Initial experience with a self-expanding retrievable stent for recanalization of large vessel occlusions in acute ischemic stroke

Introduction  

Quicker recanalization results in better clinical outcomes in patients with acute ischemic strokes. We describe our experience with the use of a self-expanding, fully retrievable stent in acute intracranial occlusions.     

Assay Formats: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

As part of the GBC (Global Bioanalysis Consortium), the L3 assay format team has focused on reviewing common platforms used to support ligand binding assays in the detection of biotherapeutics. The following review is an overview of discussions and presentations from around the globe with a group of experts from different companies to allow an international harmonization of common practices and suggestions for different platforms. Some of the major platforms include Gyrolab, Erenna, RIA, AlphaLISA, Delfia, Immuno-PCR, Luminex, BIAcore, and ELISAs. The review is meant to support bioanalysts in taking decisions between different platforms depending on the needs of the analyte with a number of recommendations to help integration of platforms into a GLP environment.     

Interventional Sialendoscopy for Parotid Ductal Calculi: Our Preliminary Experience

With this article we present our initial experience with interventional sialendoscopy of the parotid duct for the parotid calculi. We carried out a prospective study of patients of parotid calculi in a tertiary referral centre. Diagnostic and interventional sialendoscopy was performed in five cases of parotid calculi. The outcome was classified on the basis of clearance of the lumen of the duct and resolution of symptoms. Diagnostic sialendoscopy was able to diagnose the calculus in all cases. Interventional sialendoscopy was done under general anesthesia in all cases and calculus was successfully removed. The average size of sialolith was 8.2 mm. No complications occurred in any of the cases. Check sialendoscopy was done in all cases after a minimum follow up of 6 months, which showed the duct lumen to be free of stone with no stricture of the duct. Sialendoscopy is an optimal technique for removal of intraductal parotid calculi and avoids removal of the gland. In our series there was no associated morbidity and complication.     

Follow-up after coil closure of patent ductus arteriosus

A prospective serial follow-up after coil closure of patent ductus arteriosus in 84 patients showed a cumulative duct closure up to 96% at the end of 2 years. Five patients underwent transient recanalization, and 4 patients required repeat procedure for residual shunt or recanalization.     

Evolutionary design of magnetic soft continuum robots

Worldwide cardiovascular diseases such as stroke and heart disease are the leading cause of mortality. While guidewire/catheter-based minimally invasive surgery is used to treat a variety of cardiovascular disorders, existing passive guidewires and catheters suffer from several limitations such as low steerability and vessel access through complex geometry of vasculatures and imaging-related accumulation of radiation to both patients and operating surgeons. To address these limitations, magnetic soft continuum robots (MSCRs) in the form of magnetic field–controllable elastomeric fibers have recently demonstrated enhanced steerability under remotely applied magnetic fields. While the steerability of an MSCR largely relies on its workspace—the set of attainable points by its end effector—existing MSCRs based on embedding permanent magnets or uniformly dispersing magnetic particles in polymer matrices still cannot give optimal workspaces. The design and optimization of MSCRs have been challenging because of the lack of efficient tools. Here, we report a systematic set of model-based evolutionary design, fabrication, and experimental validation of an MSCR with a counterintuitive nonuniform distribution of magnetic particles to achieve an unprecedented workspace. The proposed MSCR design is enabled by integrating a theoretical model and the genetic algorithm. The current work not only achieves the optimal workspace for MSCRs but also provides a powerful tool for the efficient design and optimization of future magnetic soft robots and actuators.

Cardiovascular diseases such as stroke and heart disease are the leading cause of long-term disability and death worldwide, with an annual cost of over $300 billion in the United States alone (1, 2). Diverse cardiovascular diseases are treated with minimally invasive surgery (Fig. 1A), which is less traumatic and more effective than open surgery (3–6). The conventional minimally invasive treatments of cardiovascular diseases typically employ a passive guidewire and catheter with a preshaped tip that is manually operated under radioscopic imaging. For example, in mechanical thrombectomy, a surgeon usually inserts a guidewire/catheter combination from the patient’s femoral artery over the leg and navigates this combination using fluoroscopic imaging through the aorta into the target occluded artery (usually in the brain or lungs) for mechanical clot removal (7). As another example, in atrial fibrillation ablation, a surgeon usually threads a catheter into the patient’s heart, where the catheter’s tip applies high or low temperature to disrupt heart conduction that generates faulty electrical signals (8). This manual operation of passive guidewires and catheters, however, is often limited by low steerability through complex vasculatures, difficulty in accessing small branches, long operation times, and/or increased accumulated imaging-related radiation to both patients and operating surgeons (9). To overcome these challenges, immense efforts have been committed to exploring robotic-assisted minimally invasive treatments in a remotely operated manner. In particular, because of the untethered and biocompatible nature of magnetic fields, a promising robotic-assisted minimally invasive platform has recently emerged based on magnetic field–controllable elastomeric fibers—magnetic soft continuum robots (MSCRs) (10–13).Open in a separate windowFig. 1.MSCRs for minimally invasive treatments. (A) Cardiovascular diseases in hard-to-reach areas across the human body where MSCRs can find utility. (B) Schematic illustration of the active bending of the MSCR navigating in a complex blood vessel. The workspace is defined as the area of attainable locations by the MSCR’s end effector via tuning the actuation magnetic field. (C) Schematic illustration of operating the MSCR at lesion tissues in atrial fibrillation ablation. (D) Schematic illustration of the distal portion of an MSCR in which hard-magnetic particles (e.g., NdFeB) are dispersed in the polymer matrix (e.g., silicone).An MSCR typically consists of a magneto-active distal portion that can be actively bent by tuning the actuation magnetic field and a nonmagnetized body that can be advanced or retracted by controlling the motor connected to the MSCR’s proximal end. In a typical minimally invasive treatment, a surgeon remotely controls the motor to advance the MSCR up to locations that require active steering, such as in front of branches of blood vessels (Fig. 1B) or lesion tissues (Fig. 1C) (14, 15). At these locations, the surgeon needs to remotely apply a magnetic field to bend the distal portion of the MSCR so that the MSCR’s end effector reaches the desired location. Thereafter, the surgeon further advances or operates the MSCR actively steered by the actuation magnetic field. Evidently, the steerability of an MSCR is largely determined by the set of attainable locations by its end effector via tuning the actuation magnetic field named the workspace of the MSCR (16, 17). A larger workspace gives a higher steerability of the MSCR in minimally invasive treatments.Existing MSCRs are mostly fabricated by embedding one or more permanent magnets in the distal portion of the MSCR (18–25). More recently, a new type of MSCR has been developed by uniformly dispersing hard-magnetic particles in elastomeric fibers (16) (Fig. 1D). However, the workspaces of MSCRs with both embedded magnets and uniformly distributed hard-magnetic particles are still limited, mainly because of the lack of efficient design and optimization tools for MSCRs. Indeed, existing designs of MSCRs heavily rely on experimental trial and error or numerical simulations (26, 27) that are not ideal for design or optimization with a large number of design parameters. Hence, an efficient design strategy capable of maximizing the workspaces of MSCRs remains an important, yet unresolved, challenge in the field.Here, we report an evolutionary design strategy to maximize the workspaces of MSCRs by integrating theoretical modeling (17, 28) and the genetic algorithm (29) to identify the optimal magnetization and rigidity patterns within the MSCRs (Fig. 2A). We first develop a hard-magnetic elastica theory to calculate the deflections of an MSCR with a specific magnetization and rigidity pattern under uniform magnetic fields up to 40 mT applied along various directions in one plane (17) (SI Appendix, Fig. S1). Notably, 40 mT is a typical magnetic-field strength for operating MSCRs (16, 30). We then calculate the area of the workspace for this MSCR and repeat the calculations for MSCRs with various random magnetization and rigidity patterns. Thereafter, we only select the MSCRs with relatively large workspaces, mutate and cross over their magnetization and rigidity patterns to give a new generation of MSCRs, and then calculate the workspaces of the new generation of MSCRs (29). By repeating this evolutionary process over a few generations, we can achieve an optimal design of the MSCR with an unprecedented workspace. We further validate this evolutionary design of the MSCR by both finite element simulations and experiments.Open in a separate windowFig. 2.Designing MSCRs by programming their magnetization and rigidity pattern in the distal portion. (A) Each voxel is encoded with a specific remanent magnetization M by tuning its magnetic particle volume fraction ϕ. The direction of the remanent magnetization of all voxels is along the axial direction pointing to the distal tip. (B) The normalized magnetization strength M(ϕ)/M0 (Left, black) and shear modulus G(ϕ)/G0 (Right, red) of the MSCR as a function of particle volume fraction ϕ.     

Detection of inadvertent catheter movement into a pulmonary vein during radiofrequency catheter ablation by real-time impedance monitoring

Introduction: During radiofrequency ablation to encircle or isolate the pulmonary veins (PVs), applications of radiofrequency energy within a PV may result in stenosis. The aim of this study was to determine whether monitoring of real-time impedance facilitates detection of inadvertent catheter movement into a PV.
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004)     

Collection of peripheral blood stem cells in newly diagnosed myeloma patients without any prior cytoreductive therapy: the first step towards an 'operational cure'?

We have shown that primary therapy with non-myeloablative (140 mg/m(2)) high-dose melphalan (HDM) without hematopoietic support results in high response rates in untreated myeloma and very long-term survival of some patients. This study was designed to see if sufficient CD34 (+) cells can be harvested at presentation in newly diagnosed patients to administer myeloablative HDM (200 mg/m(2); HDM200) with autograft as primary therapy. This may improve outcome by rapid achievement of complete remission (CR) and possible avoidance of late myelodysplasia as a consequence of non-transplant induction chemotherapy. Thirty untreated patients received 1 g/m(2) methylprednisolone daily (days 1-6) and 12-16 micro g/kg G-CSF daily (days 3-6), and underwent leukapheresis on days 6 and 7. The median CD34(+) cell yield was 1.31 x10(6)/kg (range, 0.23-5.63), and was > or =1 x10(6)/kg in 73%. Cell yields were significantly lower than in 82 historical controls apheresed after completion of induction chemotherapy (median 2.16 x 10(6)/kg), and improved in patients who were apheresed again after induction chemotherapy. Three patients received primary therapy with HDM200 and autograft using these cells and attained CR. We conclude that it is possible to harvest stem cells in three-quarters of untreated myeloma patients. Increasing the number of apheresis procedures is needed to improve the number of CD34(+) cells collected.