Pediatrics

Neonatal Extra Corporeal Membrane Oxygenation: Impaired health at five years of age (Article)

Madderom, M.J. — 2012-06-27T00:00:00Z

Objective: Children treated with neonatal Extra Corporeal Membrane Oxygenation (ECMO) may show physical and mental morbidity at later age. We compared the health-related quality of life (HRQOL) of these children with normative data. Design: Prospective longitudinal follow-up study. Setting: Outpatient clinic of a III level university hospital. Patients: 95 five-year-olds who had received neonatal ECMO support between January 1999 and December 2005. Interventions: None. Measurements: The Pediatric Quality of Life Inventory (PedsQL) was administered at 5 years of age. Main results: The mothers (n=74) as proxy-reporters assigned significantly lower HRQOL scores for their children than did the parents in the healthy reference group for the total functioning scale of the PedsQL (mean difference:8.1, p<0.001). Mothers’ scores for 31 children (42%) were indicative of impaired HRQOL (≥-1 SD below the reference norm). The children (n=78) themselves scored significantly lower than did their healthy peers on total functioning (mean difference:11.0, p<0.001). Thirty-two children (41%) indicated an impaired HRQOL themselves. For the mother proxy-reports, duration of ECMO support (R2=0.009, p=0.010) and the presence of chronic lung disease (R2=0.133, p=0.002) were negatively related to total functioning. Children with a disabled health status for neuromotor functioning, maximum exercise capacity, behavior and cognitive functioning at five years of age had a higher odds ratio of also having a lower HRQOL. Health status had no influence on reported emotional functioning. Conclusions: Overall, children treated with ECMO in the neonatal period reported low HRQOL at 5 years of age. Because only emotional HRQOL was not associated with health status, the PedsQL might be a measure of health status rather than of HRQOL. In contrast with conclusions from others we found that 5-year-old children might be too young to rate their own HRQOL.

Sensorineural hearing loss and language development following neonatal extracorporeal membrane oxygenation (Article)

Hondel, D. van den — 2012-06-27T00:00:00Z

OBJECTIVE: To determine the prevalence of hearing loss in school-age children who have undergone neonatal extracorporeal membrane oxygenation (ECMO) treatment and to identify any effects of hearing loss on speech- and language development. DESIGN: Prospective longitudinal follow-up study within the framework of a structured post-ECMO follow-up program. SETTING: Outpatient clinic of a level III university hospital. RESULTS: Tone audiometry was performed by standardized protocol in 136 children aged 5 to 12 years. Hearing loss was considered clinically significant when >20dB. Hearing was normal in 75.7% of children. Five children (3.7%) had bilateral sensorineural or combined hearing loss; 3 of them received special audiological care (2.2% of total sample). Of the 24 children with congenital diaphragmatic hernia, 19 (79.2%) had normal hearing; and only 2 (8.3%) had mild SNHL, unilateral in one of them. Follow-up at 24 months of age had shown normal verbal and non-verbal developmental scores. Language development and intelligence median (range) scores at 5 years of age were also normal: receptive language development 104 (55-133); syntactical development 104 (68-132); and lexical development 101 (50-141) for 89 children; intelligence quotient was 104 (68-132) in 106 children. Scores did not differ between those with normal hearing, and those with mild hearing loss, or those with moderate to severe hearing loss (p=0.800, p=0.639, p=0.876, and p=0.886, for the respective developmental tests). CONCLUSIONS: We found normal language development and intelligence in a cohort of neonatal ECMO survivors. The prevalence of bilateral sensorineural hearing loss was in accordance with that of larger series in the United States – which exceeds the prevalence in the normal population.

Computer screen saver hand hygiene information curbs a negative trend in hand hygiene behavior (Article)

Helder, O.K. — 2012-03-13T00:00:00Z

Background: Appropriate hand hygiene among health care workers is the most important infection prevention measure; however, compliance is generally low. Gain-framed messages (ie, messages that emphasize the benefits of hand hygiene rather than the risks of noncompliance) may be most effective, but have not been tested. Methods: The study was conducted in a 27-bed neonatal intensive care unit. We performed an inter- rupted time series analysis of objectively measured hand disinfection events. We used electronic devices in hand alcohol dispensers, which continuously documented the frequency of hand disinfection events. In addition, hand hygiene compliance before and after the intervention period were directly observed. Results: The negative trend in hand hygiene events per patient-day before the intervention (decrease by 2.3 [standard error, 0.5] per week) changed to a significant positive trend (increase of 1.5 [0.5] per week) after the intervention (P < .001). The direct observations confirmed these results, showing a significant improvement in hand hygiene compliance from 193 of 303 (63.6%) observed hand hygiene events at pretest to 201 of 281 (71.5%) at posttest. Conclusions: We conclude that gain-framed messages concerning hand hygiene presented on screen savers may improve hand hygiene compliance.

The COMFORT behavior scale: Is a shorter observation period feasible? (Article)

Boerlage, A.A. — 2012-03-01T00:00:00Z

Objective: The COMFORT behavior scale has been validated for postoperative pain in 0- to 3-yr-old children. Scoring is preceded by a 2-min observation period, which nurses may consider too long. The objective of this study was to test the reliability of a 30-sec observation period. Design: Observational study. Setting: One Level III intensive care unit at a university children’s hospital. Participants: Designated pain specialist and all nursing staff. Interventions: None. Measurements: The pain specialist and caregiver nurse each conducted a bedside COMFORT behavior scale assessment and assigned an additional pain rating on the 11-point Numerical Rating Scale. Main Results: Total COMFORT behavior Scale score for the 2-min observation was 17 or higher in 19% of the patients and 11% for the 30-sec observation. The mean COMFORT behavior scale score for the 2-min observation was 13.5 (SD 3.8) and 12.7 (SD 3.7) for the 30-sec observation. The mean difference therefore was 0.8 (confidence interval 0.6–1.1, paired t test, p < .001). Sensitivity and positive predictive value for the 30-sec observa- tion were 0.44 and 0.80, respectively. Conclusions: A 30-sec COMFORT behavior scale observation increases the risk of underscoring pain. Therefore, the 2-min observation period should be adhered to in the interest of the patients.

Vascularization of prevascularized and non-prevascularized fibrin-based human adipose tissue constructs after implantation in nude mice (Article)

Verseijden, F. — 2012-03-01T00:00:00Z

Adipose regeneration strategies have been hampered by the inability to supply an adequate vascular supply following implantation. Vascularization in vitro, also called prevascularization, is a promising method that could promote the vascularization of engineered adipose tissue constructs upon implantation. In this study we compared the ability of prevascularized-to-non-prevascularized fibrin-based human adipose tissue to promote vascularization. Human adipose tissue-derived stromal cells (ASCs) and different mixtures (1:1, 1:2 and 1:5) of ASCs with human umbilical vein endothelial cells (HUVECs) were cultured in fibrin at two different densities (1.0 × 106and 10 × 106cells/ml) for 7 days. Histological analysis revealed that prevascular structures formed in 1:5 ASC/HUVEC fibrin-based constructs seeded with a total of 10 × 106cells/ml. These constructs and ASC-only constructs were implanted subcutaneously in athymic mice for 7 days and generated lipid-containing grafts. The numbers and densities of blood vessels within the ASC/HUVEC constructs were similar to those of ASC-only constructs. Furthermore, immunostaining studies demonstrated human-derived vasculature within a few of the ASC/HUVEC and ASC-only constructs. A subset of this human-derived vasculature contained erythrocytes, indicating integration with the host vasculature. In conclusion, our study indicated no difference in the rate of vascularization of prevascularized ASC/HUVEC and non-prevascularized ASC-only fibrin-based constructs, suggesting that prevascularization of these fibrin-based constructs does not promote vascularization. Our results further indicated that not only endothelial cells, but also ASCs may contribute to the formation of vascular lumina upon implantation. This finding is interesting, since it demonstrates the possibility of vascularized adipose tissue engineering from a single cell source.

Characterization of a three-dimensional mucosal equivalent: Similarities and differences with native oral mucosa (Article)

Tra, W.M.W. — 2012-02-01T00:00:00Z

The aim of this study was to create and characterize a tissue-engineered mucosal equivalent (TEM) that closely resembles native mucosa. TEM consists of human primary keratinocytes and fibroblasts isolated from biopsies taken from healthy donors and seeded onto a de-epidermized dermis and cultured for 14 days at the air/liquid interface. The structure of TEM was examined and compared with native nonkeratinizing oral mucosa (NNOM). The various components of the newly formed epidermal layer, basement membrane and underlying connective tissue were analyzed using immunohistochemistry. The mucosal substitute presented in this study showed a mature stratified squamous epithelium that was similar to that of native oral mucosa, as demonstrated by K19, desmoglein-3 and involucrin staining. In addition, the expression of basement membrane components collagen type IV, laminin-5 and integrin α6 and β4 in TEM proved to be consistent with native oral mucosa. The expression of PAS, Ki67, K10 and K13, however, appeared to be different in TEM compared to NNOM. Nevertheless, the similarities with native oral mucosa makes TEM a promising tool for studying the biology of mucosal pathologies such as oral mucositis or fibrosis as well as the development of new therapies. Copyright

The Microcirculation Is Unchanged in Neonates with Severe Respiratory Failure after the Initiation of ECMO Treatment (Article)

Top, A.P.C. — 2012-01-01T00:00:00Z

Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcircu- lation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children’s hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1) and within the first 24 hours after initiation of ECMO treatment (T2). Data were compared to data of a ventilated control group (N = 7). Results. At baseline (T1), median functional capillary density (FCD), microvascular flow index (MFI), and heterogeneity index (HI) did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4–4.2] versus 4.3 [2.8–7.4] cm/cm2 ; P value <0.001). For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure.

Screening pediatric delirium with an adapted version of the Sophia Observation withdrawal Symptoms scale (SOS) (Letter To Editor)

Dijk, M. van — 2011-12-08T00:00:00Z

Protocolized post-operative pain management in infants; do we stick to it? (Article)

Ceelie, I. — 2011-10-28T00:00:00Z

Background: The American Academy of Pediatrics states that ongoing assessment of pain is essential for adequate pain treatment. Pain assessment by means of the COMFORT behaviour scale and the Numeric Rating Scale is therefore an important component of the post-operative pain treatment protocol for neonates and infants in our intensive care unit (ICU). Aim: The study aims to determine degrees of staff compliance with this protocol. Patients and methods: This retrospective chart review concerned post-surgical patients under the age of 3 years admitted to our level III ICU over a 1-year period. The degree of compliance to the post-operative pain protocol was measured by the frequency of deviations from protocol-dictated drug treatment and pain assessments. Results: Records of 200 children with a median age at surgery of 98 days (interquartile range 6–320) were analysed. A mean of 11 assessments in the first 72 h post-operatively per patient had been recorded. A total of 2103 pain assessments were retrieved, of which 1675 (79.7%) suggested comfort. Compliance to the protocol (reassessment and correct medication) was provided in 66 (15.4%) of the 428 assessments suggesting pain or distress. Conclusion: The post-operative pain protocol applied in our ICU appears to be effective; however, full compliance to the protocol was marginal, possibly leading to under-treatment of pain.

MicroRNAs in Pediatric Acute Lymphoblastic Leukemia: Small players with huge potential (Doctoral Thesis)

Schotte, D. — 2011-09-28T00:00:00Z

Hematopoiesis is a dynamic balance of cellular proliferation, survival, apoptosis and differentiation in which the pluripotent hematopoietic stem cell gives rise to lymphoid and myeloid precursors of blood cells. The B-lymphoid precursor sequentially differentiates from proB-cells into common/preB-cells and fi nally yields mature B-lymphocytes. The T-lymphoid precursor generates thymocytes or proT-cells that further differentiate into T-lymphocytes. The myeloid precursor gives rise to granulocytes, monocytes, platelets and erythrocytes. This process is under tight surveillance by regulators including transcription factors, cytokines and growth factors. In case of defects in surveillance and/or oncogenic hits in the maturing hematopoietic cell, cells may arrest at different levels of maturation. Leukemia cells grow exponentially with limited differentiation thereby suppressing the development of normal blood cells in the bone marrow. As a consequence leukemia patients suffer from fatigue (shortage of erythrocytes or anemia), infections (shortage of mature lymphocytes and granulocytes) and bleeding (low platelet numbers). Despite the fact that multiple consecutive events are required for the development of leukemia, the clinical symptoms associated with acute leukemia occur rather abrupt and the progression of the disease is very fast if not treated instantly.

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study (Article)

Steegers, E.A.P. — 2011-08-01T00:00:00Z

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders. Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship. Further studies are needed to assess the underlying mechanisms and whether these differences in fetal kidney volume have postnatal consequences for kidney function and blood pressure.

Application to Add Midazolam to the Model List of Essential Medicines (Research Paper)

Wildschut, E.D. — 2011-08-01T00:00:00Z

Summary statement of the proposal for inclusion The benzodiazepine midazolam has proven sedative, anxiolytic and amnesic properties. It is extensively used for premedication and procedural sedation in both adults and children. In comparison to other benzodiazepine and non-benzodiazepine drugs, midazolam is equally or more effective for premedication/preoperative sedation. No evidence exists that premedication with midazolam prolongs discharge time from hospital. Its efficacy and safety have been extensively studied in both adults and children. This contrasts its comparator drug, diazepam for which data in children and elderly are scarce or lacking. Midazolam is also effective for procedural sedation as a single drug or in combination with an opioid. As a single drug, adequate sedation for procedures in the emergency room, is achieved in over 90% of all procedures. Comparative efficacy was shown for propofol. Data are insufficient to determine comparative efficacy for procedural sedation for other drugs. When administered with the appropriate precautions, e.g. titration to effect, adequate monitoring and personnel to support ventilation, midazolam is very safe. No major adverse events were seen in 847 adults who received midazolam for procedural sedation. Also, adverse effects can be antagonized with an effective antagonist, flumazenil. As midazolam is off-patent, drug costs are relatively low. Drug costs per procedure range from approximately 0.15 US$ to 2.6 US$ in an adult, depending on dose and country, with significantly lower costs in developing countries.

Impeded protein folding and function in active inflammatory bowel disease (Article)

Deuring, J.J. — 2011-08-01T00:00:00Z

The intestinal tract is covered by a total of 300 square metres of IECs (intestinal epithelial cells) that covers the entire intestinal mucosa. For protection against luminal xenobiotics, pathogens and commensal microbes, these IECs are equipped with membrane-bound transporters as well as the ability to secrete specific protective proteins. In patients with active IBD (inflammatory bowel disease), the expression of these proteins, e.g. ABC (ATP-binding cassette) transporters such as ABCG2 (ABC transporter G2) and defensins, is decreased, thereby limiting the protection against various luminal threats. Correct ER (endoplasmic reticulum)-dependent protein folding is essential for the localization and function of secreted and membrane-bound proteins. Inflammatory triggers, such as cytokines and nitric oxide, can impede protein folding, which causes the accumulation of unfolded proteins inside the ER. As a result, the unfolded protein response is activated which can lead to a cellular process named ER stress. The protein folding impairment affects the function and localization of several proteins, including those involved in protection against xenobiotics. In the present review, we discuss the possible inflammatory pathways affecting protein folding and eventually leading to IEC malfunction in patients with active IBD. ©The Authors Journal compilation

Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children (Article)

Stern, G. — 2011-08-01T00:00:00Z

Background: Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements. Objective: We characterized fractal fluctuations in daily Feno values over time and the relationship between Feno values and symptom scores. We investigated whether these are associated with asthma severity, control, and exacerbation risk. Methods: Daily Feno values and symptom scores over 192 days in 41 atopic asthmatic children from the Childhood Asthma Respiratory Inflammatory Status Monitoring study were analyzed. Two methods of time-series analysis were used: detrended fluctuation analysis to quantify fractal patterns in fluctuations in daily Feno values (α value) and cross-correlation to quantify the strength of the relationship between daily Feno values and symptom scores. The associations of α values and cross-correlation with markers of asthma severity and control were assessed by means of regression analysis. Results: Daily fluctuations in Feno values exhibited fractal-type long-range correlations. Those subjects receiving higher doses of inhaled corticosteroids at study entry had a significantly lower α value, corresponding to more random fluctuations in Feno values in those with greater inhaled corticosteroid need. The cross-correlation between Feno values and symptom scores was significantly higher in those subjects who had exacerbations. Conclusions: Fluctuation in Feno values and their cross-correlation to symptom scores contains information on asthma severity and control. Methods that quantify the complexity of asthma over time might assist in identifying asthmatic subjects with concordance between eosinophilic inflammation and symptoms and thus increased exacerbation risk.

Validation of a new automated neonatal seizure detection system: A clinician's perspective (Article)

Cherian, P.J. — 2011-08-01T00:00:00Z

Objective: To validate an improved automated electroencephalography (EEG)-based neonatal seizure detection algorithm (NeoGuard) in an independent data set. Methods: EEG background was classified into eight grades based on the evolution of discontinuity and presence of sleep-wake cycles. Patients were further sub-classified into two groups; gpI: mild to moderate (grades 1-5) and gpII: severe (grades 6-8) EEG background abnormalities. Seizures were categorised as definite and dubious. Seizure characteristics were compared between gpI and gpII. The algorithm was tested on 756. h of EEG data from 24 consecutive neonates (median 25. h per patient) with encephalopathy and recorded seizures during continuous monitoring (cEEG). No selection was made regarding the quality of EEG or presence of artefacts. Results: Seizure amplitudes significantly decreased with worsening EEG background. Seizures were detected with a total sensitivity of 61.9% (1285/2077). The detected seizure burden was 66,244/97,574 s (67.9%). Sensitivity per patient was 65.9%, with a mean positive predictive value (PPV) of 73.7%. After excluding four patients with severely abnormal EEG background, and predominantly having dubious seizures, the algorithm showed a median sensitivity per patient of 86.9%, PPV of 89.5% and false positive rate of 0.28h-1. Sensitivity tended to be better for patients in gpI. Conclusions: The algorithm detects neonatal seizures well, has a good PPV and is suited for cEEG monitoring. Changes in electrographic characteristics such as amplitude, duration and rhythmicity in relation to deteriorating EEG background tend to worsen the performance of automated seizure detection. Significance: cEEG monitoring is important for detecting seizures in the neonatal intensive care unit (NICU). Our automated algorithm reliably detects neonatal seizures that are likely to be clinically most relevant, as reflected by the associated EEG background abnormality.

A specific prebiotic mixture added to starting infant formula has long-lasting bifidogenic effects (Article)

Salvini, F. — 2011-07-01T00:00:00Z

There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning. In the present study, the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics. In this double-blind, randomized, placebo-controlled, explorative study, 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were randomly assigned to either a formula with 8 g/L of a specific prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides, ratio 9:1) or a formula containing the same amount of maltodextrin (placebo). Clinical examination including anthropometric measurements, microbiological analysis of fecal samples, and blood leukocyte population analysis were performed at birth and 3, 6, and 12mo age. At the age of 12 mo, hepatitis B vaccine-specific IgG serum titers (Hepatitis B virus surface antibodies) were also measured. Prebiotic supplementation resulted in more fecal bifidobacteria (P, 0.0001) and lactobacilli (P = 0.0044) compared with the placebo group. These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation. There was no influence of the different diets on anthropometric data or the measured immunological variables. The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota.

Practice patterns for achalasia - Room for improvement? (Letter To Editor)

Leeuwenburgh, I. — 2011-07-01T00:00:00Z

Impact of concentration of oesophageal and gastric cardia cancer surgery on long-term population-based survival (Article)

Poll-Franse, L.V. van de — 2011-07-01T00:00:00Z

Background: The objective was to evaluate the impact of concentration of surgery for oesophageal and gastric cardia cancer on long-term survival in the population-based Eindhoven Cancer Registry area. In contrast to most previous studies, this study aimed to evaluate both surgically and non-surgically treated patients, to avoid the confounding effect of selective referral. Methods: This retrospective cohort study included all patients diagnosed with oesophageal or gastric cardia cancer between 1995 and 2006. Results for the period 1995-1998 were compared with those for 1999-2006, after concentration of surgery. Results: Between 1995 and 2006, 2212 patients were registered with the diagnosis, of whom 638 underwent resection. Before 1999, 73·4 per cent of surgically treated patients underwent a resection in a low-volume hospital (fewer than 4 resections per year) and 23·2 per cent were referred to an academic hospital. After concentration, 63·2 per cent of surgically treated patients underwent resection in one of two regional high-volume centres (15-20 resections per year) and 13·8 per cent were referred to an academic hospital. Three-year survival rates increased from 32·0 to 45·1 per cent for patients who had surgery (P = 0·004), and from 13·1 to 17·9 per cent for all included patients (P = 0·026). These improvements remained after adjustment for case mix or (neo)adjuvant treatments, and were similar for patients with squamous cell carcinoma or adenocarcinoma. However, adjustment for annual hospital volume attenuated this association for patients who had surgery. Conclusion: Concentration of oesophageal and gastric cardia cancer surgery was associated with improvements in long-term, population-based overall survival for surgically as well as non-surgically treated patients, apparently mediated by an increase in volume.

Right ventricular outflow tract reconstruction with an allograft conduit in patients after tetralogy of fallot correction: Long-term follow-up (Article)

Woestijne, P.C. van de — 2011-07-01T00:00:00Z

Background: In tetralogy of Fallot (TOF) pulmonary regurgitation is a frequent complication after initial repair. The objective of the present study was to describe the long-term experience with the use of allograft conduits for right ventricular outflow tract (RVOT) reconstruction after correction of TOF in our institution. Methods: Between 1987 and 2009, 133 allografts were implanted in 126 patients (mean age, 27.8 years). The mean time from initial TOF repair to allograft implantation was 20.8 ± 8.8 years. Kaplan-Meier analyses were done for patient survival, freedom from allograft replacement and freedom from any cardiovascular event. Results: Hospital mortality was 1.5% (2 patients). Mean follow-up was 8.1 years. Ten other patients died during late follow-up, in 8 patients the cause was heart failure. Patient survival was 95% at 5 years, 91% at 10 years, and 80% at 15 years. Male sex, older patient age at the time of operation, and the use of preoperative diuretics were associated with increased risk of mortality during follow-up. Freedom from allograft replacement was 83% at 10 years and 70% at 15 years. Freedom from any valve-related event was 80% at 10 years and 67% at 15 years. Conclusions: Right ventricular outflow tract reconstruction after previous TOF repair can be performed with low risk and a low reintervention rate. Allograft conduits function satisfactorily in the pulmonary position at longer-term follow-up. Functional status after allograft implantation in patients with a previous correction of TOF remains good. There is concern about the long-term survival and the occurrence of heart failure.

Heparan sulfate glycosaminoglycan mimetic improves pressure ulcer healing in a rat model of cutaneous ischemia-reperfusion injury (Article)

Tong, M. — 2011-07-01T00:00:00Z

Pressure ulcers are a major clinical problem, with a large burden on healthcare resources. This study evaluated the effects of the heparan sulfate glycosaminoglycan mimetic, OTR4120, on pressure ulceration and healing. Ischemia-reperfusion (I-R) was evoked to induce pressure ulcers by external clamping and then removal of a pair of magnet disks on rat dorsal skin for a single ischemic period of 16 hours. Immediately after magnet removal, rats received an intramuscular injection of OTR4120 weekly for up to 1 month. During the ischemic period, normal skin perfusion was reduced by at least 60% and at least 20-45% reperfused into the ischemic region after compression release. This model caused sustained skin incomplete necrosis for up to 14 days and led to grade 2-3 ulcers. OTR4120 treatment decreased the area of skin incomplete necrosis and degree of ulceration. OTR4120 treatment also reduced inflammation and increased angiogenesis. In OTR4120-treated ulcers, the contents of vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor beta-1 were increased. Moreover, OTR4120 treatment promoted early expression of alpha-smooth muscle actin and increased collagen biosynthesis. Long-term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR4120 treatment. Taken together, we conclude that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability.