Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors.

Cancer immunotherapy is a clinically validated therapeutic modality for cancer and has been rapidly advancing in recent years. Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a viable method of controlling the immune system against cancer. Recent evidence indicates that even immune-cell-released vesicles such as NK-cell-derived exosomes also exert anticancer effect. Nevertheless, the underlying mechanisms remain elusive. In the present study, the anticancer potential of isolated extracellular vesicles (EVs) from expanded and activated NK-cell-enriched lymphocytes (NKLs) prepared by house-developed protocol was evaluated both in vitro and in vivo. Moreover, isolated EVs were characterized by using two-dimensional electrophoresis (2-DE)-based proteome and network analysis, and functional study using identified factors was performed. Our data indicated that the EVs from expanded and active NKLs had anticancer properties, and a number of molecules, such as Fas ligand, TRAIL, NKG2D, ß-actin, and fibrinogen, were identified as effector candidates based on the proteome analysis and functional study. The results of the present study suggest the possibility of NK-cell-derived EVs as a viable immunotherapeutic strategy for cancer.

Characteristics of Vanadium Oxide Thin Films Fabricated by Unbalanced Magnetron Sputtering for Smart Window Application.

Vanadium oxide (VOx) thin films were deposited by an unbalanced magnetron (UBM) sputtering system with a vanadium metal target and O2 reaction gas, and thermally treated at various annealing temperatures. In this work, the structural, electrical, and optical properties of the fabricated VOx films with various annealing temperatures were experimentally investigated. The UBM sputter grown VOx thin films exhibited amorphous structure, and had a very weak peak of V2O5 (002) owing to very thin films. However, the crystallite size of VOx films increased with increasing annealing temperature. The surface roughness of VOx films and average transmittance decreased with increasing annealing temperature. The resistivity of VOx films also decreased with increasing annealing temperature, while the electrical properties of films improved.

Characteristics of Sputtered Cr Thin Films and Application as a Working Electrode in Transparent Conductive Oxide-Less Dye-Sensitized Solar Cells.

Cr metal electrode was suggested as the working electrode material to fabricate DSSCs without the TCO, and thin films were fabricated by an unbalanced magnetron sputtering system. The surface morphologies show uniform and smooth surfaces regardless of various film thicknesses, and the small crystallites of various sizes were showed with the vertical direction on the surface of Cr thin films with the increase of film thickness. And also, the root mean square (RMS) surface roughness value of Cr thin films increased, and the sheet resistance is decreased with the increase of film thickness. The maximum cell efficiency of the TCO-less DSSC was observed when a Cr working electrode with a thickness of 80 nm was applied to the TCO-less DSSC. Consequently, these results are related to the result of the optimization of conduction characteristics, transmission properties and surface properties of Cr thin films.

Cell-assisted lipotransfer in treating uncontrollable sepsis associated perianal fistula: a pilot study.

Purpose: Surgeons can treat debilitating conditions of uncontrollable complex anorectal fistulas with sepsis, even after repeated fistula surgeries, for curative intention. Adipose-derived stem cells have shown good outcomes for refractory Crohn fistula. Unfortunately, cell therapy has some limitations, including high costs. We have therefore attempted immediate cell-assisted lipotransfer (CAL) in treating refractory complex anal fistulas and observed its outcomes. Methods: In a retrospective study, CAL, using a mixture of freshly extracted autologous stromal vascular fraction (SVF) and fat tissues, was used to treat 22 patients of refractory complex anal fistula from March 2018 to May 2021. Preoperative and postoperative assessments were performed with direct visual inspection, digital palpation, and endoanal ultrasonography. A fistula was considered completely healed if (1) the patient had no symptoms of discharge or inflammation; (2) there were no visible secondary openings of fistula tract inside and outside of the anorectal unit and even in the perineum; and (3) there was no primary opening in the anus. The endpoint of complete remission was wound healing without signs of inflammation 3 months after CAL treatment. Results: In a total of 22 patients who received CAL treatment, 19 patients showed complete remission, 1 patient showed partial improvement, and 2 patients showed no improvement. One of the 2 patients without improvement at primary endpoint showed complete remission 9 months after CAL. There were no significant adverse effects of the procedure. Conclusion: We found that the immediately-collected CAL procedure for refractory complex anal fistula showed good outcomes without adverse side effects. It can be strongly recommended as an alternative surgical option for the treatment of complex anal fistula that is uncontrollable even after repeated surgical procedures. However, considering the unpredictable characteristics of SVF, long-term follow-up is necessary.

Hydration-induced rapid growth and regression after indirect revascularization of an anterior choroidal artery aneurysm associated with Moyamoya disease: A case report.

The prevalence of aneurysm formation in adults with Moyamoya disease (MMD) is higher than that in the general population. The treatment strategy is often individualized based on the patient's disease characteristics. A 22-year-old man was diagnosed with MMD after presenting a small thalamic intracerebral and subarachnoid hemorrhage in the quadrigeminal cistern. Cerebral angiography revealed a small aneurysm (2.42 mm) in the left anterior choroidal artery. Since the hemodynamics in the left hemisphere was compromised, an indirect bypass surgery was performed. The patient's condition deteriorated postoperatively because of poor perfusion of the internal carotid artery, and massive hydration was required. During neurocritical care, the aneurysm increased in size (5.33 mm). An observation strategy was adopted because of the distal aneurysmal location and the high risk involved. Subsequently, the patient recovered, and newly developed collateral flow appeared from the external carotid artery. Additionally, a dramatic size reduction of the aneurysm (1.51 mm) was noticed. Our case suggests that MMD-related dissecting aneurysms on a distal cerebral artery, which present a high risk of embolization, could be managed by indirectly reducing the hemodynamic burden. Massive hydration in such cases should be avoided or balanced to avoid the risk of rapid growth and aneurysm rupture.

Trends in Treatment for Hemorrhoids, Fistula, and Anal Fissure: Go Along the Current Trends.

Recent trends in benign anal disease treatment are minimizing surgery to preserve normal anorectal anatomical unit and its functions. However, some surgeons still prefer and are confident with the use of conventional solid surgical methods. In this report, we will investigate the recent trends in the treatment for hemorrhoids, fistula, and anal fissure. The practice guidelines of advanced countries, including UK, Italy, France, USA, Japan, and ESCP, are referred to in this review. Opinions suggested in international meetings were also added. In the management of hemorrhoids, surgical treatments and office procedures were recommended according to a patient's status and preference. For the management of complex anal fistula, novel sphincter-preserving surgical techniques are more widely accepted than a sphincter-dividing procedure of immediate repair following fistulectomy. The treatment of anal fissures is well covered in the guidelines of the ASCRS.

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.

Value of Additional Instrumented Fusion in the Treatment of Thoracic Ossification of the Ligamentum Flavum.

OBJECTIVE: The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Surgical decompression with or without instrumented fusion is the mainstay of treatment. However, few studies have reported on the added effect of instrumented fusion. The objective of this study was to compare clinical and radiological outcomes between surgical decompression without instrumented fusion (D-group) and that with instrumented fusion (F-group). METHODS: A retrospective review was performed on 28 patients (D-group, n=17; F-group, n=11) with thoracic myelopathy due to OLF. The clinical parameters compared included scores of the Japanese Orthopedic Association (JOA), the Visual analogue scale of the back and leg (VAS-B and VAS-L), and the Korean version of the Oswestry disability index (K-ODI). Radiological parameters included the sagittal vertical axis (SVA), the pelvic tilt (PT), the sacral slope (SS), the thoracic kyphosis angle (TKA), the segmental kyphosis angle (SKA) at the operated level, and the lumbar lordosis angle (LLA; a negative value implying lordosis). These parameters were measured preoperatively, 1 year postoperatively, and 2 years postoperatively, and were compared with a linear mixed model. RESULTS: After surgery, all clinical parameters were significantly improved in both groups, while VAS-L was more improved in the Fgroup than in the D-group (-3.4±2.5 vs. -1.3±2.2, p=0.008). Radiological outcomes were significantly different in terms of changes in TKA, SKA, and LLA. Changes in TKA, SKA, and LLA were 2.3°±4.7°, -0.1°±1.4°, and -1.3°±5.6° in the F-group, which were significantly lower than 6.8°±6.1°, 3.0°±2.8°, and 2.2°±5.3° in the D-group, respectively (p=0.013, p<0.0001, and p=0.037). Symptomatic recurrence of OLF occurred in one patient of the D-group at postoperative 24 months. CONCLUSION: Clinical improvement was achieved after decompression surgery for OLF regardless of whether instrumented fusion was added. However, adding instrumented fusion resulted in better outcomes in terms of lessening the progression of local and regional kyphosis and improving leg pain. Decompression with instrumented fusion may be a better surgical option for thoracic OLF.

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.

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.

Highly Skin-Conformal Laser-Induced Graphene-Based Human Motion Monitoring Sensor.

Bio-compatible strain sensors based on elastomeric conductive polymer composites play pivotal roles in human monitoring devices. However, fabricating highly sensitive and skin-like (flexible and stretchable) strain sensors with broad working range is still an enormous challenge. Herein, we report on a novel fabrication technology for building elastomeric conductive skin-like composite by mixing polymer solutions. Our e-skin substrates were fabricated according to the weight of polydimethylsiloxane (PDMS) and photosensitive polyimide (PSPI) solutions, which could control substrate color. An e-skin and 3-D flexible strain sensor was developed with the formation of laser induced graphene (LIG) on the skin-like substrates. For a one-step process, Laser direct writing (LDW) was employed to construct superior durable LIG/PDMS/PSPI composites with a closed-pore porous structure. Graphene sheets of LIG coated on the closed-porous structure constitute a deformable conductive path. The LIG integrated with the closed-porous structure intensifies the deformation of the conductive network when tensile strain is applied, which enhances the sensitivity. Our sensor can efficiently monitor not only energetic human motions but also subtle oscillation and physiological signals for intelligent sound sensing. The skin-like strain sensor showed a perfect combination of ultrawide sensing range (120% strain), large sensitivity (gauge factor of ~380), short response time (90 ms) and recovery time (140 ms), as well as superior stability. Our sensor has great potential for innovative applications in wearable health-monitoring devices, robot tactile systems, and human-machine interface systems.

The Korean Version of the Fugl-Meyer Assessment: Reliability and Validity Evaluation.

OBJECTIVE: To systematically translate the Fugl-Meyer Assessment (FMA) into a Korean version of the FMA (K-FMA). METHODS: We translated the original FMA into the Korean version with three translators and a translation committee, which included physiatrists, physical therapists, and occupational therapists. Based on a test-retest method, each of 31 patients with stroke was assessed by two evaluators twice, once on recruitment, and again after a week. Analysis of intra- and inter-rater reliabilities was performed using the intra-class correlation coefficient, whereas validity was analysed using Pearson correlation test along with the Motricity Index (MI), Motor Assessment Scale (MAS), and Berg Balance Scale (BBS). RESULTS: The intra- and inter-rater reliabilities were significant for the total score, and good to excellent reliability was noted in all domains except for the joint range of motion of the lower extremity domain of the K-FMA. The MI and MAS scores were significantly correlated with all domains, all with p<0.01. The results for the MI ranged from r=0.639 to r=0.891 and those for the MAS from r=0.339 to r=0.555. However, the BBS was not significantly correlated with any domain, as the K-FMA lacks balance evaluation items. CONCLUSION: The K-FMA was found to have high reliability and validity. Additionally, the newly developed manual for the K-FMA may help minimise errors that can occur during evaluation and improve the reliability of motor function evaluation.

Risk Factors for Symptomatic Contralateral Foraminal Stenosis After Unilateral Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: The most common cause of contralateral symptoms after unilateral transforaminal lumbar interbody fusion (TLIF) is contralateral foraminal stenosis (FS). This retrospective cohort study aimed to investigate the cause of and risk factors for contralateral FS after unilateral TLIF with a single cage. METHODS: Patients with degenerative lumbar spinal disorders who underwent unilateral TLIF at L4-5 were divided into 2 groups: those without contralateral radicular symptoms after surgery (group A; n = 340) and those with contralateral radicular symptoms after surgery (group B; n = 16). We investigated the influence of various radiological and cage-related factors on postoperative contralateral FS with radicular symptoms. The cage location indicates whether the cage's anterior tip crosses the disc midline-exceeding 50%-and in such a case, how far. RESULTS: Group B showed significantly increased postoperative coronal angle and sagittal angle and decreased contralateral foraminal height and foraminal area. Statistically significant (P < 0.01) factors according to the multivariate logistic regression analysis were the preoperative sagittal range of motion (odds ratio [OR]: 1.562, P = 0.004) and cage location (OR: 2.047, P = 0.015). The cutoff values for the sagittal range of motion and the cage location were 9.0° and 50.5%, respectively. The preoperative and postoperative 6-month visual analog scale scores and Oswestry disability index values were not significantly different between the groups. CONCLUSIONS: The 2 most meaningful risk factors were the preoperative sagittal range of motion and cage location. Inserting the cage beyond the disc midline, especially in patients with a high preoperative sagittal range of motion (≥9.0°), would help reduce postoperative complications.

Incidentally Found Intramuscular Hemangioma, Mimicking Traumatic Hematoma after Military Training: A Case Report.

This case report showed a young soldier complained of low back pain during military training. Intramuscular hematoma accompanied by the lumbar compression fracture was observed in computed tomography. However, the possibility of intramuscular tumors could not be ruled out through additional examinations, and thus surgically removed, and was diagnosed as cavernous hemangioma. This report is a rare and instructive case in which a hemangioma mimicked bleeding with the lumbar fracture.

Features of "false positive" unruptured intracranial aneurysms on screening magnetic resonance angiography.

BACKGROUND: Physicians can find it challenging to decide whether confirmative digital subtraction angiography (DSA) should be performed in patients who present with "suspicious small aneurysm-like structures" on magnetic resonance angiography (MRA). Factors associated with "false positive aneurysms on MRA" (FPAMs)," which are finally confirmed as negative on DSA, have rarely been reported. This study aimed to identify the clinical or radiologic clues indicative of FPAM on DSA. METHODS: Patients who had undergone DSA between 2016 and 2019 for suspicious aneurysm-like structures < 5 mm in size on MRA were enrolled. Patient demographics and the details regarding the geometry of the structures were retrospectively reviewed. Univariate and multivariate logistic regression analyses were conducted to identify the associated factors. Receiver operating characteristic curve analysis was performed to assess the clinical implications. RESULTS: Of the 107 suspicious structures, 46 were indicated as being false positive on DSA (42.96%). Location (positive on C7 and negative on C5-6 ICA) and lower dome to neck ratio were found to be significant parameters in the multivariate analysis. The dome to neck ratio threshold value was 0.99. CONCLUSION: Suspicious aneurysm-like structures located not on C5-6 but on C7 ICA and having wide neck morphologies (dome to neck ratio < 0.99) are highly likely to be negative on DSA.

The Long-term Reoperation Rate Following Surgery for Lumbar Stenosis: A Nationwide Sample Cohort Study With a 10-year Follow-up.

STUDY DESIGN: Retrospective cohort study of a nationwide sample database. OBJECTIVE: The objective of the present study was to compare the long-term incidence of reoperation for lumbar spinal stenosis (LSS) after anterior fusion, posterior fusion, and decompression. SUMMARY OF BACKGROUND DATA: Surgical treatment for LSS can be largely divided into 2 categories: decompression only and decompression with fusion. A previous nationwide study reported that fusion surgery was performed in 10% of patients with LSS, and the 10-year reoperation rate was approximately 17%. However, with the development of surgical techniques and changes in surgical trends, these results should be reassessed. METHODS: The National Health Insurance Service-National Sample Cohort of the Republic of Korea was utilized to establish a cohort of adult patients (N = 1400) who first underwent surgery for LSS during 2005 to 2007. Patients were followed for 8 to 10 years. Considering death before reoperation as a competing event, reoperation hazards were compared among surgical techniques using a Fine and Gray regression model after adjustment for sex, age, diabetes, osteoporosis, Charlson comorbidity index, severity of disability, type of medical coverage, and type of hospital. RESULTS: The overall cumulative incidence of reoperation was 6.2% at 2 years, 10.8% at 5 years, and 18.4% at 10 years. The cumulative incidence of reoperation was 20.6%, 12.6%, and 18.6% after anterior fusion, posterior fusion, and decompression, respectively, at 10 years postoperatively (P = 0.44). The first surgical technique did not affect the reoperation type (P = 0.27). Decompression was selected as the surgical technique for reoperation in 83.5% of patients after decompression, in 72.7% of patients after anterior fusion, and in 64.3% of patients after posterior fusion. CONCLUSION: The initial surgical technique did not affect reoperation during the 10-year follow-up period. Decompression was the most commonly used technique for reoperation. LEVEL OF EVIDENCE: 4.

The Efficacy of Ultrasonic Bone Scalpel for Unilateral Cervical Open-Door Laminoplasty: A Randomized Controlled Trial.

BACKGROUND: In cervical open-door laminoplasty for cervical myelopathy, a high-speed rotatory drill and rongeurs are used to make unicortical troughs and bicortical openings in the laminae. The lamina is reflected at the trough to enlarge the spinal canal, followed by bone healing on the hinge side to stabilize laminoplasty. The ultrasonic bone scalpel (UBS) has been used due to theoretical advantages including a better hinge union rate, less soft tissue trauma, less neurological injury, and shorter operative time. OBJECTIVE: To assess the superiority of UBS for hinge union compared to the drill through randomized controlled trial. METHODS: In 190 randomly allocated cervical myelopathy patients, the trough and opening at the lamina were made using either the drill (n = 95) or UBS (n = 95) during 2015 to 2018. The primary outcome was the hinge union rate on 6-mo postoperative computed tomography. Secondary outcomes included the hinge union rate at 12 mo, the operative time, intraoperative/postoperative bleeding, neurological injury, complications, and clinical outcomes over a 24-mo follow-up. RESULTS: Hinge union in all laminae was achieved in 60.0% (drill) and 43.9% (UBS) of patients at 6 mo (intention-to-treat analysis; P = .02; odds ratio, 2.1) and in 91.9% (drill) and 86.5% (UBS) at 12 mo. Dural injury only occurred in the drill group (2.1%), and the UBS group showed significantly less intraoperative bleeding (P < .01). The other secondary outcomes did not differ between groups. CONCLUSION: The hinge union rate was inferior in the UBS group at 6 mo postoperatively, but UBS was efficacious in reducing dural injuries and bleeding.

Droplet-Mediated Deterministic Microtransfer Printing: Water as a Temporary Adhesive.

Deterministic transfer printing of solid objects has been introduced and demonstrated, where capillary force based on water droplet has been utilized. Droplets on pickup head form capillary bridges with chips to be picked, where the capillarity provides enough force to grip or lift the chip. Release or printing of chips can be achieved by simply drying droplet while the chip is in contact with receiver substrate. That is, water droplet acts as a temporary adhesive, adheres onto solid chip by capillary force, and releases it upon drying. The technique has unique features such as self-alignment during pickup, self-correction on pickup head by short exposure to water mist, and pickup capability of solids having a nonflat, corrugated surface, all of which originated from the fluidic nature of water droplet. The technique has been successfully applied for the fabrication of stretchable micro-light-emitting diode chip arrays. The proposed technique can find wide applications in many fields such as displays, sensors, printed electronics, photovoltaics, etc.

Progression of Ossification of the Posterior Longitudinal Ligament after Cervical Total Disc Replacement.

OBJECTIVE: Total disc replacement (TDR) is frequently performed anterior approaching method for the patients diagnosed with cervical disc herniation. This study aimed to assess the degree of ossification of the posterior longitudinal ligament (OPLL) progression after cervical TDR. METHODS: Twenty-two male soldiers who underwent cervical TDR surgery from 2009 to 2016 and were followed-up for more than 12 months were enrolled. The enrolled patients were classified as; 1) patients with pre-existing OPLL and without; and 2) patient showing progression of OPLL or not. RESULTS: Twenty-two men were included in the analysis. The mean follow-up period from the surgery was 41.4 months (range, 12-114 months). The mean age of all patients was 40.7 years (range, 31-52 years). TDR-only was used in 7 cases, and the hybrid surgery (TDR+ACDF) was used in 15 cases. The incidence of progression or newly development of OPLL was significantly higher in pre-existing OPLL group (p=0.01). In 11 cases showing the progression of the OPLL, the mean size of OPLL progression was 4.16 mm (range, 0.34-18.87 mm) in the longitudinal height and 1.57 mm (range, 0.54-3.91 mm) in thickness. CONCLUSION: The progression of OPLL after cervical TDR was more frequent in patients with pre-existing OPLL than in patients without OPLL. Even though TDR is a major alternative to the treatment of cervical lesions to preserve vertebral segmental motion, careful attention should be paid to whether TDR should be used in patients with OPLL and this should be fully explained to the patient.