Effectiveness of Acupotomy Combined with Epidural Steroid Injection for Lumbosacral Radiculopathy: A Randomized Controlled Pragmatic Pilot Study.

Background and Objectives: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine its feasibility for the main study. Materials and Methods: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5-10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits. Results: Mean ODI scores for the experimental and control groups were -9.44 (95% confidence interval [CI]: -12.71, -6.17) and -2.16 (95% CI: -5.01, 0.69) at week 4, and -9.04 (95% CI: -12.09, -5.99) and -4.76 (95% CI: -7.68, -1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (p = 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed. Conclusions: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.

Acupotomy in Korean Medicine Doctors: A Preliminary Survey on Experiences, Perceptions, and Clinical Usage Status.

Acupotomy is a widely used medical intervention in traditional East Asian medicine, and efforts are being made to improve its effectiveness and safety. As a first step toward establishing more standardized procedural guidelines, a survey was conducted to explore the current clinical practice status and perceived adverse events (AEs) by Korean Medicine (KM) practitioners. The survey was developed via expert consensus and included information on clinical usage, perception, and the AEs experienced. The largest acupotomy society in Korea, which consists of 185 KM doctors, participated in an online survey conducted in September 2021. Of the 185 KM doctors, 107 (57.8%) responded. Musculoskeletal and connective tissue diseases accounted for 80.8% of suggested indications by KM doctors. Regarding the detailed procedure, there were considerable discrepancies between KM doctors. The most frequent acupotomy-related AEs observed by KM practitioners were bruises (77.3%), fatigue (57.7%), pain (51.8%), and hematoma (51.8%). Only 1.8% of the respondents answered that they had experienced severe AEs. Survey respondents answered that the use of imaging devices during acupotomy and the development of clinical practice guidelines are the most necessary policy requirements for promoting the use and ensuring the safety of acupotomy. To the best of our knowledge, this study marks the initial exploration into the KM physicians' clinical usage status, AEs experienced, and their requests for standardized guidelines and expanded health insurance coverage concerning acupotomy. Further research should include qualitative studies to assess patient experience and prospective observational studies to examine the effects of operator skills and treatment modalities on AEs and adherence.

Organ Abnormalities Caused by Turner Syndrome.

Turner syndrome (TS), a genetic disorder due to incomplete dosage compensation of X-linked genes, affects multiple organ systems, leading to hypogonadotropic hypogonadism, short stature, cardiovascular and vascular abnormalities, liver disease, renal abnormalities, brain abnormalities, and skeletal problems. Patients with TS experience premature ovarian failure with a rapid decline in ovarian function caused by germ cell depletion, and pregnancies carry a high risk of adverse maternal and fetal outcomes. Aortic abnormalities, heart defects, obesity, hypertension, and liver abnormalities, such as steatosis, steatohepatitis, biliary involvement, liver cirrhosis, and nodular regenerative hyperplasia, are commonly observed in patients with TS. The SHOX gene plays a crucial role in short stature and abnormal skeletal phenotype in patients with TS. Abnormal structure formation of the ureter and kidney is also common in patients with TS, and a non-mosaic 45,X karyotype is significantly associated with horseshoe kidneys. TS also affects brain structure and function. In this review, we explore various phenotypic and disease manifestations of TS in different organs, including the reproductive system, cardiovascular system, liver, kidneys, brain, and skeletal system.

Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal.

Background and Objectives: DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs). Methods and Results: We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs in vitro. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells. Conclusions: Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.

Positive short term effects of an integrative korean medicine treatment package for low back pain caused by motor vehicle accidents: A retrospective chart review of real - world practice data.

Backgrounds No standard treatment exist for reducing symptoms related to sequelae of motor vehicle accidents (MVAs). In Korea, comprehensive Korean Medicine (KM) treatment that includes botanical drugs (herbal medicine), acupuncture, pharmacopuncture, tuina, moxibustion, and cupping is covered by automobile insurance and increasingly used to help alleviate such pain. This study aimed to analyze real-world data and to evaluate the effectiveness and safety of comprehensive KM treatment for low back pain caused by MVAs. Methods We conducted a retrospective chart review of patients who received KM treatment during hospitalization. Records that lacked follow-up outcome assessments were excluded. The Verbal Numerical Rating Scale (VNRS), the Korean version of the Oswestry Disability Index (K-ODI) and the Korean version of the Roland-Morris Disability Questionnaire (K-RMDQ) were evaluated at admission and discharge. Adverse events were also analyzed. A paired t-test was used to identify the effectiveness of KM treatment. Results A total of 50 patients, 30 males and 20 females, were included in the analysis. The mean age of the patients was 40.72 ± 13.31 years and the average treatment period was 7.22 ± 3.84 days. After treatment, VNRS, K-ODI and K-RMDQ were significantly improved (p < 0.001). There was a decrease from 5.06 ± 1.60 to 3.40 ± 1.81 in VNRS, 33.38 ± 16.88 to 24.54 ± 13.63 in K-ODI, and 6.84 ± 6.27 to 4.14 ± 4.38 in K-RMDQ. During this period, a total of two adverse events were reported. Discussion Although this retrospective chart review looked into the short term effects only, comprehensive KM treatment might be an effective and safe therapeutic option to reduce acute low back pain especially after MVA. Prospective research data is needed to support this hypothesis.

Progression of Ossification of Posterior Longitudinal Ligament After Anterior Cervical Discectomy and Fusion in Military Patients Exposed to Minor Trauma.

Objective: Ossification of the posterior longitudinal ligament (OPLL) can progress even after cervical spine surgery and may cause neurological injury as a result of minor trauma. The purpose of this study was to investigate the preventive factors associated with OPLL progression after anterior cervical discectomy and fusion (ACDF), a procedure commonly performed in clinical practice. Methods: We retrospectively investigated 295 male soldiers who underwent ACDF surgery between 2012 and 2017. Patients who were followed up for >12 months using dynamic radiography and computed tomography (CT) were included in the study. Radiological parameters investigated included OPLL progression, C2-C7 angles on dynamic radiography, segmental angles, C2-C7 cervical sagittal vertical axis (C2-C7 SVA), and the T1 slope. These parameters were measured preoperatively and 1 year postoperatively. Results: A total of 49 patients were enrolled, and 10 patients were confirmed to have OPLL progression. Comparison between the OPLL progression and non-progression groups showed no statistically significant differences in pre- and postoperative cervical range of motion. However, statistically significant differences were observed in the postoperative neutral C2-C7 angle (progression -3.9°±6.4° vs. non-progression -13.4°±7.9°, p=0.001) and the SVA change (progression 5.8±7.9 mm vs. non-progression -3.7±6.3 mm, p=0.00). The cutoff values were -8.01° for the postoperative neutral C2-C7 angle and 1.4 mm for SVA changes. Conclusion: Increased SVA (>1.4 mm) and a small postoperative neutral C2-C7 angle (>-8.01°) 1 year after ACDF were associated with OPLL progression. It is important to be mindful of these factors during follow-up after ACDF, because additional surgical treatment may be necessary for OPLL progression due to neurological injury caused by minor trauma.

Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study.

OBJECTIVE: Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). METHODS: This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. RESULTS: A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. CONCLUSION: The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

An Experimental Study on the Biomechanical Effectiveness of Bone Cement-Augmented Pedicle Screw Fixation with Various Types of Fenestrations.

OBJECTIVE: To analyze the effects of the number and shape of fenestrations on the mechanical strength of pedicle screws and the effects of bone cement augmentation (BCA) on the pull-out strength (POS) of screws used in conventional BCA. METHODS: For the control group, a conventional screw was defined as C1, a screw with cannulated end-holes was defined as C2, a C2 screw with six pinholes was defined as C3, and the control group type was set. Among the experimental screws, T1 was designed using symmetrically placed thru-hole type fenestrations with an elliptical shape, while T2 was designed with half-moon (HM)-shaped asymmetrical fenestrations. T3 and T4 were designed with single HM-shaped fenestrations covering three pitches and five pitches, respectively. T5 and T6 were designed with 0.6-mm and 1-mm wider fenestrations than T3. BCA was performed by injecting 3 mL of commercial bone cement in the screw, and mechanical strength and POS tests were performed according to ASTM F1717 and ASTM F543 standards. Synthetic bone (model #1522-505) made of polyurethane foam was used as a model of osteoporotic bone, and radiographic examinations were performed using computed tomography and fluoroscopy. RESULTS: In the fatigue test, at 75% ultimate load, fractures occurred 7781 and 9189 times; at 50%, they occurred 36122 and 82067 times; and at 25%, no fractures occurred. The mean ultimate load for each screw type was 219.1±52.39 N for T1, 234.74±15.9 N for T2, 220.70±59.23 N for T3, 216.45±32.4 N for T4, 181.55±54.78 N for T5, and 216.47±29.25 N for T6. In comparison with C1, T1, T2, T3, T4, and T6 showed significantly different ultimate load values (p<0.05). However, when the values for C2 and the fenestrated screws were evaluated with an unpaired t test, the ultimate load value of C2 significantly differed only from that of T2 (p=0.025). The ultimate load value of C3 differed significantly from those of T1 and T2 (C3 vs. T1 : p=0.048; C3 vs. T2 : p<0.001). Linear correlation analysis revealed a significant correlation between the fenestration area and the volume of bone cement (Pearson's correlation coefficient r=0.288, p=0.036). The bone cement volume and ultimate load significantly correlated with each other in linear correlation analysis (r=0.403, p=0.003). CONCLUSION: Fenestration yielded a superior ultimate load in comparison with standard BCA using a conventional screw. In T2 screws with asymmetrical two-way fenestrations showed the maximal increase in ultimate load. The fenestrated screws can be expected to show a stable position for the formation of the cement mass.

Leptomeningeal Spread at the Diagnosis of Glioblastoma Multiforme: A Case Report and Literature Review.

Approximately two-thirds of glioblastoma (GBM) patients progress to leptomeningeal spread (LMS) within two years. While 90% of LMS cases are diagnosed during the progression and/or recurrence of GBM (defined as secondary LMS), LMS presentation at the time of GBM diagnosis (defined as primary LMS) is very rare. 18F-fluorodeoxy glucose positron emission tomography computed tomography (18F-FDG PET/CT) study helps to diagnose the multifocal spread of the malignant primary brain tumor. Our patient was a 31-year-old man with a tumorous lesion located in the right temporal lobe, a wide area of the leptomeninges, and spinal cord (thoracic 5/6, and lumbar 1 level) involvement as a concurrent manifestation. After the removal of the right temporal tumor, the clinical status progressed rapidly, showing signs of increased intracranial pressure and hydrocephalus caused by LMS. He underwent a ventriculoperitoneal shunt a week after craniotomy. During management, progression of cord compression, paraplegia, bone marrow suppression related to radiochemotherapy, intercurrent infections, and persistent ascites due to peritoneal metastasis of the LMS through the shunt system was observed. The patient finally succumbed to the disease nine months after the diagnosis of simultaneous GBM and LMS. The overall survival of primary LMS with GBM in our case was nine months, which is shorter than that of secondary LMS with GBM. The survival period after the diagnosis of LMS did not seem to be significantly different between primary and secondary LMS. To determine the prognostic effect and difference between primary and secondary LMS, further cooperative studies with large-volume data analysis are warranted.

A comparative study of a nerve block therapy with and without a deeply inserted acupotomy applied to hyeopcheok points for lumbosacral radiculopathy: Safety, effectiveness, cost-effectiveness (a randomized controlled, two-arm, parallel study, pilot study, assessor-blind).

INTRODUCTION: The prevalence of lumbosacral radiculopathy is estimated to be approximately 3% to 5% in patient populations. Lumbosacral radiculopathy is largely caused by a complex interaction between biomechanical and biochemical factors. Nerve block therapy (NBT) mainly treats lumbosacral radiculopathy by improving the biochemical factors, whereas acupotomy mainly focuses on improving the biomechanical factors. Therefore, it is thought that synergistic effects may be obtained for the treatment of lumbosacral radiculopathy when both NBT and acupotomy are combined. However, no study in China and Korea, where acupotomy is majorly provided, has reported the effects of such a combination treatment. Therefore, this study aimed to evaluate the safety, effectiveness, and cost-effectiveness of the concurrent use of a deeply inserted acupotomy and NBT for the treatment of lumbosacral radiculopathy. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded, randomized controlled trial, which will include 50 patients with lumbosacral radiculopathy. After patients voluntarily agree to participate in the study, they will be screened, and will undergo necessary examinations and tests according to the protocol. Those who satisfy the selection criteria will be randomly assigned to either the NBT + acupotomy or NBT groups in a 1:1 ratio. Both groups will undergo 2 NBTs once every 2 weeks from 1 week after the screening test. The treatment group will receive additional acupotomy twice a week for 4 weeks. The primary endpoint is the Oswestry Disability Index, whereas the secondary endpoints are the Numeral Rating Scale, European Quality of Life 5-dimension, McGill pain Questionnaire, Roland-Morris Disability Questionnaire, safety assessment, and economic feasibility evaluation. The measurements will be made at 0, 2, 4, and 8 weeks. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS20OISE0085). We intend to submit the results of the trial to a peer-reviewed journal and/or conferences.

A Simple Method for Generating Cerebral Organoids from Human Pluripotent Stem Cells.

BACKGROUND AND OBJECTIVES: In recent years, brain organoid technologies have been the most innovative advance in neural differentiation research. In line with this, we optimized a method to establish cerebral organoids from feeder-free cultured human pluripotent stem cells. In this study, we focused on the consistent and robust production of cerebral organoids comprising neural progenitor cells and neurons. We propose an optimal protocol for cerebral organoid generation that is applicable to both human embryonic stem cells and human induced pluripotent stem cells. METHODS AND RESULTS: We investigated formation of neuroepithelium, neural tube, and neural folding by observing the morphology of embryoid bodies at each stage during the cerebral organoid differentiation process. Furthermore, we characterized the cerebral organoids via immunocytochemical staining of sectioned organoid samples, which were prepared using a Cryostat and Vibratome. Finally, we established a routine method to generate early cerebral organoids comprising a cortical layer and a neural progenitor zone. CONCLUSIONS: We developed an optimized methodology for the generation of cerebral organoids using hESCs and hiPSCs. Using this protocol, consistent and efficient cerebral organoids could be obtained from hiPSCs as well as hESCs. Further, the morphology of brain organoids could be analyzed through 2D monitoring via immunostaining and tissue sectioning, or through 3D monitoring by whole tissue staining after clarification.

Recurrent Cervical Spontaneous Spinal Epidural Hematoma with Conservative Management: A Case Report.

Cervical spontaneous spinal epidural hematoma (CSSEH) is a rare condition that can be potentially fatal if not properly diagnosed and managed. While prompt surgical decompression and evacuation of the hematoma are generally considered as the first line of treatment, mild cases that were managed through observation and conservative treatment have been reported. Our patient was a 24-year-old man who experienced two CSSEH events 8 months apart, both of which were managed conservatively. This was a rare case of recurrent CSSEH in which recovery was achieved without surgical intervention. We believe conservative treatment with close observation may be effective in CSSEH patients presenting with mild neurologic symptoms who have a tendency towards spontaneous neurologic improvement.

Efficient Generation of Neural Stem Cells from Embryonic Stem Cells Using a Three-Dimensional Differentiation System.

Mouse embryonic stem cells (ESCs) are useful tools for studying early embryonic development and tissue formation in mammals. Since neural lineage differentiation is a major subject of organogenesis, the development of efficient techniques to induce neural stem cells (NSCs) from pluripotent stem cells must be preceded. However, the currently available NSC differentiation methods are complicated and time consuming. This study aimed to propose an efficient method for the derivation of NSCs from mouse ESCs; early neural lineage commitment was achieved using a three-dimensional (3D) culture system, followed by a two-dimensional (2D) NSC derivation. To select early neural lineage cell types during differentiation, Sox1-GFP transgenic ESCs were used. They were differentiated into early neural lineage, forming spherical aggregates, which were subsequently picked for the establishment of 2D NSCs. The latter showed a morphology similar to that of brain-derived NSCs and expressed NSC markers, Musashi, Nestin, N-cadherin, and Sox2. Moreover, the NSCs could differentiate into three subtypes of neural lineages, neurons, astrocytes, and oligodendrocytes. The results together suggested that ESCs could efficiently differentiate into tripotent NSCs through specification in 3D culture (for approximately 10 days) followed by 2D culture (for seven days).

Gender differences in adult traumatic brain injury according to the Glasgow coma scale: A multicenter descriptive study.

PURPOSE: Patients' gender, which can be one of the most important determinants of traumatic brain injury (TBI) outcomes, is also likely to interact with many other outcome variables of TBI. This multicenter descriptive study investigated gender differences in epidemiological, clinical, treatment, mortality, and variable characteristics in adult TBI patients. METHODS: The selection criteria were defined as patients who had been diagnosed with TBI and were admitted to the hospital between January 1, 2016 and December 31, 2018. A total of 4468 adult TBI patients were enrolled at eight University Hospitals. Based on the list of enrolled patients, the medical records of the patients were reviewed and they were registered online at each hospital. The registered patients were classified into three groups according to the Glasgow coma scale (GCS) score: mild (13-15), moderate (9-12), and severe (3-8), and the differences between men and women in each group were investigated. The risk factors of moderated and severe TBI compared to mild TBI were also investigated. RESULTS: The study included 3075 men and 1393 women and the proportion of total males was 68.8%. Among all the TBI patients, there were significant differences between men and women in age, past history, and GCS score. While the mild and severe TBI groups showed significant differences in age, past history, and clinical symptoms, the moderate TBI group showed significant differences in age, past history, cause of justice, and diagnosis. CONCLUSION: To the best of our knowledge, this multicenter study is the first to focus on gender differences of adult patients with TBI in Korea. This study shows significant differences between men and women in many aspects of adult TBI. Therefore, gender differences should be strongly considered in TBI studies.

Posterior Approach in C2-3 Disc Herniation: C1 Laminectomy, C2-3 Laminoplasty and Posterior Fixation in C2-3 Disc Herniation.

C2-3 disc herniation is rare and a definitive treatment of choice has not been established. The purpose of this case report is to suggest posterior approach as one of the best options. A 49-year-old man visited our clinic with a 7-year history of neck pain and occipital headache and a 2-month history of right arm pain. C2-3 intervertebral disc herniation of the central type was diagnosed on magnetic resonance imaging (MRI), and surgery was performed, including C1 laminectomy, C2-3 laminoplasty, and C2-3 posterior fixation. The posterior approach was used because the patient's neck was difficult to operate anteriorly. After 3 months postoperatively, MRI showed widened cerebrospinal fluid space at the C2-3 level. The visual analogue scale score for pain improved in the occipital area and right arm. However, the untouched protruded central disc, subjective weakness in right hand grasping, and numbness persisted. In conclusion, this case highlights posterior decompression and fixation as a good treatment of choice for decompression at the C2-3 level disc herniation, from where it is difficult to remove compressive lesions directly via the anterior corridor.

Using magnetic resonance imaging to measure the depth of acupotomy points in the lumbar spine: A retrospective study.

BACKGROUND: The acupotomy is an acupuncture device recently used to stimulate lumbar vertebrae such as transverse processes (TPs) and facet joints (FJs). However, there are many organs, nerves, and blood vessels, which can lead to side effects if the needle misses the treatment target. Therefore, information regarding appropriate insertion depths, which is currently lacking, could facilitate its safe use. We retrospectively investigated the depth from the skin to the TP and FJ of the lumbar vertebrae, using magnetic resonance imaging (MRI). METHODS: This retrospective chart review was conducted at a single medical centre in Korea. From 55,129 patient records, 158 subjects were selected. Perpendicular depth from the skin to the left and right TPs and FJs was measured using T1-weighted sagittal plane MRI. Depth differences between the left and right sides were evaluated using the paired t-test and analysis of covariance (body mass index [BMI] as a covariate). The influence of BMI on depth at each location was evaluated by simple linear regression analysis. RESULTS: The mean age was 43.2 years and mean BMI was 23.6 kg/m2. The depth from skin to the TPs or FJs was unaffected by age, sex, or side. Mean depths (cm) were as follows: (TPs) L1 = 4.5, L2 = 4.9, L3 = 5.3, L4 = 5.7, L5 = 5.9; (FJs) L12 = 3.8, L23 = 4.0, L34 = 4.4, L45 = 4.6, L5S1 = 4.6. Depth was highly correlated with BMI at each location. CONCLUSION: The depth of TPs and FJs adjusted for BMI can safely and effectively be used for treatment via various invasive interventions, including acupotomy treatment, in the lumbar region.

Clinical features and treatment strategy of paraspinal arteriovenous shunt (PAVS): a systematic review with individual participants data meta-analysis.

BACKGROUND: Because of the rarity of the disease, paraspinal arteriovenous shunt (PAVS) is not well recognized, and therapeutic options remain controversial. To introduce a rare disease of PAVS and demonstrate its etiology, clinical features, treatment options, and outcomes, we presented a case report and conducted a systematic review and individual participants data (IPD) meta-analysis. METHODS: Studies regarding on PAVS were integrated and IPD were obtained including patients' demographics, disease etiology, clinical and radiologic features, clinical courses and outcomes. Clinical manifestation and treatment outcomes were reviewed, and comparison analysis (cervical versus thoracolumbar) were performed. Further, logistic regression analyses were conducted to identify the poor prognostic factors (incomplete obliteration). RESULTS: Fifty-two articles were selected, and 88 patients enrolled. General and location-specific characteristics of PAVSs were identified: '3/4 of the isolated and 1/4 of the associated etiology', 'bruit, thrill, or murmur (cervical) and weakness (thoracolumbar) as common symptoms', '40% multiple feeders', and '22% intradural venous involvement'. Endovascular treatment was usually preferred (75%). Of 88 enrolled patients, 18 patients showed incomplete obliteration (20.5%). In multivariate analysis, 'etiologies of systematic genetic dysplasia (P = 0.031) and trauma (negatively, 0.038)' were significantly associated with incomplete obliteration. The parameters of 'multiple feeders (0.066)' and 'combined approach (negatively, 0.065)' are verified only in univariate analysis. CONCLUSION: General as well as location-specific characteristics of PAVS is successfully demonstrated. Approximately 20% of the incomplete obliteration is noted, and three potential poor prognostic factors are identified, namely, 'etiology of systematic genetic dysplasia (positive) and trauma (negative)', 'combined approach (negative), and 'multiple feeders'.

Acupotomy treatment for finger joint contracture after immobilization: Case report.

INTRODUCTION: Contractures frequently occur in the finger joints after immobilization. This report describes the effect of acupotomy treatment in patients with joint contracture due to immobilization of the finger joints. PATIENT CONCERNS AND CLINICAL FINDINGS: Case 1 was of a 39-year-old male patient who had flexion limitation of the left thumb and difficulty in grasping. Case 2 was of a 41-year-old female patient who had flexion limitation of the right index finger and difficulty in typing. Stiffness occurred after tendon repair surgery and cast immobilization in both cases. In Case 1, the patient had limited flexion movement of the first metacarpophalangeal and interphalangeal joints after 5 weeks of immobilization of the left thumb in a cast. In Case 2, the patient had limited flexion movement after 3 weeks of immobilization of the second proximal interphalangeal joint of the left hand in a cast. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: We diagnosed both patients with finger joint contracture due to immobilization. Conservative treatment for approximately 4 weeks did not lead to improvement in either patient. Acupotomy is the key treatment for improving movement in Korean Medicine. Therefore, acupotomy was performed, and joint stiffness markedly improved without adverse events. Both patients reported that the daily use of the damaged fingers became comfortable. CONCLUSION: We found that acupotomy may be effective for finger joint contracture due to improper immobilization. We suggest it as a simple and safe treatment for joint contracture.

Generation of brain organoids from mouse ESCs via teratoma formation.

Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), can differentiate into all cell types in the body; therefore, they are used in the study of development and regenerative medicine. Neural lineage differentiation from PSCs is the initial step to study neurodevelopment and in vitro disease modeling. Brain organoids, which are composed of neural stem cells (NSCs) and differentiated neural lineage cell population, are a powerful in vitro system to mimic the brain tissue. Here, we aimed to establish a new method to generate brain organoids efficiently in a mouse model. We applied the in vivo teratoma formation method as a new approach to generate brain organoids. We induced teratoma formation using Sox1-GFP transgenic ESCs, in which green fluorescence protein (GFP) is expressed under the control of the early NSC marker Sox1. Sox1-GFP-expressing early NSCs were isolated as clumps and further cultured to generate brain organoids. Sox1-GFP ESC-derived brain organoids, composed of multiple layers of distinct cellular components (ventricle, ventricular zone, and cortical layer), were formed within 3 weeks of in vitro culture. We also found that neighboring cells (Sox1-GFP-) surrounding the Sox1-GFP+ clumps are essential for the formation of brain organoids. Thus, in vivo and in vitro conjugated systems-initial commitment in vivo and further specialization in vitro-could be one of the promising platforms for organoid formation that are universally applicable.

Gyejigachulbutang (Gui-Zhi-Jia-Shu-Fu-Tang, Keishikajutsubuto, TJ-18) in Degenerative Knee Osteoarthritis Patients: Lessons and Responders from a Multicenter Randomized Placebo-Controlled Double-Blind Clinical Trial.

BACKGROUND: Gyejigachulbutang (GUI-ZHI-JIA-SHU-FU-TANG, GCB) is an herbal formula widely prescribed in traditional East Asian medicine practice for arthritis and muscle pain. We evaluated the efficacy and safety of GCB for degenerative knee osteoarthritis (KOA). METHODS: Eighty patients with KOA were randomly assigned to the GCB group or the placebo group in a 1 : 1 ratio in two Korean medicine hospitals. Patients took GCB or placebo three times a day for 4 weeks. Primary outcome was the change in the visual analogue scale (VAS) score for knee pain from baseline to 4th week. Secondary outcomes were the change in the VAS score from baseline to 2nd week and 8th week, Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC), European Quality of Life Five Dimensions questionnaire (EQ-5D), and safety. RESULTS: There was no significant difference between the compared indicators of the GCB and placebo groups. However, in subgroup analysis, GCB was effective for subjects with a BMI lower than 25 kg/m2. The dose of pain medication was significantly lower in the GCB group than in the placebo group after four weeks (p=0.016). There were no serious adverse events in the GCB group. CONCLUSIONS: GCB was not effective in primary outcome analysis. In exploratory subgroup analysis, GCB might be effective for individuals with BMI lower than 25 kg/m2 for the treatment of degenerative KOA. GCB may also help reduce the consumption of pain medication. Furthermore, research is required for our hypothesis. This trial is registered with KCT0003024.