of HM15136 at 10-120 µg/kg was safe and well tolerated. The long half-life of HM15136, coupled with an increase in blood glucose for ~2 weeks, may warrant a weekly dosing regimen.

Clinical implication of intraoperative ventricular-arterial coupling in pediatric patients undergoing ventricular septal defects repair: A retrospective cohort study.

BACKGROUND: Ventricular-arterial coupling is the ratio of arterial elastance to ventricular end-systolic elastance. AIMS: The objective of this study was to determine the clinical implication of intraoperative ventricular-arterial coupling derived from the pressure-area relationship using transesophageal echocardiography. METHODS: This retrospective study reviewed the medical records of 72 pediatric patients with ventricular septal defects who underwent corrective surgery with cardiopulmonary bypass. The single-beat modified method was used to assess ventricular-arterial coupling. Logistic regression analyses were performed to determine the correlation between ventricular-arterial coupling and early postoperative outcomes, including the maximum vasoactive-inotropic score, length of mechanical ventilation, and length of hospital stay. RESULTS: Ventricular-arterial coupling after cardiopulmonary bypass significantly increased (from 1.0 ± 0.4 to 1.4 ± 0.8, p < .001), indicating a disproportionate increase in the arterial elastance index (from 11.5 ± 5.1 to 19.8 ± 7.5 mmHg/cm2 /m2 , p < .001) compared with the ventricular end-systolic elastance index (from 13.0 ± 6.9 to 16.9 ± 9.0 mmHg/cm2 /m2 , p < .001). Logistic regression analyses revealed that high postoperative ventricular-arterial coupling was independently associated with higher postoperative maximum vasoactive-inotropic score (>10; odds ratio [OR], 8.04; 95% confidence interval [CI], 1.38-46.85, p = .020), longer postoperative mechanical ventilation (>15 h; OR: 11.00; 95% CI: 1.26-96.45, p = .030), and longer postoperative hospital stay (>7 days; OR: 2.98; 95% CI: 1.04-8.58, p = .043). CONCLUSIONS: Ventricular-arterial coupling can be easily obtained from the intraoperative transesophageal echocardiography in pediatric patients undergoing ventricular septal defects repair. High postoperative ventricular-arterial coupling is strongly associated with worse early postoperative outcomes. Ventricular-arterial coupling shows promise as an intraoperative analysis tool that can provide insight into the impact of interventions on cardiovascular performance and identify potential targets for treatment in this population.

Who are at high risk of mortality and morbidity among children with congenital heart disease undergoing noncardiac surgery?

With advances in the development of surgical and medical treatments for congenital heart disease (CHD), the population of children and adults with CHD is growing. This population requires multiple surgical and diagnostic imaging procedures. Therefore, general anesthesia is inevitable. In many studies, it has been reported that children with CHD have increased anesthesia risks when undergoing noncardiac surgeries compared to children without CHD. The highest risk group included patients with functional single ventricle, suprasystemic pulmonary hypertension, left ventricular outflow obstruction, and cardiomyopathy. In this review, we provide an overview of perioperative risks in children with CHD undergoing noncardiac surgeries and anesthetic considerations in patients classified as having the highest risk.

Use of a High-Flow Nasal Cannula in a Child With a Functional Single Ventricle and Difficult Airway.

Inducing anesthesia and securing the airway without disrupting the patient's hemodynamic state are challenging in pediatric patients with a functional single ventricle (FSV). Here, the authors report effective use of a high-flow nasal cannula (HFNC) as a tool in providing oxygen supplementation for airway management in pediatric FSV patients with a history of a difficult airway. A female patient, aged 5 years 7 months, was admitted for extracardiac conduit Fontan procedure. The patient had a history of multiple failed attempts at endotracheal intubation and was diagnosed with retrognathia and severe oral trismus of less than 1 finger width. The patient had another event of mask ventilation failure after propofol sedation during the preoperative computed tomography scan a day before the surgery. The patient's preoperative cardiac catheterization report revealed that the Qp/Qs ratio of 0.82 at room air, and the patient's peripheral oxygen saturation (SpO2) ranged from 70% to 80% at room air. On entering the operating room, the preoxygenation process began with HFNC at an oxygen flow of 16 L/min, with a fraction of inspired oxygen (FIO2) set at 95% after light sedation with an intravenous bolus of midazolam, 0.1 mg/kg. After 4 minutes of applying HFNC, with SpO2 rising from 76% to 98%, anesthetic medications were administered intravenously without a neuromuscular blocking agent to preserve spontaneous breathing. The patient was not ventilated with a facemask but instead left with HFNC in place for continuous supplemental oxygenation. The patient's airway was secured in a single attempt in 80 seconds. HFNC is an ideal option for oxygen supplementation during airway management of pediatric FSV patients, as their balance of pulmonary and systemic flow is perturbed easily by subtle physiologic alteration and therapeutic maneuvers during the induction of general anesthesia and highly susceptible to rapid desaturation and cardiovascular collapse, and should be considered as having a physiologically difficult airway.

Preoperative high-sensitivity troponin I and B-type natriuretic peptide, alone and in combination, for risk stratification of mortality after liver transplantation.

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

Prognostic Value of B-Type Natriuretic Peptide in Liver Transplant Patients: Implication in Posttransplant Mortality.

BACKGROUND AND AIMS: Despite frequent cirrhotic cardiomyopathy or subclinical heart failure (HF), the prognostic value of peri-liver transplant (LT) B-type natriuretic peptide (BNP) has been poorly studied in advanced liver disease. We examined the association between BNP and mortality in a large cohort of LT patients and identified risk factors for peri-LT BNP increase. APPROACH AND RESULTS: Using prospectively collected data from the Asan LT Registry between 2008 and 2019, 3,811 patients who measured serial pretransplant BNP (preBNP) and peak BNP levels within the first 3 posttransplant days (postBNPPOD3 ) were analyzed. Thirty-day all-cause mortality predicted by adding preBNP and/or postBNPPOD3 to the traditional Revised Cardiac Risk Index (RCRI) was evaluated. PreBNP > 400 pg/mL (known cutoff of acute HF) was found in 298 (7.8%); however, postBNPPOD3  > 400 pg/mL was identified in 961 (25.2%) patients, specifically in 40.4% (531/1,315) of those with a Model for End-Liver Disease score (MELDs) > 20. Strong predictors of postBNPPOD3  > 400 pg/mL were preBNP, hyponatremia, and MELDs, whereas those of preBNP > 400 pg/mL were MELDs, kidney failure, and respiratory failure. Among 100 (2.6%) post-LT patients who died within 30 days, patients with postBNPPOD3  ≤ 150 pg/mL (43.1%, reference group), 150-400 pg/mL (31.7%), 400-1,000 pg/mL (18.5%), 1,000-2,000 pg/mL (4.7%), and >2,000 pg/mL (2.0%) had 30-day mortalities of 0.9%, 2.2%, 4.0%, 7.7%, and 22.4%, respectively. Adding preBNP, postBNPPOD3 , and both BNP to RCRI improved net reclassification index to 22.5%, 29.5%, and 33.1% of 30-day mortality, respectively. CONCLUSIONS: PostBNPPOD3  > 400 pg/mL after LT was markedly prevalent in advanced liver disease and mainly linked to elevated preBNP. Routine monitoring of peri-LT BNP provides incremental prognostic information; therefore, it could help risk stratification for mortality as a practical and useful biomarker in LT.

Cep215 is essential for morphological differentiation of astrocytes.

Cep215 (also known as Cdk5rap2) is a centrosome protein which is involved in microtubule organization. Cep215 is also placed at specific subcellular locations and organizes microtubules outside the centrosome. Here, we report that Cep215 is involved in morphological differentiation of astrocytes. Cep215 was specifically localized at the glial processes as well as centrosomes in developing astrocytes. Morphological differentiation of astrocytes was suppressed in the Cep215-deleted P19 cells and in the Cep215-depleted embryonic hippocampal culture. We confirm that the microtubule organizing function of Cep215 is critical for the glial process formation. However, Cep215 is not involved in the regulation of cell proliferation nor cell specification. Based on the results, we propose that Cep215 organizes microtubules for glial process formation during astrocyte differentiation.

Acute Change in Ventricular Contractility-Load Coupling After Corrective Surgery for Congenital Heart Defect: A Retrospective Cohort Study.

Ventricular performance and its loading condition change drastically after surgical correction of congenital heart defect. Pressure-volume loops analysis can provide quantitative information about ventriculo-arterial coupling (VAC) indicating the interaction between ventricular contractility and loading condition. Therefore, we investigated changes in VAC after corrective surgery for ventricular septal defect (VSD)/tetralogy of Fallot (TOF), and implication of ventriculo-arterial decoupling as a prognostic factor of post-operative outcomes. In children with VSD/TOF, pre- and post-operative arterial elastance (Ea), end-systolic ventricular elastance (Ees) and VAC (Ea/Ees) were non-invasively estimated using echocardiographic parameters. Post-operative outcomes included maximum vasoactive-inotropic score, the duration of mechanical ventilation and hospital stay. Preoperatively, patients with VSD had significantly lower Ea and Ees than patients with TOF; however, VAC were preserved in both. In patients with VSD, post-operative Ea increased disproportionately to change in Ees, resulting in increased VAC. Post-operative higher VAC in patients with VSD was independently associated with maximum vasoactive-inotropic score (odds ratio [OR] 63.9; 95% Confidence Interval [CI] 4.0-553.0; P = 0.003), prolonged mechanical ventilation (OR 6.3; 95% CI 1.1-37.8; P = 0.044) and longer hospitalization (OR 17.6; 95% CI 1.6-187.0; P = 0.018). In patients with TOF, Ea and Ees reduced post-operatively; however, VAC remained unchanged and was not associated with post-operative outcomes. Despite of different loading condition, preoperative VAC maintained in both of VSD and TOF. However, particularly in VSD patients, abrupt increase in post-operative loading state induces contractility-load decoupling, which leads to worse post-operative outcomes.

Low Muscle Mass as a Prognostic Factor for Early Postoperative Outcomes in Pediatric Patients Undergoing the Fontan Operation: A Retrospective Cohort Study.

The impact of low muscle mass on pediatric cardiac patients remains unclear. We investigated the impact of low muscle mass on early postoperative outcomes in patients undergoing the Fontan operation. The electronic medical records of 74 patients (aged <18 years) who underwent the Fontan operation were retrospectively reviewed. The cross-sectional areas of the erector spinae and pectoralis muscles were measured using preoperative chest computed tomography (CT), normalized to the body surface area, and combined to obtain the total skeletal muscle index (TSMI). Low muscle mass was defined as a TSMI value lower than the median TSMI for the second quintile. The incidence of major postoperative complications was higher in patients with low muscle mass than in those with high muscle mass (48% (15/31) versus 14% (6/43); P = 0.003). Multivariable analyses revealed that a higher TSMI was associated with a lower likelihood of an increased duration of intensive care unit (>5 days) and hospital stay (>14 days) (odds ratio (OR) 0.86; 95% confidence interval (CI) 0.77-0.96; P = 0.006 and OR 0.92; 95% CI 0.85-0.99; P = 0.035 per 1 cm2/m2 increase in TSMI) and incidence of major postoperative complications (OR 0.90; 95% CI 0.82-0.99; P = 0.039 per 1 cm2/m2 increase in TSMI). Preoperative low muscle mass was associated with poor early postoperative outcomes in pediatric patients undergoing the Fontan operation.

Respiratory Variations in Electrocardiographic R-Wave Amplitude during Acute Hypovolemia Induced by Inferior Vena Cava Clamping in Patients Undergoing Liver Transplantation.

The aim of this study was to analyze whether the respiratory variation in electrocardiogram (ECG) standard lead II R-wave amplitude (ΔRDII) could be used to assess intravascular volume status following inferior vena cava (IVC) clamping. This clamping causes an acute decrease in cardiac output during liver transplantation (LT). We retrospectively compared ΔRDII and related variables before and after IVC clamping in 34 recipients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to derive a cutoff value of ΔRDII for predicting pulse pressure variation (PPV). After IVC clamping, cardiac output significantly decreased while ΔRDII significantly increased (p = 0.002). The cutoff value of ΔRDII for predicting a PPV >13% was 16.9% (AUC: 0.685) with a sensitivity of 57.9% and specificity of 77.6% (95% confidence interval 0.561 - 0.793, p = 0.015). Frequency analysis of ECG also significantly increased in the respiratory frequency band (p = 0.016). Although significant changes in ΔRDII during vena cava clamping were found at norepinephrine doses <0.1 µg/kg/min (p = 0.032), such changes were not significant at norepinephrine doses >0.1 µg/kg/min (p = 0.093). ΔRDII could be a noninvasive dynamic parameter in LT recipients presenting with hemodynamic fluctuation. Based on our data, we recommended cautious interpretation of ΔRDII may be requisite according to vasopressor administration status.