Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video).

BACKGROUND: Augmentation of the lower esophageal sphincter (LES) is the primary goal of both surgical and endoscopic therapies for gastroesophageal reflux disease (GERD). The feasibility, efficacy, safety, and reversibility of a newly developed endotherapy for GERD using intraluminal magnets referred to as a magnet closure device (MCD) were evaluated. METHODS: This study involved nine cadaveric and six survival pigs. The MCD consisted of a ring neodymium magnet attached to a 2-0 polypropylene suture and suture anchor. The MCD was deployed onto the esophageal wall at the region of the LES using an endoscopic suturing device. Two to three MCDs were placed on opposing walls to induce closure of the esophageal lumen. LES pressures were measured using high-resolution manometry at the index procedure (baseline and immediately post-MCD placement) and at survival endoscopy. Endoscopic removal of the devices was performed followed by necropsy at week 2. RESULTS: MCDs were successfully deployed in all cadaveric (n = 22) and survival animals (n = 12). In cadavers, 20/22 (91%) sutures were full-thickness with no adjacent organ injury. In survival animals, mean LES pressure increased from 8.4 mmHg (baseline) to 32.4 mmHg immediately post-procedure (p < 0.01). No clinically significant adverse events occurred. Repeat endoscopy at two weeks showed intact MCDs in 4/6 (67%) animals with significant increase in median LES pressure (n = 4, 24.0 mmHg versus 7.4 mmHg [baseline], p < 0.05). Endoscopic removal of MCDs was successfully achieved. CONCLUSIONS: Endoscopic augmentation of the LES using a new MCD was feasible, safe and reversible with significantly increased LES pressures recorded. Future studies are needed to enhance durability. These preliminary results on a reversible technique are promising and may represent an attractive alternative to endoluminal GERD therapy.

Proportions of resting memory T cells and monocytes in blood have prognostic significance in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline of lung function. Here, we tested the importance of differential proportions of blood immune cells to IPF clinical outcomes. We used Cibersort to deconvolute immune cell components based on PBMCs or whole blood IPF genomics datasets. We found that a higher proportion of resting memory (RM) T cells was associated with a better survival and a higher DLco (diffusing capacity for carbon monoxide) in IPF patients. The association was also found in opposite direction for monocytes. Additionally, in IPF patients as compared to healthy controls, proportions of monocytes were observed to be higher, yet RM T cells were observed to be lower. Taken together, our result suggests a beneficial effect of RM T cells and a detrimental effect of monocytes for IPF. Future genomics studies of IPF should be more focused on these two types of cells.

Endoscopic magnet placement into subadventitial tunnels for augmenting the lower esophageal sphincter using submucosal endoscopy: ex vivo and in vivo study in a porcine model (with video).

BACKGROUND AND AIMS: Endolumenal therapies serve as a treatment option for GERD. This study aimed to determine if magnets could be placed endoscopically using the adventitial layer to create a subadventitial space near the esophagogastric junction to augment the lower esophageal sphincter using submucosal endoscopy. METHODS: This study consisted of 2 phases, ex vivo and in vivo, with domestic pig esophagus. A long submucosal tunnel was made at the mid to lower esophagus. The muscularis propria was incised by a needle-knife within the submucosal tunnel. A subadventitial tunnel was made by biliary balloon catheter blunt dissection, and a magnet was deployed in the subadventitial space. The same maneuver was done within the opposing esophageal wall, with magnet placement in the opposing subadventitial space. RESULTS: Submucosal tunnels and subadventitial tunnels were successful without perforation ex vivo in all attempts and in 9 of 10 cases, respectively. Magnets were deployed in the subadventitial space in 7 cases. Magnets connected and separated with atraumatic endoscope passage into the stomach and reconnected when the endoscope was withdrawn under fluoroscopy in 5 of 7 cases (71.4%). In vivo submucosal tunnels and subadventitial tunnels were successful in all 5 cases, and magnet augmentation was functionally active in 4 cases (80%). CONCLUSION: Subadventitial tunnels were feasible and could represent a new working space for endoscopic treatment. Endoscopic placement of magnets within the subadventitial space may be an attractive alternative endolumenal therapy for GERD.

An internal magnet traction device reduces procedure time for endoscopic submucosal dissection by expert and non-expert endoscopists: ex vivo study in a porcine colorectal model (with video).

BACKGROUND: Efficacy of an internal magnet traction device (MTD) for gastric endoscopic submucosal dissection (ESD) by an expert endoscopist has been reported. We hypothesized that use of the MTD would enhance the performance of colorectal ESD in a non-expert endoscopist in ESD compared to the conventional technique. Primary aim of this study was to compare procedure times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD) by expert and non-expert endoscopists in ESD. Secondary aims included rate of en bloc resection, iatrogenic injury, visualization score of the submucosal layer, and endoscopist satisfaction score. METHODS: A total of 56 lesions were created in an ex vivo porcine colorectum. Two endoscopists completed C-ESD (n = 28) and MTD-ESD (n = 28). Lesions measured 3 cm in diameter and were located on either the anterior or posterior colorectal wall. The MTD consisted of a small neodymium magnet and nylon monofilament attached to a through-the-scope clip. The first MTD was deployed on the opposing colorectal wall of the target lesion and a second MTD was then deployed directly onto the distal margin of the lesion. RESULTS: Total procedure time for MTD-ESD was significantly shorter than C-ESD for both expert (median: 15.8 vs. 19.3 min, p < 0.05) and non-expert (median: 21.3 vs. 33.9 min, p < 0.001) endoscopists. All lesions were resected en bloc. There was no iatrogenic muscularis propria injury in the MTD-ESD group. For both the expert and non-expert, scores for MTD-ESD were significantly higher for submucosal layer visualization (p < 0.05) and endoscopist satisfaction (p < 0.001) compared to C-ESD. CONCLUSIONS: Use of the MTD significantly reduced procedure time for both expert and non-expert endoscopists performing ESD. Improving the efficiency, safety, and satisfaction of ESD with such a device particularly for non-expert endoscopists is appealing and could potentially minimize the complexity and duration of the procedure allowing for more widespread use of the technique.

Efficacy and safety of an internal magnet traction device for endoscopic submucosal dissection: ex vivo study in a porcine model (with video).

BACKGROUND: Appropriate traction allows for safer and easier endoscopic submucosal dissection (ESD). The aim of this study was to evaluate the efficacy and safety of an internal magnet traction device (MTD) for ESD in an ex vivo porcine model. METHODS: The MTD consisted of a small neodymium magnet and a suture attached to a through-the-scope clip. A circumferential mucosal incision was completed around a 30-mm diameter template that served as the target lesion. The first MTD was deployed at the proximal edge of the lesion. A second MTD was deployed on the wall opposite the lesion. With both magnets connected, this created traction or lifting of the target lesion towards the opposing wall during submucosal dissection. Primary endpoint was comparison of submucosal dissection times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD). RESULTS: Twenty lesions along the anterior wall, posterior wall and greater curvature were resected using either C-ESD or MTD-ESD. The submucosal dissection time in MTD-ESD was significantly shorter than C-ESD (median: 6.4 [interquartile range {IQR} 4.6-8.7] min vs. 14.4 min [IQR 11.8-18.0], p < 0.05). There was a significant difference between MTD-ESD and C-ESD in total procedure times for lesions on the posterior gastric wall and greater curvature (median: 23.0 min [IQR 21.1-24.5] vs. 29.2 min [IQR 24.8-33.2], p < 0.05) with no difference for lesions on the anterior gastric wall (median: 18.8 min [IQR 15.5-20.5] vs. 17.1 min [IQR 13.1-20.0], p = 0.5). The number of muscularis propria injuries per lesion was significantly lower in MTD-ESD than C-ESD (median: 0 [IQR 0-0] vs. 1 [IQR 0-2], p < 0.05). CONCLUSIONS: MTD for ESD is effective and safe when compared to C-ESD. This approach significantly reduced submucosal dissection times with less injury to the muscularis propria. Furthermore, MTD-ESD was particularly beneficial for more challenging gastric lesions located on the posterior wall and greater curvature.

Aryl hydrocarbon receptor signaling, toxicity, and gene expression responses to mono-methylchrysenes.

Polycyclic aromatic hydrocarbons (PAHs) comprise a large family of toxic compounds that come from natural and anthropogenic sources. Chrysene is a PAH with multiple effects, but the toxic potentials of mono-methylchrysenes are less characterized. A comparison of chrysene and six mono-methylchrysenes was performed using assays for cytotoxicity, human aryl hydrocarbon receptor (AhR) reporter gene signaling, and AhR-regulated target gene and protein expression. Sulforhodamine B and trypan blue dye binding assays revealed these chrysenes to be similar in their cytotoxic effects on HepG2 cells. A yeast-based reporter assay detecting human AhR-mediated gene expression identified 4-methylchrysene as being six times more potent and 5-methylchrysene about one-third as potent as chrysene. Other methylchrysenes were more similar to chrysene in the ability to act as AhR ligands. The mono-methylchrysenes all strongly induced CYP1A1 mRNA and protein and moderately induced CYP1B1 expression in HepG2 cells. Levels of CYP1A2 mRNA were induced at higher concentrations of the chrysenes, but protein expression was not significantly altered. The PCR-based gene expression and immunoblotting analyses indicated induced expression differences across the chrysene members were similar to each other. Overall, the effects of methylated chrysenes were comparable to unsubstituted chrysene, suggesting members of this group may be considered approximately equivalent in their effects. © 2019 Wiley Periodicals, Inc.

Return-to-active-duty rates after anterior cervical spine surgery in military pilots.

OBJECTIVESymptomatic cervical spondylosis with or without radiculopathy can ground an active-duty military pilot if left untreated. Surgically treated cervical spondylosis may be a waiverable condition and allow return to flying status, but a waiver is based on expert opinion and not on recent published data. Previous studies on rates of return to active duty status following anterior cervical spine surgery have not differentiated these rates among military specialty occupations. No studies to date have documented the successful return of US military active-duty pilots who have undergone anterior cervical spine surgery with cervical fusion, disc replacement, or a combination of the two. The aim of this study was to identify the rate of return to an active duty flight status among US military pilots who had undergone anterior cervical discectomy and fusion (ACDF) or total disc replacement (TDR) for symptomatic cervical spondylosis.METHODSThe authors performed a single-center retrospective review of all active duty pilots who had undergone either ACDF or TDR at a military hospital between January 2010 and June 2017. Descriptive statistics were calculated for both groups to evaluate demographics with specific attention to preoperative flight stats, days to recommended clearance by neurosurgery, and days to return to active duty flight status.RESULTSAuthors identified a total of 812 cases of anterior cervical surgery performed between January 1, 2010, and June 1, 2017, among active duty, reserves, dependents, and Department of Defense/Veterans Affairs patients. There were 581 ACDFs and 231 TDRs. After screening for military occupation and active duty status, there were a total of 22 active duty pilots, among whom were 4 ACDFs, 17 TDRs, and 2 hybrid constructs. One patient required a second surgery. Six (27.3%) of the 22 pilots were nearing the end of their career and electively retired within a year of surgery. Of the remaining 16 pilots, 11 (68.8%) returned to active duty flying status. The average time to be released by the neurosurgeon was 128 days, and the time to return to flying was 287 days. The average follow-up period was 12.3 months.CONCLUSIONSAdhering to military service-specific waiver guidelines, military pilots may return to active duty flight status after undergoing ACDF or TDR for symptomatic cervical spondylosis.

Cost-effectiveness of adult spinal deformity surgery in a military healthcare system.

OBJECTIVEAdult spinal deformity surgery is an effective way of treating pain and disability, but little research has been done to evaluate the costs associated with changes in health outcome measures. This study determined the change in quality-adjusted life years (QALYs) and the cost per QALY in patients undergoing spinal deformity surgery in the unique environment of a military healthcare system (MHS).METHODSPatients were enrolled between 2011 and 2017. Patients were eligible to participate if they were undergoing a thoracolumbar spinal fusion spanning more than 6 levels to treat an underlying deformity. Patients completed the 36-Item Short Form Health Survey (SF-36) prior to surgery and 6 and 12 months after surgery. The authors used paired t-tests to compare SF-36 Physical Component Summary (PCS) scores between baseline and postsurgery. To estimate the cost per QALY of complex spine surgery in this population, the authors extended the change in health-related quality of life (HRQOL) between baseline and follow-up over 5 years. Data on the cost of surgery were obtained from the MHS and include all facility and physician costs.RESULTSHRQOL and surgical data were available for 49 of 91 eligible patients. Thirty-one patients met additional criteria allowing for cost-effectiveness analysis. Over 12 months, patients demonstrated significant improvement (p < 0.01) in SF-36 PCS scores. A majority of patients met the minimum clinically important difference (MCID; 83.7%) and substantive clinical benefit threshold (SCBT; 83.7%). The average change in QALY was an increase of 0.08. Extended across 5 years, including the 3.5% discounting per year, study participants increased their QALYs by 0.39, resulting in an average cost per QALY of $181,649.20. Nineteen percent of patients met the < $100,000/QALY threshold with half of the patients meeting the < $100,000/QALY mark by 10 years. A sensitivity analysis showed that patients who scored below 60 on their preoperative SF-36 PCS had an average increase in QALYs of 0.10 per year or 0.47 over 5 years.CONCLUSIONSWith a 5-year extended analysis, patients who receive spinal deformity surgery in the MHS increased their QALYs by 0.39, with 19% of patients meeting the $100,000/QALY threshold. The majority of patients met the threshold for MCID and SCBT at 1 year postoperatively. Consideration of preoperative functional status (SF-36 PCS score < 60) may be an important factor in determining which patients benefit the most from spinal deformity surgery.

Activation of aryl hydrocarbon receptor signaling by extracts of teak and other wood dusts.

Wood dusts, as a group, are categorized as known human carcinogens, but the risks of exposure to specific types of wood dusts and the carcinogenic chemicals they contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is linked to the carcinogenic action of specific classes of chemicals. Here we examined whether chemicals in various wood dusts had the potential to activate AhR signaling as a potential toxic mechanism of action. We found that methanol extracts of teak, walnut, mahogany, and poplar dusts contained a wide range of AhR ligand activity, whereas extracts of oak, pine, and other softwoods did not contain appreciable activity. Teak dust extract, being particularly potent, was subjected to chemical analysis. The 2-methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ potently induced AhR signaling (EC50 115 nM), confirming that this was the active ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble at bioactive concentrations in physiologically relevant fluids. The high concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic effects through activation of AhR signaling in exposed wood workers.

Endoscopic band ligation for closure of GI perforations in a porcine animal model (with video).

BACKGROUND: GI perforations occur rarely during endoscopy but have life-threatening implications. OBJECTIVE: To evaluate endoscopic band ligation (EBL) for closure of acute GI perforations by using a porcine model. DESIGN: Investigator-initiated interventional pilot study by using an in vivo porcine model. SETTING: Tertiary-care institution. SUBJECTS: Ten domestic pigs. INTERVENTION: Each animal underwent a single endoscopic procedure, with creation of a single GI lumen perforation. Perforations of 10 to 20 mm were created in the esophagus, stomach, duodenum, and colon. EBL was used for closure. Fourteen days later, the pigs were killed, microbial cultures were obtained, and histologic review was done. MAIN OUTCOME MEASUREMENTS: Immediate and delayed endoscopic closure of the perforation site, evidence of clinical peritonitis during the 14-day follow-up. RESULTS: Ten pigs completed the protocol and survived without clinical peritonitis during the 14-day follow-up. Endoscopic closure of a 15-mm esophageal perforation failed, thus, no attempt was made to close a 20-mm esophageal perforation. Closure of all other perforations was successful. At necropsy, fibrinous peritonitis was suspected in one animal with a 10-mm duodenal perforation. Chronic inflammation and fibroplasia at the perforation sites were the most common histologic findings. LIMITATIONS: The applicability of widespread use in humans remains unknown despite successful case reports in the medical literature. CONCLUSION: EBL can be used successfully to close 10 to 20 mm perforations within normal stomach, duodenum, and colon and can prevent clinically relevant intra-abdominal infections. However, for esophageal perforations, closure may be limited to small (≤10 mm), iatrogenic perforations.

Assessment of the In Vitro Phosphatidylinositol Glycan Class A (PIG-A) Gene Mutation Assay Using Human TK6 and Mouse Hepa1c1c7 Cell Lines.

Gene mutations linked to diseases like cancer may be caused by exposure to environmental chemicals. The X-linked phosphatidylinositol glycan class A (PIG-A) gene, required for glycosylphosphatidylinositol (GPI) anchor biosynthesis, is a key target locus for in vitro genetic toxicity assays. Various organisms and cell lines may respond differently to genotoxic agents. Here, we compared the mutagenic potential of directly genotoxic ethyl methane sulfonate (EMS) to metabolically activated pro-mutagenic polycyclic aromatic hydrocarbons (PAHs). The two classes of mutagens were compared in an in vitro PIG-A gene mutation test using the metabolically active murine hepatoma Hepa1c1c7 cell line and the human TK6 cell line, which has limited metabolic capability. Determination of cell viability is required for quantifying mutagenicity. Two common cell viability tests, the MTT assay and propidium iodide (PI) staining measured by flow cytometry, were evaluated. The MTT assay overestimated cell viability in adherent cells at high benzo[a]pyrene (B[a]P) exposure concentrations, so PI-based cytotoxicity was used in calculations. The spontaneous mutation rates for TK6 and Hepa1c1c7 cells were 1.87 and 1.57 per million cells per cell cycle, respectively. TK6 cells exposed to 600 µM and 800 µM EMS showed significantly higher mutation frequencies (36 and 47 per million cells per cell cycle, respectively). Exposure to the pro-mutagen benzo[a]pyrene (B[a]P, 10 µM) did not increase mutation frequency in TK6 cells. In Hepa1c1c7 cells, mutation frequencies varied across exposure groups (50, 50, 29, and 81 per million cells per cell cycle when exposed to 10 µM B[a]P, 5-methylcholanthrene (5-MC), chrysene, or 16,000 µM EMS, respectively). We demonstrate that the choice of cytotoxicity assay and cell line can determine the outcome of the Pig-A mutagenesis assay when assessing a specific mutagen.

Current Indications, Trends, and Long-Term Results of 233 Bypasses to Treat Complex Intracranial Aneurysms: A Location-Specific Analysis.

BACKGROUND AND OBJECTIVES: Advances in endovascular flow diverters have led to a secular shift in the management of brain aneurysms, causing debate on current bypass indications. We therefore sought to investigate the long-term results, current indications, and trends of bypasses for brain aneurysms. METHODS: We retrospectively reviewed bypasses performed between 2005 and 2022 to treat brain aneurysms. Demographic, clinical, and radiological data were collected till the most recent follow-up. Aneurysm occlusion and graft patency was noted on cerebral angiogram in the immediate postoperative, 3-month, and most recent follow-up periods. Clinical outcomes (modified Rankin scores) and complications were assessed at 3 month and most recent follow-up. Trends in bypass volume and graft patency were assessed in 5-year epochs. Results were dichotomized based on aneurysm location to generate location-specific results and trends. RESULTS: Overall, 203 patients (mean age 50 years, 57% female patients) with 207 cerebral aneurysms were treated with 233 cerebral bypasses with a mean follow-up of 2 years. Fusiform morphology was the most common bypass indication. Aneurysm occlusion on immediate postoperative and final follow-up angiogram was 89% (184/207) and 96% (198/207), respectively. Graft patency rate in the immediate postoperative period and most recent follow-up was 95% (222/233) and 92% (215/233), respectively. Of 207 aneurysms, 5 (2%) recurred. Of 203 patients, 81% (165) patients had modified Rankin scores of 0-2 at the 3-month follow-up and 11 patients died (mortality 5%). Although there was a steady decrease in the bypass volume over the study period, the proportion of bypasses for recurrent aneurysms increased serially. Posterior circulation aneurysms had lower rates of aneurysm occlusion and significantly higher incidence of postoperative strokes and deaths (P = .0035), with basilar artery aneurysms having the worst outcomes. CONCLUSION: Bypass indications have evolved with the inception of novel flow diverters. However, they remain relevant in the cerebrovascular surgeon's armamentarium, and long-term results are excellent.

Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study.

BACKGROUND: The pathogenesis of several common gastric motility diseases and functional GI disorders remains essentially unexplained. Gastric wall biopsies that include the muscularis propria to evaluate the enteric nervous system, interstitial cells of Cajal, and immune cells can provide important insights for our understanding of the etiology of these disorders. OBJECTIVES: To determine the technical feasibility, reproducibility, and safety of performing a full-thickness gastric biopsy (FTGB) by using a submucosal endoscopy with mucosal flap (SEMF) technique; the technical feasibility, reproducibility, and safety of tissue closure by using an endoscopic suturing device; the ability to identify myenteric ganglia in resected specimens; and the long-term safety. DESIGN: Single center, preclinical survival study. SETTING: Animal research laboratory, developmental endoscopy unit. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: Animals underwent an SEMF procedure with gastric muscularis propria resection. The resultant offset mucosal entry site was closed by using an endoscopic suturing device. Animals were kept alive for 2 weeks. MAIN OUTCOME MEASUREMENTS: The technical feasibility, reproducibility, and safety of the procedure; the clinical course of the animals; the histological and immunochemical evaluation of the resected specimen to determine whether myenteric ganglia were present in the sample. RESULTS: FTGB was performed by using the SEMF technique in all 12 animals. The offset mucosal entry site was successfully closed by using the suturing device in all animals. The mean resected tissue specimen size was 11 mm. Mean total procedure time was 61 minutes with 2 to 4 interrupted sutures placed per animal. Histology showed muscularis propria and serosa, confirming full-thickness resections in all animals. Myenteric ganglia were visualized in 11 of 12 animals. The clinical course was uneventful. Repeat endoscopy and necropsy at 2 weeks showed absence of ulceration at both the mucosal entry sites and overlying the more distal muscularis propria resection sites. There was complete healing of the serosa in all animals with minimal single-band adhesions in 5 of 12 animals. Retained sutures were present in 10 of 12 animals. LIMITATIONS: Animal experiment. CONCLUSIONS: FTGB by using the SEMF technique and an endoscopic suturing device is technically feasible, reproducible, and safe. Larger tissue specimens will allow improved analysis of multiple cell types.

Traumatic Pseudoaneurysm of the Occipital Artery Treated with Open Surgical Ligation: 2-Dimensional Operative Video.

Scalp pseudoaneurysms occur most commonly because of trauma and are often in the superficial temporal artery due to the lack of soft tissue coverage between skin and bone, making it more vulnerable anatomically.1,2 Pseudoaneurysms of the occipital artery (OA) also occur but are extremely rare.2-4 An 80-year-old man presented with scalp bleeding and a small left-sided posterior scalp laceration after a fall and head strike 10 days prior. He was admitted and during his 2-week hospital stay, the occipital laceration continued to rebleed (Video 1). He developed a 2-cm pulsatile ulcerative mass with central necrosis on the left nuchal ridge. Computed tomography angiography revealed an ovoid left occipital lesion measuring 1.3 × 2.5 × 2.3 cm with delayed contrast filling and partial thrombosis. The base of the lesion had dense contrast filling continuous with the OA, diagnostic of OA pseudoaneurysm. OA pseudoaneurysm may be treated endovascularly or surgically. While surgical resection is the most common treatment, minimally invasive techniques have been successfully done through direct injection of N-butyl cyanoacrylate or endovascular embolization. The clinical presentation of this case was unique because this patient had an ulcerated lesion with central necrosis overlying the pseudoaneurysm. Endovascular management alone would not address the open lesion, which is at high risk for infection. The risk of infection would increase after embolization of the occipital artery, causing further necrosis of the tissue.

Fusion for subaxial bow hunter's syndrome results in remote osseous remodeling of the hyperostotic growth responsible for vertebral artery compression.

BACKGROUND: The authors present a previously unreported case of a patient with diffuse idiopathic skeletal hyperostosis (DISH) who developed bow hunter's syndrome (BHS) or positional vertebrobasilar insufficiency. In addition, the authors demonstrate angiographic evidence of remote osseous remodeling after segmental fusion without direct decompression of the offending bony growth. BHS is a rare, yet well established, cause of posterior circulation ischemia and ischemic stroke. Several etiologies such as segmental instability and spondylosis have been described as causes, however, DISH has not been associated with BHS before this publication. CASE DESCRIPTION: A 77-year-old man who presented with BHS was found to have cervical spine changes consistent with DISH, and angiography confirmed right vertebral artery (VA) stenosis at C4-5 from a large pathological elongation of the right C5 lateral mass. Head rotation resulted in occlusion of the VA. The patient underwent an anterior cervical discectomy and fusion and reported complete resolution of his symptoms. A delayed angiogram and CT of the cervical spine demonstrated complete resolution of the baseline stenosis, no dynamic compression, and remote osseous remodeling of the growth, respectively. CONCLUSION: This case represents the first publication in the literature of DISH as a causative etiology of BHS and of angiographic data demonstrating resolution of a compressive osseous pathology without direct decompression in BHS.

Neural Correlates of Vocal Auditory Feedback Processing: Unique Insights from Electrocorticography Recordings in a Human Cochlear Implant User.

There is considerable interest in understanding cortical processing and the function of top-down and bottom-up human neural circuits that control speech production. Research efforts to investigate these circuits are aided by analysis of spectro-temporal response characteristics of neural activity recorded by electrocorticography (ECoG). Further, cortical processing may be altered in the case of hearing-impaired cochlear implant (CI) users, as electric excitation of the auditory nerve creates a markedly different neural code for speech compared with that of the functionally intact hearing system. Studies of cortical activity in CI users typically record scalp potentials and are hampered by stimulus artifact contamination and by spatiotemporal filtering imposed by the skull. We present a unique case of a CI user who required direct recordings from the cortical surface using subdural electrodes implanted for epilepsy assessment. Using experimental conditions where the subject vocalized in the presence (CIs ON) or absence (CIs OFF) of auditory feedback, or listened to playback of self-vocalizations without production, we observed ECoG activity primarily in γ (32-70 Hz) and high γ (70-150 Hz) bands at focal regions on the lateral surface of the superior temporal gyrus (STG). High γ band responses differed in their amplitudes across conditions and cortical sites, possibly reflecting different rates of stimulus presentation and differing levels of neural adaptation. STG γ responses to playback and vocalization with auditory feedback were not different from responses to vocalization without feedback, indicating this activity reflects not only auditory, but also attentional, efference-copy, and sensorimotor processing during speech production.

Direct Vertebral Artery Access for Coil Embolization of a Partially Thrombosed Mid-Basilar Trunk Aneurysm: Technical Limitations.

BACKGROUND AND IMPORTANCE: Partially thrombosed basilar aneurysms have a high morbidity from the rupture risk and mass effect prompting early treatment. Depending on the size and location, they pose a surgical challenge often requiring multiple endovascular treatment modalities. Here we present a partially thrombosed mid-basilar aneurysm successfully coil embolized with direct vertebral artery access and discuss the technical limitations of direct V1 access. CLINICAL PRESENTATION: A 70-yr-old woman presented with acute onset headache, nausea, and vomiting. A computed tomography (CT) head demonstrated a hyperdense prepontine mass which was further characterized as a partially thrombosed basilar aneurysm on CT angiography. After multiple failed attempts to access the vertebral artery via femoral and radial access the patient was taken to the operating room (OR) for surgical exposure of the right V1 segment and direct cannulation of the vertebral artery. The aneurysm was successfully coiled and the vertebral artery closed primarily. The patient was discharged home without any neurological deficits. CONCLUSION: Partially thrombosed mid-basilar aneurysms are difficult to treat both surgically and endovascularly. We present a case where endovascular access to the aneurysm was very challenging requiring direct exposure and cannulation of the V1 segment to successfully embolize with coils and discuss the technical limitations of this approach.

Transpacific Aeromedical Evacuation for a Ruptured Brain Arteriovenous Malformation During the COVID-19 Pandemic.

The COVID-19 pandemic has altered preexisting patient treatment algorithms and referral patterns, which has affected neurosurgical care worldwide. Brain arteriovenous malformations are complex vascular lesions that frequently present with intracerebral hemorrhage. Care for these patients is best performed at large medical centers by specialists with high volumes. The authors describe the care of a patient who presented in extremis to a resource-limited, community-sized military treatment facility (MTF) in Southeast Asia. In the MTF, the patient underwent emergent neurosurgical therapy. However, given newly implemented restrictions enacted to mitigate COVID-19 spread, local transfer for definitive care to a tertiary care facility was not possible. In order to attain definitive care for the patient, a transpacific aeromedical evacuation augmented with a critical care air transport team was utilized for transfer to a tertiary care, teaching hospital. This case demonstrates the safe treatment of a patient with hemorrhagic arteriovenous malformations and postoperative management under limited conditions in an MTF outside the CONUS. Given the unique circumstances and challenges the pandemic presented, the authors feel that this patient's outcome was only possible by leveraging all the capability military medicine has to offer.

Treatment of In-Stent Stenosis Following Flow Diversion of Intracranial Aneurysms with Cilostazol and Clopidogrel.

In-stent stenosis is a feared complication of flow diversion treatment for cerebral aneurysms. We present 2 cases of patients treated with pipeline flow diversion for unruptured cerebral aneurysms. Initial perioperative dual antiplatelet therapy (DAPT) consisted of standard aspirin plus clopidogrel. At 6-month follow-up cerebral angiography, the patients were noted to have developed significant in-stent stenosis (63% and 53%). The patients were treated with cilostazol and clopidogrel for at least 6 months. Subsequent angiography at 1-year post-treatment showed significant improvement of the in-stent stenosis from 63% to 34% and 53% to 21%. The role of cilostazol as treatment of intracranial in-stent stenosis has not been previously described. Cilostazol's vasodilatory effect and suppression of vascular smooth muscle proliferation provides ideal benefits in this setting. Cilostazol plus clopidogrel may be a safe and effective alternative to standard DAPT for treatment of in-stent stenosis following flow diversion and warrants further consideration and investigation.