Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury.

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

Efficacy of a Disease Management Program of a Tertiary Center and Ophthalmologic Practitioners for the Treatment of Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of the study was to examine real-world data of patients with neovascular age-related macular degeneration (nAMD) within a disease management program (DMP) treated with anti-VEGF. METHODS: A monocentric, retrospective chart review of 379 eyes of a local DMP was conducted at the Department of Ophthalmology, Kepler University Clinic Linz. Eyes were treated either with bevacizumab or aflibercept using a pro re nata scheme, consisting of 3 injections every 4 weeks in case of presence of disease activity. The observational period was up to 24 months. Disease activity was monitored by visual acuity (VA), clinical examination, and optical coherence tomography (OCT). For (re-)treatments, ophthalmologic practitioners referred patients directly to the intravitreal injection, avoiding redundant examinations. RESULTS: VA improved significantly for all patients after 2 months (logMAR 0.47 ± 0.36; p = 0.000) compared to baseline (0.55 ± 0.37), and for the aflibercept group for up to 6 months (0.36 ± 0.27; p = 0.018). After 12 months, VA remained stable without further significant improvement and decreased by 24 months compared to baseline. The median number of injections was 6 over the first 12 months and 4 in the second year. CONCLUSION: Data revealed the efficacy of a DMP for nAMD involving both ophthalmologic practitioners and a tertiary center. Avoiding redundant examinations increased the efficacy of a clinical setting.

Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.

Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries.

Contact damage tolerance of alumina-based layered ceramics with tailored microstructures.

This work demonstrates how to enhance contact damage resistance of alumina-based ceramics combining tailored microstructures in a multilayer architecture. The multilayer system designed with textured alumina layers under compressive residual stresses embedded between alumina-zirconia layers was investigated under Hertzian contact loading and compared to the corresponding monolithic reference materials. Critical forces for crack initiation under spherical contact were detected through an acoustic emission system. Damage was assessed by combining cross-section polishing and ion-slicing techniques. It was found that a textured microstructure can accommodate the damage below the surface by shear-driven, quasi-plastic deformation instead of the classical Hertzian cone cracking observed in equiaxed alumina. In the multilayer system, a combination of both mechanisms, namely Hertzian cone cracking on the top (equiaxed) surface layer and quasi-plastic deformation within the embedded textured layer, was identified. Further propagation of cone cracks at higher loads was hindered and/or deflected owed to the combined action of the textured microstructure and compressive residual stresses. These findings demonstrate the potential of embedding textured layers as a strategy to enhance the contact damage tolerance in alumina ceramics.

Congenital diaphragmatic hernia: a single-centre experience at Kepler University Hospital Linz.

Congenital diaphragmatic hernia (CDH) is found in about 1 of 3000 live births and is often complicated by pulmonary hypoplasia and alteration of the pulmonary arterial wall with resulting pulmonary hypertension. Since 2005, with the fusion of the children's hospital and the maternity clinic of the Kepler University Hospital Linz, affected neonates have been treated according to a standard protocol at our perinatal centre. Some prenatally measured parameters have been used to predict mortality, e.g., observed-to-expected lung-to-head ratio or lung volume measurements by nuclear magnetic resonance imaging. We performed a retrospective chart review of 67 new-borns with CDH treated at our institution to detect any predictors of hospital mortality from parameters routinely collected within the first 24 h of life. The term "liver up" was identified as a predictor of hospital mortality; OR 9.2 (95% CI 1.9-51.1, p = 0.002, sensitivity 79%, specificity 71%). In addition, the need for application of high-frequency oscillatory ventilation during the first 24 h was associated with mortality; OR 44.4 (95% CI 6.3-412.1, p = 0.001, sensitivity 85.7%, specificity 88%).

The Gigantocellular Reticular Nucleus Plays a Significant Role in Locomotor Recovery after Incomplete Spinal Cord Injury.

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics.

Safety and Feasibility of Lumbar Cerebrospinal Fluid Pressure and Intraspinal Pressure Studies in Cervical Stenosis: A Case Series.

INTRODUCTION: Degenerative cervical myelopathy (DCM) leads to functional impairment by compression of the spinal cord and nerve roots. In DCM, the dynamics of cerebrospinal fluid pressure (CSFP) and intraspinal pressure (ISP), as well as spinal cord perfusion pressure (SCPP) remain not investigated yet. Recent technical advances have enabled investigation of these parameters in acute spinal cord injury (SCI). We aim to investigate the properties of CSFP/ISP and spinal cord hemodynamics during and after decompressive surgery in DCM. MATERIALS AND METHODS: Four patients with DCM were enrolled; during surgery and 24 h postoperative, ISP at level was measured in one patient, and CSFP was measured in two patients. In one patient, CSFP was recorded at bedside before surgery. RESULTS: All measurements were conducted without adverse events and were well tolerated. With CSFP analysis, post-decompression Queckenstedt's test was responsive in two patients (i.e., jugular vein compression resulted in an elevation of CSFP pressure). In the patient whose CSFP was tested at bedside, Queckenstedt's test was not responsive before decompression. Individual optimum SCPPs were calculated to be between 70 and 75 mmHg. CONCLUSION: ISP and CSFP can reflect spinal compression and sufficient decompression. A better understanding and systematic monitoring possibly lead to improved hemodynamic management and may allow early recognition of postoperative complications such as swelling and bleeding.

Anti-Nogo-A Antibodies As a Potential Causal Therapy for Lower Urinary Tract Dysfunction after Spinal Cord Injury.

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically.SIGNIFICANCE STATEMENT After spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction.

Enhancing rehabilitation and functional recovery after brain and spinal cord trauma with electrical neuromodulation.

PURPOSE OF REVIEW: This review discusses recent advances in the rehabilitation of motor deficits after traumatic brain injury (TBI) and spinal cord injury (SCI) using neuromodulatory techniques. RECENT FINDINGS: Neurorehabilitation is currently the only treatment option for long-term improvement of motor functions that can be offered to patients with TBI or SCI. Major advances have been made in recent years in both preclinical and clinical rehabilitation. Activity-dependent plasticity of neuronal connections and circuits is considered key for successful recovery of motor functions, and great therapeutic potential is attributed to the combination of high-intensity training with electrical neuromodulation. First clinical case reports have demonstrated that repetitive training enabled or enhanced by electrical spinal cord stimulation can yield substantial improvements in motor function. Described achievements include regaining of overground walking capacity, independent standing and stepping, and improved pinch strength that recovered even years after injury. SUMMARY: Promising treatment options have emerged from research in recent years using neurostimulation to enable or enhance intense training. However, characterizing long-term benefits and side-effects in clinical trials and identifying patient subsets who can benefit are crucial. Regaining lost motor function remains challenging.

Video Tutorials Increase Precision in Minimally Invasive Surgery Training - a Prospective Randomised Trial and Follow-up Study. / Video-Tutorials erhöhen die Präzision im minimalinvasiven Operationstraining ­ eine prospektiv randomisierte Studie und Nachuntersuchung.

BACKGROUND: Simulation-based practice has become increasingly important in minimally invasive surgery (MIS) training. Nevertheless, personnel resources for demonstration and mentoring simulation-based practice are limited. Video tutorials could be a useful tool to overcome this dilemma. However, the effect of video tutorials on MIS training and improvement of MIS skills is unclear. METHODS: A prospective randomised trial (n = 24 MIS novices) was conducted. A video-trainer with three different tasks (#1 - 3) was used for standardised goal-directed MIS training. The subjects were randomised to two groups with standard instructional videos (group A, n = 12) versus comprehensive video tutorials for each training task watched at specific times of repetition (group B, n = 12). Performance was analysed using the MISTELS score. At the beginning and following the curriculum, an MIS cholecystectomy (CHE) was performed on a porcine organ model and analysed using the GOALS score. After 18 weeks, participants performed 10 repetitions of tasks #1 - 3 for follow-up analysis. RESULTS: More participants completed tasks #1 and #2 in group B (83.3 and 75%) than in group A (66.7 and 50%, ns). For task #2, there was a significant improvement in precision in group B (p < 0.001). For the entire cohort, the GOALS-Scores were 12.9 before and 18.9 after the curriculum (p < 0.001), with no significant difference between groups. Upon follow-up, 84.2% (task#1), 26.3% (task#2) and 100% (task#3) of MIS novices were able to reach the defined goals (A vs. B ns). There was a trend for a better MISTELS score in group B upon follow-up. CONCLUSIONS: Standardised comprehensive video tutorials watched frequently throughout practice can significantly improve precision in MIC training. This aspect should be incorporated in MIS training.

Urodynamic measurements reflect physiological bladder function in rats.

AIMS: Our objective was to investigate and compare bladder function in rats assessed by metabolic cage and by urodynamic measurements in fully awake animals. METHODS: Bladder function of female Lewis rats was investigated in naïve animals by metabolic cage at baseline, 14-16 days after bladder catheter and external urethral sphincter electromyography electrode implantation in fully awake animals by urodynamics, and again by metabolic cage. RESULTS: Investigating the same animals (n = 8), voided volume, average flow, and duration of voiding were similar (P > 0.05) in naïve animals measured by metabolic cage and after catheter implantation by urodynamic measurements and by metabolic cage. In naïve animals measured by metabolic cage, voided volumes were significantly different in the light (resting phase) versus the dark (active phase) part of the 24 h cycle (mean difference 0.14 mL, 21%, P = 0.004, n = 27). CONCLUSIONS: Lower urinary tract function assessed by metabolic cage or by urodynamic meaurements in fully awake rats was indistinguishable. Thus, catheter implantation did not significantly change physiological bladder function. This shows that urodynamic measurements in awake animals are an appropriate approach to study lower urinary tract function in health and disease in animal models, directly paralleling the human diagnostic procedures.

Conception of the Lübeck Toolbox curriculum for basic minimally invasive surgery skills.

PURPOSE: Difficulties at the beginning of the learning curve in minimally invasive surgery (MIS) can well be overcome by simulation outside the operating room. Despite a great number of available devices, standardized, structured, and validated training curricula for video simulators are scarce. METHODS: The Lübeck Toolbox (LTB) video trainer provides six training modules and online video tutorials. Proficiency levels for the tasks were defined by performance analysis of MIS experts (n = 15). Mean values of the best performed repetitions were set as benchmarks for a validation study with n = 30 MIS novices and the learning curves calculated. The novices performed a cholecystectomy on a pig organ model before and after the curriculum which were analyzed using the GOALS score. RESULTS: Benchmarks defined by expert performance for the task Nos. 1 to 6 were 72 s (± 8) (Pack Your Luggage), 49 s (± 9) (Weaving), 66 s (± 10) (Chinese Jump Rope), 89 s (± 28) (Triangle Cut), 138 s (± 44) (Hammer Cut), and 98 (± 22) (Suturing). The median numbers of required repetitions by the novices to reach the proficiency level were n = 42 (7-80), n = 26 (9-55), n = 32 (14-77), n = 44 (15-59), n = 19 (6-68), and n = 26 (15-60). These values were all located at the beginning of the plateau phase of the learning curves. GOALS score improved significantly after completion of the curriculum (18.0 (± 2.6) vs. 10.9 (± 1.6), p < 0.0001). CONCLUSION: The LTB curriculum constitutes a new highly standardized and proficiency level-based training program for basic skills in MIS. Transferability of the task content to a (sub)-realistic environment could be demonstrated. Still, future trials will have to further validate the effectiveness of the LTB curriculum.

Effect of airborne particle abrasion and regeneration firing on the strength of 3D-printed 3Y and 5Y zirconia ceramics.

OBJECTIVES: This study aimed to assess the effect of airborne particle abrasion (APA) and regeneration firing (RF) on the subsurface damage and strength distribution of 3D-printed 3Y-TZP and 5Y-PSZ zirconia parts for dental applications. METHODS: Disc-shaped specimens were prepared using vat photopolymerization (VPP) technology from 3Y and 5Y zirconia ceramics, followed by thermal debinding and sintering. APA treatment with 50 µm Al2O3 particles and RF at 1000 °C for 15 min were applied. Microstructural analysis was conducted using FIB-SEM, and XRD analysis determined crystalline phase content. Biaxial flexural strength was measured using the ball on three balls method and analyzed with Weibull statistics. ANOVA and Tukey HSD test were employed to compare strength differences between groups. RESULTS: APA treatment increased the flexural strength of the 3Y specimens but decreased it for the 5Y specimens. RF treatment reversed the effect, restoring the strength to as-sintered levels for both materials. APA-treated 3Y specimens exhibited characteristic strength values above 1400 MPa, attributed to phase-transformation toughening. As sintered 5Y specimens showed strength values above 600 MPa. APA treatment increased the Weibull modulus of the 5Y specimens, indicating a narrower defect size distribution. SIGNIFICANCE: The study demonstrates that the impact of APA and RF treatments on the mechanical properties and reliability of VPP-fabricated 3Y-TZP and 5Y-PSZ ceramics is comparable to conventionally prepared zirconia. VPP technology for 3D printing provides a viable approach for future manufacturing of dental restorations with potential clinical applications.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Cranio-cervical and traumatic brain injury patterns-do they differ between electric bicycle, bicycle, and motorcycle-induced accidents?

PURPOSE: With the growing technical options of power transmission and energy-saving options in electric drives, the number of E-bike-related accidents especially in an elderly population has increased. The aim of the current study was to compare if the increased velocity in comparison to conventional bikes translates into different injury patterns in the cranio-cervical and head region. METHODS: A retrospective cohort study was performed in patients admitted to our level one trauma center between 2009 and 2019 after being involved in an accident with either an E-bike, bicycle, or motorcycle and suffered cranio-cervical or traumatic brain injury. OUTCOMES: cranio-cervical/intracranial injury pattern. Data interpretation was conducted in an interdisciplinary approach. RESULTS: From 3292 patients treated in this period, we included 1068 patients. E-bikers were significantly older than bicyclists (or motorcyclists) and lay between the other two groups in terms of helmet use. Overall injury patterns of E-bikers resembled those found in motorcyclists rather than in bicyclists. E-bikers had a higher incidence of different cerebral bleedings, especially if no helmet was worn. Helmet protection of E-bikers resulted in a comparable frequency of intracranial bleeding to the helmeted bicyclists. CONCLUSION: The overall pattern of head and cervical injuries in E-bikers resembles more to that of motorcyclists than that of bicyclists. As they are used by a more senior population, multiple risk factors apply in terms of complications and secondary intracranial bleeding. Our study suggests that preventive measures should be reinforced, i.e., use of helmets to prevent from intracranial injury.

Six percent hydroxyethyl starch 130/0.4 (Voluven®) versus 5% human serum albumin for volume replacement therapy during elective open-heart surgery in pediatric patients.

BACKGROUND: Although 5% albumin (human serum albumin [HSA]) is widely used in cardiac surgery children, synthetic colloids may provide a valuable alternative. This study compared 6% hydroxyethyl starch (HES) 130/0.4 with HSA for volume replacement in this population. METHODS: The study was a two-center, randomized, controlled, parallel-group, double-blind trial performed in children aged 2-12 yr undergoing elective surgery for congenital heart disease under extracorporeal circulation. The primary objective was to demonstrate equivalence between HES and HSA with regard to the total volume of colloid infusion for intraoperative volume replacement including priming of the extracorporeal circuitery. RESULTS: In the per-protocol population, mean volume of colloid required until end of surgery was (mean ± SD) 36.6 ± 11.8 ml/kg body weight in the HES group (N = 29) and 37.0 ± 11.9 ml/kg body weight in the HSA group (N = 26; ratio of means HES/HSA = 0.98 [95% CI, 0.84-1.16]). Intraoperative fluid balance was less positive in the HES group (P = 0.047). No difference was found regarding hemodynamics, the use of vasoactive and inotropic drugs. Blood loss, erythrocytes transfusion, and renal function were not different between groups. The incidence of adverse events up to postoperative day 28 did not differ between the groups. CONCLUSIONS: In pediatric cardiac surgery, HES showed equivalence to HSA with regard to volume replacement therapy in children aged from 2 to 12 yr. Although there was no suggestion of an imbalance of safety measures between HES and HSA, the study was not powered to provide any firm conclusions about safety of tetrastarch in this population.

Levosimendan versus milrinone in neonates and infants after corrective open-heart surgery: a pilot study.

OBJECTIVE: Low cardiac output syndrome commonly complicates the postoperative course after open-heart surgery in children. To prevent low cardiac output syndrome, prophylactic administration of milrinone after cardiopulmonary bypass is commonly used in small children. The aim of this study was to compare the effect of prophylactically administered levosimendan and milrinone on cardiac index in neonates and infants after corrective open-heart surgery. DESIGN: Prospective, single-center, double-blind, randomized pilot study. SETTING: Tertiary care center, postoperative pediatric cardiac intensive care unit. PATIENTS: After written informed consent, 40 infants undergoing corrective open-heart surgery were included. INTERVENTIONS: At weaning from cardiopulmonary bypass, either a 24-hr infusion of 0.1 µg/kg/min levosimendan or of 0.5 µg/kg/min milrinone were administered. Cardiac output was evaluated at 2, 6, 9, 12, 18, 24, and 48 hrs after cardiopulmonary bypass using a transesophageal Doppler technique (Cardio-QP, Deltex Medical, Chichester, UK). Cardiac index was calculated from cardiac output and the patients' respective body surface area. RESULTS: Intention-to-treat data of 39 patients (19 in the levosimendan and 20 in the milrinone group) were analyzed using analysis of variance for repeated measurements for statistics. Analysis of variance revealed for both, cardiac index and cardiac output, similar results with no significant differences of the factors group and time. A significant interaction for cardiac output (p = .005) and cardiac index (p = .007) was found, which indicates different time courses of cardiac index in the two groups. Both drugs were well tolerated; no death or serious adverse event occurred. CONCLUSIONS: In our small study, postoperative cardiac index over time was similar in patients with prophylactically administered levosimendan and patients with prophylactically given milrinone. We observed an increase in cardiac output and cardiac index over time in the levosimendan group, whereas cardiac output and cardiac index remained stable in the milrinone group. This pilot study has primarily served to obtain experience using the new drug levosimendan in neonates and infants and to initiate further multicenter trials in pediatric patients.

ABO incompatibility and mild factor VIII deficiency in the neonate: Not too much of a problem but a challenge on ECMO.

Coagulopathy and bleeding on extracorporeal membrane oxygenation (ECMO) contribute to a worse outcome, and hyperbilirubinemia is an additional threat for newborn babies. We report a case of a newborn boy with congenital diaphragmatic hernia (CDH) associated with ABO incompatibility and an inherited mild hemophilia A. Due to respiratory failure he needed ECMO on his first day of life. During ECMO an exchange transfusion was performed after an extensive hyperbilirubinemia had evolved. Thereafter severe bleeding occurred, and a very low factor VIII level was found causative for that. After factor VIII substitution bleeding was under control and the baby eventually could be weaned from ECMO, underwent corrective surgery, and recovered.

Effect of binder system on the thermophysical properties of 3D-printed zirconia ceramics.

Fabrication of 3D-printed ceramic parts with high complexity and high spatial resolution often demands low wall thickness as well as high stiffness at the green state, whereas printing simpler geometries may tolerate thicker, more compliant walls with the advantage of a rapid binder-burn-out and sintering process. In this work, the influence of the binder system on the thermophysical properties of 3D-printed stabilized zirconia ceramics was investigated. Samples were fabricated with the lithography-based ceramic manufacturing (LCM) technology using two different photosensitive ceramic suspensions (LithaCon 3Y230 and LithaCon 3Y210), with the same ZrO2 powder. A significant difference in stiffness in the green state (~3 MPa vs. ~32 MPa for LithaCon 3Y230 and LithaCon 3Y210, respectively) was measured, associated with a rather loose or a linked network formed in the binder due to photopolymerization. Both materials reached high relative densities, that is, >99%, exhibiting a homogeneous fine-grained microstructure. No significant differences on the coefficient of thermal expansion (11.18 ppm/K vs. 11.17 ppm/K) or Young's modulus (207 GPa vs. 205 GPa) were measured, thus demonstrating the potential of tailoring binder systems to achieve the required accuracy in 3D-printed parts, without detrimental effects on material's microstructure and thermophysical properties at the sintered state.

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats.

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function-in particular, non-voiding bladder contractions and intravesical pressure-immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.