Vergleichende radiologische Untersuchungen zum Einheilungsverhalten intervertebraler Cages mit unterschiedlichem Design im Fusionsmodell der Schafshalswirbelsäule

Einleitung: Experimentelle Daten zu Designparametern von Cages fehlen weitgehend. Ziel dieser Untersuchung war es, am Modell der Schafshalswirbelsäule den Effekt von Designparametern (Auflagefläche/Porengröße) auf das Einheilungsverhalten von Cages radiologisch zu untersuchen. Material und Methode: Bei 24 Merino-Schafen wurde eine intervertebrale zervikale Fusion C3/C4 mit 3 verschiedenen Stabilisierungsverfahren (n=8) durchgeführt. Gruppe1: autologer Beckenkammspan; Gruppe2: Syncage-C + autologe Spongiosa; Gruppe3: Harmscage + autologe Spongiosa. Während der Standzeit wurden radiologische Verlaufsuntersuchungen durchgeführt. Nach der 12-wöchigen Standzeit erfolgten funktionsradiologische Untersuchungen sowie computertomographische Untersuchungen am Präparat. Der Status der Fusion wurde anhand eines Fusionsscores bestimmt. Ergebnisse: Im Vergleich zum Beckenkammspan waren beide Cages in der Lage, die Höhe des Bandscheibenraums und den Intervertebralwinkel signifikant besser zu erhalten. Bezüglich der Sinterungsparameter, der radiologischen Funktionsuntersuchungen und des Fusionsscores waren bis auf den Zeitpunkt Woche 1 (Cage im Box-Design mit geringster Sinterung) keine signifikanten Unterschiede zwischen beiden Cages nachweisbar. Bei der Evaluation des Kallusvolumens zeigte sich für den Cage im Zylinder-Design eine größere Kallusformation, als für den Cage im Box-Design. Schlussfolgerung: Innerhalb der ersten 12 Wochen lassen sich nur in der frühen postoperativen Phase designspezifische Unterschiede zwischen beiden Cages nachweisen. Die Ergebnisse dieser Studie zeigen, dass die Auflagefläche für das Sinterungsverhalten eines Cage in vivo nur von untergeordneter Bedeutung ist. Ein signifikanter Einfluss der Porengröße der Cages auf das Einheilungsverhalten konnte radiologisch nicht nachgewiesen werden. Ein Einfluss der Primärstabilität des Implantats auf die Kallusformation kann postuliert werden.Introduction: Experimental data of design parameters of cages are lacking. The purpose of this study was to compare the effect of design parameters (endplate-implant contact area/maximum contiguous pore) on interbody fusion in a sheep cervical spine model by radiological methods. Material and Method: Twenty-four sheep underwent C3-4 discectomy and fusion in which the following were used: Group 1, autologous tricortical iliac crest bone graft (n=8); Group 2, titanium cylinder-design cage + autologous bone graft (n=8); and Group 3, titanium box-design cage filled with autologous bone graft (n=8). During the evaluation period radiography was performed. After the 12 weeks' evaluation period, functional radiographs and quantitative computerized tomography scans were acquired. Status of fusion has been evaluated by means of a fusion score. Results: Over a 12 weeks' period significantly higher values for disc space height and intervertebral angle were shown in cage-treated sheep than in those that received bone graft. Comparing the cage-groups no significant difference could be found in disk-space height, functional radiographic assessment and fusion score except week one. At this time the box-design cage showed significantly better distractive properties. The cylinder-design cage showed significantly higher values for bone callus volume in comparison to the box-design cage. Conclusion: In the 12 weeks' period, no significant design specific differences between both cages could be stated except during the early post-operative period. This study shows that the parameter endplate-implant contact-area was not able to determine subsidence of cages. An influence of maximum contiguous pore on the fusion's result could not be shown by radiological data. Primary stiffness must have an influence on bone callus formation

Radiographic and safety details of vertebral body stenting : results from a multicenter chart review

Background: Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented. Methods: During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author. Results: 100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1°. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9°. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group. Conclusions: VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation

Role of iodine oxoacids in atmospheric aerosol nucleation

Iodic acid (HIO₃) is known to form aerosol particles in coastal marine regions, but predicted nucleation and growth rates are lacking. Using the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we find that the nucleation rates of HIO₃ particles are rapid, even exceeding sulfuric acid–ammonia rates under similar conditions. We also find that ion-induced nucleation involves IO₃⁻ and the sequential addition of HIO₃ and that it proceeds at the kinetic limit below +10°C. In contrast, neutral nucleation involves the repeated sequential addition of iodous acid (HIO₂) followed by HIO₃, showing that HIO₂ plays a key stabilizing role. Freshly formed particles are composed almost entirely of HIO₃, which drives rapid particle growth at the kinetic limit. Our measurements indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H2SO4). Despite their importance, accurate prediction of MSA and H2SO4from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H2SO4production is modestly affected. This leads to a gas-phase H2SO4-to-MSA ratio (H2SO4/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NOxeffect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H2SO4/MSA measurements

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H$_{2}$SO$_{4}$). Despite their importance, accurate prediction of MSA and H$_{2}$SO$_{4}$ from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to −10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H$_{2}$SO$_{4}$ production is modestly affected. This leads to a gas-phase H$_{2}$SO$_{4}$-to-MSA ratio (H$_{2}$SO$_{4}$/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH$_{3}$S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2–10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NO$_{x}$ effect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H$_{2}$SO$_{4}$/MSA measurements

Molecular understanding of the suppression of new-particle formation by isoprene

Nucleation of atmospheric vapours produces more than half of global cloud condensation nuclei and so has an important influence on climate. Recent studies show that monoterpene (C10H16) oxidation yields highly oxygenated products that can nucleate with or without sulfuric acid. Monoterpenes are emitted mainly by trees, frequently together with isoprene (C5H8), which has the highest global emission of all organic vapours. Previous studies have shown that isoprene suppresses new-particle formation from monoterpenes, but the cause of this suppression is under debate. Here, in experiments performed under atmospheric conditions in the CERN CLOUD chamber, we show that isoprene reduces the yield of highly oxygenated dimers with 19 or 20 carbon atoms - which drive particle nucleation and early growth - while increasing the production of dimers with 14 or 15 carbon atoms. The dimers (termed C-20 and C-15, respectively) are produced by termination reactions between pairs of peroxy radicals (RO2 center dot) arising from monoterpenes or isoprene. Compared with pure monoterpene conditions, isoprene reduces nucleation rates at 1.7 nm (depending on the isoprene = monoterpene ratio) and approximately halves particle growth rates between 1.3 and 3.2 nm. However, above 3.2 nm, C-15 dimers contribute to secondary organic aerosol, and the growth rates are unaffected by isoprene. We further show that increased hydroxyl radical (OH center dot) reduces particle formation in our chemical system rather than enhances it as previously proposed, since it increases isoprene-derived RO2 center dot radicals that reduce C-20 formation. RO2 center dot termination emerges as the critical step that determines the highly oxygenated organic molecule (HOM) distribution and the corresponding nucleation capability. Species that reduce the C-20 yield, such as NO, HO2 and as we show isoprene, can thus effectively reduce biogenic nucleation and early growth. Therefore the formation rate of organic aerosol in a particular region of the atmosphere under study will vary according to the precise ambient conditions.Peer reviewe

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system