Surgical procedure and initial radiographic results of a new augmentation technique for vertebral compression fractures

Purpose

Recently, a new minimally invasive technique called ‘vertebral body stenting’ (VBS) was introduced for the treatment of osteoporotic vertebral fractures. The technique was developed to prevent the loss of reduction after deflation of the balloon and to reduce the complication rate associated with cement leakage.

Methods

The amount of kyphosis correction, improvement of vertebral body height and quantitative cement leakage rate by applying CT-based quantitative volumetry after VBS were measured in 27 patients (55 vertebra) and compared with a control group (29 patients, 61 vertebrae), which was treated with conventional vertebroplasty.

Results

After VBS, a significant improvement was seen in vertebral height, compared to conventional vertebroplasty. The mean improvement in segmental kyphosis and vertebral kyphosis were 5.8° (p < 0.05) and 3.5° (p < 0.05), respectively. In the VBS group, the mean injected volume of cement per vertebral body was 7.33 cm³ (3.34–10.19 cm³). The average amount of cement outside the vertebrae was 0.28 cm³ (0.01–1.64 cm³), which was 1.36 % of the applied total cement volume. In the vertebroplasty group, the applied mean volume of the cement per level was 2.7 cm³ (1–5.8 cm³) and the average amount of cement outside the vertebrae was 0.15 cm³ (0.01–1.8 cm³), which was 11.5 % (0.2–60 %) of the applied total volume of cement.

Conclusion

The frequency of cement leakage after VBS was 25.5 % compared to 42.1 % in the vertebroplasty group. VBS led to a significant decrease in the leakage rate compared with conventional vertebroplasty.     

Footprint mismatch in total cervical disc arthroplasty

Purpose

Cervical disc arthroplasty has become a commonplace surgery for the treatment of cervical radiculopathy and myelopathy. Most manufacturers derive their implant dimensions from early published cadaver studies. Ideal footprint match of the prosthesis is essential for good surgical outcome.

Methods

We measured the dimensions of cervical vertebrae from computed tomography (CT) scans and to assess the accuracy of match achieved with the most common cervical disc prostheses [Bryan (Medtronic), Prestige LP (Medtronic), Discover (DePuy) Prodisc-C (Synthes)]. A total of 192 endplates in 24 patients (56.3 years) were assessed. The anterior–posterior and mediolateral diameters of the superior and inferior endplates were measured with a digital measuring system.

Results

Overall, 53.5 % of the largest device footprints were smaller in the anterior–posterior diameter and 51.1 % in the mediolateral diameter were smaller than cervical endplate diameters. For levels C5/C6 and C6/C7 an inappropriate size match was noted in 61.9 % as calculated from the anteroposterior diameter. Mismatch at the center mediolateral diameter was noted in 56.8 %. Of the endplates in the current study up to 58.1 % of C5/C6 and C6/C7, and up to 45.3 % of C3/C4 and C4/C5 were larger than the most frequently implanted cervical disc devices.

Conclusion

Surgeons and manufacturers should be aware of the size mismatch in currently available cervical disc prostheses, which may endanger the safety and efficacy of the procedure. Undersizing the prosthetic device may lead to subsidence, loosening, heterotopic ossification and biomechanical failure caused by an incorrect center of rotation and load distribution, affecting the facet joints.     

Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society     

The extent of soil loss across the US Corn Belt

Soil erosion in agricultural landscapes reduces crop yields, leads to loss of ecosystem services, and influences the global carbon cycle. Despite decades of soil erosion research, the magnitude of historical soil loss remains poorly quantified across large agricultural regions because preagricultural soil data are rare, and it is challenging to extrapolate local-scale erosion observations across time and space. Here we focus on the Corn Belt of the midwestern United States and use a remote-sensing method to map areas in agricultural fields that have no remaining organic carbon-rich A-horizon. We use satellite and LiDAR data to develop a relationship between A-horizon loss and topographic curvature and then use topographic data to scale-up soil loss predictions across 3.9 × 10⁵ km² of the Corn Belt. Our results indicate that 35 ± 11% of the cultivated area has lost A-horizon soil and that prior estimates of soil degradation from soil survey-based methods have significantly underestimated A-horizon soil loss. Convex hilltops throughout the region are often completely denuded of A-horizon soil. The association between soil loss and convex topography indicates that tillage-induced erosion is an important driver of soil loss, yet tillage erosion is not simulated in models used to assess nationwide soil loss trends in the United States. We estimate that A-horizon loss decreases crop yields by 6 ± 2%, causing $2.8 ± $0.9 billion in annual economic losses. Regionally, we estimate 1.4 ± 0.5 Pg of carbon have been removed from hillslopes by erosion of the A-horizon, much of which likely remains buried in depositional areas within the fields.

Productive agricultural soils are vital for producing food for a growing global population (1–3). However, degradation of soil quality by erosion reduces crop yields, which can result in food insecurity, conflict (3), and the decline of civilizations (4). Degradation of soils leads not only to economic losses for farmers but also a loss in ecosystem services (5), which alters the ability of soils to regulate hydrologic and biogeochemical cycles. Widespread use of synthetic fertilizers to enhance the function of degraded soils increases food production costs (6) and impairs water resources (7), which negatively impacts human health (8) and aquatic ecosystems (9).Globally, the reservoir of carbon stored in soils is three times that in the atmosphere (10) and given the extent of agricultural land use (11), understanding soil carbon dynamics in agricultural systems is critical to understanding the carbon cycle (12). Whether soil erosion constitutes a net carbon sink or source depends on both the depositional fate of the eroded carbon and the ability to replace carbon in degraded soils (13–15). If biological productivity replaces eroded carbon, and decomposition of carbon stored in sedimentary deposits is halted or slowed, then soil erosion is a net sink of atmospheric carbon (14–17). However, if eroded carbon rapidly decomposes and is not replaced in eroded soil horizons, then soil erosion constitutes a carbon source. Restoring carbon to degraded soils therefore has potential to both reestablish soil function and sequester atmospheric CO₂ (10). However, quantifying the impacts of soil degradation on agricultural productivity and the carbon cycle first requires robust estimates of the magnitude of agriculturally induced soil loss (14, 16).Although thousands of soil erosion measurements have been made globally (18), the lack of a robust and scalable method for estimating the magnitude of erosion in agricultural landscapes remains a major gap in soil erosion research (19). Large-scale assessments of soil erosion are often based on model predictions (20–22) or qualitative information from soil surveys regarding the degree of soil degradation (23). In the United States, for example, nationwide soil loss trends (24) are simulated using water and wind erosion models that have been calibrated with erosion measurements made on small plots over a period of decades (21, 25). It has been debated whether upscaling such predictions to regional or national scales results in an accurate assessment of the current magnitude of soil loss in the United States (26, 27). Whereas such models are useful for assessing relative rates of erosion for soil conservation planning, the soil loss predictions do not provide information regarding the cumulative soil loss that has occurred since the initiation of cultivation, and hence the overall magnitude of agricultural soil degradation.To assess the degree of cumulative soil degradation, soil surveys conducted by the US Department of Agriculture have assigned erosion classes to soils based on the percentage of the original A horizon that has been eroded (28). Because the A horizon has the largest fraction of soil organic carbon within the soil profile, it is a key component of water and nutrient retention and soil productivity (29). Soils where 100% of the A-horizon thickness has been removed are designated as Class 4 eroded soils, and other classes represent lesser reductions in A-horizon thickness (<25%, 25 to 75%, and >75% for Classes 1, 2, and 3, respectively). A major disadvantage of the use of erosion classes is that properly assigning classes based on the percentage of A-horizon loss requires accurate determination of the original A-horizon thickness on all topographic positions (30). Hence, although soil erosion classes indicate soil degradation is widespread (23) we do not have a robust, quantitative understanding of how much soil has already been lost.Here we present results from a remote sensing method used to estimate the spatial extent of agriculturally induced loss of A-horizon soil for a major global agricultural region, the Corn Belt of the midwestern United States. Rather than simulate or measure short-term soil loss rates, we combine measurements of soil-surface reflectance in the visible spectrum (soil color) with high-resolution satellite imagery to directly measure the proportion of the agriculturally cultivated landscape that has completely lost its original A horizon. Combining our spectral analysis with relationships between A-horizon soil loss and topography derived from high-resolution LiDAR topographic data allows us to predict A-horizon soil loss in areas where images are not available. We find that historical soil erosion has completely removed A-horizon soil from approximately one-third of the Corn Belt. The spatial patterns of soil loss suggest that key erosion mechanisms are not simulated in nationwide assessments of soil erosion trends in the United States and that soil survey data greatly underestimate the extent of A-horizon loss.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B

In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B.     

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n?=?302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20–30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53–10.7)?months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.