Health-Related Quality of Life after Fractures of the Distal Forearm in Children and Adolescents-Results from a Center in Switzerland in 432 Patients.

(1) Background: We aimed to evaluate the health-related quality of life (HRQoL) in children with fractures of the distal forearm and to assess if HRQoL was associated with fracture classification; (2) Methods: We followed up on 432 patients (185 girls, 247 boys) who sustained a fracture of the distal radius or forearm from 1/2007 to 6/2007, 1/2014 to 6/2014, and 11/2016 to 10/2017. Patients filled in the Quick-DASH (primary outcome) and the Peds-QL; (3) Results: The radius was fractured in 429 and the ulna in 175 cases. The most frequent injury of the radius was a buckle fracture (51%, mean age 8.5 years), followed by a complete metaphyseal fracture (22%, 9.5 years), Salter-Harris-2 fracture (14%, 11.4 years), greenstick fracture (10%, 9.3 years), Salter-Harris-1 fracture (1%, 12.6 years), and other rare injuries. The most common treatment was closed reduction and an above-elbow cast in 138 cases (32%), followed by a cast without reduction (30%), splint (28%), and K-wire fixation and cast (9%). Definite treatment was performed initially in 95.8%, a new cast or cast wedging was performed in 1.6%, and revision surgery was performed in 2.5%. There were no open reductions and no plate fixations. After a mean follow-up of 4.2 years, patients with buckle fractures had a mean Quick-DASH of 3.3 (scale of 0-100) (complete fracture: 1.5; greenstick: 1.5; SH-1: 0.9; SH-2: 4.1; others: 0.9). The mean function score of the PedsQL ranged from 93.0 for SH-2 fractures to 97.9 for complete fractures; (4) Conclusions: In this cohort of 432 children with fractures of the distal forearm, there was equally good mean mid- and long-term HRQoL when assessed by the Quick-DASH and the PedsQL. There was a trend for children with complete metaphyseal fractures reporting better HRQoL than patients with buckle fractures or patients with Salter-Harris II fractures, however, these differences were not statistically significant nor clinically relevant.

[Perioperative lethality after endovascular and open repair of ruptured abdominal aortic aneurysms: An analysis of administrative data of the AOK health insurance fund]. / Zur perioperativen Letalität des rupturierten Bauchaortenaneurysmas nach endovaskulärer und offener Versorgung: eine Analyse von Routinedaten der AOK Gesundheit.

OBJECTIVE: In this paper we will report the perioperative outcome after endovascular (EVAR) and open (OAR) repair of ruptured abdominal aortic aneurysms (rAAA) in Germany based on data of the AOK health insurance fund. METHODS: Anonymised data of all patients with rAAA (n = 3,227) who were treated from 01/01/2010 to 12/31/2016 were analysed, using SPSS 27 (IBM Deutschland GmbH, Ehningen, Germany). RESULTS: 41.9% (1,353/3,227) of the patients were treated with EVAR and 58.1% (1,874/3,227) with OAR. Patients ≥80 years made up 38.4% for EVAR and 32.9% for OAR (p = 0.002). The proportion of patients undergoing surgery within 24 hours after admission was significantly higher for OAR (87.8%) than for EVAR (73.0%) (p = 0.000). The perioperative lethality rate for OAR was 42.4%, and thus almost twice as high as for EVAR with 21.3% (p = 0.000). Women had higher perioperative lethality rates for both EVAR (perioperative lethality 24.6%) and OAR (perioperative lethality 51.7%) compared to men with 20.6% (EVAR) and 40.2% (OAR), respectively. With EVAR, 35.8% of the patients showed a complication-free postoperative course, with OAR it was 17.7% (p = 0.000). Blood transfusions (whole blood, red cell concentrates, and autotransfusions) were administered in 57.6% of the patients with EVAR, but in 92.3% with OAR (p = 0.000). The highest perioperative lethality was found in EVAR and OAR patients who received both surgery within 24 hours after admission and blood transfusions (perioperative lethality EVAR 36.0%, OAR 46.0%; p = 0.000). In contrast, patients who did not require blood transfusions and were treated later than 24 hours after admission had the lowest perioperative lethality with 3.2% for EVAR vs. 5.4% for OAR (p = 0.623). CONCLUSION: The data confirm the observation that the perioperative mortality of rAAA patients is lower with EVAR than with OAR. However, strict attention must be paid to the time of the intervention. The low perioperative lethality of patients who were treated later than 24 hours after hospital admission and who did not require blood transfusions indicates that cases of symptomatic AAA without rupture have also been recorded in this administrative database under the diagnosis rAAA. One point of criticism is that the decision not to adjust for the patient groups with EVAR and with OAR in order to be able to better analyse the properties of routine data includes a considerable risk of bias in the statements of this work due to confounding variables.

Health-Related Quality of Life after Adolescent Fractures of the Femoral Shaft Stabilized by a Lateral Entry Femoral Nail.

(1) Background: In adolescents, fractures of the femoral shaft that are not suitable for elastic-stable-intramedullary-nailing (ESIN), are challenging. We aimed to evaluate the health-related quality of life (HRQoL) and complications in adolescents treated with intramedullary rodding using the adolescent lateral trochanteric entry femoral nail (ALFN), and to assess if HRQoL was associated with additional injuries. (2) Methods: We followed-up on 15 adolescents with a diaphyseal femoral fracture who were treated with an ALFN from 2004 to 2017. Patients were asked to fill in a questionnaire that includes the iHOT, Peds-QL, and the Pedi-IKDC. (3) Results: The ALFN was used as a primary method of fixation in 13 patients, and as a fixation for failed ESIN in two cases. All 15 fractures healed radiographically. One distal locking screw broke. After a mean follow-up of 2.8 years, the mean iHOT-12 was 14.0 (SD 15.4), PedsQL-function was 85.7 (SD 19.3), PedsQL-social-score was 86.2 (SD 12.5), and the mean Pedi-IKDC was 77.2 (SD 11.3). In patients where the femoral fracture was an isolated injury, the HRQoL-scores were consistently higher compared with patients who sustained additional injures. (4) Conclusions: Treating diaphyseal fractures in adolescents with an ALFN resulted in good radiographic outcomes in all our cases. HRQoL, as measured by the iHOT, PedsQL, and Pedi-IKDC, was good to excellent; but it was consistently inferior in patients with additional injuries. These results suggest that the ALFN is a good alternative when patients are not suitable for ESIN, and that the HRQoL of adolescents who were treated with an ALFN is mainly influenced by the presence of additional injures, and less by the fracture of the femur itself.

A biosynthetic route for polysialylating proteins in Escherichia coli.

Polysialic acid (polySia) is a posttranslational modification found on only a handful of proteins in the central nervous and immune systems. The addition of polySia to therapeutic proteins improves pharmacokinetics and reduces immunogenicity. To date, polysialylation of therapeutic proteins has only been achieved in vitro by chemical or chemoenzymatic strategies. In this work, we develop a biosynthetic pathway for site-specific polysialylation of recombinant proteins in the cytoplasm of Escherichia coli. The pathway takes advantage of a bacterial cytoplasmic polypeptide-glycosyltransferase to establish a site-specific primer on the target protein. The glucose primer is extended by glycosyltransferases derived from lipooligosaccharide, lipopolysaccharide and capsular polysaccharide biosynthesis from different bacterial species to synthesize long chain polySia. We demonstrate the new biosynthetic route by modifying green fluorescent proteins and a therapeutic DARPin (designed ankyrin repeat protein).

Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.

BACKGROUND: We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes. METHODS: Former preterm infants randomly assigned to receive darbepoetin (10 µg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups. RESULTS: Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group. CONCLUSIONS: ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely.

Voltage-clamp analysis and computational model of dopaminergic neurons from mouse retina.

Isolated dopaminergic amacrine (DA) cells in mouse retina fire rhythmic, spontaneous action potentials and respond to depolarizing current with trains of low-frequency action potentials. To investigate the roles of voltage-gated ion channels in these processes, the transient A-type K+ current (I(K,A)) and Ca2+ current (I(Ca)) in isolated mouse DA cells were analyzed by voltage clamp. The I(K,A) activated at -60 mV and inactivated rapidly. I(Ca) activated at around -30 mV and reached a peak at 10 mV without apparent inactivation. We also extended our previous computational model of the mouse DA cell to include the new electrophysiological data. The model consisted of a membrane capacitance in parallel with eight currents: Na+ transient (I(Na,T)), Na+ persistent (I(Na,P)), delayed rectifier potassium (I(Kdr)), I(K,A), calcium-dependent potassium (I(K,Ca)), L-type Ca2+ I(Ca), hyperpolarization-activated cation current (I(h)), and a leak current (I(L)). Hodgkin-Huxley type equations were used to define the voltage- and time-dependent activation and inactivation. The simulations were implemented using the neurosimulator SNNAP. The model DA cell was spontaneously active from a wide range of initial membrane potentials. The spontaneous action potentials reached 35 mV at the peak and hyperpolarized to -76 mV between spikes. The spontaneous firing frequency in the model was 6 Hz. The model DA cell responded to prolonged depolarizing current injection by increasing its spiking frequency and eventually reaching a depolarization block at membrane potentials greater than -10 mV. The most important current for determining the firing rate was I(K,A). When the amplitude of I(K,A) was decreased, the firing rate increased. I(Ca) and I(K,Ca) also affected the width of action potentials but had only minor effects on the firing rate. Ih affected the firing rate slightly but did not change the waveform of the action potentials.

Spontaneous activity of dopaminergic retinal neurons.

Dopaminergic local circuit neurons in the retina (DA cells) show robust, spontaneous, tetrodotoxin-sensitive pacemaking. To investigate the mechanism underlying this behavior, we characterized the sodium current and a subset of the potassium currents in the cells in voltage-clamp experiments. We found that there is a persistent component of the sodium current in DA cells which activates at more depolarized potentials than the transient component of the current. The transient component was completely inactivated at -50 mV, but DA cells remained able to fire spontaneous action potentials when potassium channels were partially blocked and the membrane potential remained above -40 mV. Based on these electrophysiological data, we developed a reduced computer model that reproduced the major features of DA cells. In simulations at the physiological resting potential, the persistent component of the sodium current was both necessary and sufficient to account for spontaneous activity, and the major contribution of the transient component of the sodium current was to initiate the depolarization of the model cell during the interspike interval. When tonic inhibition was simulated by lowering the input impedance of the model cell, the transient component played a larger role.