Transcranial Doppler emboli monitoring for stroke prevention after flow diverting stents.

OBJECTIVE: Flow diverting stents (FDS) are increasingly used for the treatment of intracranial aneurysms. While FDS can provide flow diversion of parent vessels, their high metal surface coverage can cause thromboembolism. Transcranial Doppler (TCD) emboli monitoring can be used to identify subclinical embolic phenomena after neurovascular procedures. Limited data exists regarding the use of TCDs for emboli monitoring in the periprocedural period after FDS placement. We evaluated the rate of positive TCDs microembolic signals and stroke after FDS deployment at our institution. METHODS: We retrospectively evaluated 105 patients who underwent FDS treatment between 2012 and 2016 using the Pipeline stent (Medtronic, Minneapolis, MN, USA). Patients were pretreated with aspirin and clopidogrel. All patients were therapeutic on clopidogrel pre-operatively. TCD emboli monitoring was performed immediately after the procedure. Microembolic signals (mES) were classified as "positive" (<15 mES/hour) and "strongly positive" (>15 mES/hour). Clinical stroke rates were determined at 2-week and 6-month post-operatively. RESULTS: A total of 132 intracranial aneurysms were treated in 105 patients. TCD emboli monitoring was "positive" in 11.4% (n=12) post-operatively and "strongly positive" in 4.8% (n=5). These positive cases were treated with heparin drips or modification of the antiplatelet regimen, and TCDs were repeated. Following medical management modifications, normalization of mES was achieved in 92% of cases. The overall stroke rates at 2-week and 6-months were 3.8% and 4.8%, respectively. CONCLUSIONS: TCD emboli monitoring may help early in the identification of thromboembolic events after flow diversion stenting. This allows for modification of medical therapy and, potentially, preventionf of escalation into post-operative strokes.

Atomically Thin Metal-Dielectric Heterostructures by Atomic Layer Deposition.

Heterostructures increasingly attracted attention over the past several years to enable various optoelectronic and photonic applications. In this work, atomically thin interfaces of Ir/Al2O3 heterostructures compatible with micro-optoelectronic technologies are reported. Their structural and optical properties were determined by spectroscopic and microscopic techniques (XRR, XPS, HRTEM, spectroscopic ellipsometry, and UV/vis/NIR spectrophotometry). The XRR and HRTEM analyses reveal a layer-by-layer growth mechanism of Ir in atomic scale heterostructures, which is different from the typical island-type growth of metals on dielectrics. Alongside, XPS investigations imply the formation of Ir-O-Al bonding at the interfaces for lower Ir concentrations, in contrast to the nanoparticle core-shell structure formation. Precisely tuning the ratio of the constituents ensures the control of the dispersion profile along with a transition from effective dielectric to metallic heterostructures. The Ir coating thickness was varied ranging from a few angstroms to films of about 7 nm in the heterostructures. The transition has been observed in the structures containing individual Ir coating thicknesses of about 2-4 nm. Following this, we show epsilon-near-zero metamaterials with tunable dielectric constants by precisely varying the composition of such heterostructures. Overall, a comprehensive study on structural and optical properties of the metal-dielectric interfaces of Ir/Al2O3 heterostructures was addressed, indicating an extension of the material portfolio available for novel optical functionalities.

[Ibrutinib-associated atrial fibrillation : A therapeutic challenge]. / Fibrillation atriale associée à l'ibrutinib : un challenge thérapeutique.

Ibrutinib is a potent Bruton tyrosine kinase inhibitor and is an effective and well-tolerated treatment for a variety of lymphoid diseases. However, its use is associated with an increased incidence of atrial fibrillation ranging from 4% to 16%. New onset atrial fibrillation in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation must be carefully weighed against this increased risk of bleeding. It is well-known that the anti-arrhythmic and antithrombotic strategy for atrial fibrillation related to ibrutinib has its own characteristics. Physicians should be familiar with the special management considerations imposed by this drug. Indeed, the co-prescription of therapy in combination with ibrutinib must be carefully weighed in view of its numerous drug interactions. We review the potential mechanisms and incidence of ibrutinib-associated atrial fibrillation.

Plasma-Enhanced Atomic Layer Deposition of HfO2 with Substrate Biasing: Thin Films for High-Reflective Mirrors.

Tuning ion energies in plasma-enhanced atomic layer deposition (PEALD) processes enables fine control over the material properties of functional coatings. The growth, structural, mechanical, and optical properties of HfO2 thin films are presented in detail toward photonic applications. The influence of the film thickness and bias value on the properties of HfO2 thin films deposited at 100 °C using tetrakis(dimethylamino)hafnium (TDMAH) and oxygen plasma using substrate biasing is systematically analyzed. The HfO2 films deposited without a substrate bias show an amorphous microstructure with a low density, low refractive index, high incorporation of residual hydroxyl (OH) content, and high residual tensile stress. The material properties of HfO2 films significantly improved at a low bias voltage due to the interaction with oxygen ions accelerated to the film. Such HfO2 films have a higher density, higher refractive index, and lower residual OH incorporation than films without bias. The mechanical stress becomes compressive depending on the bias values. Further increasing the ion energies by applying a larger substrate bias results in a decrease of the film density, refractive index, and a higher residual OH incorporation as well as crystalline inclusions. The comparable material properties of the HfO2 films have been reported using tris(dimethylamino)cyclopentadienyl hafnium (TDMACpH) in a different apparatus, indicating that this approach can be transferred to various systems and is highly versatile. Finally, the substrate biasing technique has been introduced to deposit stress-compensated, crack- and delamination-free high-reflective (HR) mirrors at 355 and 532 nm wavelengths using HfO2 and SiO2 as high and low refractive index materials, respectively. Such mirrors could not be obtained without the substrate biasing during the deposition because of the high tensile stress of HfO2, leading to cracks in thick multilayer systems. An HR mirror for 532 nm wavelength shows a high reflectance of 99.93%, a residual transmittance of ∼530 ppm, and a low absorption of ∼11 ppm, as well as low scattering losses of ∼4 ppm, high laser-induced damage threshold, low mechanical stress, and high environmental stability.

Influence of seed layers on the reflectance of sputtered aluminum thin films.

The fabrication of highly reflective aluminum coatings is still an important part of current research due to their high intrinsic reflectivity in a broad spectral range. By using thin seed layers of Cu, CuOx, Cr, CrOx, Au, and Ag, the morphology of sputtered (unprotected) aluminum layers and, consequently, their reflectance can be influenced. In this long-term study, the reflectance behavior was measured continuously using spectrophotometry. Particular seed layer materials enhance the reflectance of aluminum coatings significantly and reduce their long-term degradation. Combining such seed layers with evaporation processes and suitable protective layers could further increase the reflectance of aluminum coatings.

Optical bandgap control in Al2O3/TiO2 heterostructures by plasma enhanced atomic layer deposition: Toward quantizing structures and tailored binary oxides.

Atomically thin heterostructures and superlattices are promising candidates for various optoelectronic and photonic applications. Different combinations of Al2O3/TiO2 composites are obtained by plasma enhanced atomic layer deposition (PEALD). Their growth, composition, dispersion relation, and optical bandgap are systematically studied by means of UV/VIS spectrophotometry, spectroscopic ellipsometry (SE), x-ray reflectometry (XRR), scanning transmission electron microscopy(STEM) and x-ray photoelectron spectroscopy (XPS). Besides, an effective medium approximation (EMA) approach is applied to model the heterostructures theoretically. The refractive index and the indirect bandgap of the heterostructures depend on the ratio of the two oxides, while the bandgap is very sensitive to the thicknesses of the barrier and quantum well layers. A large blue shift of the absorption edge from 400 nm to 320 nm is obtained by changing the TiO2 (quantum well) thickness from ~2 nm to ~0.1 nm separated by ~2 nm of Al2O3 (barrier) layers. PEALD unfolds the possibility of achieving optical quantizing effects within complex heterostructures enabling control of their structures down to atomic scale. It enables a path towards atomic scale processing of new 'artificial' materials with desired refractive indices and bandgap combinations by precise control of their compositions.

Epidemiological, clinical, and echocardiographic features of twenty 'Takotsubo-like' reversible myocardial dysfunction cases with normal coronarography following immersion pulmonary oedema.

BACKGROUND: Pulmonary immersion oedema is a frequent diving accident. Although its outcome is generally favourable within 72 h, it can nonetheless lead to heart failure or sudden death. Cases of transient myocardial dysfunction have been reported in the literature. This phenomenon is similar to Takotsubo syndrome in many ways. It is characterised by transient myocardial hypokinesia, without associated coronary lesions. METHODS: We report on 20 cases of patients who showed transient alteration of left ventricular kinetics with normal coronary angiography over the course of an immersion pulmonary oedema. RESULTS: The echocardiographic localisation of the myocardial damage was generally focal and not centred on the apex with an average left ventricular ejection fraction of 45%. The main anomalies in the electrocardiographic repolarisation were T wave inversion with corrected QT interval prolongation. We also observed a moderate increase in troponin levels, with discordance between the enzymatic peak and the severity of the left ventricle segmental dysfunction. CONCLUSION: These cases suggest the incidence of a clinical entity strongly reminiscent of Takotsubo phenomenon of atypical topography as a consequence of diving accidents.

Structural, optical, and mechanical properties of TiO2 nanolaminates.

The structural, optical, and mechanical properties of TiO2 nanolaminate films grown by plasma-enhanced atomic layer deposition are discussed. Several TiO2/Al2O3 and TiO2/SiO2 compositions have been investigated to study the effect of the relative number of ALD oxide cycles on the film properties to obtain a high refractive index coating with low optical losses, low roughness, and low mechanical stress. The formation of crystalline TiO2 observed at high deposition temperature, or film thickness was inhibited by periodically introducing ultra-thin amorphous layers into the film. Only 4 ALD cycles of Al2O3 (corresponding to ca. 0.5 nm) between 335 ALD cycles of TiO2 (ca. 11 nm) form a closed, distinct layer suppressing the crystallization in TiO2 film. Consequently, the roughness of the pure TiO2 film is reduced from ca. 20 nm rms to 1 nm rms in the 335/4 nanolaminate, with only a slight decrease of the refractive index from 2.46 to 2.44 in 100 nm pure TiO2 and the nanolaminate, respectively. The refractive indices of the nanolaminates in various compositions vary between 2.38 and 2.50 at 632 nm, and the corresponding optical losses from the films are low. The mechanical stress was reduced to about 140 MPa in several TiO2/Al2O3 nanolaminates; however, lower mechanical stress has not been obtained with the studied compositions. The nanolaminate structure is preserved up to 600 °C annealing temperature. After annealing at 800 °C, the individual layers interdiffuse into each other so that no distinct nanolaminate structure is detected. By using TiO2/Al2O3 nanolaminates with reduced mechanical stress, a narrow bandpass filter was realized on various substrates, including half-ball and aspherical lenses.

Wafer-level integration of self-aligned high aspect ratio silicon 3D structures using the MACE method with Au, Pd, Pt, Cu, and Ir.

The wafer-level integration of high aspect ratio silicon nanostructures is an essential part of the fabrication of nanodevices. Metal-assisted chemical etching (MACE) is a promising low-cost and high-volume technique for the generation of vertically aligned silicon nanowires. Noble metal nanoparticles were used to locally etch the silicon substrate. This work demonstrates a bottom-up self-assembly approach for noble metal nanoparticle formation and the subsequent silicon wet etching. The macroscopic wafer patterning has been done by using a poly(methyl methacrylate) masking layer. Different metals (Au, Pt, Pd, Cu, and Ir) were investigated to derive a set of technologies as platform for specific applications. Especially, the shape of the 3D structures and the resulting reflectance have been investigated. The Si nanostructures fabricated using Au nanoparticles show a perfect light absorption with a reflectance below 0.3%. The demonstrated technology can be integrated into common fabrication processes for microelectromechanical systems.

A Low-Cost Beam-Scanning Second Harmonic Generation Microscope with Application for Agrochemical Development and Testing.

A low-cost second harmonic generation (SHG) microscope was constructed, and, for the first time, SHG microscopy was used for imaging agrochemical materials directly on the surface of common commercial crop leaves. The microscope uses a chromatically fixed (1560 nm) femtosecond fiber laser, a commercial 2D galvanometer mirror system, and a PCIe digital oscilloscope card, which together kept total instrument costs under $40 000 (USD), a significant decrease in cost and complexity from common systems (commercial and home-built) using tunable lasers and faster beam-scanning architectures. The figures of merit of the low-cost system still enabled a variety of measurements of agrochemical materials. Following confirmation of largely background-free SHG imaging of common crop leaves (soybean, maize, wheatgrass), SHG microscopy was used to image active ingredient crystallization after solution-phase deposition directly on the leaf surface, including at industrially relevant active ingredient concentrations (<0.05% w/w). Crystallization was also followed in real-time, with differences in crystallization time observed for different application procedures (spraying vs single droplet deposition). A strong dependency of active ingredient crystallization on the substrate was found, with an increased crystallization tendency observed on leaves vs on glass slides. Different crystal habits for the same active ingredient were also observed on different plant species. Finally, a model extended-release formulation was prepared, with a decrease in active ingredient crystallinity observed vs solution-phase deposition. These collective results demonstrate the need for making diagnostic measurements directly on the leaf surface and could help inform the next generation of pesticide products that ensure optimized agricultural output for a growing world population.

Internal Thoracic Artery to Vertebral Artery Bypass Surgery: A Cadaveric Feasibility Study.

OBJECTIVE: Posterior circulation strokes account for over one quarter of all ischemic strokes. The frequency of vertebral artery origin stenosis (VAOS) in patients with vertebrobasilar insufficiency (VBI) has been estimated to be as high 26%-32%, and VAOS is the direct cause of posterior circulation strokes in 9% of patients. This association could have a significant genetic component. This study examines the feasibility of the internal thoracic artery (ITA) as a donor vessel for revascularization in patients with VAOS. METHODS: Ten sides from 5 fresh-frozen white cadaveric necks derived from 3 women and 2 men were used in this study. The mean age of the cadavers at death was 77.2 years (range, 68-88 years). The subclavian artery, vertebral artery, and ITA were dissected. The length and diameter (proximal and distal) of the V1 segment and the length and diameter of the ITA were recorded. Finally, the ITA was transposed to the V1 segment of the vertebral artery (VA1). RESULTS: The mean length of the VA1 and its diameter at the proximal and distal parts were 35.51 and 3.69 mm, respectively. The mean length and diameter of the ITA were 26.53 and 3.27 mm, respectively. Rerouting the ITA to the VA1 was feasible without tension on all sides. CONCLUSIONS: This study indicates that the ITA is anatomically and hemodynamically an excellent option for bypass surgery in a VAOS scenario. We present convincing and reproducible data to aid neurosurgeons in choosing the procedure best suited to their patients.

Spindle cell oncocytoma of the pituitary gland.

OBJECTIVE: The authors report the diagnosis, management, and outcomes of 6 cases of spindle cell oncocytoma (SCO) in an effort to guide clinical diagnosis and management of these uncommon lesions. METHODS: This study is a retrospective review of cases involving adult patients who underwent resection of pituitary lesions at the authors' institutions between January 2000 and October 2017. The authors identified patients with histopathological confirmation of SCO and collected clinical data, including preoperative, perioperative, and postoperative management, complications, and outcomes. RESULTS: Six patients with SCO were identified. Clinical findings at initial presentation included visual disturbances, dizziness, and headache. All patients underwent resection. Four resections were initially performed by the transsphenoidal approach, and 2 resections were performed by craniotomy at an outside institution with subsequent transsphenoidal reoperations. Neither necrosis nor increased mitotic activity was seen in the tumor samples. All samples stained positive for S100 protein and thyroid transcription factor 1 and negative for glial fibrillary acidic protein and pituitary hormones. Five of the samples stained positive for epithelial membrane antigen. The average MIB-1 index was 8.3% (range 2-17). Postoperatively, 3 of the 6 patients received further treatment for progression of residual tumor or for recurrence, 2 have stable residual tumor, and 1 has had no recurrence after gross-total resection. Two patients developed postoperative complications of transient sixth cranial nerve palsy and diplopia. There were no other complications. CONCLUSIONS: SCO poses both a diagnostic and therapeutic challenge. These tumors are often initially misdiagnosed as nonfunctional pituitary adenomas because of their sellar location and nonspecific symptomatology. Postoperatively, SCO must also be distinguished from other neoplasms of the posterior pituitary gland through histopathological examination. Resection of SCO can be challenging, given its highly vascular and adherent nature. Long-term follow-up is critical, as the tumor is associated with higher recurrence and progression rates compared to other benign neoplasms of the sella.

Calibration-Free Second Harmonic Generation (SHG) Image Analysis for Quantification of Trace Crystallinity Within Final Dosage Forms of Amorphous Solid Dispersions.

A statistical model enables auto-calibration of second harmonic generation (SHG) images for quantifying trace crystallinity within amorphous solid dispersions (ASDs) over a wide dynamic range of crystallinity. In this paper, we demonstrate particle-counting approaches for quantifying trace crystallinity, combined with analytical expressions correcting for particle overlap bias in higher crystallinity regimes to extend the continuous dynamic range of standard particle-counting algorithms through to the signal averaging regime. The reliability of the values recovered by these expressions was demonstrated with simulated data as well as experimental data obtained for an amorphous solid dispersion formulation containing evacetrapib, an Eli Lilly and Company compound. Since particle counting independently recovers the crystalline volume and the SHG intensity, the average SHG intensity per unit volume can be used as an internal calibrant for quantifying crystallinity at higher volume fractions, for which particle counting is no longer applicable.

Second harmonic generation microscopy as a tool for the early detection of crystallization in spray dried dispersions.

Various techniques have been used to detect crystallization in amorphous solid dispersions (ASD). However, most of these techniques do not enable the detection of very low levels of crystallinity (<1%). The aim of the current study was to compare the sensitivity of second harmonic generation (SHG) microscopy with powder X-ray diffraction (XRPD) in detecting the presence of crystals in low drug loading amorphous solid dispersions. Amorphous solid dispersions of the poorly water soluble compounds, flutamide (FTM, 15wt.% drug loading) and ezetimibe (EZT, 30wt.% drug loading) with hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared by spray drying. To induce crystallization, samples were subsequently stored at 75% or 82% relative humidity (RH) and 40°C. Crystallization was monitored by XRPD and by SHG microscopy. Solid state nuclear magnetic resonance spectroscopy (ssNMR) was used to further investigate crystallinity in selected samples. For flutamide, crystals were detected by SHG microscopy after 8days of storage at 40°C/82% RH, whereas no evidence of crystallinity could be observed by XRPD until 26days. Correspondingly, for FTM samples stored at 40°C/75% RH, crystals were detected after 11days by SHG microscopy and after 53days by XRPD. The evolution of crystals, that is an increase in the number and size of crystalline regions, with time could be readily monitored from the SHG images, and revealed the formation of needle-shaped crystals. Further investigation with scanning electron microscopy indicated an unexpected mechanism of crystallization, whereby flutamide crystals grew as needle-shaped projections from the surface of the spray dried particles. Similarly, EZT crystals could be detected at earlier time points (15days) with SHG microscopy relative to with XRPD (60days). Thus, SHG microscopy was found to be a highly sensitive method for detecting and monitoring the evolution of crystals formed from spray dried particles, providing much earlier detection of crystallinity than XRPD under comparable run times.

Transorbital Approach for Endovascular Occlusion of Carotid-Cavernous Fistulas: Technical Note and Review of the Literature.

Carotid-cavernous fistulas (CCFs) pose an anatomically and physiologically challenging problem for clinicians. The most common method of treatment for these lesions is transvenous endovascular embolization via the inferior petrosal sinus or the facial vein. When transvenous access is not possible, an alternate approach must be devised. We describe a case example with bilateral Barrow Type B CCFs, which were inaccessible using the traditional transvenous approach. Hence, a direct transorbital approach, performed under fluoroscopic guidance, was employed to successfully obliterate the CCF. At five months follow-up, the patient was recovering without complications. This case delineates the technical aspects of transorbital CCF embolization and demonstrates that this approach is a viable alternative to conventional transvenous methods for appropriately selected CCF cases. We supplement our case example and technical note with a literature review of this approach.

Recent Advances in Nonlinear Optical Analyses of Pharmaceutical Materials in the Solid State.

The past decade has seen an increase in the use of nonlinear optical (NLO) techniques such as second harmonic generation, coherent antistokes Raman scattering, stimulated Raman scattering, and two-photon fluorescence for the solid-state characterization of pharmaceutical materials. These combined techniques offer several advantages (e.g., speed, selectivity, quantitation) of potential interest to the pharmaceutical community, as decreased characterization times in formulation development and testing could help decrease the time required to bring new, higher quality drugs to market. The large body of literature recently published in this field merits a review. Literature will be discussed in order of drug development, starting with applications in initial therapeutic molecule crystallization and polymorphic analysis, followed by final dosage form characterization, and ending with drug product performance testing.

Imaging the Nonlinear Susceptibility Tensor of Collagen by Nonlinear Optical Stokes Ellipsometry.

Nonlinear optical Stokes ellipsometric (NOSE) microscopy was demonstrated for the analysis of collagen-rich biological tissues. NOSE is based on polarization-dependent second harmonic generation imaging. NOSE was used to access the molecular-level distribution of collagen fibril orientation relative to the local fiber axis at every position within the field of view. Fibril tilt-angle distribution was investigated by combining the NOSE measurements with ab initio calculations of the predicted molecular nonlinear optical response of a single collagen triple helix. The results were compared with results obtained previously by scanning electron microscopy, nuclear magnetic resonance imaging, and electron tomography. These results were enabled by first measuring the laboratory-frame Jones nonlinear susceptibility tensor, then extending to the local-frame tensor through pixel-by-pixel corrections based on local orientation.

Rapid Discrimination of Polymorphic Crystal Forms by Nonlinear Optical Stokes Ellipsometric Microscopy.

The use of nonlinear optical Stokes ellipsometric (NOSE) microscopy for rapid discrimination of two polymorphic forms of the small molecule d-mannitol is presented. Fast (8 MHz) polarization modulated beam-scanning microscopy and a recently developed iterative, nonlinear least-squares fitting algorithm were combined to allow discrimination of orthorhombic and monoclinic crystal structures of d-mannitol with data acquisition times of <7 s per field of view with a signal-to-noise ratio (SNR) of ∼300. Discrimination between polymorphic forms within the 99.99% confidence interval was achieved by standard statistical tests of the recovered probability density functions for the measured observables following two class linear discriminant analysis. These measurements target bottlenecks in small-volume, high-throughput solid form screening experiments for polymorph discovery in the development of emerging active pharmaceutical ingredients.

Endovascular Treatment of a Fusiform Aneurysm at the M3-M4 Junction of the Middle Cerebral Artery Using the Pipeline Embolization Device.

BACKGROUND: Peripheral fusiform cerebral aneurysms remain difficult to treat. Current surgical approaches to the treatment of fusiform aneurysms include wrapping, clip occlusion or vessel reconstruction without parent vessel sacrifice, and aneurysm trapping with or without bypass, although these may carry high morbidity (36%). Classic endovascular approaches to the treatment of peripheral aneurysms include selective or parent artery occlusion, which imparts the risk of distal infarction. It may be possible to use a flow diversion device off label to treat the aneurysm and preserve flow to the distal territory. CASE DESCRIPTION: After a presyncopal event, a patient was found to have an unruptured fusiform aneurysm at the junction of the M3 and M4 segments of the right middle cerebral artery. After initiating dual antiplatelet therapy, the aneurysm was successfully treated with a Pipeline embolization device. Three months after treatment, the aneurysm has completely thrombosed, the parent artery remains widely patent, and the patient remains at her neurologic baseline. CONCLUSIONS: Flow diversion devices may provide the neurointerventional surgeon with an opportunity to treat fusiform peripheral aneurysms and preserve flow to the distal territory.

Long-Segment Fusion for Adult Spinal Deformity Correction Using Low-Dose Recombinant Human Bone Morphogenetic Protein-2: A Retrospective Review of Fusion Rates.

BACKGROUND: Although use of very high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported to markedly improve fusion rates in adult spinal deformity (ASD) surgery, most centers use much lower doses due to cost constraints. How effective these lower doses are for fusion enhancement remains unclear. OBJECTIVE: To assess fusion rates using relatively low-dose rhBMP-2 for ASD surgery. METHODS: This was a retrospective review of consecutive ASD patients that underwent thoracic to sacral fusion. Patients that achieved 2-year follow-up were analyzed. Impact of patient and surgical factors on fusion rate was assessed, and fusion rates were compared with historical cohorts. RESULTS: Of 219 patients, 172 (78.5%) achieved 2-year follow-up and were analyzed. Using an average rhBMP-2 dose of 3.1 mg/level (average total dose = 35.9 mg/case), the 2-year fusion rate was 73.8%. Cancellous allograft, local autograft, and very limited iliac crest bone graft (<20 mL, obtained during iliac bolt placement) were also used. On multivariate analysis, female sex was associated with a higher fusion rate, whereas age, comorbidity score, deformity type, and 3-column osteotomy were not. There were no complications directly attributable to rhBMP-2. CONCLUSION: Fusion rates for ASD using low-dose rhBMP-2 were comparable to those reported for iliac crest bone graft but lower than for high-dose rhBMP-2. Importantly, there were substantial differences between patients in the present series and those in the historical comparison groups that could not be fully adjusted for based on available data. Prospective evaluation of rhBMP-2 dosing for ASD surgery is warranted to define the most appropriate dose that balances benefits, risks, and costs. ABBREVIATIONS: ASD, adult spinal deformityICBG, iliac crest bone graftOR, odds ratiorhBMP-2, recombinant human bone morphogenetic protein-2RR, risk ratioTCO, 3-column osteotomy.