Postoperative Kolonischämie nach Aortenoperationen: Analyse von klinischen Besonderheiten und chirurgischen Therapieergebnissen

Die Kolonischämie stellt eine relativ seltene, aber schwerwiegende Komplikation im Anschluss an einen gefäßchirurgischen Eingriff an der abdominellen Aorta dar. Es konnte mehrfach gezeigt werden, dass eine postoperative Kolonischämie eine Erhöhung des Morbidität- und Mortalitätsrisikos verursacht. Durch eine engmaschige postoperative Überwachung und stetige Weiterentwicklung diagnostischer Verfahren kann diese Komplikation häufiger frühzeitig erkannt werden und durch geeignete therapeutische Verfahren wirksamer behandelt werden. Die standardisierte postoperative Endoskopie, insbesondere bei Risikopatienten, wird in vielen gefäßchirurgischen Zentren diskutiert. Besondere Bedeutung kommt der Prävention zu, die durch die Identifikation von Risikofaktoren individualisierte Stratifizierungen und Handlungsanweisungen ermöglicht. Ziel dieser Arbeit war es, klinische Besonderheiten der Kolonischämie im Anschluss an gefäßchirurgische Eingriffe an der Aorta zu beschreiben, Risikofaktoren für das Auftreten einer Kolonischämie zu identifizieren und den Einfluss der Kolonischämie auf den postoperativen Verlauf sowie auf die Mortalität und das Langzeitüberleben darzustellen. Im untersuchten Zeitraum wurden bei 38 Patienten (2,8%) eine Kolonischämie diagnostiziert. Der Zeitpunkt der Diagnosestellung war durchschnittlich 7,2 ± 1,6 Tage nach dem gefäßchirurgischen Eingriff an der Aorta, wobei 79,0% der Patienten abdominelle Symptome zeigten. Bei den übrigen 21,1% traten keine abdominellen Beschwerden auf. Bei den meisten Patienten (73,7%) wurde die Diagnose durch eine Koloskopie gestellt. Deutlicher seltener erfolgte die Diagnosestellung mittels Computertomographie oder diagnostischer Laparotomie. Eine operative Therapie war bei 81,6% der Patienten notwendig, wobei der Umfang des Eingriffs von der Lokalisation und Ausdehnung der Kolonischämie abhängig war. Um Risikofaktoren für das Auftreten einer Kolonischämie definieren zu können, erfolgte in dieser Arbeit eine Gegenüberstellung von Patienten mit nachgewiesener Kolonischämie und einer, mittels Matched Pair-Analyse erstellten, Kontrollgruppe. Als präoperative Risikofaktoren konnten eine vorbestehende Herzinsuffizienz (p = 0,0004), arterieller Hypertonus (p = 0,0029), KHK (p = 0,0038), Herzrhythmusstörungen (p = 0,04), COPD (p = 0,0294), pAVK (p = 0,0082), erhöhtes Kreatinin (p = 0,0467) bzw. vorbekannte Niereninsuffizienz (p = 0,0249) und ein anamnestischer Nikotinabusus (p = 0,0307) identifiziert werden. Die intraoperativen Risikofaktoren waren eine längere Operationsdauer (p < 0,0001), ein höherer Blutverlust (p = 0,0132), Transfusion von Erythrozytenkonzentraten (p = 0,0244) und gefrorenem Frischplasma (p = 0,004), Hypothermien (p = 0,0289) und arterielle Hypotonien (p = 0,0185). Bei den Patienten mit einer Kolonischämie traten im postoperativen Verlauf signifikant häufiger pulmonale (p = 0,0001), kardiozirkulatorische (p = 0,0001) und renale (p = 0,0227) Komplikationen auf. Dies spiegelte sich auch in einem signifikant längeren Krankenhaus- (p < 0,0001) und Intensivaufenthalt (p < 0,0001) wider. Zusätzlich war die intrahospitale (p = 0,0001) und die 30-Tage-Mortalität (p = 0,0001) in der Kolonischämiegruppe signifikant höher. Auch bei der Analyse des Langzeitüberlebens zeigte sich ein signifikant kürzeres Überleben nach einer Kolonischämie. Die hier dargestellten Ergebnisse untermauern und ergänzen die Ergebnisse vergleichbarer Studien. Trotz fehlender klinischer Symptome oder laborchemischer Veränderungen sollten Risikopatienten eine frühzeitige endoskopische Diagnostik im Anschluss an einen gefäßchirurgischen Eingriff an der Aorta erhalten. Hiermit kann eine Kolonischämie möglicherweise in frühen Stadien diagnostizieren werden und mit weniger invasiven und komplikationsreichen Therapien behandelt werden. Zusätzlich sollte der Prävention, unter anderem durch die Optimierung bzw. Ausschaltung hier identifizierter Risikofaktoren, große Bedeutung geschenkt werden

Professional engineering ethics education: just how effective is it?.

Professional engineering degrees that are endorsed through independent protocols, (such as the Washington Accord), must ensure that students are given sufficient background to enable them to practise in an ethically professional manner. Graduates are expected to have a full understanding of the pertinent code(s) of ethics under which they can be expected to function as engineers. Further, they need to be able to appreciate the nuances involved in issues such as &#039;conflict of interest&#039;, sustainability, resource use, quadruple bottom line (the &#039;4Es&#039;) as well as &#039;good practice&#039;. This paper provides a review of the course Ethics and the Professional, currently being offered in four universities in three countries, that was established to directly address the need for professional ethics education. Over the last few years, student satisfaction surveys of this course have been undertaken in Australia, New Zealand and Germany; the results of these are provided herein. In addition to these assessments a further, novel approach, devised to assess the overall effectiveness of the professional ethics course is presented. This assessment provides a valuable tool through which we may monitor any apparent change in student attitudes that developed during the course

Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation

<p>Abstract</p> <p>Background</p> <p>Submicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing.</p> <p>Results</p> <p>296 patients with MR and a normal karyotype (500–550 bands) were screened for subtelomeric imbalances by using qPCR combined with SYBR green detection. In total, 17 patients (5.8%) with 20 subtelomeric imbalances were identified. Six of the aberrations (2%) were classified as causative for the symptoms, because they occurred either <it>de novo </it>in the patients (5 cases) or the aberration were be detected in the patient and an equally affected parent (1 case). The extent of the deletions ranged from 1.8 to approximately 10 Mb, duplications were 1.8 to approximately 5 Mb in size. In 6 patients, the copy number variations (CNVs) were rated as benign polymorphisms, and the clinical relevance of these CNVs remains unclear in 5 patients (1.7%). Therefore, the overall frequency of clinically relevant imbalances ranges between 2% and 3.7% in our cohort.</p> <p>Conclusion</p> <p>This study illustrates that the qPCR/SYBR green technique represents a rapid and versatile method for the detection of subtelomeric imbalances and the option to map the breakpoint. Thus, this technique is highly suitable for genotype/phenotype studies in patients with MR/developmental delay and/or congenital defects.</p

Succinate in dystrophic white matter: A proton magnetic resonance spectroscopy finding characteristic for complex II deficiency

A deficiency of succinate dehydrogenase is a rare cause of mitochondrial encephalomyopathy. Three patients, 2 sisters and I boy from an unrelated family, presented with symptoms and magnetic resonance imaging signs of leukoencephalopathy. Localized proton magnetic resonance spectroscopy indicated a prominent singlet at 2.40ppm in cerebral and cerebellar white matter not present in gray matter or basal ganglia. The signal was also elevated in cerebrospinal fluid and could be identified as originating from the two equivalent methylene groups of succinate. Subsequently, an isolated deficiency of complex II (succinate:ubiquinone oxidoreductase) was demonstrated in 2 patients in muscle and fibroblasts. One of the sisters died at the age of 18 months. Postmortem examination showed the neuropathological characteristics of Leigh syndrome. Her younger sister, now 12 months old, is also severely affected; the boy, now 6 years old, follows a Milder, fluctuating clinical course. Magnetic resonance spectroscopy provides a characteristic pattern in succinate dehydrogenase deficiency

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding

Regionalized Pathology Correlates with Augmentation of mtDNA Copy Numbers in a Patient with Myoclonic Epilepsy with Ragged-Red Fibers (MERRF-Syndrome)

Human patients with myoclonic epilepsy with ragged-red fibers (MERRF) suffer from regionalized pathology caused by a mutation in the mitochondrial DNA (m.8344A→G). In MERRF-syndrome brain and skeletal muscles are predominantly affected, despite mtDNA being present in any tissue. In the past such tissue-specificity could not be explained by varying mtDNA mutation loads. In search for a region-specific pathology in human individuals we determined the mtDNA/nDNA ratios along with the mutation loads in 43 different post mortem tissue samples of a 16-year-old female MERRF patient and in four previously healthy victims of motor vehicle accidents. In brain and muscle we further determined the quantity of mitochondrial proteins (COX subunits II and IV), transcription factors (NRF1 and TFAM), and VDAC1 (Porin) as a marker for the mitochondrial mass. In the patient the mutation loads varied merely between 89–100%. However, mtDNA copy numbers were increased 3–7 fold in predominantly affected brain areas (e.g. hippocampus, cortex and putamen) and in skeletal muscle. Similar increases were absent in unaffected tissues (e.g. heart, lung, kidney, liver, and gastrointestinal organs). Such mtDNA copy number increase was not paralleled by an augmentation of mitochondrial mass in some investigated tissues, predominantly in the most affected tissue regions of the brain. We thus conclude that “futile” stimulation of mtDNA replication per se or a secondary failure to increase the mitochondrial mass may contribute to the regionalized pathology seen in MERRF-syndrome

Investigation of the Role of Mitochondrial DNA in Multiple Sclerosis Susceptibility

Several lines of evidence suggest that mitochondrial genetic factors may influence susceptibility to multiple sclerosis. To explore this hypothesis further, we re-sequenced the mitochondrial genome (mtDNA) from 159 patients with multiple sclerosis and completed a haplogroup analysis including a further 835 patients and 1,506 controls. A trend towards over-representation of super-haplogroup U was the only evidence for association with mtDNA that we identified in these samples. In a parallel analysis of nuclear encoded mitochondrial genes, we also found a trend towards association with the complex I gene, NDUFS2. These results add to the evidence suggesting that variation in mtDNA and nuclear encoded mitochondrial genes may contribute to disease susceptibility in multiple sclerosis

The effectiveness of technology-supported personalised learning in low- and middle-income countries: A meta-analysis

AbstractDigital technology offers the potential to address educational challenges in resource‐poor settings. This meta‐analysis examines the impact of students' use of technology that personalises and adapts to learning level in low‐ and middle‐income countries. Following a systematic search for research between 2007 and 2020, 16 randomised controlled trials were identified in five countries. Studies involved 53,029 learners aged 6–15 years. Coding examined learning domain (mathematics and literacy); personalisation level and delivery; technology use; and intervention duration and intensity. Overall, technology‐supported personalised learning was found to have a statistically significant—if moderate—positive effect size of 0.18 on learning (p = 0.001). Meta‐regression reveals how more personalised approaches which adapt or adjust to learners' level led to significantly greater impact (an effect size of 0.35) than those only linking to learners' interests or providing personalised feedback, support, and/or assessment. Avenues for future research include investigating cost implications, optimum programme length, and teachers' role in making personalised learning with technology effective. Practitioner notesWhat is already known about this topic? Promoting personalised learning is an established aim of educators. Using technology to support personalised learning in low‐ and middle‐income countries (LMICs) could play an important role in ensuring more inclusive and equitable access to education, particularly in the aftermath of COVID‐19. There is currently no rigorous overview of evidence on the effectiveness of using technology to enable personalised learning in LMICs. What this paper adds? The meta‐analysis is the first to evaluate the effectiveness of technology‐supported personalised learning in improving learning outcomes for school‐aged children in LMICs. Technology‐supported personalised learning has a statistically significant, positive effect on learning outcomes. Interventions are similarly effective for mathematics and literacy and whether or not teachers also have an active role in the personalisation. Personalised approaches that adapt or adjust to the learner led to significantly greater impact, although whether these warrant the additional investment likely necessary for implementation at scale needs to be investigated. Personalised technology implementation of moderate duration and intensity had similar positive effects to that of stronger duration and intensity, although further research is needed to confirm this. Implications for practice and/or policy: The inclusion of more adaptive personalisation features in technology‐assisted learning environments can lead to greater learning gains. Personalised technology approaches featuring moderate personalisation may also yield learning rewards. While it is not known whether personalised technology can be scaled in a cost‐effective and contextually appropriate way, there are indications that this is possible. The appropriateness of teachers integrating personalised approaches in their practice should be explored given ‘supplementary’ uses of personalised technology (ie, additional sessions involving technology outside of regular instruction) are common. </jats:sec

Effect and safety of treatment with ACE-inhibitor Enalapril and β-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial

Background: X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. Methods, Trial design: Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. Inclusion criteria: DMD boys aged 10–14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS &lt; 28%. Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events. Results: From 3/2010 to 12/2013, 38 patients from 10 sites were centrally randomized after run-in, with 21 patients continuing enalapril and metoprolol medication and 17 patients receiving placebo. Until end of study 12/2015, LV-FS &lt; 28% was reached in 6/21 versus 7/17 patients. Cox regression adjusted for LV-FS after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio: 0.38; 95% confidence interval: 0.12 to 1.22; p = 0.10). Analysis of secondary outcome measures revealed a time-dependent deterioration of LV-FS with no statistically significant differences between the two study arms. Blood pressure, maximal heart rate and mean-NN values were significantly lower at the end of open run-in treatment compared to baseline. Outcome analysis 19 months after randomization displayed significantly lower maximum heart rate and higher noradrenalin and renin values in the intervention group. No difference between treatments was seen for quality of life. As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed. Conclusions: Our analysis of enalapril and metoprolol treatment in DMD patients with preserved left ventricular function is suggestive to delay the progression of the intrinsic cardiomyopathy to left ventricular failure, but did not reach statistical significance, probably due to insufficient sample size. Clinical trial registration: DRKS-number 00000115, EudraCT-number 2009–009871-36