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BACKGROUND: Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes. METHODS: The Pediatric Heart Transplant Society database was queried for patients <18 years of age indicated for heart transplantation between January 1, 2010 to December 31, 2021. Waitlist mortality was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support. RESULTS: In total 5974 children met study criteria of which 3928 were status 1A, 1012 were status 1B, 963 were listed status 2, and 65 were listed status 7. Because of the significant burden of WM experienced by 1A patients, further analysis was performed in only patients indicated as 1A. Within that group of patients, those with smaller size and lower eGFR had higher WM, whereas those patients without congenital heart disease or support from a ventricular assist device (VAD) at time of listing had decreased WM. In the smallest size cohort, cardiac diagnoses other than dilated cardiomyopathy were risk factors for WM. Previous cardiac surgery was a risk factor in the 0.3 to 0.7 m2 and >0.7 m2 BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts. CONCLUSIONS: There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Purpose: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. Methods: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle–Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. Results: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C–E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33–0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46–0.66). Conclusion: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence. [ABSTRACT FROM AUTHOR]

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Background: Cardiogenic shock (CS) exhibits high (~50%) in-hospital mortality. The recently published Extracorporeal life Support in Cardiogenic Shock (ECLS-SHOCK) trial demonstrated the neutral effects of the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on all-cause death, as well as on all secondary outcomes in subjects presenting with myocardial-infarction (MI)-related CS. Here, we compared ECLS-SHOCK eligibility criteria with a real-world cohort of CS patients. Methods and Results: ECLS-SHOCK eligibility criteria were applied to a prospective single-center CS registry (the PREPARE CS registry) consisting of 557 patients who were consecutively admitted to the catheterization laboratory (cath lab) of the Medical University of Graz, Austria, due to CS (SCAI C-E). Overall use of mechanical circulatory support (MCS) in this cohort was 19%. Sixty-nine percent of the entire cohort had MI-related CS, 38% of whom would have met ECLS-SHOCK eligibility criteria, thus representing only 27% of the PREPARE CS registry. Exclusion from the ECLS-SHOCK trial was based on patients with initial lactate values below 3 mmol/L (n = 168; 43.6%), aged over 80 years (n = 65; 16.9%), and with a duration of cardiopulmonary resuscitation (CPR) exceeding 45 min (n = 22; 5.7%). The 30-day mortality of patients of the PREPARE CS registry who met the ECLS-SHOCK eligibility criteria was 57.0%, compared to 48.4% of patients in the ECLS-SHOCK trial. The patients' baseline characteristics, however, differed considerably with respect to type of infarction, age, and gender. Conclusions: In a real-world cohort of patients with MI-related CS, only 38% of patients met the eligibility criteria of the ECLS-SHOCK trial. Thus, the impact of the use of VA-ECMO on outcome parameters in MI-related CS, as observed in the ECLS-SHOCK trial, may differ in a more heterogeneous real-world CS population of the PREPARE CS registry. [ABSTRACT FROM AUTHOR]

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is a form of temporary mechanical circulatory support and simultaneous extracorporeal gas exchange for acute cardiorespiratory failure, including refractory cardiogenic shock (CS) and cardiac arrest (CA). Few studies have assessed predictors of successful weaning (SW) from VA ECMO. This systematic review and meta-analysis aimed to identify a multiparameter strategy associated with SW from VA ECMO. PubMed and the Cochrane Library and the International Clinical Trials Registry Platform were searched. Studies reporting adult patients with CS or CA treated with VA ECMO published from the year 2000 onwards were included. Primary outcomes were hemodynamic, laboratory, and echocardiography parameters associated with a VA ECMO SW. A total of 11 studies (n=653) were included in this review. Pooled VA ECMO SW was 45% (95%CI: 39–50%, I2 7%) and in-hospital mortality rate was 46.6% (95%CI: 33–60%; I2 36%). In the SW group, pulse pressure [MD 12.7 (95%CI: 7.3–18) I2 = 0%] and mean blood pressure [MD 20.15 (95%CI: 13.8–26.4 I2 = 0) were higher. They also had lower values of creatinine [MD –0.59 (95%CI: –0.9 to –0.2) I2 = 7%], lactate [MD –3.1 (95%CI: –5.4 to –0.7) I2 = 89%], and creatine kinase [–2779.5 (95%CI: –5387 to –171) I2 = 38%]. And higher left and right ventricular ejection fraction, MD 17.9% (95%CI: –0.2–36.2) I2 = 91%, and MD 15.9% (95%CI 11.9–20) I2 = 0%, respectively. Different hemodynamic, laboratory, and echocardiographic parameters were associated with successful device removal. This systematic review demonstrated the relationship of multiparametric assessment on VA ECMO SW. [ABSTRACT FROM AUTHOR]

Background: Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. Methods: Data of 354 patients undergoing ECLS with one‐, two, three‐, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. Results: The median follow‐up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30‐day survival and 1‐year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR = 2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). Conclusion: MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi‐organ dysfunction. [ABSTRACT FROM AUTHOR]

Objective: When patients deteriorate after decannulation from extracorporeal membrane oxygenation (ECMO), a second run of extracorporeal support may be considered. However, repeat cannulation can be difficult and poor outcomes associated with multiple ECMO runs are a concern. The aim of this study was to evaluate outcomes and identify factors associated with survival and mortality in cases of multiple runs of extracorporeal membrane oxygenation. Design: Retrospective cohort analysis of the Extracorporeal Life Support Organization Registry. Setting: The Extracorporeal Life Support Organization’s registry was queried for neonates, children, and adults receiving 2 or more runs of ECMO during the same hospitalization, for any indication, from 1998 to 2015. Patients: 1,818 patients from the Extracorporeal Life Support Organization Registry. Results: Of the 1,818 patients, 1,648 underwent 2 runs and 170 underwent 3 or more runs of ECMO. The survival to discharge rate was 36.7% for 2 runs and 29.4% for 3 or more runs. No significant differences in survival were detected in analysis by decade of ECMO run (p = 0.21). Pediatric patients had less mortality than adults (OR: 0.45, 95%CI: 0.24-0.82). Cardiac support on the first run portrayed worse mortality than pulmonary support regardless of final run indication (OR:1.38, 95%CI: 1.09-1.75). Across all age groups, patients receiving pulmonary support on the last run tended to have higher survival rates regardless of support type on the first run. The only first run complication independently predictive of mortality on the final run was renal complications (OR: 1.60, 95%CI: 1.28-1.99). Conclusions: Though the use of multiple runs of ECMO is growing, outcomes remain poor for most cohorts. Survival decreases with each additional run. Patients requiring additional runs for a pulmonary indication should be considered prime candidates. Renal complications on the first run significantly increases the risk of mortality on subsequent runs, and as such, careful consideration should be applied in these cases. [ABSTRACT FROM AUTHOR]

Timing and causes of hospital mortality in adult patients undergoing veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) have been poorly described. Aim of the current review was to investigate the timing and causes of death of adult patients supported with V‐A ECMO and subsequently define the "V‐A ECMO gap," which represents the patients who are successfully weaned of ECMO but eventually die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V‐A ECMO patients from January 1993 to December 2020 were screened. The studies included in this review were studies that reported more than 10 adult, human patients, and no mechanical circulatory support other than V‐A ECMO. Information extracted from each study included mainly mortality and causes of death on ECMO and after weaning. Complications and discharge rates were also extracted. Sixty studies with 9181 patients were included for analysis in this systematic review. Overall mortality was 38.0% (95% confidence intervals [CIs] 34.2%‐41.9%) during V‐A ECMO support (reported by 60 studies) and 15.3% (95% CI 11.1%‐19.5%, reported by 57 studies) after weaning. Finally, 44.0% of patients (95% CI 39.8‐52.2) were discharged from hospital (reported by 60 studies). Most common causes of death on ECMO were multiple organ failure, followed by cardiac failure and neurological causes. More than one‐third of V‐A ECMO patients die during ECMO support. Additionally, many of successfully weaned patients still decease during hospital stay, defining the "V‐A ECMO gap." Underreporting and lack of uniformity in reporting of important parameters remains problematic in ECMO research. Future studies should uniformly define timing and causes of death in V‐A ECMO patients to better understand the effectiveness and complications of this support. [ABSTRACT FROM AUTHOR]

The effectiveness of intra‐aortic balloon pump (IABP) combined with venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in patients with cardiogenic shock or cardiac arrest remains controversial. The aim of this systematic review and meta‐analysis was to investigate the short‐term clinical outcomes of IABP combined with VA‐ECMO versus VA‐ECMO alone. We searched PubMed, Embase, and the Cochrane Library for English language articles published from inception to August 18, 2018. Observational studies comparing IABP combined with VA‐ECMO with VA‐ECMO were considered eligible for the current study. Twelve observational studies with 3704 patients were included. In the IABP combined with VA‐ECMO group mortality was 59.7%, compared with 65.8% in the VA‐ECMO alone group. The risk ratio (RR) for this comparison was 0.90 (95% confidence interval [CI], 0.80–1.02; P = 0.107; 59.7% vs. 65.8%). In the one‐way sensitivity analysis for estimating the effect of each study on mortality, omission of each study did not make a significant difference. Furthermore, the proportion of patients weaned from VA‐ECMO was significantly higher in IABP combined VA‐ECMO group than in the VA‐ECMO alone group (RR, 1.28; 95% CI, 1.21–1.35; P < 0.001; 77.9% vs. 61.2%). IABP combined with VA‐ECMO could improve success rate of weaning from VA‐ECMO, but did not reduce in‐hospital mortality in patients with cardiogenic shock or cardiac arrest. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic complications. Optimal anti-coagulation monitoring is controversial. We compared coagulation tests evaluating the heparin effect in pediatric ECLS. Methods: A retrospective study of children (<18yrs) undergoing ECLS over 12 months in a tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), activated clotting time (ACT) and thromboelastogram (TEG®6s) parameters: ratio and delta reaction (R) times (the ratio and difference, respectively, between R times in kaolin assays with and without heparinase). Test results were correlated with unfractionated heparin infusion rate (IU/kg/hr) at the time of sampling. Mean test results of each ECLS run were evaluated according to the presence/absence of complications. Results: Thirty-two ECLS runs (31 patients) generated 695 data-points for correlation. PICU mortality was 22% and the thrombotic complication rate was 66%. The proportion of variation in coagulation test results explained by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta R time, compared with <1% for ACT and aPTT. Incorporating individual variation, age and antithrombin activity in a model with heparin dose explained less than 50% of the variation in test results. Correlation varied according to age, day of ECLS run and between individuals, with parallel dose-response lines noted between patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and runs with thrombosis. Conclusion: Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6®s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between individuals. Population pharmacokinetic/pharmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non- ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non- ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non- ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome. [ABSTRACT FROM AUTHOR]

OBJECTIVES We observed early acute lung injury (ALI) after a switch from veno-arterial extracorporeal life support (VA-ECLS) to long-term mechanical circulatory support (MCS). The aim of our study was to analyse the frequency, impact on mortality and characteristics of patients presenting ALI after MCS implantation in the bridge-to-bridge (BTB) strategy. METHODS We retrospectively analysed data from 55 consecutive cardiogenic shock patients who underwent a BTB strategy between January 2004 and March 2012 in our centre. ALI was defined as severe acute respiratory failure (PaO2/FiO2 <200) with or without need for iterative VA-ECLS or veno-venous (VV)-exracorporeal membrane oxygenation (ECMO) occurring within 48 h of MCS implantation. RESULTS ALI was observed in 15 of 55 (27%) patients. Eleven patients required VV-ECMO or VA-ECLS and 4 were treated medically. The median (interquartile range) duration of support under a long-term device was 47.5 (168.8) days. Mortality while on long-term support was significantly higher in patients who developed ALI (13 of 15, 87%) than in those who did not (21 of 40, 53%; P = 0.03). Hazard ratio for death while on support in patients who developed ALI when compared with those who did not was 3.390 (95% confidence interval, 1.636–7.026, P = 0.001). Univariate risk factors for postimplant ALI included: signs of pulmonary oedema while under extracorporeal life support (ECLS) during the week preceding long-term device implantation; mechanical ventilation, the incomplete recovery of renal and hepatic functions and the number of red blood cell units transfused at the time of long-term device implantation, and use of pulsatile, biventricular support. CONCLUSIONS Implantation of a long-term MCS device in patients on ECLS can result in severe ALI, which is associated with ominous outcomes. Various preimplant risk factors for ALI have been identified and might allow devising strategies to prevent this complication. [ABSTRACT FROM AUTHOR]

Purpose: The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation. Methods: This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines. Results: The survival rate in patients treated with ECMO was 68 %. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR = 1.52, 95 % CI 1.12-2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52-3.52, p < 0.001), creatinine (OR = 7.38, 95 % CI 1.43-38.11, p = 0.02) and hematocrit values (OR = 0.82, 95 % CI 0.72-0.94, p = 0.006); and mean arterial pressure (OR = 0.92, 95 % CI 0.88-0.97, p < 0.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis ( c = 0.857, 95 % CI 0.754-0.959, p < 0.001) and by an independent external validation analysis ( c = 0.694, 95 % CI 0.562-0.826, p = 0.004). Conclusions: Mortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) can provide short-term cardiopulmonary support to critically ill patients. Among ECMO patients, acute renal failure requiring dialysis has an ominous prognosis. However, a prognostic scoring system and risk factors adjustment for hospital mortality in these patients have not been elucidated previously. A multicenter observational cohort study was conducted from January 2002 to December 2006. Information obtained included demographics, biochemical variables, Acute Physiology and Chronic Health Evaluation (APACHE) II, III, and IV scores at ICU admission and initial acute dialysis, and hospital mortality in 102 non-coronary artery bypass graft (CABG) patients receiving ECMO support with acute dialysis. This retrospective cohort study included 70 men and 32 women with a mean age of 47.9 ± 15.7 years. Seventy-two patients (70.6%) had hospital mortality. The area under the receiver operating characteristic curve showed APACHE IV (0.653) had a better discriminative power to predict hospital mortality than APACHE II (0.584) and APACHE III (0.634) at initializing dialysis. Hosmer-Lemeshow statistics showed good calibration for all three scores to predict hospital mortality at initializing dialysis (APACHE IV, P = 0.392; APACHE III, P = 0.094; and APACHE II, P = 0.673). Independent predictors for hospital mortality by multivariate logistic regression analysis were higher central venous pressure (odds ratio [OR], 1.11; confidence interval [CI] 95%, 1.02-1.20; P = 0.016), higher APACHE IV score at initializing dialysis (OR, 1.03; CI 95%, 1.01-1.05; P = 0.003), and latency from hospital admission to dialysis (OR, 1.04; CI 95%, 1.00-1.08; P = 0.033). High mortality rate was noted in non-CABG patients receiving ECMO and acute dialysis. Predialysis APACHE IV scores had good calibration and moderate discrimination in predicting hospital mortality in these patients. Because ECMO support could stabilize cardiopulmonary status, APACHE IV scores would likewise underestimate disease severity at lower score ranges in these patients. [ABSTRACT FROM AUTHOR]

Serious pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO) when other treatment has failed. The aim of this study was to analyze preoperative risk factors of early mortality in patients who underwent either veno-arterial (VA) ECMO or venovenous (VV) ECMO for pulmonary failure. We studied a total of 26 risk factors in 72 patients with severe pulmonary insufficiency treated with ECMO. All consecutive cases treated at our institution between Sept 1990 and Aug 2007 were included. Univariate analysis and multiple logistic regression analysis were performed on 26 risk factors. The end point was early mortality (any death within 30 days of ECMO treatment). Thirty-six (50%) of the patients died within 30 days of treatment. Age, gender, body mass index(BMI)(adults), cause of pulmonary failure, pre-ECMO treatment with nitric oxide (NO), intra-aortic balloon pump(IABP), and type of ventilation did not significantly influence early mortality. Neither pre-operative blood gas results, oxygenation index or pre-operative PaO2/FiO2 ratio, nor mean ventilator days prior to ECMO gave any indications on early mortality. Liver function did not predict early mortality, but pre-ECMO serum creatinine levels were significantly lower in patients who survived. Treatment with ECMO in patients with severe pulmonary failure may save lives. It is, however, difficult to predict outcome when initiating ECMO. In this analysis, only pre-operative serum creatinine levels correlated with survival. None of the other parameters, including those which were used to select patients for ECMO treatment, could significantly predict the outcome. [ABSTRACT FROM AUTHOR]

Mechanical support is often the only therapeutic option in low cardiac output (LCO) following cardiac operation using extracorporeal circulation (ECC). However, the question whether primary ventricular assist device (VAD) or primary extracorporeal membrane oxygenation (ECMO) followed by secondary VAD implantation is superior remains unclear. We analyzed the outcome of 183 patients with LCO following ECC. Primary VAD implantation (VAD) was performed on 20 patients and 163 patients underwent ECMO implantation (ECMO). Out of this group, 13 patients received a secondary VAD (ECMO-VAD). Age was significantly lower in the VAD group, while gender and type of operation were similarly distributed. Thirty-day mortalities were 50, 75, and 46% (VAD, ECMO, and ECMO-VAD, respectively; P < 0.05 ECMO vs. VAD and ECMO-VAD). Survival was best with VAD implantation 1.2 ± 1.2 days following LCO. In conclusion, the outcome of LCO following ECC remains poor. Early VAD support provides best survival. Primary or secondary VAD implantation has no impact on survival. [ABSTRACT FROM AUTHOR]