Applications of navigation in full-endoscopic spine surgery.

PURPOSE: Advancement in all surgery continues to progress towards more minimally invasive surgical (MIS) approaches. One of the platform technologies which has helped drive this trend within spine surgery is the development of endoscopy; however, the limited anatomic view experienced when performing endoscopic spine surgery requires a significant learning curve. The use of intraoperative navigation has been adapted for endoscopic spine surgery, as this provides computer-reconstructed visual data presented in three dimensions, which can increase feasibility of this technique to more surgeons. METHODS: This paper will describe the principles, technical considerations, and applications of stereotactic navigation-guided endoscopic spine surgery. RESULTS: Full-endoscopic spine surgery has advanced in recent years such that it can be utilized in both decompressive and fusion surgeries. One of the major pitfalls to any minimally invasive surgery (including endoscopic) is that the limited surgical view can often complicate the surgery or confuse the surgeon, leading to longer operative times, higher risks, among others. This is the real utility to using navigation in conjunction with the endoscope-when registered correctly and utilized appropriately, navigated endoscopic spine surgery can take some of the guesswork out of the minimally invasive approach. CONCLUSIONS: Using navigation with endoscopy in spine surgery can potentially expand this technique to surgeons who have yet to master endoscopy as the assistance provided by the navigation can alleviate some of the complexities with anatomic understanding and surgical planning.

Bibliometric analysis and description of research trends on transforaminal full-endoscopic approach on the spine for the last two-decades.

OBJECTIVE: The study aims to assess the current development status of transforaminal full-endoscopic spine surgery (TFES) by exploring and analyzing the published literature to obtain an overview of this field and discover the evolution and emerging topics that are underrepresented. METHODS: Using Bibliometrix, CiteSpace, and VOSviewer, we analyzed the bibliometric data selected from the Web of Science Core Collection between January 2002 and November 2022. The descriptive and evaluative analyses of authors, institutes, countries, journals, keywords, and references are compiled. The quantity of research productivity was measured by the number of publications that were published. A quality indicator was thought to be the number of citations. In the bibliometric analysis of authors, areas, institutes, and references, we calculated and ranked the research impact by various metrics, such as the h-index and m-index. RESULTS: A total of 628 articles were identified in the field of TFES by the 18.73% annual growth rate of research on the subject from 2002 to 2022, constituting the documents are by 1961 authors affiliated with 661 institutions in 42 countries or regions and published in 117 journals. The USA (n = 0.20) has the highest international collaboration rate, South Korea has the highest H-index value (h = 33), and China is ranked as the most productive country (n = 348). Brown univ., Tongji univ., and Wooridul Spine represented the most productive institutes ranked by the number of publications. Wooridul Spine Hospital demonstrated the highest quality of paper publication. The Pain Physician had the highest h-index (n = 18), and the most cited journal with the earliest publication year in the area of FEDS is Spine (t = 1855). CONCLUSION: The bibliometric study showed a growing trend of research on transforaminal full-endoscopic spine surgery over the past 20 years. It has shown a significant increase in the number of authors, institutions, and international collaborating countries. South Korea, the United States, and China dominate the related areas. A growing body of evidence has revealed that TFES has leapfrogged from its infancy stage and gradually entered a mature development stage.

Comparison of percutaneous endoscopic and open posterior lumbar interbody fusion for the treatment of single-segmental lumbar degenerative diseases.

BACKGROUND: Endoscopic lumbar interbody fusion has become an emerging technique. Some researchers have reported the technique of percutaneous endoscopic transforaminal lumbar interbody fusion. We propose percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) as an alternative approach. The purpose of this study was to assess the clinical efficacy of PE-PLIF by comparing percutaneous endoscopic and open posterior lumbar interbody fusion (PLIF). METHODS: Thirty patients were enrolled in each group. Demographic data, perioperative data, and radiological parameters were collected prospectively. The clinical outcomes were evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. RESULTS: The background data were comparable between the two groups. The mean operation time was longer in the PE-PLIF group. The PE-PLIF group showed benefits in less blood loss and shorter hospital stay. VAS and ODI scores significantly improved in both groups. However, the VAS score of low-back pain was lower in the PE-PLIF group. The satisfaction rate was 96.7% in both groups. The radiological outcomes were similar in both groups. In the PE-PLIF group, the fusion rate was 93.3%, and the cage subsidence rate was 6.7%; in the open PLIF group, the fusion and cage subsidence rates were 96.7% and 16.7%. There were minor complications in one patient in the PE-PLIF group and two in the open PLIF group. CONCLUSIONS: The current study revealed that PE-PLIF is safe and effective compared with open PLIF. In addition, this minimally invasive technique may enhance postoperative recovery by reducing tissue damage and blood loss.

The impact of needle location on clinical outcome of radiofrequency rhizotomy for trigeminal neuralgia.

BACKGROUND: Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors. METHODS: The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures. RESULTS: Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p < 0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern. CONCLUSIONS: This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

Full-endoscopic versus microscopic unilateral laminotomy for bilateral decompression of lumbar spinal stenosis at L4-L5: comparative study.

PURPOSE: Full-endoscopic spine surgery for degenerative lumbar diseases is growing in popularity and has shown favourable outcomes. Lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has been used to treat lumbar spinal stenosis (LSS). However, studies comparing LE-ULBD to microscopic ULBD are lacking. This study compared the clinical efficacy and radiological outcomes between the LE-ULBD and microscopic ULBD. METHODS: The study retrospectively enrolled patients undergoing either LE-ULBD or microscopic ULBD for spinal stenosis at the L4-L5 level. The demographic data, operative details, radiological images, clinical outcomes, and complications of patients from the two groups were compared through matched-pairs analysis. The minimum follow-up duration was 24 months. RESULTS: There were 93 patients undergoing either LE-ULBD (n = 42) or microscopic ULBD (n = 51). The patient demographics were similar between the two groups. The LE-ULBD group had significantly less estimated blood loss, less analgesic use, and shorter hospitalization duration (P < .05). The endoscopic group had a significantly lower visual analog scale for back pain at all follow-up intervals compared with the microscopic group (P < .05). There were no significant differences in leg pain or Oswestry Disability Index. The cross-section area of the spinal canal was significantly wider after microscopic ULBD. There were no significant differences in post-operative degenerative changes in disc height, translational motion, or facet preservation rate. CONCLUSIONS: LE-ULBD is comparable in clinical and radiological outcomes with enhanced recovery for single-level LSS. The endoscopic approach might further minimize tissue injury and enhance post-operative recovery.

Bibliometric analysis and visualization of research trends on oblique lumbar interbody fusion surgery.

PURPOSE: To determine trends and hot subjects in the field of oblique lumbar interbody fusion (OLIF) research during the last decade using bibliometric analysis and visualization tools, in order to assist researchers in exploring new directions for future research in that field. METHODS: Articles published from January 1, 2012, to August 15, 2021, were screened in the Web of Science database. The data were analyzed with CiteSpace software, which generated visualization knowledge maps. All literature was assessed for the following parameters: the number of total publications, distribution, h-index, institutions, journals, authors, co-occurrence state, and research hotspots. RESULTS: A total of 173 articles were identified. The country with the largest number of articles was China (41.04%), followed by South Korea (20.81%), the USA (15.61%), Japan (9.83%), and Thailand (2.89%). South Korea and the USA had the highest h-index (9), followed by China (8), Japan (7), and Thailand (2). Catholic University of Korea was the organization that produced the most literature. World Neurosurgery published the most papers about OLIF (12.50%), but articles in Spine were most frequently cited (151). Kim JS was the most productive author, whereas Silvestre C was the most cited author. The main research hotspots are anatomy, discectomy, approach, injure, and diseases. CONCLUSIONS: The number of publications in the field of OLIF has increased considerably in recent years. The USA, China, South Korea, and Japan have made substantial contributions to this field. Anatomy, complications, decompression surgery, and application in various degenerative lumbar diseases have been the research hotspots in recent years.

Prediction of Prognosis in Patients with Trauma by Using Machine Learning.

Background and Objectives: We developed a machine learning algorithm to analyze trauma-related data and predict the mortality and chronic care needs of patients with trauma. Materials and Methods: We recruited admitted patients with trauma during 2015 and 2016 and collected their clinical data. Then, we subjected this database to different machine learning techniques and chose the one with the highest accuracy by using cross-validation. The primary endpoint was mortality, and the secondary endpoint was requirement for chronic care. Results: Data of 5871 patients were collected. We then used the eXtreme Gradient Boosting (xGBT) machine learning model to create two algorithms: a complete model and a short-term model. The complete model exhibited an 86% recall for recovery, 30% for chronic care, 67% for mortality, and 80% for complications; the short-term model fitted for ED displayed an 89% recall for recovery, 25% for chronic care, and 41% for mortality. Conclusions: We developed a machine learning algorithm that displayed good recall for the healthy recovery group but unsatisfactory results for those requiring chronic care or having a risk of mortality. The prediction power of this algorithm may be improved by implementing features such as age group classification, severity selection, and score calibration of trauma-related variables.

How I do it? Fully endoscopic rhizotomy assisted with three-dimensional robotic C-arm navigation for sacroiliac joint pain.

BACKGROUND: In some cases, the conventional C-arm fluoroscopy can barely identify anatomical landmarks such as the dorsal sacral foramen. A fully endoscopic rhizotomy under three-dimensional (3D) provides satisfactory results in the treatment of sacroiliac (SI) joint pain. METHODS: The workflow of a fully endoscopic rhizotomy under 3D robotic C-arm navigation system is introduced. CONCLUSION: The presented technique is novel, effective, and safe for the treatment of SI joint pain. The 3D navigation system guides the operator to easily locate the target points for finding the medial branches of L5 and sacral lateral branches from S1, S2, and S3 dorsal foramina under endoscopic visualization.

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured -34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 µg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

How I do it? Interlaminar contralateral endoscopic lumbar foraminotomy assisted with the O-arm navigation.

BACKGROUND: The interlaminar contralateral endoscopic lumbar foraminotomy (ICELF) provides access to the foraminal pathology with less violation to facet than the ipsilateral approach. However, it is technically challenging even for an experienced surgeon. METHODS: We introduce the step-by-step workflow of the interlaminar contralateral endoscopic lumbar foraminotomy assisted with O-arm navigation system. CONCLUSION: The ICELF assisted with O-arm navigation is safe, accurate, and efficient for the treatment of lumbar foraminal stenosis. The CT-based navigation reshapes the learning curve of the advanced endoscopic technique, reducing the risk of facet joint violation, and minimizes radiation exposure to surgeons.

Foramen ovale cannulation guided by intraoperative computed tomography with magnetic resonance image fusion plays a role in improving the long-term outcome of percutaneous radiofrequency trigeminal rhizotomy.

BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief. METHOD: This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging. RESULT: The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness. CONCLUSION: This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief.

Comparison between Polybutylcyanoacrylate Nanoparticles with Either Surface-Adsorbed or Encapsulated Brain-Derived Neurotrophic Factor on the Neural Differentiation of iPSCs.

The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry; the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood⁻brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.

Percutaneous dorsal root ganglion block for treating lumbar compression fracture-related pain.

BACKGROUND: The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. METHODS: We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. RESULTS: Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. CONCLUSIONS: PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

Ocular Jellyfish Stings: Report of 2 Cases and Literature Review.

An ocular jellyfish sting is an ophthalmic emergency and is rarely reported in the medical literature. With the evolution of aquatic activities and entertainment in recent decades, we anticipate that more patients with ocular jellyfish stings may be taken to the emergency department. However, most physicians are unaware of the typical presentations, suitable treatments, prognosis, and possible complications of ocular jellyfish stings. We reported 2 cases with ocular jellyfish stings and collected cases series from literature review. The most common clinical features of ocular jellyfish stings were pain, conjunctival injection, corneal lesion, and photophobia. All patients who sustained ocular stings did so during aquatic activities, and the best management at the scene was proper analgesics and copious irrigation of affected eyes with seawater or saline. The ocular lesions were treated with topical cycloplegics, topical steroids, topical antibiotics, topical antihistamines, and removal of nematocysts. The prognosis was good, and all patients recovered without any permanent sequelae. However, symptoms in some patients may last longer than 1 week. Reported complications included iritis, increased intraocular pressures, mydriasis, decreased accommodation, and peripheral anterior synechiae.

Application of MRI and intraoperative CT fusion images with integrated neuronavigation in percutaneous radiofrequency trigeminal rhizotomy.

BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) has been an effective treatment modality for medically refractory trigeminal neuralgia. Our group has established a protocol for this procedure that includes intraoperative computed tomography (iCT) navigation. The depth of the puncture needle in our protocol was based on cadaveric studies, and anatomical localization was mainly by electric stimulation test. The limitation of the invisibility of the trigeminal cistern on CT imaging and bias from the patient's subjective expression during neurophysiologic stimulation might affect the accuracy of the needle tip and the treatment effect.This study aimed to evaluate the feasibility and preliminary results of the application of magnetic resonance imaging (MRI) and iCT fusion imaging in RF-TR. METHOD: The study included 13 patients who received RF-TR with iCT navigation and with recurrence within 3 years. Repeated RF-TR was performed with real-time guidance by MRI and iCT fusion imaging. RESULTS: A pain-free or partial satisfactory response was reported with 12 patients (92 %). There was a statistically significant difference in the depth of the needle tip before and after application of MRI and iCT fusion imaging. CONCLUSIONS: This preliminary study demonstrated that the application of MRI and iCT fusion could help with anatomical localization of the trigeminal cistern intraoperatively. The improvement in neuronavigation provides a choice in the treatment of recurrent or persistent trigeminal neuralgia after previous intervention. Long-term follow-up of the result is necessary to evaluate the benefit in terms of durability of therapeutic efficacy.

Comorbidities and complications influence the diagnosis and management of geriatric supraglottitis.

INTRODUCTION: This study aimed to assess the differences in the clinical characteristics, management, and outcomes of supraglottitis between geriatric and nongeriatric adults over a 30-month period. METHODS: All adult patients admitted to the emergency department with suspected supraglottitis and who underwent laryngoscopy for confirmation were included. We collected the clinical characteristics, management, and outcomes of these patients and compared geriatric (≥60 years old) and nongeriatric (12-59 years old) groups in terms of these data. RESULTS: Eighty-one geriatric patients and 205 nongeriatric patients were reviewed during the study period. The accuracies of the clinical suspicions of supraglottitis were lower in the geriatric group (geriatric vs nongeriatric, 29.4% vs 47.3%, P = .008). The geriatric group constituted 19.8% of all supraglottitis patients. Comorbidities were discovered in 74.1% of the geriatric group and 25.4% of the nongeriatric group (P = .000). The complication rate in the geriatric patients was almost twice that of the nongeriatric patients (20.8% vs 10.8%). Additionally, the geriatric patients exhibited tendencies toward longer periods of intubation, hospitalization, and stay in the intensive care unit. CONCLUSIONS: The clinical characteristics and management were similar between the geriatric and nongeriatric supraglottitis patients. Nevertheless, the comorbidities altered the clinical presentations of the geriatric patients and resulted in lower diagnostic accuracy. Additionally, the elevated complication rates of the geriatric patient might have negatively affected their outcomes.

Systemic lupus erythematosus presenting with cardiac symptoms.

BACKGROUND: The objective of this study was to describe the characteristics of patients presenting to the emergency department with cardiac symptoms subsequently diagnosed to have systemic lupus erythematosus (SLE). METHODS: The authors performed a review of newly diagnosed SLE patients at 2 hospitals in Tainan city between January 2010 and December 2013. Patients initially presenting with cardiac symptoms were included. Demographic data, presenting symptomatology, laboratory data, and imaging studies were obtained and analyzed. RESULTS: Eight cases, including 5 female and 3 male patients, were identified during the 4-year study period. The mean age was 37 (range, 15-54) years. Pericardial effusion (63%) and mitral regurgitation (63%) were the most common cardiac abnormalities, followed by impairment of left ventricular systolic function (25%) and tricuspid regurgitation (13%). Most patients showed signs of increased generalized inflammation and immunological activity with elevated levels of C-reactive protein (100%) and anti-dsDNA (88%) and decreased complement levels (63%). The median duration from admission to the diagnosis of SLE was 6.3 (range, 1-13) days, and all patients showed multiple-organ involvement in addition to the cardiovascular system. CONCLUSIONS: Patients presenting to the emergency department with cardiac symptoms without a history of cardiopulmonary disease or traditional cardiovascular disease risk factors should be assessed for an underlying cause of cardiac decompensation. If the patients exhibit extracardiac manifestations or their illnesses involve multiple-organ systems, screening tests for autoimmune diseases such as SLE are mandatory.

Trans-foramen ovale biopsy of a parasellar lesion guided by intraoperative CT neuronavigation with MRI fusion: a case report.

A 23-year-old male presented with a parasellar lesion which was suspected as disseminated intracranial germ cell tumour. The diagnosis of germinoma was made using immunohistochemistry from percutaneous trans-foramen ovale biopsy. This report describes the role of neuronavigation-guided biopsy through the foramen ovale for lesions in the parasellar region.