Severe thoracic trauma – still an independent predictor for death in multiple injured patients?

Background: Over the past, the severe thoracic trauma has had decisive influence on the outcome of multiple injured patients. Today, new therapies (e.g. extracorporeal membrane oxygenation (ECMO), protective ventilation methods and new forms of patient positioning) are available and applied regularly. What impact on the patient's outcome does the thoracic trauma have today? Methods: Prospective data collection of multiple injured patients in a level-I trauma center was performed between 2008 and 2014. Patients with an ISS >= 16 were included and divided into 2 groups: Severe thoracic trauma (STT: AIS(Thorax) >= 3) and mild thoracic trauma (MTT: AIS(Thorax) < 3). In addition to preclinical and trauma room care, detailed information about clinical course and outcome were assessed. Results: In total, 529 patients (STT: n = 317; MTT: n = 212) met the in-and exclusion criteria. The mean Injury Severity Score (ISS) was significantly higher in patients of the STT group (STT: 33.5 vs. MTT: 24.7; p < 0.001), while the RISC II Score showed no significant differences (STT: 20.0 vs. MTT: 17.1; p = 0.241). Preclinical data revealed a higher intubation rate, more chest tube insertions and a higher use of catecholamines in the STT group (p < 0.05). Clinically, we found significant differences in the duration of invasive ventilation (STT: 7.3d vs. MTT: 5.4d; p = 0.001) and ICU stay (STT: 12.3d vs. MTT: 9.4d; p < 0.001). While the complication rate was higher for the STT group (sepsis (STT: 11.4% vs. MTT: 5.7%; p = 0.017); lung failure (STT: 23.7% vs. MTT: 12.3%; p = 0,001)), neither the non-adjusted lethality rate (STT: 13.2% vs. MTT: 13.7%; p = 0.493) nor the Standardized Mortality Ratio (SMR) showed significant differences (STT: 0.66 vs. MTT: 0.80; p = 0.397). The multivariate regressive analysis confirmed that severe thoracic trauma is not an independent risk factor for lethality in our patient cohort. Conclusion: Despite a higher injury severity, the extended need of emergency measures and a higher rate of complications in injured patients with severe blunt thoracic trauma, no influence on lethality can be proved. The reduction of the complication rate should be a goal for the next decades

47 patients with FLNA associated periventricular nodular heterotopia

Background: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Methods: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Results: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males

Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome

Objective: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS). Methods: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study. Results: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirtyfive children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p = 1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%. Conclusions: Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course

Hämatologische Referenzwerte von Frühgeborenen unter 1500 g Geburtsgewicht

Diagnostische und therapeutische Entscheidungen hängen bei der Behandlung von VLBW Frühgeborenen (In very low birth weight (VLBW) infants, diagnostic and therapeutic decisions depend on hematologic values. As few data are available, we studied the course during the first 6 weeks of life. Four prospective longitudinal cohort studies were retrospectively combined assessing hematologic profiles of 562 VLBW infants. We showed by metaanalysis that the values between the different four studies are not significantly different. For characterization of red blood cells and ferritin, infants receiving erythropoietin were excluded. For characterization of white blood cells and platelets, infants receiving antibiotics were excluded. Red cell parameters of VLBW infants were significantly lower than those of mature newborns. 29% of VLBW infants have thromboctopenia at the age of 3 days. Neutrophils decreased steadily, and wer

FAUSTLOS - a Curriculum for an Increase of Social Skills and for the Prevention of Aggressive and Potentially Violent Behavior in Children

FAUSTLOS ist ein für die Arbeit im Kindergarten und in der Grundschule entwickeltes Curriculum zur Prävention von aggressivem und gewaltbereitem Verhalten bei Kindern. Aggressives und gewaltbereites Verhalten resultiert wesentlich aus einem Mangel an sozialen Kompetenzen, der eine konstruktive Form der Problem und Konfliktbewältigung nicht zuläßt. Aus diesem Grund steht die Förderung und Erweiterung prosozialer Verhaltensfertigkeiten von Kindern bei EAUSTLOS im Mittelpunkt. FAUSTLOS ist die deutsche Version des US-amerikanischen Programms Second Step, das vom Committee for Children in Seattle entwickelt wurde und seit etwa acht Jahren in vielen amerikanischen Bundesstaaten erfolgreich angewendet wird. Vom Projekt „Kinder und Gewalt" wurde es für den deutschsprachigen Raum adaptiert. FAUSTLOS befindet sich z.Zt. in der Pilotphase. Im folgenden wollen wir einen Überblick über den Ansatz, den Inhalt und die Methodik des Curriculums sowie über die Planung und Durchführung der Pilotphase geben.(DIPF/Orig.)FAUSTLOS is a curriculum that has been developed for the prevention of aggression and potentially violent behavior in children in nursery and primary school. A lack of social skills is regarded as one of the fundamental causes that detoriates problem and conflict solving. FAUSTLOS is the German Version of an American program called Second Step that has been developed by the Committee for Children in Seattle and has been successfully put into practice in several American states over the last eight years. The project "Kinder und Gewalt" has adapted it for the German speaking countries. FAUSTLOS is at present in its pilot phase. The following is a general survey of the inception, contents and methods of the curriculum and the planning and execution of the pilot phase.(DIPF/Orig.

Selective Oxidation of Methionine and Tryptophan Residues in a Therapeutic IgG1 Molecule

Oxidation of methionine and tryptophan are common degradation pathways for monoclonal antibodies and present major analytical challenges in biotechnology. Generally, protein oxidation is detectable in stability and/or stressed samples (e.g., exposed to hydrogen peroxide, UV light, or metal ions). The induced chemical modifications may impact the biological activity of antibodies and may have biological consequences. However, these effects and the contribution of individual protein modifications are difficult to delineate as different amino acids are often oxidized simultaneously and accompanied by other degradants such as aggregates, especially in forced degradation studies. Here, we report a new method to obtain selective oxidation of methionine or tryptophan by using oxidation reagents combined with large excess of free tryptophan or methionine, correspondingly. More specifically, using hydrogen peroxide or tert-butyl hydroperoxide in combination with addition of free tryptophan allowed for selective oxidation of methionine. Conversely, the use of 2,2-azobis(2-amidinopropane) dihydrochloride in combination with free methionine resulted in selective tryptophan oxidation, whereas methionine oxidation was not significantly altered. This novel stress model system may prove to be valuable tool in future mechanistic studies of oxidative degradation of protein therapeutics