EEG-Veränderungen vor und nach Herzoperationen bei Kindern mit angeborenen Herzfehlern

Zusammenfassung Hintergrund: Neurologische Komplikationen und kognitive Beeinträchtigungen können nach einer Herzkor rekturoperation unter Einsatz der Herz-Lungen-Maschine (HLM) mit oder ohne Kreislaufstill stand auftreten. Die häufigsten neurologischen Komplikationen nach Herzoperation bei Kin dern mit angeborenen Herzfehlern unter Einsatz der HLM sind zerebrale Ischämien und Hä morrhagien sowie zerebrale Krampfanfälle und eine daraus resultierende mögliche dauerhafte physische und kognitive Beeinträchtigung. Verschiedene neurophysiologische Überwachungssysteme wurden eingesetzt, um neurologi sche Komplikationen und mögliche Hirnverletzungen bei Säuglingen und Kindern während und nach Herzoperationen frühzeitig zu erkennen. Die Rolle der Elektroenzephalographie (EEG) bei Säuglingen und Kindern nach Herzoperati onen unter Verwendung der HLM mit einem Risiko für neurologische Folgeerkrankungen wurde nur in sehr wenigen Studien systematisch untersucht. Patienten und Methode: Retrospektive Kohortenstudie im Zeitraum von 01/2004 bis 12/2007 am Universitätsklinikum des Saarlandes (Klinik für Pädiatrische Kardiologie und Klinik für All gemeine Pädiatrie und Neonatologie). Fragestellung: Ziel dieser retrospektiven Studie war die Untersuchung der Rolle von routinemäßigen EEG Untersuchungen zur Detektion neurologischer Komplikationen nach Herzoperationen bei Kin dern mit angeborenen Herzfehlern unter Verwendung der HLM. Ergebnisse: Bei 313 Patienten (Alter: 54,2±55,7 Monate) mit initialem unauffälligen EEG nach Herzoperation unter Verwendung einer HLM (Operationsdauer: 146,0±58,9 Minuten; Aorten klemmzeit: 34,1±19,1 Minuten) wurde im Durchschnitt 2,4±1,8 Tage vor und 11,6 ± 5,3 Tage nach Herzoperation eine 19-Kanal-EEG-Aufzeichnung durchgeführt. Ein pathologisches EEG wurde nur bei 8 von 313 Patienten (2,5%; fokale Verlangsamung (1), generalisierte Verlang samung (5), epileptiforme Entladungen (2) festgestellt, während das EEG bei den übrigen 305 Patienten (97,5%) normal war. Bei einem Patienten wurde eine intrazerebrale Pathologie im cMRT (Ischämie) beobachtet; bei 5 der 8 Patienten wurden EEG-Kontrollen durchgeführt, die normale Befunde ergaben. Keines der 8 Kinder zeigte post-operativ zum Zeitpunkt der Entlas sung aus der stationären Akutbehandlung neue fokale neurologische Defizite oder psychomo torische Beeinträchtigungen im Vergleich zum prä-operativen Status. Allerdings zeigten 33 Kinder (9,7%) geringfügige Auffälligkeiten (z. B. subtile motorische Asymmetrie, Erhöhung des Muskeltonus usw.), die nicht mit pathologischen EEG-Befunden in Zusammenhang standen. 8 Diskussion: Wir schlussfolgern somit, dass die routinemäßige Aufzeichnung von EEG-Unter suchungen bei Kindern vor und nach korrigierenden oder palliativen Herzoperationen bei an geborenen Herzfehlern unter Verwendung der HLM nicht zu empfehlen ist. Bis weitere valide intraoperative Neuromonitoring-Methoden mit sofortiger Intervention für den routinemäßigen klinischen Einsatz zur Verfügung stehen, kommt der prä- und post-operativen neurologischen Untersuchung die entscheidende Rolle zu, neu aufgetretene neurologische Defizite zu detek tieren.Summary Background: Neurological dysfunction may occur after corrective cardiac surgery using cardio-pulmonary bypass (CPB) with or without circulatory arrest. Different neurophysiological monitoring sys-tems have been employed to detect neurological complications and possible brain injury in infants and children during and after cardiac surgery. The value of Electroencephalography (EEG) in infants and children after cardiac surgery using HLM with a risk of neurological sequelae has been systematically investigated in only very few studies. Patients and methods: Sequential performance of two EEGs before and after cardiac surgery at a tertiary University Hospital to screen for possible brain injury after cardiac surgery in neonates and children un-dergoing CPB surgery. In addition, a complete neurological examination and assessment by a physiotherapist was performed. Results Over a 4-year period (01/2004 - 12/2017), in 313 patients (age: 54.2 ± 55.7 months; normal initial EEG) after cardiac surgery CPB (duration of surgery: 146.0 ± 58.9 min; aortic cross clamp time: 34.1 ± 19.1 min), a 19-channel EEG recording was performed 2.4 ± 1.8 days prior to and 11.6 ± 5.3 days after cardiac surgery. An abnormal EEG was detected in only 8 of 313 patients (2.5%; focal slowing: 1, generalised slowing: 5, epiletiform discharges: 2) after cardiac surgery, while the EEG was normal in the remaining 305 patients (97.5%). In 1 patient, an intra-cerebral pathology was seen on MRI (ischemic); in 5 patients, follow-up EEGs were performed, which revealed normalized findings. None of the 8 patients demonstrated new focal neurological deficits on physical examination, but 33 (9.7%) children demonstrated minor ab-normalities (e.g., subtle motor asymmetry, increase in muscle tone, etc.), which were unrelated to abnormal EEG findings. Conclusions: According to the used protocol, pathological EEG findings were very infrequent in our study cohort. The routine and indiscriminative recording of EEGs in children before and after corrective or palliative cardiac surgery for congenital heart disease using CPB is not rec-ommended. Further intra-operative neuromonitoring methods with immediate intervention should be eval-uated. Until intra-operative neurophysiological monitoring will become standard of care, metic-ulous neurological examination – prior and after CPB surgery – is key in the early detection of neurological injury in these highly susceptible patients

Efficacy of a new injury prevention programme (FUNBALL) in young male football (soccer) players: a cluster-randomised controlled trial

Objectives To evaluate the efficacy of a new multicomponent, exercise-based injury prevention programme in football players 13–19 years old. Methods Two-arm cluster-randomised controlled trial with clubs as the unit of randomisation. 55 football teams from Kosovo of the under 15, under 17 and under 19 age groups were randomly assigned to the intervention (INT; 28 teams) or the control group (CON; 27 teams) and were followed for one football season (August 2021–May 2022). The INT group performed the ’FUNBALL’ programme after their usual warm-up at least twice per week, while the CON group followed their usual training routine. The primary outcome measure was the overall number of football-related injuries. Secondary outcomes were region-specific injuries of the lower limbs (hip/groin, thigh, knee, lower leg, ankle and foot) and injury severity. Results 319 injuries occurred, 132 in the INT and 187 in the CON group. The INT group used the ’FUNBALL’ programme in 72.2% of all training sessions, on average 2.2 times per week. There was a significantly lower incidence in the INT group regarding the overall number of injuries (incidence rate ratio (IRR) 0.69, 95%CI 0.55 to 0.87), the number of thigh injuries (IRR 0.62, 95%CI 0.39 to 0.98), of moderate (time loss between 7 and 28 days) (IRR 0.65, 95%CI 0.44 to 0.97) and of severe injuries (time loss >28 days) (IRR 0.51, 95%CI 0.28 to 0.91). Conclusion The ’FUNBALL’ programme reduced the incidence of football-related injuries among male adolescent football players, and its regular use for injury prevention in this population is recommended. Trial registration number NCT05137015

The RNA binding protein IGF2BP2/IMP2 alters the cargo of cancer cell-derived extracellular vesicles supporting tumor-associated macrophages

Background Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated macrophages (TAMs). High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. However, there is a lack of understanding of whether IMP2 afects the cargo of cancer cell-derived EVs, thereby modulating macrophage polarization. Methods EVs were isolated from IMP2-expressing HCT116 parental cells (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells. EVs were characterized according to MISEV guidelines, microRNA cargo was assessed by microRNA-Seq, and the protein cargo was analyzed by proteomics. Primary human monocyte-derived macrophages (HMDMs) were polarized by EVs, and the expression of genes and surface markers was assessed using qPCR and fow cytometry, respectively. Morphological changes of macrophages, as well as the migratory potential of cancer cells, were assessed by the Incucyte® system and macrophage matrix degradation potential by zymography. Changes in the meta‑ bolic activity of macrophages were quantifed using a Seahorse® analyzer. For in vivo studies, EVs were injected into the yolk sac of zebrafsh larvae, and macrophages were isolated by fuorescence-activated cell sorting. Results EVs from WT and KO cells had a similar size and concentration and were positive for 25 vesicle mark‑ ers. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs than KO EVs, while the expression of TNF and IL6 was reduced. A similar pattern was observed in macrophages from zebrafsh larvae treated in vivo. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. MicroRNA-Seq revealed a signif‑ cant diference in the microRNA composition of WT and KO EVs, particularly a high abundance of miR-181a-5p in WT EVs, which was absent in KO EVs. Inhibitors of macropinocytosis and phagocytosis antagonized the delivery of miR181a-5p into macrophages and the downregulation of the miR-181a-5p target DUSP6. Proteomics data showed diferences in protein cargo in KO vs. WT EVs, with the diferentially abundant proteins mainly involved in metabolic pathways. WT EV-treated macrophages exhibited a higher basal oxygen consumption rate and a lower extracellular acidifcation rate than KO EV-treated cells. Conclusion Our results show that IMP2 determines the cargo of EVs released by cancer cells, thereby modulating the EVs’ actions on macrophages. Expression of IMP2 is linked to the secretion of EVs that polarize macrophages towards a tumor-promoting phenotype

Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 ◦C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis

Vector analysis of corneal astigmatism in cataractous eyes based on IOLMaster 700 biometry

Purpose The purpose of this study was to investigate the effect of the corneal back surface by comparing the keratometric astigmatism (K, derived from the corneal front surface) of a modern optical biometer against astigmatism of Total Keratometry (TK, derived from both corneal surfaces) in a large population with cataractous eyes. The results were then used to define linear prediction models to map K to TK. Methods From a large dataset containing bilateral biometric measurements (IOLMaster 700) in 9736 patients prior to cataract surgery, the total corneal astigmatism was decomposed into vectors for K, corneal back surface (BS), and TK. A multivariate prediction model (MV), simplified model with separation of vector components (SM) and a constant model (CM) were defined to map K to TK vector components. Results The K centroid (X/Y) showed some astigmatism with-the-rule (0.1981/-0.0211 dioptre (dpt)) whereas the TK centroid was located around zero (-0.0071/-0.0381 dpt against-the-rule) and the BS centroid showed systematic astigmatism against-the-rule (-0.2367/-0.0145 dpt). The respective TK–K centroid was located at -0.2052/-0.0302 dpt. The MV model showed the same performance (i.e. mean absolute residuum) as the SM did (0.1098 and 0.1099 dpt respectively) while the CM performed only slightly worse (0.1121 dpt mean absolute residuum). Conclusion In cases where tomographic data are unavailable statistical models could be used to consider the overall contribution of the back surface to the total corneal astigmatism. Since the performance of the CM is sufficiently close to that of MV and SM we recommend using the CM which can be directly considered e.g. as surgically induced astigmatism

Towards clinical adherence monitoring of oral endocrine breast cancer therapies by LC-HRMS-method development, validation, comparison of four sample matrices, and proof of concept

Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side efects. Therefore, adherence to OET is an important issue and of high clinical signifcance for breast cancer patients’ caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and highresolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four diferent biomatrices (plasma, urine, fnger prick blood by volumetric absorptive microsampling (VAMS), oral fuid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantifcation ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using diferent biomatrices with distinct restrictions. Sample collection of VAMS was difcult in most cases due to circulatory restraints and peripheral neuropathy in fngers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations

Arithmeticity of the Kontsevich–Zorich monodromies of certain families of square‐tiled surfaces II

In this note, we extend the scope of our previous work joint with Bonnafoux, Kattler, Niño, Sedano-Mendoza, Valdez, and Weitze-Schmithüsen by showing the arithmeticity of the Kontsevich–Zorich monodromies of infinite families of square-tiled surfaces of genera four, five, and six.Deutsche Forschungsgemeinschaft DFG(

Morphologische Veränderungen des Gaumens nach transversaler Erweiterung mit Plattenapparaturen : Kurzzeiteffekte und Langzeitstabilität

Hintergrund und Ziel: Konstriktionen des Oberkiefers führen nicht nur zu einem relativen Missverhältnis zum Unterkiefer, sondern können auch die Nasenatmung beeinträchtigen und bereits im Kindesalter Schnarchen begünstigen. Die Behandlung erfolgt oft mit festsitzenden Apparaturen, die durch die Art der Aktivierung entweder innerhalb von Tagen (schnell) oder innerhalb mehrerer Wochen und Monate (langsam) durch Kombination dentoalveolärer und skelettaler Effekte zu einer Erweiterung des Oberkiefers führt. Als Alternative ist eine Behandlung mit Plattenapparaturen möglich. Bislang liegen jedoch keine Daten zur Veränderung der Gaumenmorphologie infolge Behandlung mit herausnehmbaren Apparaturen zur transversalen Erweiterung des Oberkiefers vor. Ziel der vorliegenden Studie war deshalb zu überprüfen, wie sich die dentalen und gingivalen Abstände im Oberkiefer, Gaumenflächen und Gaumenhöhen bei Kindern und Jugendlichen während der Behandlung mit Plattenapparaturen, die Dehnschrauben als aktive Elemente enthalten, verändern und ob diese langfristig stabil bleiben. Patienten und Methoden: In der vorliegenden monozentrischen retrospektiven Studie wurden die Daten von insgesamt 90 Patienten (je 30 pro Patientengruppe, PG: PG1 unter 10 Jahre, PG2 zwischen 10 und 12 Jahren, PG3 älter als 12 Jahre) ausgewertet. Der Mundraum wur- de entweder direkt intraoral gescannt oder es wurden Gipsmodelle, die nach Alginatabformung erstellt wurden, eingescannt. Die Auswertung erfolgte digital mittels einer Diagnosesoftware. Folgende Daten wurden erhoben: dentale und gingivale Breiten zwischen den Eckzähnen, den ersten und zweiten Milch- bzw. Prämolaren sowie den ersten Molaren, Gaumenhöhen zwischen den jeweils genannten Zähnen und Gaumenflächen (anterior, posterior, gesamt). Ergebnisse: Während der Aktivierungsphase, die im Durchschnitt 16,8 ± 7,4 Monate dauerte, vergrößerten sich alle untersuchten Parameter in den 3 Patientengruppen statistisch signifikant. Während der Weiterbehandlungsphase (21,5 ± 9,8 Monate) ist die Veränderung der Werte mehrheitlich nicht signifikant. Schlussfolgerungen: Die transversale Gaumenerweiterung mit Plattenapparaturen ist bei Kindern und Jugendlichen unterschiedlichen Alters vergleichbar effizient und bleibt langfristig stabil. Allerdings konnte mit der angewendeten Methode nicht überprüft werden, ob und in welchem Ausmaß es sich dabei nur um dentoalveoläre oder auch um skelettale Effekte handelte.Background and Aim: Narrowing of the upper jaw not only leads to a relative disproportion to the lower jaw but can also impair nasal breathing and promote snoring even in childhood. Treatment is often carried out with a fixed palatal expander appliance, which, depending on the type of activation, leads to an expansion of the upper jaw either within days (fast) or within several weeks to months (slow) through a combination of dentoalveolar and skeletal effects. Alternatively, treatment with removable plate appliances is also possible. To date, however, no data are available on the change in palatal morphology following treatment with removable appliances for transversal expansion of the maxilla. The aim of the present study was therefore to investigate how the dental and gingival distances in the maxilla, the palatal surfaces and the palatal heights in children and adolescents change during treatment with removeble plate ap pliances with expansion screws as active elements and whether these remain stable in the long term. Patients and Methods: In the present monocentric retrospective study, the data of a total of 90 patients (30 patients per patient group, PG: PG1 under 10 years old, PG2 between 10 and 12 years old, PG3 older than 12 years old) were analyzed. The oral cavity was either scanned directly intraorally or plaster casts created after alginate impressions were scanned. The eval uation was carried out digitally using diagnostic software. The following data were collected: dental and gingival widths between the canines, the first and second deciduous or premolar teeth as well as the first molars, palatal heights between the respective teeth, and palatal sur faces (anterior, posterior, total). Results: During the activation phase, which lasted an average of 16.8 ± 7.4 months, all param eters examined in all three patient groups increased statistically significantly. During the follow up treatment phase (21.5 ± 9.8 months), the values generally did not change. Conclusions: Transversal palatal expansion with removable plate appliances is comparably efficient in children and adolescents of different ages and remains stable in the long term. However, the applied method could not determine whether and to what extent the effects were solely dentoalveolar or also skeletal

Treatment of chronic syndesmotic rupture – What is the current evidence?

Akute Verletzungen im oberen Sprunggelenk ko¨nnen langfristig in bis zu 30% der Fa¨lle zu chronischen Instabilita¨ten fu¨hren. Ein anatomisch widerhergestelltes distales Tibiofibulargelenk stellt einen wesentlichen Faktor fu¨r das klinische Outcome von Patienten dar. Auffa¨lligkeiten in der klinischen Untersuchung bei Verdacht auf eine chronische Syndesmosenverletzung sollten zur weiteren Diagnostik fu¨hren. Stabile La¨sion sollte mittels konservativer Maßnahmen therapiert werden. Zur operativen Versorgung der instabilen chronischen Syndesmosenverletzung ist eine große Vielfalt an Therapiemethoden in der Literatur beschrieben. Die publizierten Operationsmethoden reichen vom arthroskopischen De´bridement bis hin zu komplexen operativen Versorgungen mittels Syndesmosenrekonstruktion oder auch der tibiofibula¨rer Fusion. Die Evidenz der verschiedenen Therapiemethoden ist gering und beruht maßgeblich auf Expertenempfehlungen. Zum aktuellen Zeitpunkt kann kein Therapieregime uneingeschra¨nkt bevorzugt empfohlen werden (2023).Acute injuries to the ankle joint can lead to chronic instability in up to 30% of cases in the long term. An anatomically restored distal tibiofibular joint is a significant factor in the clinical outcome of patients. Abnormalities in the clinical examination when a chronic syndesmosis injury is suspected should lead to further diagnostics. Stable lesions should be treated with conservative measures. A wide variety of treatment methods have been described in the literature for the surgical treatment of unstable chronic syndesmosis injuries. The published surgical methods range from arthroscopic debridement to complex surgical treatment using syndesmosis reconstruction or tibiofibular fusion. The evidence for the various treatment methods is limited and is largely based on expert recommendations. At the present time, no treatment regimen can be recommended without reservation (2023)

Analytical study of a generalised Dirichlet–Neumann operator and application to three-dimensional water waves on Beltrami flows

We consider three-dimensional doubly periodic steady water waves with vorticity, under the action of gravity and surface tension; in particular we consider so-called Beltrami flows, for which the velocity field and the vorticity are collinear. We adapt a recent formulation of the corresponding problem for localised waves which involves a generalisation of the classical Dirichlet–Neumann operator. We study this operator in detail, extending some well-known results for the classical Dirichlet–Neumann operator, such as the Taylor expansion in homogeneous powers of the wave profile, the computation of its differential and the asymptotic expansion of its associated symbol. A new formulation of the problem as a single equation for the wave profile is also presented and discussed in a similar vein. As an application of these results we prove existence of doubly periodic gravity-capillary steady waves and construct approximate doubly periodic gravity steady waves