Implementation and validation of a novel instrument for the grading of unexpected events in paediatric surgery: Clavien–Madadi classification

Background: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children./ Methods: A multidisciplinary group of experts modified the Clavien–Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien–Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien–Dindo and Clavien–Madadi classifications were compared and correlated with procedure complexity./ Results: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien–Madadi classification identified 449 additional events (organizational and management errors) over the Clavien–Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien–Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien–Dindo classification (ρ = 0.198)./ Conclusion: The Clavien–Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use

Nickel contamination after minimally-invasive repair of pectus excavatum persists after bar removal

Background Minimally-invasive repair of pectus excavatum (MIRPE) has been shown to be associated with high release of trace metals into patient’s body. The aim of our study was to analyze the kinetics of metal contamination after MIRPE and after bar removal. Methods We prospectively assessed nickel and chromium changes in blood, urine, and local tissue in patients undergoing MIRPE with stainless-steel bar(s). Baseline samples were taken prior to surgery, further samples were taken at six defined time points until 30 months after bar removal. Clinical symptoms were evaluated at the time of every sample collection. Results 28 patients were included (mean age 16.4 years). At four weeks after MIRPE and persisting up to bar removal, we found significantly elevated trace metal levels in blood and urine. Tissue nickel and chromium levels were significantly elevated at the time of bar removal. After bar removal, the concentration of trace metal in urine and the concentration of chromium in plasma decreased gradually. In contrast, nickel levels in blood further increased. Five patients showed irritative symptoms after MIRPE, all symptomatic patients had elevated metal levels. Conclusions Following MIRPE, we found a rapid systemic increase of nickel and chromium. Our data indicate that trace metal release could cause irritative symptoms. The prolonged elevated systemic nickel levels beyond bar removal necessitate further investigations of the long-term side effects of MIRPE

High temperature behaviour of a CuO/Al2O3 oxygen carrier for Chemical-Looping Combustion

8 pages, 10 figures, 2 tables.- Available online April 13, 2011.Chemical-Looping Combustion (CLC) is a combustion technology with inherent CO2 separation and, therefore, without energy losses. CLC is based on the transfer of oxygen from the air to the fuel by means of an oxygen carrier (OC) in the form of a metal oxide. The OC circulates between two interconnected reactors, the fuel (FR) and the air reactor (AR). To scale up the CLC process for industrial application OCs materials suitable to work at high temperatures are needed. So far, Cu-based OCs had been proved to fulfil the requirements for an OC material, although operating temperatures lower than 1073 K are recommended. In this work, the behaviour of an impregnated Cu-based oxygen carrier (CuO-Al2O3) was studied in a continuous CLC unit of 500 Wth during long-term tests using methane as fuel gas and FR temperatures up to 1173 K and AR temperatures up to 1223 K. The behaviour of the oxygen carrier on the process performance was evaluated taking into account important aspects such as combustion efficiency, resistance to attrition, fluidization behaviour and preservation of the oxygen transport capacity and reactivity. It was found that both TFR and TAR had a great influence on the resistance to attrition of the particles. Stable operation for more than 60 h was only feasible at TFR =1073 K and TAR = 1173 K. However agglomeration or deactivation of the particles was never detected in any of the temperatures used. This is the first time that a CuO-Al2O3 OC, prepared by a commercial manufacturing method, and used at 1073K in the FR and 1173 K in the AR exhibits such a good properties: high reactivity together with high mechanical durability and absence of agglomeration. This result opens new possibilities for the application of Cu-based materials in industrial-scale CLC processes.This research was conducted with financial support from the Spanish Ministry of Science and Innovation (MICINN, Project CTQ2007-64400) and C.S.I.C. (200480E619).Peer reviewe

Titanium nitride coating of pectus bar increases metal contamination after minimally-invasive repair of pectus excavatum

Introduction Previous studies demonstrated a release of toxic metals, e.g. nickel and chromium, from stainless steel bars used for minimally invasive repair of pectus excavatum (MIRPE). In the present study, we investigated the impact of titanium nitride coating on the metal release and exposure of MIRPE patients. Material and methods We analyzed the courses of nickel and chromium levels in blood, urine and local tissue in patients undergoing MIRPE with a titanium nitride coated pectus bar between 03/2017 and 10/2018. Sample collection was scheduled prior to MIRPE, at defined postoperative time points and at bar removal. Additionally, we evaluated irritative symptoms. Results were compared to a control group who received uncoated stainless steel bars in a previous time period (03/2015–02/2017). Results 12 patients received coated pectus bars (mean age 15.7 years). The control group included 28 patients. After implantation of a titanium nitride coated bar, significant increase in systemic nickel and chromium levels after one, two and three years was noted. In an interim analysis one year after MIRPE, we observed patients with coated bars to have significantly elevated trace metal values compared to the control group. This elevation persisted throughout the observation period. Tissue metal values were also significantly increased. Irritative symptoms occurred significantly more often in study patients compared to controls (50.0% vs. 14.3%). Conclusions Coating of pectus bars with titanium nitride failed to reduce metal contamination after MIRPE. Instead, it resulted in a significant increase of trace metal levels after MIRPE, compared to patients with stainless steel bars, which may be explained by wear of the coating and inter-component mobilization processes. </jats:sec

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444-143839360)-(159119486-159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition

Activation of Regulatory T Cells during Inflammatory Response Is Not an Exclusive Property of Stem Cells

BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS) remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS) in wild type mice (C3H/HeN). Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS) and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays), T cell subpopulations (flow-cytometry) and pulmonary neutrophil influx (immunohistochemistry). To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK) was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not exclusive attributes of stem cells

Trace metal release after minimally-invasive repair of pectus excavatum

Background Several studies have shown a high incidence of metal allergy after minimally-invasive repair of pectus excavatum (MIRPE). We postulated that MIRPE is associated with a significant release of trace metal ions, possibly causing the allergic symptoms. Methods We evaluated the concentration with chromium, cobalt and nickel in blood, urine and tissue in patients prior to MIRPE and in patients who underwent an explantation of the stainless-steel bar(s) after three years. Results Our study group consisted of 20 patients (mean age 19 years) who had bar explantation and our control group included 20 patients (mean age 16 years) prior to MIRPE. At the time of bar removal we detected significantly elevated concentrations of chromium and nickel in the tissue compared to patients prior to the procedure (p<0,001). We also found a significant increase in the levels of chromium in urine and nickel in blood in patients three years post MIRPE (p<0,001). Four patients temporarily developed symptoms of metal allergy, all had elevated metal values in blood and urine at explantation. Conclusions Minimally-invasive repair of pectus excavatum can lead to a significant trace metal exposure

Selection of Quality Indicators to Evaluate Quality of Care for Patients with Esophageal Atresia Using a Delphi Method

Objective Survival of neonates with esophageal atresia (EA) is relatively high and stable, resulting in increased attention to optimizing care and longer-term morbidity. This study aimed to reach consensus on a quality indicator set for benchmarking EA care between hospitals, regions, or countries in a European clinical audit.Methods Using an online Delphi method, a panel of EA health care professionals and patient representatives rated potential outcome, structure, and process indicators for EA care identified through systematic literature and guideline review on a nine-point Likert scale in three questionnaires. Items were included based on predefined criteria. In rounds 2 and 3, participants were asked to select the five to ten most essential of the included indicators.Results An international panel of 14 patient representatives and 71 multidisciplinary health care professionals representing 41 European hospitals completed all questionnaires (response rate: 81%), eventually including 22 baseline characteristics and 32 indicators. After ranking, 10 indicators were prioritized by both stakeholder groups. In addition, each stakeholder group highly prioritized one additional indicator. Following an additional online vote by the other group, these were both added to the final set.Conclusion This study established a core indicator set of twenty-two baseline characteristics, eight outcome indicators, one structure indicator, and three process indicators for evaluating (quality of) EA care in Europe. These indicators, covering various aspects of EA care, will be implemented in the European Pediatric Surgical Audit to enable recognition of practice variation and focus EA care improvement initiatives

Selection of Quality Indicators to Evaluate Quality of Care for Patients with Esophageal Atresia Using a Delphi Method

Objective Survival of neonates with esophageal atresia (EA) is relatively high and stable, resulting in increased attention to optimizing care and longer-term morbidity. This study aimed to reach consensus on a quality indicator set for benchmarking EA care between hospitals, regions, or countries in a European clinical audit.Methods Using an online Delphi method, a panel of EA health care professionals and patient representatives rated potential outcome, structure, and process indicators for EA care identified through systematic literature and guideline review on a nine-point Likert scale in three questionnaires. Items were included based on predefined criteria. In rounds 2 and 3, participants were asked to select the five to ten most essential of the included indicators.Results An international panel of 14 patient representatives and 71 multidisciplinary health care professionals representing 41 European hospitals completed all questionnaires (response rate: 81%), eventually including 22 baseline characteristics and 32 indicators. After ranking, 10 indicators were prioritized by both stakeholder groups. In addition, each stakeholder group highly prioritized one additional indicator. Following an additional online vote by the other group, these were both added to the final set.Conclusion This study established a core indicator set of twenty-two baseline characteristics, eight outcome indicators, one structure indicator, and three process indicators for evaluating (quality of) EA care in Europe. These indicators, covering various aspects of EA care, will be implemented in the European Pediatric Surgical Audit to enable recognition of practice variation and focus EA care improvement initiatives