Citations

AbstractThe histone deacetylases (HDACs) occur in 11 different isoforms, and these enzymes regulate the activity of a large number of proteins involved in cancer initiation and progression. The discovery of isoform‐selective HDAC inhibitors (HDACIs) is desirable, as it is likely that such compounds would avoid some of the undesirable side effects found with the first‐generation inhibitors. A series of HDACIs previously reported by us were found to display some selectivity for HDAC6 and to induce cell‐cycle arrest and apoptosis in pancreatic cancer cells. In the present work, we show that structural modification of these isoxazole‐based inhibitors leads to high potency and selectivity for HDAC6 over HDAC1–3 and HDAC10, while unexpectedly abolishing their ability to block cell growth. Three inhibitors with lower HDAC6 selectivity inhibit the growth of cell lines BxPC3 and L3.6pl, and they only induce apoptosis in L3.6pl cells. We conclude that HDAC6 inhibition alone is insufficient for disruption of cell growth, and that some degree of class 1 HDAC inhibition is required. Moreover, the highly selective HDAC6Is reported herein that are weakly cytotoxic may find use in cancer immune system reactivation.

Abstract Treatment of femoroacetabular impingement through an arthroscopic approach has gained widespread popularity in recent years. Although outcomes are generally favorable, one of the most common reasons for failure is incomplete resection of cam lesions of the femoral neck. As a result, the T‐capsulotomy has been introduced as a method for improving access to the femoral head‐neck junction, which is not always visible through a standard interportal capsulotomy. The T‐capsulotomy has the benefits of improving arthroscopic visualization of the femoral neck, reducing overall fluoroscopy exposure for the patient and surgeon, and facilitating capsular plication. We present a reliable and efficient method for creating and repairing the T‐capsulotomy. We routinely perform this technique in patients with cam lesions that are too large or too distal to safely visualize and decompress through an interportal capsulotomy. Technique Video video See video under supplementary data.

Abstract Capsulotomy is typically performed during arthroscopic treatment for femoroacetabular impingement. As the frequency of hip arthroscopy continues to expand rapidly, increased attention is being paid to the implications of interportal capsulotomy and the need for repair. To minimize the risk of postoperative instability, capsular closure has been recommended to restore the anatomy and biomechanical function of the capsule. We present a reliable, efficient, and effective method for arthroscopic closure of the interportal capsulotomy after hip arthroscopy. Technique Video video See video under supplementary data.

Embolic coiling is one of the most effective treatments for cerebral aneurysms (CAs), largely due to the hemodynamic modifications that the treatment effects in the aneurysmal environment. However, coiling can have very different hemodynamic outcomes in aneurysms with different geometries. Previous work in the field of biofluid mechanics has demonstrated on a general level that geometry is a driving factor behind aneurysmal hemodynamics. The goal of this study was to relate two specific geometric factors that describe CAs (i.e., dome size (DS) and parent-vessel contact-angle (PV-CA)) and one factor that describes treatment (i.e., coil packing density (PD)) to three clinically relevant hemodynamic responses (i.e., aneurysmal root-mean-square velocity (Vrms), aneurysmal wall shear stress (WSS), and cross-neck flow (CNF)). Idealized models of basilar tip aneurysms were created in both virtual and physical forms to satisfy two-level multifactorial experimental designs. Steady and pulsatile flow hemodynamics were then evaluated in the virtual models using computational fluid dynamics (CFD) (before and after virtual treatment with finite element (FE) embolic coil models), and hemodynamics were also evaluated in the physical models using particle image velocimetry (PIV) (before and after treatment with actual embolic coils). Results showed that among the factors considered, PD made the greatest contributions to effects on hemodynamic responses in and around the aneurysmal sac (i.e., Vrms and WSS), while DS made the greatest contributions to effects on hemodynamics at the neck (i.e., CNF). Results also showed that while a geometric factor (e.g., PV-CA) may play a relatively minor role in dictating hemodynamics in the untreated case, the same factor can play a much greater role after coiling. We consider the significance of these findings in the context of aneurysmal recurrence and rupture, and explore potential roles for the proposed methods in endovascular treatment planning.

Abstract The progressive establishment of endovascular management in treating intracranial aneurysms had lead to continuous technique advancements and development of innovative technologies. Flow diverters are “stent-like” devices currently used for complex unruptured aneurysms allowing endoluminal reconstruction of the parent artery and occlusion of the aneurysm sac. In the present article, we review the development of flow diversion devices through in vitro and in vivo studies to clinical practice and summarize recent clinical data.

Abstract Background. Transforaminal epidural steroid injections (TFESI) have demonstrated efficacy and effectiveness in treatment of radicular pain. Despite little evidence of efficacy/effectiveness, interlaminar epidural steroid injections (ILESI) are advocated by some as primary therapy for radicular pain due to purported greater safety. Objective. To assess immediate and delayed adverse event rates of TFESI and ILESI injections at three academic medical centers utilizing International Spine Intervention Society practice guidelines. Methods. Quality assurance databases from a Radiology and two physical medicine and rehabilitation (PM&R) practices were interrogated. Medical records were reviewed, verifying immediate and delayed adverse events. Results. There were no immediate major adverse events of neurologic injury or hemorrhage in 16,638 consecutive procedures in all spine segments (14,956 TFESI; 1,682 ILESI). Vasovagal reactions occurred in 1.2% of procedures, more frequently ( P = 0.004) in TFESI (1.3%) than ILESI (0.5%). Dural punctures occurred in 0.06% of procedures, more commonly after ILESI (0.2% vs 0.04%, P = 0.006). Delayed follow up on PM&R patients (92.5% and 78.5, next business day) and radiology patients (63.1%, 2 weeks) identified no major adverse events of neurologic injury, hemorrhage, or infection. There were no significant differences in delayed minor adverse event rates. Central steroid response (sleeplessness, flushing, nonpositional headache) was seen in 2.6% of both TFESI and ILESI patients. 2.1% of TFESI and 1.8% of ILESI patients reported increased pain. No long-term sequelae were seen from any immediate or delayed minor adverse event. Conclusions. Both transforaminal and ILESI are safely performed with low immediate and delayed adverse event rates when informed by evidence-based procedural guidelines. By demonstrating comparable safety, this study suggests that the choice between ILESI and TFESIs can be based on documented efficacy and effectiveness and not driven by safety concerns.