Acute myocardial infarction due to spontaneous coronary artery dissection in a 6-year-old boy with ADHD on the third day of treatment with methylphenidate.

Methylphenidate (MPH) is an indirect-acting sympathomimetic drug and structurally related to amphetamine. It is widely used to treat children aged 6 years and older, as well as adolescents who have attention-deficit/hyperactivity disorder (ADHD). We report on a 6-year-old boy who presented with typical angina symptoms occurring several hours after intake of an increased dose of MPH, which had been initiated for ADHD treatment 2 days earlier. Despite typical angina symptoms, the diagnosis of myocardial infarction due to spontaneous coronary artery dissection of the right coronary artery was delayed. Most epidemiological studies could not detect an increased risk for cardiovascular events in association with ADHD medications. However, the direct temporal relationship in our case indicates the possibility that MPH may trigger spontaneous coronary artery dissection in predisposed patients. Since myocardial infarction in children is rare but comprises various etiologies, awareness of this possible catastrophic event among medical staff may be lower and may delay immediate life-saving diagnostic and therapeutic measures.

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

[Quality of Pediatric Palliative Care Crisis Intervention - A Retrospective Survey]. / Qualität der kinderpalliativmedizinischen Krisenintervention ­ eine retrospektive Befragungsstudie.

BACKGROUND: In addition to palliative care in the dying phase, the care of sick children and their families is becoming increasingly important in times of crisis of a life-limiting illness. The families are supported by a specialised ambulatory palliative team for children and adolescents (SAPV-team for children and adolescents). The aim of the retrospective survey was to determine the quality of these palliative care crisis interventions for the families. METHODOLOGY: A retrospective questionnaire on medical care and family burden was developed. The "Hospital Anxiety and Depression Scale" was used to measure the burden of the families, and is aimed to assess anxiety and depression symptoms of the relatives. All families who were cared for by the pediatric palliative care team of the Children's and Adolescent Clinic of the University of Erlangen-Nuremberg in the context of crisis interventions between January 2012 and August 2017 received the questionnaire with the request for cooperation. RESULTS: The response rate of the questionnaires was 52,1%. The support and security from the palliative team, the 24-hour on-call service and the support in the organization of medical aids were rated particularly highly. The crisis intervention significantly improved the burden on patients and the family, as well as symptom control and communication. DISCUSSION: The present study demonstrates the tremendous psychological and physical stress with reduced quality of life of both sick children and their families in crisis situations. Specialized outpatient pediatric palliative care is able to help patients and families.

[Improving the Safety of Drug Therapy through a Hospital-Internal Reporting System - Analysis of Reports over 15 Years from a Children's Hospital]. / Verbesserung der Arzneimitteltherapiesicherheit durch ein klinikinternes Meldesystem ­ Analyse der Meldungen über 15 Jahre einer Kinderklinik.

BACKGROUND: Patient safety is a major challenge and has high priority in the inpatient care. Notably, drug therapy is considered critical after surgery. The medication process is particularly difficult and problematic in newborns and children. METHOD: In a retrospective analysis, hospital-internal spontaneous reports on Drug-related Problems (DRP) from a children's hospital were analysed, which were reported between 2000 and 2014. RESULTS: 229 spontaneous reports on DRP were considered for analysis. 72.5% of these were due to a Medication Error. Nearly half of the DRP occurred during drug dispensing (44.5%), followed by problems during administration (38.0%) and prescribing (11.4%). 61.4% of Medication Errors were dispensing errors (esp. confusion of patients, wrong dose). Almost all Other Incidents happened during drug administration (mainly extravasations). 40.6% of DRP reports were associated with clinically relevant patient harm and occurred particularly during drug administration. CONCLUSION: These results show that drug therapy in paediatrics is a complex and hazardous process. The system of hospital-internal spontaneous reports has led to regular training and raising awareness of the employees for critical situations. In addition, it fosters a safety culture to report mistakes. Spontaneous reporting is suitable for increasing the safety of drug therapy in paediatrics.

Time Tracking of Standard Ultrasound Examinations in Pediatric Hospitals and Pediatric Medical Practices - A Multicenter Study by the Pediatric Section of the German Society of Ultrasound in Medicine (DEGUM).

PURPOSE: Ultrasonography is the primary imaging modality in pediatrics but still lacks sufficient reimbursement in Germany. In this multicenter study, national data for the duration of standard ultrasound in pediatrics were systematically documented in order to specify the actual time required. MATERIALS AND METHODS: N = 10 hospitals (N = 5 university hospitals, N = 5 non-university hospitals) and N = 3 medical practices in Germany recorded the entire process of an ultrasound examination in a special protocol developed by the Pediatric Section of the DEGUM. The duration of each of seven single steps during ultrasonography (from data input to final discussion of the results) of different organ systems was logged. RESULTS: In total, N = 2118 examinations from different organ systems were recorded. N = 10 organ systems were examined frequently (> 30 times). The total duration of an ultrasound examination was statistically significantly longer in hospitals compared to medical practices (median (IQR) 27 min. (18-38) vs. 12 min. (9-17), p < 0.001). The "hands-on" patient time was approximately one half of the total required time in both settings (49.9 % vs. 48.9 %). Ultrasonography of the abdomen and brain lasted longer in university hospitals than in non-university hospitals (p < 0.001, and p = 0.04, respectively). Cooperation and age did not uniformly correlate with the total duration. CONCLUSION: This study provides novel comprehensive national data for the duration of standardized ultrasound examinations of children and adolescents in Germany. These data are essential for a further evaluation of the economic costs and should support better remuneration in the future.

Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study.

BACKGROUND: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare. METHODS: Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015. RESULTS: At the time of diagnosis, median age was 13.7 (interquartile range 11.8-15.8) years; 86% showed WHO histology class IV, nephrotic range proteinuria was noted in 55%, and median estimated glomerular filtration rate amounted to 75 ml/min/1.73 m2. At 12 months, the percentage of patients with complete and partial remission was 38% and 41%, respectively. Six percent of patients were non-responders and 15% presented with renal flare. Nephrotic range proteinuria at the time of diagnosis was associated with inferior renal outcome (odds ratio 5.34, 95% confidence interval 1.26-22.62, p = 0.02), whereas all other variables including mode of immune-suppressive treatment (e.g., induction treatment with cyclophosphamide (IVCYC) versus mycophenolate mofetil (MMF)) were not significant correlates. Complications were reported in 80% of patients including glucocorticoid toxicity in 42% (Cushingoid appearance, striae distensae, cataract, or osteonecrosis), leukopenia in 37%, infection in 23%, and menstrual disorder in 20%. Growth impairment, more pronounced in boys than girls, was noted in 78% of patients. CONCLUSIONS: In this cohort of juvenile proliferative LN, renal outcome at 12 months was good irrespectively if patients received induction treatment with MMF or IVCYC, but glucocorticoid toxicity was very high underscoring the need for corticoid sparing protocols. Graphical abstract.

Arterial Hypertension in Children.

Pharmacological treatment of arterial hypertension in children is mainly based on individual experience, but there is evidence that blocking the angiotensin system reduces systolic and diastolic blood when compared to placebo, and these drugs are safe to use for a short duration, also in children under 6 years of age. Blocking the angiotensin system either by angiotensin-converting enzyme inhibitors or by antagonizing the angiotensin 1 receptor is effective, but did not display a consistent dose-response relationship with escalating doses, but the effective doses are known. Calcium channel antagonists are effective antihypertensives in children, but the evidence is limited. Based on small-sized studies, beta-blockers modestly reduce systolic blood pressure, but have no significant effect on diastolic blood pressure compared to placebo. They act in combination to antagonize reflex tachycardia induced by vasodilators. The most commonly used antihypertensive agents are safe to use in short-term studies.

Next-generation reference intervals for pediatric hematology.

Background Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions. Methods We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905-1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores (www.pedref.org/hematology) and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases. Results We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases. Conclusions The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.

[Continuous Non-Invasive Blood Pressure Measurement Using Pulse Transit Time in Children and Adolescents]. / Kontinuierliche nicht-invasive Blutdruckmessung mittels Pulswellen-Transit-Zeit bei Kindern und Jugendlichen.

BACKGROUND: As an alternative to ambulatory 24-h blood pressure monitors, the continuous, non-invasive blood pressure recording using pulse transit time (PTT) was compared with both oscillometric and intra-arterial measurement. METHODS: In 144 pediatric patients (9.4±5.2 years) acute blood pressure was determined using three different methods of measurement. In 57 patients (11.4±4.9 years) of the pediatric normal ward, the blood pressure was simultaneously determined continuously by means of PTT compared to the intermittent oscillometric long-term measurement. In 9 patients (9.8±6.8 years) of the pediatric intensive care unit with continuous intra-arterial blood pressure measurement, the blood pressure was measured in parallel by means of PTT. RESULTS: Compared to the gold standard sphygmomanometry, mean systolic blood pressure values were comparable to 2 different oscillometric devices, but in the case of diastolic pressure measurement the pressure values were significantly lower or higher than with sphygmomanometry and auscultation. The results of the non-invasive comparative long-term measurements showed better correlations for systolic rather than diastolic pressure. Similar results were obtained comparing the direct intra-arterial blood pressure measurement with the SOMNOtouch™ NIBP device which measures blood pressure using the PTT. CONCLUSION: Continuous, indirect blood pressure recording using pulse transit time provides good correlations to the reference measurements for long-term measurement of blood pressure in children and adolescents and appears to be a usable method to measure the blood pressure of children especially at rest.

[How often do SmPCs Contain Contraindications and Special Warnings that are Specific for the Paediatric Population]. / Wie häufig betreffen Gegenanzeigen und Warnhinweise in deutschen Fachinformationen pädiatrische Patienten.

BACKGROUND: 3.2-3.8% of all medicine prescriptions for minor outpatients are off-label only because of the patients' age group. The younger, the more patients are affected by this issue. Only one fifth of the most commonly used medicines for newborns are licensed for this age group. The aim of this study is to analyse all German SmPCs whether they contain contraindications and warnings that specifically concern paediatric patients. METHODS: All available SmPCs were processed to search the sections Contraindications and Special warnings and precautions for information on paediatric age groups. Results were evaluated for differences between age groups, ATC classification and routes of application. RESULTS: 13547 SmPCs (22863 medicinal products) were evaluated. For 3603 (15.8%) medicinal products the SmPC contained contraindications for at least one paediatric age group. For 9687 (42.4%) medicinal products contraindications or warnings were found, including 2833 (12.4%) where all patients below 18 years were affected. Preterms were particularly affected (n=9581, 41.9%) as well as the ATC therapeutic subgroups contrast media (89.0%), cough and cold preparations (86.2%) and Corticosteroids (topical 88.2%, systemic 86.6%). Concerning liquids for oral use the proportion was higher than average (58.2%). CONCLUSION: It can be assumed that for most medicinal products the contraindications for paediatrics result from a lack of data and age specific formulations rather than from pharmacokinetic or -dynamic differences in paediatric patients. The EU Paediatric Regulation did not significantly stimulate the conduction of paediatric studies in off-patent medicines to this day.

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells.

BACKGROUND/AIMS: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC. METHODS: MC were isolated from wild type (WT) and Itga8-/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and Itga8-/- MC via fluorescence microscopy and FACS analysis. RESULTS: Itga8-/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in Itga8-/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by Itga8-/- MC. CONCLUSION: The expression of Itga8 facilitates phagocytosis in MC, likely mediated by Itga8-cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in Itga8-/- mice.

[Flight Routes to Germany of Seriously Ill Children and Adolescents From Former Eastern Bloc Countries for Treatment of Renal Failure]. / Fluchtwege von schwerkranken Kindern und Jugendlichen aus den ehemaligen Ostblockländern nach Deutschland zur Behandlung des Nierenversagens.

BACKGROUND: Increased patient mobility and restricted treatment of children with end-stage renal disease forced families from the former Eastern Bloc countries to flee with their children to Germany for adequate medical treatment. METHODS: In a case study, the patients' charts were analysed retrospectively. In structured interviews, parents and patients were asked about their flight routes to Germany, their medical treatment and their integration. RESULTS: From 2003 to 2013, eight children and adolescents with renal failure were treated with dialysis or renal transplantation in Erlangen. Most patients came with the help of human traffickers and a tourist visa. They often told that they had lost their papers in the excitement. One family received new passports from the trafficker with fake names and birth dates. The families had to pay high amounts of money in order to save their child's life. Although dialysis therapy was often difficult because of lower adherence, the overall course was satisfactory. Four patients have been transplanted successfully so far. CONCLUSION: This case study reveals new facets of patient mobility, since leaving home was the only way for the family to ensure their child´s survival. An ethical problems arose, as a chronic dialysis treatment in children seems ethically only justifiable if a kidney transplant is the therapeutic goal. .

A Comparison of GFR Estimation Formulae in Pediatric Oncology.

BACKGROUND: Application of potentially nephrotoxic chemotherapy requires continuous monitoring of renal function for toxicity and dosing. Novel pediatric glomerular filtration rate (GFR) estimating equations including cystatin C have been proposed to enhance the reliability of GFR calculation. MATERIALS AND METHODS: We examined a pediatric oncologic data set with a total of 363 GFR measurements. An analysis of distribution characteristics and comparison of medians was performed to compare creatinine and cystatin C-based GFR estimating formulae. Furthermore, we investigated the clinical impact of different equations in regard to therapeutic consequences. RESULTS: Significant differences in estimated GFR values were calculated depending on the applied formula (range of median GFR from 94.8 to 180.9 mL/min per 1.73 m2) which may result in different therapeutic consequences for the use of potentially nephrotoxic chemotherapeutic agents. Significant correlation for all examined formulae was identified, however there were large fluctuations among the correlation coefficients ranging from 0.254 to 1.0. CONCLUSION: This study compares proposed pediatric GFR estimating equations in a clinical setting. It underlines the current limitations and difficulties of GFR estimation including potential dosing errors. Cystitis C-based equations can be used as alternatives to creatinine-based estimations when the appropriate laboratory method has been applied. A comparative calculator for pediatric GFR estimating equations along with background information is provided at http://gfr.pedz.de and may support clinical decision-making.

[Medication safety in children : What role do dosing and formulations play?] / Arzneimitteltherapiesicherheit bei Kindern : Welche Rolle spielen Dosis und Darreichungsform?

Medication errors are more common in children compared to adults due to often missing efficacy evidence and limited or missing regulatory approvals for paediatric drugs.Roots of errors are located at different levels. They result, for example, from missing clinical studies that particularly investigate efficacy and correct dosing in younger age groups, the lack of age-appropriate dosage forms, the use of harmful ingredients, as well as the complicated and high-risk prescribing process.Electronic systems may improve the quality of drug prescriptions and reduce medication errors. The basic assumption is valid, evidence-based data behind such a system. In contrast to other countries, such a database is not yet available in Germany. The Plan of Action for the improvement of medication safety in Germany 2016-2019 (Aktionsplan) contains an action point "Creation of a database for dosing of paediatric medicines". Initial funding for 2 years has been granted for its implementation.Through systematic literature searches and the availability and provision of up-to-date knowledge on paediatric medicines, medication safety for children and adolescents can be improved. A database with relevant information to support more correct prescriptions within the paediatric population appears productive. The Aktionsplan has paved the way for the dissemination of evidence-based drug information for the country's paediatric population.

Pediatric reference intervals for alkaline phosphatase.

BACKGROUND: Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyte as closely linked to growth as alkaline phosphatase. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, resulting in limitations when clinical decisions are based on alkaline phosphatase activity. METHODS: We applied an indirect method to generate percentile charts for alkaline phosphatase activity using clinical laboratory data collected during the clinical care of patients. A total of 361,405 samples from 124,440 patients from six German tertiary care centers and one German laboratory service provider measured between January 2004 and June 2015 were analyzed. Measurement of alkaline phosphatase activity was performed on Roche Cobas analyzers using the IFCC's photometric method. RESULTS: We created percentile charts for alkaline phosphatase activity in girls and boys from birth to 18 years which can be used as reference intervals. Additionally, data tables of age- and sex-specific percentile values allow the incorporation of these results into laboratory information systems. CONCLUSIONS: The percentile charts provided enable the appropriate differential diagnosis of changes in alkaline phosphatase activity due to disease and changes due to physiological development. After local validation, integration of the provided percentile charts into result reporting facilitates precise assessment of alkaline phosphatase dynamics in pediatrics.

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

BACKGROUND: Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. CASE PRESENTATION: Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. CONCLUSIONS: Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

[Establishment of Specialized Pediatric Palliative Home Care in the Medical Valley of the European Metropolitan Area Nuremberg]. / Praktische Umsetzung einer spezialisierten ambulanten pädiatrischen Palliativversorgung im Medical Valley der Europäischen Metropolregion Nürnberg.

Background As part of the 2007 health reform in Germany the structure of outpatient palliative care for children and adolescents was adopted for the first time and then implemented in Erlangen-Nuremberg in 2009. Methods The introduction of Pediatric Palliative Home Care (PPHC) at the Hospital for Children and Adolescents at the University of Erlangen-Nuremberg was retrospectively analyzed between the years 2009 to 2014. Referring medical records (paper-based and electronic) were evaluated systematically. Results Considering 69 patients within this study, 44 (63.8%) died during the investigated period and 61% of these Patients deceased at home. 60 patients (87%) had a written emergency plan, which was jointly developed with patients and particularly their parents and relatives in cooperation with the PPHC team. Over the years and with increasing experience, the number and duration of emergency hospitalization decreased. Even complex therapies, such as patient-controlled analgesia with PCA pump could be implemented on an outpatient basis. Conclusion The descriptive cohort study demonstrates that palliative care for children, despite the medical and structural complexity is possible in an ambulatory setting. It allows a similar, if not better care, compared to inpatient palliative care for children and adolescents, not only for the affected patients, but also for their families.

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth.

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

Under-expression of α8 integrin aggravates experimental atherosclerosis.

Integrins play an important role in vascular biology. The α8 integrin chain attenuates smooth muscle cell migration but its functional role in the development of atherosclerosis is unclear. Therefore, we studied the contribution of α8 integrin to atherosclerosis and vascular remodelling. We hypothesized that α8 integrin expression is reduced in atherosclerotic lesions, and that its under-expression leads to a more severe course of atherosclerosis. α8 Integrin was detected by immunohistochemistry and qPCR and α8 integrin-deficient mice were used to induce two models of atherosclerotic lesions. First, ligation of the carotid artery led to medial thickening and neointima formation, which was quantified in carotid cross-sections. Second, after crossing into ApoE-deficient mice, the formation of advanced vascular lesions with atherosclerotic plaques was quantified in aortic en face preparations stained with Sudan IV. Parameters of renal physiology and histopathology were assessed: α8 integrin was detected in the media of human and murine vascular tissue and was down-regulated in arteries with advanced atherosclerotic lesions. In α8 integrin-deficient mice (α8(-/-) ) as well as α8(+/-) and α8(+/+) littermates, carotid artery ligation increased media:lumen ratios in all genotypes, with higher values in ligated α8(-/-) and α8(+/-) compared to ligated α8(+/+) animals. Carotid artery ligation increased smooth muscle cell number in the media of α8(+/+) mice and, more prominently, of α8(-/-) or α8(+/-) mice. On an ApoE(-/-) background, α8(+/-) and α8(-/-) mice developed more atherosclerotic plaques than α8(+/+) mice. α8 Integrin expression was reduced in α8(+/-) animals. Renal damage with increased serum creatinine and glomerulosclerosis was detected in α8(-/-) mice only. Thus, under-expression of α8 integrin aggravates vascular lesions, while a complete loss of α8 integrin results in reduced renal mass and additional renal disease in the presence of generalized atherosclerosis. Our data support the hypothesis that integrin α8ß1 has a protective role in arterial remodelling and atherosclerosis.

Timing of first arteriovenous fistula cannulation in children on hemodialysis.

BACKGROUND: Due to lower complication rates in comparison to central venous catheter (CVC) arteriovenous fistulas (AVFs) are now the preferred hemodialysis access. Recommendations for the first access cannulation range from 6 to 12 weeks, which could lead to temporary or even permanent preference for CVC while awaiting the maturation of the newly created AVF. The aim of this study was to evaluate the influence of first cannulation of AVFs on primary (PP) and secondary (SP) patency rates in children on hemodialysis (HD). METHODS: This was a retrospective cohort study of 42 pediatric patients with a median age of 14 (range 7-17) years. At the time of surgical AVF creation 21 patients (end-stage renal disease) were still on HD via CVC or peritoneal catheter, while 21 were pre-emptive with initiation of HD expected within a few weeks. All patients received an AVF by the same experienced surgeon between February 1993 and May 2014. Primary failure (PF) was defined as the inability to use the AVF even once due to absent maturation or occlusion within 4 weeks after creation. PP was defined as the interval from time of access placement to any intervention designed to maintain or reestablish patency, to access thrombosis or the time of measurement of patency, while SP was defined as the total lifespan from creation to access abandonment, end of follow-up or loss. RESULTS: Primary failure was observed in six (14.3 %) of 42 AVFs (all radiocephalic fistulas) within the first 10 days after cannulation. Excluding PF, the PP/SP rates at 1, 3, 6, 12, 18 and 24 months were 100/100, 91/99, 86/98, 76/95, 55/85 and 44/77 %, respectively. There was a significant decrease in PP when first cannulation was performed within the first 30 days after creation compared to first cannulation performed after 30 days (p = 0.004). In terms of PP/SP outcome and timing of the first cannulation, there was no significant difference in thee outcome of PP/SP between first cannulation within the first 45 days after creation and that after 45 days (p = 0.091/0.883). CONCLUSIONS: The findings suggest that cannulation of AVF within 30 days after surgical creation reduces PP, while SP may be influenced less by time until cannulation. We also found no significant differences in PP after maturing periods of >45 days.