Abstract
Objective
There are several treatment options for patients suffering from lumbar spinal stenosis, including surgical and conservative care. Interspinous spacer decompression using the ...Superion device offers a less invasive procedure for patients who fail conservative treatment before traditional decompression surgery. This review assesses the current cost-effectiveness, safety, and performance of lumbar spinal stenosis treatment modalities compared with the Superion interspinous spacer procedure.
Methods
EMBASE and PubMed were searched to find studies reporting on the cost-effectiveness, safety, and performance of conservative treatment, including medicinal treatments, epidural injections, physical therapy, and alternative methods, as well as surgical treatment, including laminectomy, laminectomy with fusion, and interspinous spacer decompression. Results were supplemented with manual searches.
Results
Despite substantial costs, persistent conservative treatment (>12 weeks) of lumbar spinal stenosis showed only minimal improvement in pain and functionality. When conservative treatment fails, surgery is more effective than continuing conservative treatment. Lumbar laminectomy with fusion has considerably greater cost than laminectomy alone, as the length of hospital stay increases, the costs for implants are substantial, and complications increase. Although laminectomy and the Superion have comparable outcomes, the Superion implant is positioned percutaneously. This approach may minimize the direct and indirect costs of outpatient rehabilitation and absenteeism, respectively.
Conclusions
Superion interspinous lumbar decompression is a minimally invasive procedure for patients with lumbar spinal stenosis who have failed conservative treatment. Compared with extending conservative treatment or traditional spinal surgery, interspinous lumbar decompression reduces the direct and indirect costs associated with lumbar spinal stenosis.
Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminth-derived glycoproteins ...for the treatment of immune-related diseases, like allergies and autoimmune diseases. Studies are however hampered by the limited availability of native parasite-derived proteins. Moreover, recombinant protein production systems have thus far been unable to reconstitute helminth-like glycosylation essential for the functionality of some helminth glycoproteins. Here we exploited the flexibility of the N-glycosylation machinery of plants to reconstruct the helminth glycoproteins omega-1 and kappa-5, two major constituents of immunomodulatory Schistosoma mansoni soluble egg antigens. Fine-tuning transient co-expression of specific glycosyltransferases in Nicotiana benthamiana enabled the synthesis of Lewis X (LeX) and LDN/LDN-F glycan motifs as found on natural omega-1 and kappa-5, respectively. In vitro and in vivo evaluation of the introduction of native LeX motifs on plant-produced omega-1 confirmed that LeX on omega-1 contributes to the glycoprotein's Th2-inducing properties. These data indicate that mimicking the complex carbohydrate structures of helminths in plants is a promising strategy to allow targeted evaluation of therapeutic glycoproteins for the treatment of inflammatory disorders. In addition, our results offer perspectives for the development of effective anti-helminthic vaccines by reconstructing native parasite glycoprotein antigens.
Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses. Many of these immunomodulatory compounds are modified with complex sugar structures ...(or glycans), which play an important role at the host-parasite interface. As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids. Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized. To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants. All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs. This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions. The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation. Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
Glycoproteins are the dominant category among approved biopharmaceuticals, indicating their importance as therapeutic proteins. Glycoproteins are decorated with carbohydrate structures (or glycans) ...in a process called glycosylation. Glycosylation is a post-translational modification that is present in all kingdoms of life, albeit with differences in core modifications, terminal glycan structures, and incorporation of different sugar residues. Glycans play pivotal roles in many biological processes and can impact the efficacy of therapeutic glycoproteins. The majority of biopharmaceuticals are based on human glycoproteins, but non-human glycoproteins, originating from for instance parasitic worms (helminths), form an untapped pool of potential therapeutics for immune-related diseases and vaccine candidates. The production of sufficient quantities of correctly glycosylated putative therapeutic helminth proteins is often challenging and requires extensive engineering of the glycosylation pathway. Therefore, a flexible glycoprotein production system is required that allows straightforward introduction of heterologous glycosylation machinery composed of glycosyltransferases and glycosidases to obtain desired glycan structures. The glycome of plants creates an ideal starting point for
- and
-glyco-engineering of helminth glycans. Plants are also tolerant toward the introduction of heterologous glycosylation enzymes as well as the obtained glycans. Thus, a potent production platform emerges that enables the production of recombinant helminth proteins with unusual glycans. In this review, we discuss recent advances in plant glyco-engineering of potentially therapeutic helminth glycoproteins, challenges and their future prospects.
This study sought to quantify EndoAnchor (Medtronic Vascular, Santa Rosa, Calif) penetration into the aortic wall in patients undergoing endovascular abdominal aortic aneurysm repair and to assess ...predictors of successful penetration and its relationship to postprocedural type IA endoleak.
A subset of patients from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) were included if they met the following criteria: the indication for EndoAnchor use was to treat a type IA endoleak, and postprocedure contrast-enhanced computed tomography (CT) scans of sufficient quality were available for core laboratory review. Patients undergoing implantation of cuffs or stents during the EndoAnchor implantation procedure were excluded. Baseline anatomic characteristics were recorded. The cohort was divided into patients with and without persistent type IA endoleaks at the first postoperative CT scan. Penetration of each EndoAnchor measured on this CT scan was defined as good penetration when the EndoAnchor penetrated ≥2 mm into the aortic wall, borderline penetration when EndoAnchor penetration was <2 mm or a gap remained between the endograft and aortic wall, or no penetration when the EndoAnchor did not penetrate into the aortic wall. Differences between the groups were analyzed with the Mann-Whitney U test or Fisher exact test. Multivariate analyses were performed to identify independent predictors of EndoAnchor penetration, and procedural success was defined by absence of type IA endoleak.
Eighty-six patients of the primary (n = 61 71%) and revision (n = 25 29%) arms of the ANCHOR registry were included. There were 53 (62%) without and 33 (38%) with persistent type IA endoleaks on the first postprocedural CT scan. The median number of EndoAnchors with good penetration was significantly greater in the cohort without endoleaks, 4 (interquartile range, 3-5) vs 3 (interquartile range, 1.5-4), respectively (P = .002). A multivariate model for EndoAnchor penetration identified use of a Medtronic Endurant endograft as a factor associated with good penetration (P = .001), whereas poor penetration was associated with a larger aortic neck diameter 10 mm distal to the lowest renal artery (P < .001) and greater proximal neck calcium thickness (P = .004). EndoAnchor penetration was the only variable that attained significance (P < .001) in the multivariate model for successful treatment of a type IA endoleak.
Adequate EndoAnchor penetration into the aortic wall is less likely when the aortic neck diameter is large or when the neck contains significant mural calcium. No penetration of the EndoAnchor was the only factor predictive of postprocedural type IA endoleak. This study stresses the importance of careful selection of patients based on preoperative assessment of the infrarenal neck on CT angiography and emphasizes careful deployment of EndoAnchors into the aortic wall to improve successful treatment of type IA endoleaks.
Purpose: To evaluate the association between aortic curvature and other preoperative anatomical characteristics and late (>1 year) type Ia endoleak and endograft migration in endovascular aneurysm ...repair (EVAR) patients. Methods: Eight high-volume EVAR centers contributed 116 EVAR patients (mean age 81±7 years; 103 men) to the study: 36 patients (mean age 82±7 years; 31 men) with endograft migration and/or type Ia endoleak diagnosed >1 year after the initial EVAR and 80 controls without early or late complications. Aortic curvature was calculated from the preoperative computed tomography scan as the maximum and average curvature over 5 predefined aortic segments: the entire infrarenal aortic neck, aneurysm sac, and the suprarenal, juxtarenal, and infrarenal aorta. Other morphological characteristics included neck length, neck diameter, mural neck calcification and thrombus, suprarenal and infrarenal angulation, and largest aneurysm sac diameter. Independent risk factors were identified using backward stepwise logistic regression. Relevant cutoff values for each of the variables in the final regression model were determined with the receiver operator characteristic curve. Results: Logistic regression identified maximum curvature over the length of the aneurysm sac (>47 m−1; p=0.023), largest aneurysm sac diameter (>56 mm; p=0.028), and mural neck thrombus (>11° circumference; p<0.001) as independent predictors of late migration and type Ia endoleak. Conclusion: Aortic curvature is a predictor for late type Ia endoleak and endograft migration after EVAR. These findings suggest that aortic curvature is a better parameter than angulation to predict post-EVAR failure and should be included as a hostile neck parameter.
Secretions of parasitic worms (helminths) contain a wide collection of immunomodulatory glycoproteins with the potential to treat inflammatory disorders, like autoimmune diseases. Yet, the ...identification of single molecules that can be developed into novel biopharmaceuticals is hampered by the limited availability of native parasite-derived proteins. Recently, pioneering work has shown that helminth glycoproteins can be produced transiently in
plants while simultaneously mimicking their native helminth N-glycan composition by co-expression of desired glycosyltransferases. However, efficient "helminthization" of N-glycans in plants by glyco-engineering seems to be hampered by the undesired truncation of complex N-glycans by β-
-acetyl-hexosaminidases, in particular when aiming for the synthesis of N-glycans with antennary GalNAcβ1-4GlcNAc (LacdiNAc or LDN). In this study, we cloned novel β-hexosaminidase open reading frames from
and characterized the biochemical activity of these enzymes. We identified HEXO2 and HEXO3 as enzymes responsible for the cleavage of antennary GalNAc residues of N-glycans on the model helminth glycoprotein kappa-5. Furthermore, we reveal that each member of the HEXO family has a distinct specificity for N-glycan substrates, where HEXO2 has strict β-galactosaminidase activity, whereas HEXO3 cleaves both GlcNAc and GalNAc. The identification of HEXO2 and HEXO3 as major targets for LDN cleavage will enable a targeted genome editing approach to reduce undesired processing of these N-glycans. Effective knockout of these enzymes could allow the production of therapeutically relevant glycoproteins with tailor-made helminth N-glycans in plants.
Purpose: To identify preoperative anatomical aortic characteristics that predict seal failures after endovascular aneurysm sealing (EVAS) and compare the incidence of events experienced by patients ...treated within vs outside the instructions for use (IFU). Methods: Of 355 patients treated with the Nellix EndoVascular Aneurysm Sealing System (generation 3SQ+) at 3 high-volume centers from March 2013 to December 2015, 94 patients were excluded, leaving 261 patients (mean age 76±8 years; 229 men) for regression analysis. Of these, 83 (31.8%) suffered one or more of the following events: distal migration ⩾5 mm of one or both stent frames, any endoleak, and/or aneurysm growth >5 mm. Anatomical characteristics were determined on preoperative computed tomography (CT) scans. Patients were divided into 3 groups: treated within the original IFU (n=166), outside the original IFU (n=95), and within the 2016 revised IFU (n=46). Categorical data are presented as the median (interquartile range Q1, Q3). Results: Neck diameter was significantly larger in the any-event cohort vs the control cohort 23.7 mm (21.7, 26.3) vs 23.0 mm (20.9, 25.2) mm, p=0.022. Neck length was significantly shorter in the any-event cohort 15.0 mm (10.0, 22.5) vs 19.0 mm (10.0, 21.8), p=0.006. Maximum abdominal aortic aneurysm (AAA) diameter and the ratio between the maximum AAA diameter and lumen diameter in the any-event group were significantly larger than the control group (p=0.041 and p=0.002, respectively). Regression analysis showed aortic neck diameter (p=0.006), neck length (p=0.001), and the diameter ratio (p=0.011) as significant predictors of any event. In the comparison of events to IFU status, 52 (31.3%) of 166 patients in the inside the original IFU group suffered an event compared to 13 (28.3%) of 46 patients inside the 2016 IFU group (p=0.690). Conclusion: Large neck diameter, short aortic neck length, and the ratio between the maximum AAA and lumen diameters are preoperative anatomical predictors of the occurrence of migration (⩾5 mm), any endoleak, and/or aneurysm growth (>5 mm) after EVAS. Even under the refined 2016 IFU, more than a quarter of patients suffered from an event. Improvements in the device seem to be necessary before this technique can be implemented on a large scale in endovascular AAA repair.
Objective: Aortic pulse-wave-velocity (aPWV) is a measure for arterial stiffness, which is associated with increased cardiovascular risk. Recent evidence suggests aPWV increases after ...endograft-placement for aortic aneurysms. The aim of this study was to investigate the influence of different aortic endoprostheses on aPWV and structural stiffness in vitro. Approach: Three different abdominal aortic endoprostheses (AFX, Endurant II, and Nellix) were implanted in identical silicone aneurysm models. One model was left untreated, and another model contained an aortic tube graft (Gelweave). The models were placed in an in vitro flow set-up that mimics physiological flow. aPWV was measured as the transit time of the pressure wave over the flow trajectory of the suprarenal to iliac segment. Structural stiffness corrected for lumen diameter was calculated for each model. Results: aPWV was significantly lower for the control compared to the AFX, Endurant, Nellix and tube graft models (13.00 ± 1.20, 13.40 ± 1.17, 18.18 ± 1.20, 16.19 ± 1.25 and 15.41 ± 0.87 m s−1, respectively (P < 0.05)). Structural stiffness of the AFX model was significant lower compared to the control model (4718 N m−1 versus 5115 N m−1 (P < 0.001), respectively), whereas all other models showed higher structural stiffness. Significance: Endograft placement resulted in a higher aPWV compared to a non-treated aortic flow model. All models showed increased structural stiffness over the flow trajectory compared to the control model, except for the AFX endoprosthesis. Future studies in patients treated with an endograft are needed to evaluate the current results in vivo.
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